Clinical efficacy of bronchodilators in equine asthma: Looking for minimal important difference.

BACKGROUND: Airway obstruction is the main trait of severe equine asthma that affects respiratory function and elicits detrimental effects on clinical presentation. Only few and underpowered clinical studies have investigated the impact of improvement in lung function induced by bronchodilators on the clinical signs of asthma-affected horses. OBJECTIVES: To identify the minimal important difference (MID) in lung function elicited by bronchodilator leading to a meaningful improvement in clinical signs. STUDY DESIGN: Pairwise meta-analysis and meta-regression analysis. METHODS: Literature searches were performed for studies that investigated the effect of bronchodilator therapy on lung function and clinical condition of asthmatic horses. The relationship between the change in lung function variables and clinical score was analysed via random-effect meta-regression. One-point change of the Improved clinically Detectable Equine Asthma Scoring System (IDEASS) score was used to identify the MID. RESULTS: A significant (P<0.05) relationship was found between the changes in IDEASS score and maximum change in transpulmonary pressure (ΔPplmax ) or pulmonary resistance (RL ). Since only the model resulting for RL passed through the origin (Y-intercept when X = 0: -0.31, 95% CI -0.75 to 0.14), this variable was used to identify the MID correlated with a meaningful improvement in clinical signs. The resulting MID value was a change in RL of 0.63 cm H2 O/L/s (95% CI 0.33-0.94), representing the slope of meta-regression model (high quality of evidence). MAIN LIMITATIONS: No long-term studies investigated the effect of bronchodilator agents on both lung function and clinical signs in asthmatic horses. CONCLUSIONS: In conclusion, bronchodilator pharmacotherapy in equine asthma elicits clinically meaningful effect when RL increases ≥1 cm H2 O/L/s, a value indicating the MID. Assessing the MID based on change in RL may improve the quality of evidence and the scientific impact of future clinical trials as it extends beyond the simple, and limiting, evaluation of statistical significance.

Safety and efficacy of kunzea oil-containing formulations for the management of psoriasis: a randomized, controlled trial.

WHAT IS KNOWN AND OBJECTIVE: Anecdotally, topical kunzea oil has been used to treat various skin conditions, including psoriasis and eczema, with good results. This study compared the clinical efficacy of kunzea oil (20%)-containing formulations in mild to moderate psoriasis. METHODS: A randomized, comparative, double-blind, 8-week study was undertaken. Thirty patients (age range: 25-74 years and mean ± SD: 52·8 ± 13·6 years) with mild to moderate psoriasis (affecting at least 10% of one or more body regions: arms, head, legs and trunk) randomly received ointment and/or scalp lotion containing 20% kunzea oil (test group) or control medications not containing kunzea oil (control group). Formulations in both treatment arms also contained 5% liquor carbonis detergens (LCD) and 3% salicylic acid. The clinical responses to the test and control formulations were evaluated using the Psoriasis Area and Severity Index (PASI). RESULTS AND DISCUSSION: After 8 weeks of treatment, both test and control groups demonstrated a significant (P < 0·05) improvement in PASI scores. Subjects in the test group had a decrease in mean±SD PASI score from 12·7 ± 7·9 to 6·7 ± 7·2, whereas the control group showed a decrease in PASI score from 8·1 ± 4·6 to 3·5 ± 4·7. Comparative efficacy analysis between the test and control groups did not reveal any significant difference (P > 0·05). WHAT IS NEW AND CONCLUSIONS: The inclusion of kunzea oil made no difference to the efficacy of topical formulations containing LCD and salicylic acid for the treatment of psoriasis.

Toenail onychomycosis: an important global disease burden.

