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The effect of hydroxypropyl-beta-cyclodextrin (HPbetaCD) on the chemical stability of sulfamethoxazole and trimethoprim (co-trimoxazole) under oxidation stress at 50 +/- 2 degrees C was investigated. The concentrations of sulfamethoxazole and trimethoprim in aqueous solutions (pH 5.4) containing 0, 1%, 2%, 5%, 10% and 15% w/v hydroxypropyl-beta-cyclodextrin were measured by HPLC. Both sulfamethoxazole and trimethoprim degradation appeared to follow pseudo-first order kinetics in the presence and in the absence of hydroxypropyl-beta-cyclodextrin. The observed half-lives for sulfamethoxazole and trimethoprim in 15% w/v hydroxypropyl-beta-cyclodextrin were 910 h and 609 h respectively, 11.8 and 3.4 times greater than in solutions without hydroxypropyl-beta-cyclodextrin. Using a Lineweaver-Burk equation, the half-lives for sulfamethoxazole and trimethoprim outside the complex in a solution containing 15% w/v hydroxypropyl-beta-cyclodextrin were estimated at 77 h and 193 h respectively, whereas inside the complex the half-lives were estimated at 850 h and 821 h. In terms of relative increases in stability under oxidation stress the half-lives for sulfamethoxazole and trimethoprim inside the complex were 11.0 times and 4.2 times greater than their half-lives outside the complex. In conclusion, chemical stability of sulfamethoxazole and trimethoprim in co-trimoxazole aqueous solutions under oxidation stress at 50 +/- 2 degrees C can be increased using hydroxypropyl-beta-cyclodextrin as a molecular inclusion excipient.

Although the Code of Federal Regulations has provided guidelines regarding research involving vulnerable participants, persons not traditionally identified may also be considered vulnerable at a given time due to emergent or acute illness, end-of-life needs, or circumstances encountered that challenge capacity to provide informed consent. In this column, the author presents an overview of institutional review board roles, responsibilities, processes, and suggestions regarding assessment of vulnerability and capacity to consent that is responsive to current societal and healthcare needs.

Neurones are noisy elements. Noise arises from both intrinsic and extrinsic sources, and manifests itself as fluctuations in the membrane potential. These fluctuations limit the accuracy of a neurone's output but have also been suggested to play a computational role. We present a detailed study of the amplitude and spectrum of voltage noise recorded at the soma of layer IV-V pyramidal neurones in slices taken from rat neocortex. The dependence of the noise on holding potential, synaptic activity and Na+ conductance is systematically analysed. We demonstrate that voltage noise increases non-linearly as the cell depolarizes (from a standard deviation (s.d.) of 0.19 mV at -75 mV to an s.d. of 0.54 mV at -55 mV). The increase in voltage noise is accompanied by an increase in the cell impedance, due to voltage dependence of Na+ conductance. The impedance increase accounts for the majority (70%) of the voltage noise increase. The increase in voltage noise and impedance is restricted to the low-frequency range (0.2-2 Hz). At the high frequency range (5-100 Hz) the voltage noise is dominated by synaptic activity. In our slice preparation, synaptic noise has little effect on the cell impedance. A minimal model reproduces qualitatively these data. Our results imply that ion channel noise contributes significantly to membrane voltage fluctuations at the subthreshold voltage range, and that Na+ conductance plays a key role in determining the amplitude of this noise by acting as a voltage-dependent amplifier of low-frequency transients.

Interest in the economics of trachoma is high because of the refinement of a strategy to control trachomatous blindness, an ongoing global effort to eliminate incident blindness from trachoma by 2020, and an azithromycin donation program that is a component of trachoma control programs in several countries. This report comments on the economic distribution of blindness from trachoma and adds insight to published data on the burden of trachoma and the comparative costs and effects of trachoma control. Results suggest that 1) trichiasis without visual impairment may result in an economic burden comparable to trachomatous low vision and blindness so that 2) the monetary burden of trachoma may be 50% higher than conservative, published figures; 3) within some regions more productive economies are associated with less national blindness from trachoma; and 4) the ability to achieve a positive net benefit of trachoma control depends importantly on the cost per dose of antibiotic.

