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Biomedical subjects

R Beasley

Publications and source records attributed to R Beasley.

At least 19 recordsLinked to original sources
PubMed2006

Inhaled fluticasone propionate and adrenal effects in adult asthma: systematic review and meta-analysis.

The dose-response relationship of inhaled fluticasone propionate (FP) for adrenal suppression in adults with asthma is not clear. The current authors carried out a systematic review and meta-analysis of placebo-controlled randomised dose-response studies of >or=4 weeks' duration, which assessed the adrenal effects of FP by cosyntropin stimulation tests in adult asthma. The main outcome measure was the proportion of subjects with adrenal function below the lower limit of the normal range. Five studies, with a total of 732 subjects with asthma, met the inclusion criteria. Data on daily doses >1,000 mug were limited to one study. The proportion of subjects with adrenal function below the lower limit of the normal range on placebo was 3.9%; for a 500-microg per day increase in FP dose the odds of an abnormality increased by 1.38 (95% confidence interval 1.01-1.59). The continuous secondary outcome measures showed an inverse linear relationship with the FP dose up to 2,000 microg.day(-1). In conclusion, for routine prescribing within the established therapeutic dose-response range (50-500 microg.day(-1)), fluticasone propionate has minimal effects on adrenal function. This conclusion is limited by the paucity of long-term studies of daily doses of fluticasone propionate >1,000 mug and by the considerable individual variability in the response.

Adrenal Insufficiency↗
PubMed2005

Benefits of omalizumab as add-on therapy in patients with severe persistent asthma who are inadequately controlled despite best available therapy (GINA 2002 step 4 treatment): INNOVATE.

BACKGROUND: Patients with severe persistent asthma who are inadequately controlled despite Global Initiative for Asthma (GINA) 2002 step 4 therapy are a challenging population with significant unmet medical need. We determined the effect of omalizumab on clinically significant asthma exacerbations (requiring systemic corticosteroids) in the first omalizumab study to exclusively enrol patients from this difficult-to-treat patient population. METHODS: Following a run-in phase, patients (12-75 years) inadequately controlled despite therapy with high-dose inhaled corticosteroids (ICS) and long-acting beta(2)-agonists (LABA) with reduced lung function and a recent history of clinically significant exacerbations were randomized to receive omalizumab or placebo for 28 weeks in a double-blind, parallel-group, multicentre study. RESULTS: A total of 419 patients were included in the efficacy analyses. The clinically significant asthma exacerbation rate (primary efficacy variable), adjusted for an observed relevant imbalance in history of clinically significant asthma exacerbations, was 0.68 with omalizumab and 0.91 with placebo (26% reduction) during the 28-week treatment phase (P = 0.042). Without adjustment, a similar magnitude of effect was seen (19% reduction), but this did not reach statistical significance. Omalizumab significantly reduced severe asthma exacerbation rate (0.24 vs 0.48, P = 0.002) and emergency visit rate (0.24 vs 0.43, P = 0.038). Omalizumab significantly improved asthma-related quality of life, morning peak expiratory flow and asthma symptom scores. The incidence of adverse events was similar between treatment groups. CONCLUSIONS: In patients with inadequately controlled severe persistent asthma, despite high-dose ICS and LABA therapy, and often additional therapy, omalizumab significantly reduced the rate of clinically significant asthma exacerbations, severe exacerbations and emergency visits. Omalizumab is effective and should be considered as add-on therapy for patients with inadequately controlled severe persistent asthma who have a significant unmet need despite best available therapy.

Administration, Inhalation↗
PubMed2005

Determinants of plasma D-dimer levels in a traveling population.

BACKGROUND: Plasma D-dimer measurement is a widely used diagnostic test for assessing individuals with suspected venous thromboembolism (VTE). Whilst a negative test is helpful in ruling out thrombosis, the significance and determinants of an elevated plasma D-dimer level in otherwise healthy subjects are poorly understood. OBJECTIVES: To determine the association between recognized risk factors for VTE and plasma D-dimer levels in an adult population. SUBJECTS AND METHODS: Blood samples for measurement of plasma D-dimer levels were obtained from 1000 adults aged <70 years who were participating in a study investigating the incidence of VTE in long distance air travellers. The relationship between D-dimer levels and selected risks factors for VTE including thrombophilia status was investigated. RESULTS: The median (Inter-quartile range) D-dimer level was 243 ng mL(-1) (175-345). Multivariate analysis showed that plasma D-dimer levels were positively associated with increasing age, larger body mass index, female gender, the use of hormone therapy, thrombophilia state, and the presence of co-morbid conditions. CONCLUSION: Plasma D-dimer levels vary markedly between individuals and are associated with known risk factors for VTE, including the presence of thrombophilia conditions. The potential role for the measurement of plasma D-dimer as a marker for thrombosis risk requires further investigation.