Onychomycosis is a fungal infection of the nail plate or nail bed. It does not usually cure itself and it can trigger more infectious lesions in other parts of the body. The reported prevalence of onychomycosis is increasing in Western countries, presumably due to lifestyle changes and the ageing of the population. Approximately 10% of the general population, 20% of the population aged>60 years, up to 50% of people aged>70 years and up to one-third of diabetic individuals have onychomycosis. Care should be taken for the accurate diagnosis and timely treatment of toenail onychomycosis to prevent complications. Current treatment options have relatively limited therapeutic success, particularly long-term. Oral medications are associated with high recurrence rates and treatment failure, and are not suitable for many cases due to potential adverse effects. Topical medications are recommended only for mild to moderate cases. The cost of therapies may also be prohibitive in some cases. In the light of these issues, more research is warranted for the investigation and development of more effective and economical options for the treatment and prophylaxis of toenail onychomycosis. In patient populations such as diabetic individuals, where onychomycosis can provoke lower extremity complications, professional podiatry care of toenails and feet should be encouraged.

Volatile organic compounds in runners near a roadway: increased blood levels after short-duration exercise.

OBJECTIVE: To determine if non-elite athletes undertaking short duration running exercise adjacent to a busy roadway experience increased blood levels of common pollutant volatile organic compounds (benzene, toluene, ethylbenzene and xylene (BTEX)). DESIGN AND SETTING: The study was observational in design. Participants (nine males/one female non-elite athletes) ran for 20 min, near a busy roadway along a 100 m defined course at their own pace. Blood levels of BTEX were determined both pre- and post-exercise by SPME-GC-MS. Environmental BTEX levels were determined by passive adsorption samplers. RESULTS: Subjects completed a mean (range) distance of 4.4 (3.4 to 5.2) km over 20 min (4.5 (3.8 to 5.9) min/km pace), with a mean (SD) exercise intensity of 93 (2.3)% HR(max), and mean (SD) ventilation significantly elevated compared with resting levels (86.2 (2.3) vs 8.7 (0.9) l/min; p<0.001). The mean (SD) environmental levels (time weighted average) were determined as 53.1 (4.2), 428 (83), and 80.0 (3.7) microg/m(3) for toluene, ethylbenzene and xylenes, respectively, while benzene was below the detectable limit due to the short exposure period. Significant increases in blood BTEX levels were observed in runners between pre- and postexercise for toluene (mean increase of 1.4 ng/ml; p=0.002), ethylbenzene (0.7 ng/ml; p=0.0003), m/p-xylene (2.0 ng/ml; p=0.004) and o-xylene (1.1 ng/ml; p=0.002), but no change was observed for benzene. CONCLUSIONS: Blood BTEX levels are increased during high-intensity exercise such as running undertaken in areas with BTEX pollution, even with a short duration of exercise. This may have health implications for runners who regularly exercise near roadways.

Evaluation of repellent properties of volatile extracts from the Australian native plant Kunzea ambigua against Aedes aegypti (Diptera: Culcidae).

Kunzea ambigua (Smith) Druce (Myrtaceae) is an Australian native plant, commonly known as tick bush. The essential oil of the plant has been proposed as a potential mosquito repellent. Commercial K. ambigua oil was analyzed by gas chromatography-mass spectrometry (GC-MS) and its composition compared with that of oils from two individual K. ambigua plants and citronella oil. K. ambigua oils were studied for their repellency against Aedes aegypti L. Formulations of three different K. ambigua essential oils (30% vol:vol) were tested for repellency to mosquitoes using human volunteers. One oil was compared with citronella and N,N'-diethyl-3-methylbenzamide (deet) for repellency. Oil formulations were also tested for repellency with and without the addition of 5% vanillin. The formulation containing commercially produced K. ambigua oil had a mean complete protection time (CPT) of 49 +/- 24 (SD) min. All the K. ambigua formulations had comparable repellency to 40% citronella. However, the 60% citronella formulation showed higher repellency than the 40% K. ambigua formulation. The addition of 5% vanillin did not increase the repellency of K. ambigua oil. Both K. ambigua oil and citronella were significantly less repellent than deet. The K. ambigua essential oil formulations should not be advocated for use as repellents in regions prone to mosquito-borne disease.