Objective: Salbutamol is commonly delivered as a racemic mixture of pharmacologically active (R)-salbutamol and inactive (S)-salbutamol. This study investigated inactive (S)- and active (R)-salbutamol plasma levels and their relationship to dose in patients with severe asthma., Methods: Basic demographics, racemic-salbutamol dose in the preceding 24 h, lung function tests at baseline and 1 h, and a 10 mL plasma sample were obtained from subjects presenting to the Department of Emergency Medicine with acute asthma. Plasma determinations were carried out using an LC-MS assay with solid phase extraction., Results: All patients (n = 5) had detectable levels of drug in plasma with range of 0.9-7.7 and 4.7-27.4 ng/mL for (R)-salbutamol and (S)-salbutamol respectively. These were correlated to total racemic salbutamol dose. The range of the (S) : (R) ratio was 2.0-5.2, with (R)-salbutamol representing 16-33% of the total plasma concentration, which did not correlate with total salbutamol dose., Conclusion: Only a small fraction of total plasma salbutamol concentration was found to consist of active enantiomer in patients with an acute severe exacerbation of asthma actively undergoing treatment with racemic-salbutamol. As a result of the possible contribution of (S)-salbutamol to poor asthma control further enantioselective investigations are warranted in severe asthma.

The correlation between low level time-weighted average (TWA) atmospheric xylene exposure (p.p.m.) and urinary methylhippuric acid (MHA) expressed per gram of creatinine was examined. Subjects were recruited from workplaces that utilized xylene. Ambient monitoring of o-, m- and p-xylene isomers was carried out using passive diffusion vapour monitors. Adjusted (post-shift minus pre-shift) and post-shift urinary levels of xylene metabolites (2-, 3- and 4-MHA) were determined by GC-MS. Twenty subjects were recruited into the study. Total xylene TWA exposures were 3.36 +/- 3.63 p.p.m. (mean +/- SD) with a range of 0.03-14.44 p.p.m. The r(2) values for the regression equations between xylene exposure and individual and total adjusted MHA isomers were 0.390, 0.709, 0.677 and 0.631 for o-, m-, p- and total xylenes, respectively, which was greater than the respective correlations between non-adjusted samples. In conclusion, biological monitoring of occupational xylene exposure at levels <15 p.p.m. using urinary MHA showed a good correlation with atmospheric levels and is a valid complement to ambient monitoring. Even though occupational xylene exposure in the workplaces studied was generally low, MHA was found in the pre-shift urine of all workers and the use of adjusted values showed modest improvements in correlations. Recent exposure prior to sampling, either from occupational or non-occupational sources, should be considered when biological monitoring of xylene is undertaken. Extrapolation of data from this study predicted a MHA concentration in post-shift urine of 1.3 g/g creatinine after exposure to a TWA of 100 p.p.m. xylene.

A sensitive enantioselective liquid chromatography-mass spectrometry (LC-MS) assay using a manual solid-phase extraction (SPE) procedure, a non-deuterated internal standard and an ion trap LC-MS was developed to measure (R)- and (S)-albuterol in plasma. Sample extraction from plasma was achieved by a manual SPE extraction procedure with methoxyphenamine added as the internal standard. Chiral separation was achieved using a teicoplanin-based stationary phase and a mobile phase consisting of methanol, acetic acid and 28% (w/v) ammonia (1000:5:1, v/v/v). Samples were analyzed by selected reaction monitoring of product ions from the protonated molecular ions. The detection limit of the assay was 0.1 ng/ml with a conservative lower limit of quantification of 0.25 ng/ml for each enantiomer. Recovery of albuterol enantiomers from plasma spiked at 10 ng/ml of racemate was determined to be 89+/-5.8% (mean+/-S.D.). Reproducibility at 10 ng/ml of racemate assessed by the coefficient of variation was found to be 6.5% (n=5). Instrument precision (measured as coefficient of variation) was 1.4% (n=5). The correlation coefficient r(2) determined from the calibration curve over the range 0.5-50.0 ng/ml racemate in plasma was 0.998. This assay allows adequate sensitivity, recovery and reproducibility for the application to studies of inhaled albuterol.