Age Factors↗
PubMed2005

Efficacy of bupropion in the indigenous Maori population in New Zealand.

BACKGROUND: Smoking rates are high in indigenous populations and contribute to their poor health. In New Zealand the indigenous Maori population has a high rate of smoking, with around 50% of adults being smokers compared with 20% of the adult European population. A study was undertaken to determine whether bupropion is effective in the treatment of smoking cessation in the indigenous Maori population in New Zealand. METHODS: A randomised, placebo controlled, double blind, parallel group study was performed in 134 Maori smokers aged 16-70 years who smoked more than 10 cigarettes per day. The main outcome measures were continued abstinence from smoking at 3 and 12 months. RESULTS: At each time point continued abstinence was better for the subjects allocated to bupropion, with a risk ratio for abstinence over all time points of 2.44 (95% CI 1.22 to 4.88). The rates of continued abstinence in the bupropion and placebo groups at 3 months were 44.3% and 17.4%, respectively, with a risk ratio of 2.54 (95% CI 1.30 to 5.00). The corresponding figures at 12 months were 21.6% and 10.9%, respectively, with a risk ratio of 1.99 (95% CI 0.79 to 5.00). CONCLUSION: Bupropion is an effective treatment for smoking cessation in the indigenous Maori population in New Zealand.

Adolescent↗
PubMed2005

Moderate dose inhaled corticosteroids plus salmeterol versus higher doses of inhaled corticosteroids in symptomatic asthma.

BACKGROUND: There is uncertainty as to the dose of inhaled corticosteroids (ICS) at which to start concomitant long acting beta agonist (LABA) treatment in patients with asthma not adequately controlled by ICS alone. METHODS: A meta-analysis was carried out of randomised, double blind clinical trials that compared the efficacy of adding salmeterol to moderate doses of ICS (fluticasone propionate 200 mug/day or equivalent) with increasing the ICS dose by at least twofold in symptomatic adult patients with asthma. The main outcome measures were the number of subjects withdrawn from the study due to asthma and the number of subjects with at least one moderate or severe exacerbation. RESULTS: Twelve studies with a total of 4576 subjects met the inclusion criteria for the analyses. The number of subjects withdrawn due to asthma and with at least one moderate or severe exacerbation was higher in the high dose ICS group (odds ratios 1.58, 95% CI 1.12 to 2.24 and 1.35, 95% CI 1.10 to 1.66, respectively). For the secondary outcome variables (forced expiratory volume in 1 second, morning and evening peak expiratory flow, and daytime beta agonist use) there was significantly greater benefit in the salmeterol group. CONCLUSIONS: This meta-analysis shows that the addition of salmeterol to moderate doses of ICS (fluticasone 200 mug/day or equivalent) in patients with asthma symptomatic at that dose results in significantly greater clinical benefit than increasing the dose of ICS by twofold or more.

Administration, Inhalation↗
PubMed2005

The international study of asthma and allergies in childhood (ISAAC): phase three rationale and methods.

The International Study of Asthma and Allergies in Childhood (ISAAC) programme commenced in 1991 to study the aetiology of asthma, allergic rhinoconjunctivitis and atopic eczema in children in different populations using standardised methodology and facilitating international collaboration. ISAAC Phase One (1992-1996) found marked differences in the prevalence of symptoms of asthma and allergic disease throughout the world which have not been explained by the current understanding of these diseases. ISAAC Phase Two (1998-2004) uses intensive investigations to further examine the potential role of risk and protective factors that may contribute to the international difference observed in Phase One. Phase Three (2000-2003) essentially represents a repeat of Phase One, in which more detailed standardised data are obtained to enable the time trends of symptom prevalence to be determined as well as the development of a more comprehensive 'world map'. The ISAAC Phase Three rationale and methods are described in this paper. With over 280 centres in 106 countries, we anticipate that ISAAC Phase Three will comprehensively determine the prevalence of symptoms of asthma and allergic disease worldwide, explore recent time trends in the prevalence of these symptoms and cast new light on the aetiology of asthma and allergic disease.

Asthma↗
PubMed2004

Effect of repeated intradermal injections of heat-inactivated Mycobacterium bovis bacillus Calmette-Guérin in adult asthma.