Randomised controlled trial of the treatment of pastern dermatitis with a formulation containing kunzea oil.

The efficacy of an ointment containing kunzea oil for the treatment of horses with localised acute or chronic pastern dermatitis was assessed. Thirty-seven horses were randomly allocated to treatment with an ointment containing either 20 per cent kunzea oil (test) or 2 per cent ketoconazole (control). Only 21 of the horses completed the study. The severity of the lesions was assessed before and after seven days of treatment. The kunzea oil formulation resulted in a significant decrease in the median total area of the lesions from 40 cm(2) (range 3 to 252 cm(2)) to 0 cm(2) (range 0 to 34 cm(2)), with complete resolution of the signs of pastern dermatitis in seven of 11 cases. The control formulation resulted in no significant change in the total area of the lesions, and the signs of pastern dermatitis resolved completely in only two of the 10 cases.

Elevated plasma glutathione peroxidase concentration in acute severe asthma: comparison with plasma glutathione peroxidase activity, selenium and malondialdehyde.

OBJECTIVE: To investigate plasma glutathione peroxidase concentration, glutathione peroxidase activity, plasma selenium and oxidative stress in acute severe asthma. MATERIAL AND METHODS: The study was case-control in design, with cases presenting to the emergency department with acute severe asthma and controls randomly selected from a larger cross-sectional study. Plasma malondialdehyde (MDA) was used as a measure of oxidative stress and plasma selenium was measured using ICP-MS. Glutathione peroxidase (GPx) activity was analysed using a colorimetric GPx assay and plasma GPx level was measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: Fifteen cases [mean (range) predicted peak expiratory flow rate (PEFR) of 43% (20-69)] and 15 matched controls were recruited. MDA levels (mean+/-SD) were higher in acute asthma subjects (1.30+/-0.56 micromol/L) than in controls (0.86+/-0.53 micromol/L; p<0.05). There were no differences between cases and controls for selenium (99+/-34 microg/L versus 109+/-17 microg/L) or for GPx activity (39+/-25 nmol min(-1) mL(-1) versus 38+/-24 nmol min(-1) mL(-1)), however, GPx plasma levels measured by ELISA were higher in cases than controls (22.5+/-10.8 mg/L versus 13.8+/-7.3 mg/L; p<0.05). CONCLUSIONS: Patients with acute severe asthma demonstrated increased MDA levels but no differences in plasma selenium levels or GPx activity. GPx levels measured by ELISA were elevated in severe asthma. These results are consistent with an adaptive up-regulation of GPx to protect against oxidative stress.

Effect of celecoxib on cyclooxygenase-2 expression and possible variants in a patient with Barrett's esophagus.

Cyclooxygenase-2 (COX-2) expression is increased in metaplastic and dysplastic Barrett's esophageal epithelium and it is thought that selective COX-2 inhibitors could offer hope as chemoprevention therapy. The aim of the study was to investigate the in vivo effect of celecoxib on COX-2 expression in patients with Barrett's esophagus and no recent history of non-steroidal anti-inflammatory drug use. Endoscopic mucosal biopsy specimens were collected at baseline and after 28 days of therapy in a patient treated with celecoxib 200 mg twice daily. Samples were analyzed for COX-2 expression by immunoblot analysis with chemiluminescence detection. COX-2 expression was found to decline 20% and 44% at two different biopsy sites compared to the baseline sample. Longer exposures revealed a number of previously unidentified proteins above and below the 67 kDa COX-2 protein including 38 kDa and 45 kDa proteins which were present only at study completion consistent with up-regulation after celecoxib therapy. Further investigations of the 38 kDa and 45 kDa proteins were undertaken using two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) with immunoblot and MALDI-TOF (matrix assisted laser desorption ionization - time of flight) analysis but no matches were found and results were inconclusive. Unmatched masses from MALDI-TOF peptide mass fingerprinting were compared with human COX-2 (67 kDa) and COX-2b (39 kDa) using unspecific cleavage. Peptide sequence homology with COX-2 and COX-2b was found for a length of 19 amino acids. Based on immunodetection, molecular weight and equivical MALDI-TOF results, one of these up-regulated proteins may be COX-2b.