Background: 3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (statin) therapy has proven efficacy in reducing the rate of coronary and cerebrovascular events in patients 75 years of age or younger with a history of myocardial infarction. However, in patients older than 75 years of age, the efficacy and potential cost-effectiveness of statins are unknown., Objective: To estimate the incremental cost-effectiveness of statin therapy compared with usual care in patients 75 to 84 years of age with previous myocardial infarction., Design: Cost-effectiveness analysis., Data Sources: Published data from cohort studies., Target Population: Patients 75 to 84 years of age with a history of myocardial infarction., Time Horizon: Lifetime., Perspective: Societal., Intervention: Statin therapy., Outcome Measures: Life expectancy, quality-adjusted life expectancy, and incremental cost-effectiveness., Results of Base-Case Analysis: The incremental cost-effectiveness of statin therapy compared with usual care in patients 75 to 84 years of age with previous myocardial infarction was $18800 per quality-adjusted life-year (QALY)., Results of Sensitivity Analysis: On the basis of a probabilistic sensitivity analysis, there is a 75% chance that statin therapy costs less than $39800 per QALY compared with usual care. If the cost of statin therapy and efficacy of statin therapy at reducing myocardial infarction were set to their most favorable values, statin therapy cost $5400 per QALY; if cost and efficacy were set to their least favorable values, statin therapy cost $97800 per QALY., Conclusions: The cost-effectiveness ratios of statin therapy in older patients with previous myocardial infarction are reasonable under a wide variety of assumptions about drug efficacy, drug cost, and rates of cardiac and cerebrovascular events. Pending results of randomized, controlled trials of secondary prevention in patients in this age group, statin therapy seems to be as cost-effective as many routinely accepted medical interventions in this setting.

A descriptive exploratory study using Peplau's theory was conducted to investigate the experiences of parenting among those who have been identified as having positive parenting processes. Using guide questions developed from the objectives of the study, the researcher interviewed 16 parents who had at least one child who had completed high school. Transcribed interviews were examined for themes following the analysis-synthesis procedure. The findings illustrated parents' beliefs that their children's contentment, connectedness, and independence were indications of positive outcomes and that parents' communication of expectations, active strategies, and responses to challenges were critical in facilitating their children's growth. Recommendations for practice, research, and education are suggested.

Data on bicycle injury presentations at a public hospital emergency department for 1991-95 inclusive were analysed to determine the nature and extent of bicycle injuries in the community. There were 599 bicycle injury presentations during the study period, representing more than 2.0% of all injury-related presentations to the emergency department. The main outcome measures were severity and type of injury. Distribution by gender, age, helmet use (1991 and 1992 only), location and mechanism was examined. Rider-only injuries (falls or collisions with stationary objects) accounted for 79.3% of all presentations with only 5.2% due to collisions on a public road or footpath with other moving traffic. Of all injuries where a location was determined, 61.6% occurred in off-road locations. There was little difference in the overall proportions of hospital admissions from injuries on-road (12.4%) and off-road (9.0%). Cyclists injured in on-road collisions with traffic had a higher proportion of hospital admissions (40.0%) than those injured on-road by other mechanisms (7.6%). Children under 10 years of age who had been riding without a helmet suffered a much higher proportion of injuries to the head (53.2% of all injuries) than older cyclists riding without a helmet (19.4%). The majority (83.1%) of head injuries in children under 10 years of age occurred off-road and helmet use was lowest in this group (28.6%). Given previous evidence that helmet use can prevent head injuries, strategies to increase helmet use among cyclists, particularly young children, while riding both on and off-road, should be given a high priority. Rider-only injuries are also an important public health issue.

