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Biomedical subjects

Richard Beasley

Publications and source records attributed to Richard Beasley.

At least 19 recordsLinked to original sources

The 24 h duration of bronchodilator action of the budesonide/formoterol combination inhaler.

INTRODUCTION: The duration of bronchodilator action of the long-acting beta-agonist formoterol when administered in the evening has not been investigated. In this study we have investigated whether a single evening dose of formoterol, administered from the combination budesonide/formoterol (BUD/F) Turbuhaler significantly attenuates the circadian rhythm in airway tone over 24 h. METHODS: Twenty subjects with mild to moderate asthma (mean FEV1 84% predicted) participated in a double-blind, placebo-controlled, cross-over study. Subjects inhaled, in random order, placebo or BUD/F (2x100/6 microg) administered in the evening (2000 h) on two separate occasions. Lung function measurements including FEV1, specific airways conductance (sGaw) and maximum expiratory flow at 25-75% of vital capacity (MEF(25-75%)) were assessed at baseline, at 1 h and subsequently every 4 h post-dose for 24 h. RESULTS: Compared with placebo, BUD/F significantly improved the three measures of airways function throughout the 24 h period, with a difference in FEV1 at 24 h of 0.20L (0.04-0.35L). BUD/F attenuated the biphasic pattern of the circadian rhythm in airway tone. CONCLUSION: The single evening administration of formoterol from the combination BUD/F inhaler resulted in a duration of bronchodilation of at least 24 h.

Administration, Inhalation↗

Raised plasma homocysteine levels in alcoholism: increasing the risk of heart disease and dementia?

BACKGROUND: Raised plasma homocysteine levels, which may contribute to the increased risk of cardiovascular disease and dementia associated with alcoholism, have been observed in alcohol-dependent male subjects. METHODS: In this study, we measured plasma homocysteine levels in 20 female and 31 male alcoholic subjects admitted to hospital for detoxification. Nutritional status and clinical factors that might predict plasma homocysteine levels were assessed by measurement of red cell folate, vitamin B12, blood alcohol, and liver function tests. RESULTS: The median (interquartile range) plasma homocysteine level on admission was 15.4 micromol/L (11.1 to 19.7), with 27 (53%) subjects having a raised homocysteine level, greater than 15 micromol/L. There was no difference in admission plasma homocysteine levels between the male and female subjects (difference, male versus female 1.9 micromol/L, 95% CI=2.4 to 6.0, p=0.4). Red cell folate, vitamin B12 levels, and blood alcohol level on admission were not significant predictors of admission homocysteine level. CONCLUSION: Severe alcohol dependence is associated with markedly raised plasma homocysteine levels in both females and males. The common condition of alcohol dependence may be an under-recognised risk factor contributing to raised plasma homocysteine levels and the associated risk of vascular and intellectual impairment.

Adult↗

PHARMAC and tobacco control in New Zealand: government policy 'up in smoke'.

There is increasing concerning amongst the medical profession in New Zealand about the adverse effect that PHARMAC has on the health of New Zealanders through restricting the availability of medications. In this article, the circumstances surrounding the restrictions limiting the availability of the smoking cessation treatment bupropion are presented. The authors conclude that the decision by PHARMAC not to fund bupropion is directly contrary to Government policy and is inconsistent with evidence-based medicine and international recommendations. It is suggested that the PHARMAC decision seriously questions the Ministry of Health's commitment to smoking cessation and the health of disadvantaged groups in New Zealand, particularly Maori.

Antidepressive Agents, Second-Generation↗

SIT (seated immobility thromboembolism) syndrome: a 21st century lifestyle hazard.

The association between prolonged seated immobility and venous thromboembolism (VTE) is well recognised in relation to travel. In this case series, we report the occurrence of deep vein thrombosis (DVT) or pulmonary embolism (PE) following prolonged sitting in relation to work and/or recreation. The cases were characterised by the considerable length of time the individuals sat, the extensive nature of the VTE events in young individuals without other recognised risk factors, and the lack of recognition by the attending doctors of seated immobility as the likely major risk factor. While recognising that the association may be coincidental rather than causal, we propose the acronym 'SIT' (seated immobility thromboembolism) syndrome to encompass all forms of seated immobility associated with VTE.

Adult↗

Metered dose inhalers: a need for dose counters.

OBJECTIVES: This study investigated the ability of patients to assess when a metered dose inhaler (MDI) is empty. METHODOLOGY: A total of 17 patients assessed, by shaking, the number of doses remaining in a salbutamol MDI that had been partially emptied. Another 100 patients were asked to collect all salbutamol MDIs they considered to be empty and would have thrown away. These MDI canisters were weighed and the number of doses that had been used was estimated. RESULTS: Using the 'shaking method', patients overestimated the amount remaining by around 40 doses. The mean number of doses delivered from an MDI labelled to contain 200 doses before it was discarded was 224 (range, 155-289). CONCLUSIONS: These findings confirm that patients are unable to determine when an MDI should be discarded, resulting in insufficient drug delivery at the end of the life of an MDI for the majority of patients, and wastage of the drug for others.

