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Biomedical subjects

Richard Beasley

Publications and source records attributed to Richard Beasley.

At least 19 recordsLinked to original sources
PubMed2006

External validity of randomized controlled trials in COPD.

BACKGROUND: COPD is a heterogeneous disease comprising a wide range of clinical phenotypes, depending on the degree to which emphysema, chronic bronchitis, reversible bronchospasm and small airways inflammation are present. Not all of these phenotypes may be represented among the subjects included in randomized controlled drug trials (RCTs) in COPD, making it difficult for doctors to know to what extent RCT evidence applies to individual patients. From a respiratory health survey of adults randomly selected from the community, we have estimated the proportion of subjects with COPD who would have been eligible for inclusion in major COPD RCTs. METHODS: A postal survey was sent to 3500 randomly selected individuals aged 25-75 years. Respondents were invited to complete a detailed respiratory questionnaire and pulmonary function tests. Subjects with COPD defined by post-bronchodilator spirometry were assessed against the eligibility criteria of 18 major RCTs cited in the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines. FINDINGS: Of 749 subjects completing the full survey, 117 had COPD. Of these, a median of 5% (range 0-20%) of subjects met inclusion criteria for the major RCTs. Of 55 subjects with COPD receiving treatment, 0-9% (median 5%) met inclusion criteria for the major RCTs. INTERPRETATION: The major COPD RCTs on which the GOLD treatment guidelines are based may have limited external validity. Over 90% of the COPD subjects in the community who were taking medication, did so on the basis of RCTs for which they would not have been eligible.

Adult↗
PubMed2006

External validity of randomised controlled trials in asthma: to whom do the results of the trials apply?

BACKGROUND: Asthma is a heterogeneous disease with a wide range of clinical phenotypes, not all of which may be encompassed in the subjects included in randomised controlled trials (RCTs). This makes it difficult for clinicians to know to what extent the evidence derived from RCTs applies to a given patient. AIM: To calculate the proportion of individuals with asthma who would have been eligible for the major asthma RCTs from the data of a random community survey of respiratory health. METHODS: A postal survey was sent to 3500 randomly selected individuals aged 25-75 years. Respondents were invited to complete a detailed respiratory questionnaire and pulmonary function testing. Participants with current asthma were assessed against the eligibility criteria of the 17 major asthma RCTs cited in the Global Initiative for Asthma (GINA) guidelines. FINDINGS: A total of 749 participants completed the full survey, of whom 179 had current asthma. A median 4% of participants with current asthma (range 0-36%) met the eligibility criteria for the included RCTs. A median 6% (range 0-43%) of participants with current asthma on treatment met the eligibility criteria. INTERPRETATION: This study shows that the major asthma RCTs on which the GINA guidelines are based may have limited external validity as they have been performed on highly selected patient populations. Most of the participants with current asthma on treatment in the community would not have been eligible for these RCTs.

Adult↗
PubMed2006

Complete reference ranges for pulmonary function tests from a single New Zealand population.

AIM: Reference equations are prerequisites for interpretation of pulmonary function tests and are important in diagnosis, assessment, and management of a range of respiratory conditions. Such equations should be derived from populations who are closely ethnically and anthropomorphically matched to those in whom the equations will be used. This paper uses measurements from a single cohort of New Zealand adults to derive reference equations for all major pulmonary function tests. METHODS: Detailed pulmonary function test results including measurement of FEV6 and airway resistance were obtained from a cohort of 212 adult New Zealanders of European origin, who were never smokers with no respiratory disease or symptoms. Equations were developed by linear regression, including sex and other candidate variables based on prior univariate analysis. Comparisons between measured and predicted values using the reference equations of the European Respiratory Society (ERS) were made. RESULTS: Reference equations were produced with high values of explained variance (R2) for many commonly used clinical parameters. When compared with ERS equations, measured values for spirometry and most lung volumes were significantly higher than predicted (mean difference FEV1: male 0.48 L, female 0.36 L, mean difference TLC male 1.14 L, female 0.89 L, SVC male and female 0.66 L). CONCLUSIONS: This study provides a complete set of contemporary pulmonary function reference equations for a New Zealand population of European origin.

Adolescent↗
PubMed2006

Recent air travel and venous thromboembolism resulting in hospital admission.

OBJECTIVE: The objective of the study was to determine the proportion of patients admitted to hospital with a deep vein thrombosis (DVT) or pulmonary embolism (PE) in whom recent air travel was documented in the medical records. METHODS: A retrospective review of the medical records of patients with a primary or secondary discharge diagnosis of DVT or PE in four hospitals in New Zealand was undertaken. From the medical records information was collected on demographic details, documentation of the presence of risk factors and results of radiological investigations. Strict radiological criteria were applied to ensure that the diagnosis of DVT or PE was firmly established. RESULTS: In 60 of 576 (10.4%) patients with a confirmed venous thromboembolism there was documentation of recent air travel; in 31 of these 60 subjects no other risk factors were recorded. In those cases in whom details of the air travel had been recorded, it had been undertaken in the previous 1 week in 65.0%, and in 43.3% the air travel was of at least 10-h duration. CONCLUSION: Long distance air travel is an important risk factor for venous thromboembolism requiring hospital admission and represents a significant public health problem in New Zealand.