Aim: Some studies have indicated that over-reliance on inhaled bronchodilator (beta 2-agonist) therapy may worsen asthma control and increase morbidity. The aim of this study was to measure urinary concentrations of salbutamol, the most commonly used bronchodilator, in a relatively large sample of asthmatic patients and examine the potential value of the concentration as an indicator of over-use of salbutamol., Method: The urinary concentrations of the drug were measured in 'spot' urine samples from 102 asthmatic patients (64 community patients and 38 hospital inpatients). A solid-phase extraction technique, using a phenyl-bonded phase and a reversed-phase ion-pair high-performance liquid chromatography assay with UV-detection were developed and used to measure both unchanged salbutamol concentrations and total salbutamol concentrations after enzymatic hydrolysis of the metabolite. In addition, salbutamol concentrations were corrected for urine dilution, with the measured drug expressed per gram of urinary creatinine., Results: The hospital patients were generally older, had greater disease severity, were more likely to be receiving prophylactic therapy and had received more salbutamol in the past 24 h. The urinary concentrations of salbutamol varied enormously between patients. The median concentrations of unchanged and total drug were 0.38 microgram/ml (range 0-34.4 micrograms/ml) and 2.55 micrograms/ml (range 0-49.8 micrograms/ml), respectively. Even when controlling for dosage in the preceding 24 h, there was a 262-fold and 810-fold variation in the urinary concentrations for unchanged and total salbutamol, respectively, among the community patients. Modest correlations were found between salbutamol concentrations and dosage administered in the preceding 24 h (Spearman's r = 0.67 and 0.54 for unchanged and total drug, respectively; P < 0.001). The correlations improved only slightly with correction for urine dilution (Spearman's r = 0.69 and 0.57 for unchanged and total drug, respectively; P < 0.001)., Conclusion: This enormous inter-patient variability, which may be largely due to differences in the pharmacokinetics of salbutamol and inhaler technique, may play a role in the observed worsening of asthma control with the regular use of inhaled bronchodilator drugs and warrants further investigation. Measuring urinary concentrations of salbutamol in spot samples provides only a relatively crude indication of the extent of use of inhaled salbutamol in the preceding 24 h.

In recent years there has been a change in asthma pharmacotherapy, with considerably greater emphasis placed on the use of preventive therapy (inhaled corticosteroids and sodium cromoglycate) and less reliance on bronchodilator therapy. This study examined Tasmanian prescribing trends to determine whether the recommended changes in the treatment of asthma had transpired into practice and to compare the State prescribing trends with national Australian data. Computerized dispensing records, consisting of summarized monthly lists of all drugs dispensed, from almost one-third of all the community pharmacies within the State were retrospectively collected at intervals of 6 months between 1991 and 1994. Anti-asthma drugs were grouped into beta-agonists, inhaled corticosteroids, theophylline, ipratropium bromide and sodium cromoglycate, and quantities were converted to defined daily doses (DDDs)/1000 population/day, by extrapolation to the entire Tasmanian population. The Tasmanian data were compared with estimated national dispensing data for anti-asthma drugs provided by the Drug Utilization Subcommittee of the Pharmaceutical Benefits Advisory Committee. Tasmanian prescribing was generally similar to the national data, with large rises in the prescribing of inhaled corticosteroids (61% increase), ipratropium bromide (138% increase) and sodium cromoglycate (52% increase), and a decline in theophylline usage (43% decrease) over the period of the study. The prescribing of beta-agonists remained fairly stable over the period of the study, while there was a marked decrease in the ratio of dispensed DDDs of beta-agonists: inhaled corticosteroids (from 2.9 to 1.7). The overall usage of anti-asthma medication in Tasmania was found to be significantly higher than the national data for 1991 and 1992, with an April 1994 level of 74.7 DDDs/1000 population/day (an increase of 6% from April 1991). Tasmanian and national prescribing of anti-asthma drugs appears to have changed in line with current management guidelines, with greater emphasis on the use of inhaled corticosteroids. More attention could also be given to the prescribing of anti-allergy preventive drugs.