Administration, Inhalation↗

Fluticasone given once versus twice a day: meta-analysis.

OBJECTIVE: The aim of this study was to examine the efficacy of fluticasone administered once daily compared to twice daily in asthma. METHODOLOGY: A meta-analysis was performed of randomized double-blind trials of at least 4 weeks duration that compared fluticasone administered once versus twice a day and presented data on at least one clinical outcome measure. RESULTS: Six studies of 1517 children and adults with asthma met the inclusion criteria. Studies were predominantly in subjects with moderate asthma, treated with doses of fluticasone ranging from 200 to 500 microg per day. Twice-daily dosing was associated with significantly greater efficacy compared with once-daily dosing, for all outcome measures except night wakenings. The mean (95% CI) differences between twice and once-daily administration for FEV(1) and peak expiratory flow were 0.11 L (0.07-0.16) and 12.9 L/min (8.6-17.1), respectively. Twice-daily fluticasone was associated with significantly fewer withdrawals due to asthma than once-daily fluticasone, with an odds ratio of 0.44 (0.30-0.67). CONCLUSION: The findings suggest that twice-daily administration of fluticasone will provide greater therapeutic benefit than a once-daily morning regimen.

Adolescent↗

Specific oral contraceptive use and venous thromboembolism resulting in hospital admission.

OBJECTIVE: To determine whether there is an increased risk of venous thromboembolism (VTE) with anti-androgen oral contraceptives containing cyproterone acetate and ethinyloestradiol. METHODS: Comparison of the frequency of specific oral contraceptive use in patients aged 15 to 55 years discharged from hospital with radiologically confirmed deep vein thrombosis (DVT) and/or pulmonary embolism (PE) with the expected frequency of use derived from national prescription data. MAIN OUTCOME MEASURE: Ratio of observed frequency of specific oral contraceptive use in patients with VTE versus expected frequency of use. RESULTS: The rank order for observed versus expected use was anti-androgen > third-generation, > second-generation, > progestogen-only oral contraceptive agents with ratios of 1.93, 1.36, 0.70, and 0.39, respectively. CONCLUSION: The risk of VTE resulting in hospital admission associated with anti-androgen oral contraceptive use is at least as high as with third generation use.

Adolescent↗

The 24 h duration of bronchodilator action of the salmeterol/fluticasone combination inhaler.

INTRODUCTION: The duration of bronchodilator action of the long-acting beta agonist salmeterol when administered in the evening has not been investigated. In this study we have investigated whether a single evening dose of salmeterol, administered from the combination salmeterol/fluticasone (SFC) Accuhaler significantly attenuates the circadian rhythm in airway tone over 24 h. METHODS: Eighteen subjects with mild to moderate asthma (mean FEV1 84% predicted) participated in a double-blind, double dummy, placebo controlled, cross-over study. Subjects inhaled, in random order, placebo, salbutamol (200 microg) or SFC (50/100 microg) administered in the evening (2000 h) on three separate occasions. Lung function measurements including FEV1, specific airways conductance (sGaw) and maximum expiratory flow at 25-75% of vital capacity (MEF(25-75%)) were assessed at baseline, at 1 h and subsequently every 4 h post-dose for 24 h. RESULTS: Compared with placebo, SFC significantly improved the three measures of airways function throughout the 24 h period, with a difference in FEV1 at 24 h of 0.24 l (0.00-0.47 l). SFC abolished the biphasic pattern of the circadian rhythm in airway tone. In contrast, salbutamol had a significant bronchodilator action of 4-8 h, depending on the lung function parameter measured. CONCLUSION: The single evening administration of SFC via the Accuhaler resulted in a duration of bronchodilation of at least 24 h, with the abolition of the accentuated biphasic circadian variation in airway tone observed in asthma.

Administration, Inhalation↗

The dose-response relationship of inhaled corticosteroids in asthma.

Inhaled corticosteroids are the only class of asthma medication that can reduce symptoms, improve lung function, reduce the frequency of severe exacerbations, including hospital and ICU admissions, and decrease the risk of mortality. The therapeutic dose range for all clinical outcome measures in adults is 100 to 1000 mg/d of beclomethasone dipropionate or budesonide, or 50 to 500 mg/d of fluticasone propionate. Doses in excess of this range are not recommended for routine use because they are likely to increase the risk of systemic side-effects without further major improvement in efficacy. The recommendations are qualified by the recognition that there is considerable individual variability in the response to inhaled corticosteroids in asthma, which would suggest that some patients might obtain greater benefit at higher doses, just as some might obtain maximum benefit at lower doses.

Administration, Inhalation↗

Association of asthma therapy and Churg-Strauss syndrome: an analysis of postmarketing surveillance data.