Selenium status in Southern Tasmania.

OBJECTIVE: To assess the selenium status of Southern Tasmanians. DESIGN: Cross-sectional. SETTINGS: One thousand and five hundred adults randomly selected from the electoral roll living in the Greater Hobart region of Southern Tasmania, Australia, were invited to participate. SUBJECTS: The overall response rate was 22% (335/1500). INTERVENTIONS: A venous blood sample was collected and a questionnaire administered (consisting of brief demographic details and health questions) to subjects who granted informed consent. A previously validated assay using magnetic sector ICP-MS was employed for plasma analysis. RESULTS: Total plasma selenium levels for this sample population were normally distributed with a mean level of 110 microg/l (range 67-268 microg/l) indicating that the majority of the subjects were not selenium-depleted (71% with levels greater than 100 microg/l). Adjustment for differential age/gender response rates produced similar values. More women under 50 (42%) and men over 50 (32%) had selenium levels <100 microg/l with the potential for sub-optimal selenoprotein activity. Low education attainment was associated with low total selenium level (P<0.02). CONCLUSIONS: The majority of participants were not deficient in selenium. Given the narrow therapeutic window of supplementation, dietary advice to increase foods rich in selenium, particularly to higher risk groups, may be an effective means of increasing plasma selenium toward target levels.

Determination of ceftiofur in bovine plasma by HPLC-DAD.

Ceftiofur sodium is a third generation broad-spectrum cephalosporin, formulated as an intramuscular injection, which is used to treat respiratory diseases in swine, ruminants and horses. The thioester bond on ceftiofur is rapidly cleaved to give desfuroylceftiofur which is further metabolized to a disulfide dimer and various desfuroylceftiofur-protein and amino acid conjugates. Methods of analysis of ceftiofur rely on cleavage by dithioerythritol to produce desfuroylceftiofur, which is further stabilized by derivatization to desfuroylceftiofur acetamide using iodoacetamide. Previous analytical methods have extracted derivatized analyte from plasma and tissue using solid-phase extraction clean-up steps followed by HPLC analysis with results reported as ceftiofur-free acid equivalents (CFAE). The simplified method presented here involves direct HPLC injection of a cleaved and derivatized sample following a protein precipitation step with calibration by external standardization and selectivity achieved based on chromatography and diode-array detection (DAD). The assay was linear over the calibration range 0.4-40 microg/ml in plasma. Intra-batch reproducibility R.S.D. was 10.3% and intra-batch sample repeatability R.S.D. was 2.1% at the 5 microg/ml level. The mean accuracy over the range of the calibration curve was -4.2% and the detection limit was 0.15 microg/ml. The assay was successfully applied to bovine plasma following intramuscular injection of ceftiofur sodium. This simplified method is suitable for pharmacokinetic applications involving ceftiofur at normal therapeutic levels.

Enhanced stability of sulfamethoxazole and trimethoprim against oxidation using hydroxypropyl-beta-cyclodextrin.

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.

(R,S)-salbutamol plasma concentrations in severe asthma.

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.

Biological monitoring of low level occupational xylene exposure and the role of recent exposure.

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.

LC-MS method for the determination of albuterol enantiomers in human plasma using manual solid-phase extraction and a non-deuterated internal standard.

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.

Cost-effectiveness of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor therapy in older patients with myocardial infarction.

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.

Parenting processes: a descriptive exploratory study using Peplau's theory.

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.

Bicycle injuries: road trauma is not the only concern.

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.

Investigation of urinary levels of salbutamol in asthmatic patients receiving inhaled therapy.

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.

Prescribing trends for anti-asthma drugs in Tasmania following the National Asthma Campaign.

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.

The impact of violence in the health care setting upon nursing education.

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.