As the incidence of violence and potential risks for violence have increased in the health care workplace, the safety of nurses and nursing students has emerged as a critical concern for the profession. This article provides a review of the literature focusing on the incidence of violence toward nurses, factors that contribute to the occurrence of violence, the management of violent or potentially violent situations, and the effects on nurse victims of violence. Additionally, the costs of violence to the health care system and the various ways that violence has been defined are reviewed. The literature on violence occurs primarily in the clinical specialty areas of psychiatric-mental health, emergency department, long-term care, and home care nursing. To address the need to prepare students to deal with the issue of violence in the health care setting, strategies for nursing education are presented which include role playing, videotape playbacks, and debriefing sessions. Suggested content consists of student self-awareness, assessment, and diagnosis of violent or potentially violent clients, and nursing care planning, interventions, and evaluation for the immediate situation, as well as long-term treatment goals. The authors emphasize the obligation of nurse educators to prepare students to deal with violence in the health care setting.

As part of a larger study of parent-child communication, young adolescents (n = 847), aged 11 to 14 years, responded with brief written answers to the question: "Using your own words, list any happenings that occurred in the family that you feel may have been difficult and have long-lasting effects." The sample was chiefly seventh- and eighth-grade students from two-parent, White, middle-class, urban homes. Content analyses of their responses resulted in the following themes: feelings of loss due to death, divorce, relocation, or a sibling leaving the family; feelings of threat toward family relationships or integrity, personal or family health, personal or family safety and well-being, and violence; feelings of being hassled due to parents' expectations and limits and siblings' disagreements and conflicts; and testing maturity. The data provide significant examples of the life events of families. Recommendations to identify and care for families and young adolescents experiencing these events are proposed.

A reversed-phase ion-pair high-performance liquid chromatography assay was developed for the simultaneous determination of ipratropium bromide, fenoterol hydrobromide, salbutamol sulphate and terbutaline sulphate in nebulizer solution. Chromatographic separation was achieved with a Nova-Pak C18 4 microns 10 cm x 8 mm i.d. Radial-pak cartridge inside a Waters RCM 8 x 10 compression module using ternary gradient analysis. Detection was performed using UV detection at 220 nm. The standard curves were linear over the following ranges: ipratropium bromide 20.8-250.0 micrograms ml-1, fenoterol hydrobromide 27.8-500.0 micrograms ml-1, salbutamol sulphate 34.7-2500.0 micrograms ml-1 and terbutaline sulphate 69.5-2500 micrograms ml-1. Inter-day and intra-day relative standard deviations for each compound ranged from 4.5-5.2% and 3.5-3.9%, respectively. The assay procedure was developed to allow the accurate determination of constituents in various combinations of nebulizer solution, as well as for stability indicating purposes. This provides a convenient means of testing long-term compatibility and stability following the post-manufacture mixing of commonly used nebulized preparations.

Objective: To gather data on the prescribing of psychoactive drugs (benzodiazepines, antidepressants and antipsychotics) using a network of Tasmanian community pharmacies., Design Setting and Participants: The prescribing of psychoactive drugs in the community was studied during 1989 using data retrospectively obtained from computerised dispensing systems in 11 community pharmacies in Tasmania. The data collection procedure included all prescriptions dispensed in the pharmacies, irrespective of supply under the Pharmaceutical Benefits Scheme, the Repatriation Pharmaceutical Benefits Scheme or as a private prescription., Main Outcome Measures: Results of the pooled data were quantified by both the number of prescriptions and the defined daily doses (DDDs) dispensed for the psychoactive drugs., Results: When extrapolated to the population of Tasmania, the estimated annual prescribing rates for the benzodiazepines, antidepressants and antipsychotics (including lithium) were 853.3, 316.2 and 54.8 prescriptions per 1000 persons, respectively. Prescriptions for the psychoactive drugs accounted for 13.2% of all prescriptions dispensed. In terms of DDDs, the estimated prescribing rates for the total Tasmanian population for the benzodiazepines, antidepressants and antipsychotics were 47.8, 12.5 and 2.1 DDDs per 1000 persons per day, respectively. The rate of benzodiazepine prescribing appeared to be high in comparison with the limited Australian data available. The relative prescribing rates of the long acting benzodiazepine hypnotics, flunitrazepam and nitrazepam, were also disturbingly high., Conclusions: This study has demonstrated the potential value of comprehensive pharmacoepidemiological data obtained from a network of community pharmacists and will form the basis for future studies using an expanded collection procedure.