BACKGROUND: Churg-Strauss syndrome (CSS), also known as allergic granulomatous angiitis (AGA), is a rare vasculitis that occurs in patients with bronchial asthma. The nature of the association of CSS with various asthma therapies is unclear. OBJECTIVE: This study investigated the associations of different multidrug asthma therapy regimens and the reporting of AGA (the preferred code for CSS in the coding dictionary for the Adverse Event Reporting System [AERS]) by applying an iterative method of disproportionally analysis to th AERS database maintained by the US Food and Drug Administration. METHODS: The public-release version of the AERS database was used to identify reports of AGA in patients receiving asthma therapy. Reporting of AGA was examined using iterative disproportionality methods in patients receiving > or =1 of the following drug classes: inhaled corticosteroid (ICS), leukotriene receptor antagonist (LTRA), short-acting beta(2)-agonist (SABA), or long-acting beta(2)-agonist (LABA). The Bayesian data-mining algorithm known as the multi-item gamma poisson shrinker was used to determine the relative reporting rates by calculation of the empirical Bayes geometric mean (EBGM) and its 90% CI (EB05 = lower limit and EB95 = upper limit) for each drug. Subset analyses were performed for each drug with different medication combinations to differentiate the relative reporting of AGA for each. RESULTS: A strong association was found between LTRA use and AGA (EBGM = 104.0, EB05 = 95.0, EB95 = 113.8) that persisted with all combinations of therapy studied. AGA was also associated with the ICS, SABA and LABA classes (EBGM values of 27.8, 14.6 and 40.4, respectively). However, the latter associations were mostly dependent on the presence of concurrent LTRA and, to a lesser extemt, oral corticosteroid therapy and became negligible (ie, EB05 < 2) for patients who were not receiving these concurrent treatments. CONCLUSIONS: Differences based on relative reporting were observed in the patterns of association of AGA with LTRA, ICS, and beta(2)-agonist therapies. A strong association between LTRA use and AGA was present regardless of the use of other asthma drugs.

Administration, Inhalation↗

Rates and characteristics of intensive care unit admissions and intubations among asthma-related hospitalizations.

BACKGROUND: A life-threatening attack of asthma that leads to intensive care unit (ICU) admission, intubation, or both identifies patients at high risk of subsequent morbidity and mortality and represents a major cost burden. OBJECTIVE: To assess the rates, characteristics, and costs of ICU admissions and intubations among asthma-related hospitalizations. METHODS: This analysis was performed using a database of 215 hospitals representing more than 3 million annual inpatient visits. Asthma-related hospital admissions were identified by a primary diagnosis code for asthma during 2000. Logistic regression was used to estimate the odds ratios (ORs) for predictors of ICU admission, intubation, and in-hospital mortality. Ordinary least squares regression was used to estimate adjusted mean costs and length of stay. RESULTS: Of 29,430 admissions with a primary diagnosis of asthma, 10.1% were admitted to the ICU and 2.1% were intubated. The risk of in-hospital death was significantly greater in patients who were intubated but not admitted to the ICU (OR, 96.20; 95% confidence interval [CI], 50.24-184.20), those who were admitted to the ICU and intubated (OR, 62.69; 95% CI, 38.17-102.96), and patients with more severe comorbidities (OR, 1.53; 95% CI, 1.38-1.70). On average, intubated patients stayed in the hospital 4.5 days longer and incurred more than $11,000 in additional costs; patients admitted to the ICU stayed 1 day longer and accounted for $3,000 in additional costs vs standard admissions. CONCLUSIONS: The inpatient mortality, morbidity, and cost burden of life-threatening asthma in the United States is considerable. This study characterizes patients with asthma at risk of ICU admissions and intubations. Appropriate recognition and treatment are needed to prevent these severe and potentially life-threatening events.

Adolescent↗

The pulmonary and extra-pulmonary effects of high-dose formoterol in COPD: a comparison with salbutamol.

OBJECTIVES: Formoterol, a beta(2) agonist with a rapid onset of effect and long duration of action, can be used as maintenance and reliever medication for asthma and COPD. We compared the pulmonary and extra-pulmonary effects of cumulative doses of formoterol and salbutamol in patients with COPD to assess efficacy and safety. METHODOLOGY: In a randomized, double-blind, cross-over study, 12 patients with moderate to severe COPD inhaled, via Turbuhaler, 10 doses of formoterol (total metered dose, 120 microg, equivalent to a 90- microg delivered dose), salbutamol (total metered dose 2000 microg) or placebo at 2-min intervals on separate days. The effects on lung function (FEV(1) and PEF), heart rate, blood pressure, oxygen saturation, corrected QT interval (QTc), T-wave height and plasma potassium were assessed before each dose, 15 min after each dose, and at half-hourly intervals for 3 h following the final dose. RESULTS: Inhalation of formoterol or salbutamol resulted in significant improvement in lung function (measured 30 min after the last dose) when compared with placebo. There were no clinically important or statistically significant changes in heart rate, QTc, T-wave height, plasma potassium, oxygen saturation, or systolic and diastolic blood pressures with formoterol or salbutamol. One patient developed ventricular trigeminy after both formoterol and salbutamol. She had had ventricular ectopics on her screening electrocardiogram. CONCLUSION: Formoterol and salbutamol both produced significant improvement in lung function and were similarly well tolerated in high doses, as might be taken by a patient for relief of COPD symptoms.

Adrenergic beta-Agonists↗