BACKGROUND: There are a number of reports in the Chinese medical literature from the last 30 years regarding the efficacy of repeated doses of heat-inactivated bacillus Calmette-Guérin (BCG) in established asthma. There is also epidemiological and experimental evidence that exposure to mycobacteria has the potential to suppress the development of asthma/atopy. METHODS: Thirty-one Mantoux-negative adults with stable moderately severe asthma who were skin prick test positive to house dust mite were randomized to receive one injection (0.1 mL) a week for 4 weeks of heat-inactivated BCG or normal saline. Markers of asthma severity (including peak flow, forced expiratory volume in 1 s, major and minor exacerbations, symptom scores and beta-agonist use), blood eosinophil and IgE levels were monitored for 3 months. RESULTS: There were no statistically significant differences between the treatment group and placebo for any of the outcome variables. The recruitment to the trial was halted early and the number of injections reduced in a number of patients due to excessive local reactions to BCG. CONCLUSIONS: In addition to the lack of efficacy of repeated heat-inactivated BCG injections, the occurrence of severe local reactions will limit the therapeutic application of this approach in asthma.

Adolescent↗
PubMed2004

Systematic review of the dose-response relation of inhaled fluticasone propionate.

AIMS: To examine the dose-response relation of inhaled fluticasone for both efficacy and adrenal function in children with asthma. METHODS: Systematic review of double blind randomised dose-response studies of fluticasone in children of at least 4 weeks duration. MAIN OUTCOME MEASURES: FEV1, morning peak expiratory flow, night awakenings, beta agonist use, major exacerbations, 12 or 24 hour urinary cortisol, peak plasma cortisol post-stimulation. RESULTS: Seven studies of 1733 children with asthma met the inclusion criteria for efficacy. The dose-response curve for each efficacy outcome measure suggested that the response began to plateau between 100 and 200 microg per day with additional efficacy at the 400 microg per day dose shown in one study of severe asthmatics. Five studies of 1096 children with asthma met the inclusion criteria for assessment of adrenal function. The largest placebo controlled study of 437 children reported no difference in 24 hour urinary cortisol between placebo and fluticasone at doses of 100 and 200 microg per day. The non-placebo controlled study of 528 children reported significant suppression of overnight urinary cortisol levels with fluticasone at 400 compared with 200 microg per day. CONCLUSIONS: There is insufficient data to determine the dose-response of fluticasone in children at doses >400 microg per day. The dose-response curve for fluticasone appears to plateau between 100 and 200 microg per day for efficacy. There was additional efficacy at the 400 microg per day dose in children with severe asthma; however there was evidence of adrenal suppression at this dose.

Administration, Inhalation↗
PubMed2004

Dose-response relationship of inhaled budesonide in adult asthma: a meta-analysis.

The aim of this study was to examine the dose-response relationship of inhaled budesonide in adolescents and adults with asthma. A meta-analysis was carried out on placebo-controlled, randomised clinical trials, presenting data on at least one outcome measure of asthma and using at least two doses of budesonide, delivered by turbuhaler or metered-dose inhaler + spacer twice daily. A total of six studies of 1,435 adolescents and adults, with mild to moderately severe asthma, met the inclusion criteria for the meta-analysis. A negative exponential model indicated that 80% of the benefit at 1,600 micrograms.day-1 was achieved at doses of approximately 200-400 micrograms.day-1 and 90% by 300-600 micrograms.day-1. Meta-regression with a quadratic term in dose showed that the maximum effect was obtained with doses of approximately 1,000 micrograms.day-1. In conclusion, the available published data indicate that, in adolescents and adults with mild to moderate asthma, most of the therapeutic benefit of budesonide delivered by turbuhaler or metered-dose inhaler + spacer is achieved with a dose of approximately 400 micrograms.day-1 and the maximum effect is achieved at approximately 1,000 micrograms.day-1. This conclusion is qualified by the recognition that there is considerable individual variability in the response to inhaled corticosteroids and that the subjects included in this meta-analysis had predominantly mild to moderate asthma.

Administration, Inhalation↗
PubMed2004

Clinical dose-response relationship of fluticasone propionate in adults with asthma.

BACKGROUND: A study was undertaken to examine the dose-response relation of inhaled fluticasone in adolescents and adults with asthma. METHODS: A meta-analysis was carried out of randomised clinical trials that presented data on at least one outcome measure of asthma and that used at least two doses of fluticasone given twice daily. The main outcome measures were forced expiratory volume in 1 second (FEV1), morning peak expiratory flow (amPEF), beta agonist use, and withdrawals due to exacerbations of asthma. RESULTS: Seven studies of 2431 adolescents and adults with moderate to severe asthma met the inclusion criteria for the meta-analysis. Four studies examined a dose of >500 microg/day. For all outcome measures there were no statistically significant differences between a dose of 200 v 500 microg/day, 500 v 1000 microg/day, and 200 v > or =500 microg/day, although the point estimates favoured the higher doses. The mean improvement for FEV1 and amPEF resulting from an increase in dose from 200 to > or =500 microg/day was 0.07 l (95% CI -0.01 to 0.14) and 5.9 l/min (95% CI -3.0 to 15.3), respectively. The odds ratio for withdrawals with 200 microg/day compared with > or =500 microg/day was 1.27 (95% CI 0.78 to 2.07). CONCLUSIONS: In adolescents and adults with asthma, most of the therapeutic benefit of fluticasone is achieved with a total daily dose of 200 microg/day with minimal further clinical benefit achieved with higher doses. This conclusion is qualified by the recognition that there is considerable individual variability in the response to inhaled corticosteroids in asthma, which would suggest that some patients may obtain a greater clinical benefit at higher doses.

Administration, Inhalation↗
PubMed2003

Frequency of venous thromboembolism in low to moderate risk long distance air travellers: the New Zealand Air Traveller's Thrombosis (NZATT) study.

BACKGROUND: The frequency and role of risk factors for venous thromboembolism related to air travel is uncertain. We aimed to establish the frequency of this disorder in a group of long distance air travellers and to investigate the role of potential risk factors. METHODS: We designed a prospective study into which we recruited individuals aged between 18 and 70 years, travelling for 4 h or more by aircraft. D-dimer measurement was done before and after travel. Participants with a negative D-dimer (<500 ng/L) before travel were included in the study. Those who became D-dimer positive or developed high clinical probability symptoms during the 3 months after travel were investigated with bilateral compression ultrasonography and CT pulmonary angiography. Suspected clinical and thrombophilic risk factors, and use of prophylactic measures, were assessed. FINDINGS: 1000 individuals were recruited, with 878 meeting inclusion criteria and completing the study. All participants travelled at least 10 h, with a mean total duration of air travel of 39 h (SD 12.5). 112 patients underwent radiological assessment on return. Frequency of venous thromboembolism associated with travel was 1.0% (9/878, 95% CI 0.5-1.9), which included four cases of pulmonary embolism and five of deep venous thrombosis. Six patients with venous thromboembolism had pre-existing clinical risk factors, two had a recognised thrombophilic risk factor, two travelled exclusively in business class, five used aspirin, and four wore compression stockings. INTERPRETATION: Our results suggest an association between multiple long distance air flights and venous thromboembolism, even in individuals at low to moderate risk. The role of traditional risk factors and prophylactic measures in air travel-related venous thromboembolism needs further investigation.

Adolescent↗
PubMed2003

eThrombosis: the 21st century variant of venous thromboembolism associated with immobility.

The association between immobility with prolonged sitting and venous thromboembolism has been recognised for > 60 yrs, most recently with long distance air travel. The case of a 32-yr-old male, in whom immobility associated with sitting for long periods at a computer represented the major provoking risk factor for his life-threatening venous thromboembolism, is presented. The authors propose the term "eThrombosis" to describe this 21st Century variant of venous thromboembolism associated with immobility from prolonged sitting. In view of the widespread use of computers in relation to work, recreation and personal communication, the potential burden of eThrombosis may be considerable.

Adult↗
PubMed2003

Agreement between written and video questions for comparing asthma symptoms in ISAAC.

Phase One of the International Study of Asthma and Allergies in Childhood (ISAAC) has reported the prevalence of asthma, rhinitis and eczema symptoms in children. In 99 centres from 40 countries, a total of just under 317,000 13-14-yr-old children also completed a video questionnaire, showing the symptoms and signs of asthma. This first video sequence has been compared to the ISAAC written question asking about current wheezing to explore variations in agreement and the contribution of each questionnaire to wheezing prevalence between centres, by region and language groups. In general, responses to the video questionnaire gave a lower prevalence than the siritten questionnaire and responses were closely correlated. The overall proportion of agreement was high, mean 0.89. but unbalanced, with good negative agreement but poor positive agreement. Chance corrected agreement using Cohen's kappa coefficient, was generally low, with onl 20 centres with kappa >0.4. The contribution of each questionnaire to wheezing prevalence also varied between centres and suggests that written questions about wheezing are variably understood and interpreted by 13-14 yr olds. International comparisons of wheezing and its audiovisual presentation suggest that adolescents interpret a written question about wheezing differently from its audiovisual presentation and that this interpretation shows variation between centres. This relationship and the interpretation of both written and audiovisual presentation of symptoms requires further study in order to better predict asthma.

Adolescent↗