Adult↗
PubMed2006

Duration of action of the salmeterol/fluticasone combination inhaler administered in the evening: a randomized controlled trial in childhood asthma.

OBJECTIVE AND BACKGROUND: To investigate the duration of bronchodilator action of a salmeterol/fluticasone combination (SFC) inhaler when administered in the evening to children with asthma. METHODOLOGY DESIGN: A double-blind, placebo-controlled, cross-over study. SETTING: Hospital inpatient. SUBJECTS: Fourteen children aged between 4 and 11 years with mild to moderate asthma (FEV(1) > 60% predicted) who exhibited a 15% increase in FEV(1) with bronchodilator. INTERVENTIONS: SUBJECTS inhaled, in random order, either SFC (100/50 microg) or placebo, via accuhaler, at 20.00 hours on two separate occasions with at least 3 days between study days. OUTCOME MEASURES: Lung function measurements including FEV(1), PEF, specific airways conductance (sGaw) and maximum expiratory flow at 25-75% of vital capacity were measured at baseline, 2, 12, 16, 20 and 24 h. RESULTS: For all lung function parameters SFC resulted in significantly greater bronchodilation than placebo for at least 20 h after inhalation. At 24 h, the increase in FEV(1) and PEF compared with placebo was 0.08 L (95% confidence interval: -0.18 to 0.02, P = 0.16) and 27 L/min (95% confidence interval: -47 to -6, P = 0.004), respectively. CONCLUSIONS: The single administration of SFC via an accuhaler in the evening resulted in significant bronchodilation for at least 20 h in children with asthma.

Administration, Inhalation↗
PubMed2006

Risk of cardiovascular events and celecoxib: a systematic review and meta-analysis.

OBJECTIVES: To examine whether the increased risk of cardiovascular events with rofecoxib represents a class effect of cyclooxygenase-2 (COX-2) specific inhibitors. DESIGN: Systematic review and meta-analysis of randomized double-blind clinical trials of celecoxib of at least 6 weeks' duration and presented data on serious cardiovascular thromboembolic events. Data sources included six bibliographic databases, the relevant files of the United States Food and Drug Administration, and pharmaceutical company websites. MAIN OUTCOME MEASURES: Pooled fixed effects estimates of the odds ratios for risk of cardiovascular events with celecoxib compared with comparator treatment were calculated using the inverse variance weight method. The main outcome measure was myocardial infarction. RESULTS: Four placebo-controlled trials with 4422 patients were included in the primary meta-analysis comparing celecoxib with placebo. The odds ratio of myocardial infarction with celecoxib compared to placebo was 2.26 (95%confidence interval 1.0 to 5.1). For composite cardiovascular events [odd ratio 1.38 (95% CI 0.91 to 2.10)], cardiovascular deaths [OR 1.06 (95% CI 0.38 to 2.95)] and stroke [OR 1.0(95% CI 0.51 to 1.84)] there was no significant increase in risk with celecoxib. The secondary meta-analysis which included a total of six studies (with placebo, diclofenac, ibuprofen, and paracetamol as comparators) of 12 780 patients, showed similar findings with a significant increased risk with celecoxib for myocardial infarction [OR 1.88 (95% CI 1.15 to 3.08)] but not other outcome measures. CONCLUSION: The available data indicate an increased risk of myocardial infarction with celecoxib therapy, consistent with a class effect for COX-2 specific inhibitors.

Cardiovascular Diseases↗
PubMed2005

Increased risk of cardiovascular events with parecoxib/valdecoxib: a systematic review and meta-analysis.

OBJECTIVE: To determine the risk of serious cardiovascular events associated with the use of the COX-2 inhibitor valdecoxib and its prodrug parecoxib following major surgery. METHODS: A systematic review and meta-analysis of placebo-controlled randomised double-blind clinical trials of IV parecoxib followed by oral valdecoxib treatment, that presented data on serious cardiovascular events. Studies were identified from six databases including Medline and the FDA website on parecoxib/valdecoxib. The main outcome measure was major cardiovascular events. The pooled fixed effects estimates for the odds ratio for risk of cardiovascular events for the use of parecoxib/valdecoxib were calculated using the inverse variance weighting method. RESULTS: Three studies with a total of 2,604 subjects were included in the meta-analysis. Parecoxib/valdecoxib was associated with a significantly increased risk of major cardiovascular events, with an odds ratio of 2.3 (95% CI: 1.1-4.7). CONCLUSION: There is an increased cardiovascular risk associated with parecoxib/valdecoxib therapy in the post-surgical situation. These findings are consistent with a class effect for COX-2 inhibitors increasing the risk of cardiovascular events.

Cardiac Surgical Procedures↗
PubMed2005

Systematic review and meta-analysis of the risk of major cardiovascular events with etoricoxib therapy.

OBJECTIVE: To determine the risk of thromboembolic cardiovascular events associated with the use of etoricoxib, a COX-2 inhibitor. DESIGN: Systematic review and meta-analysis of placebo-controlled randomised double-blind clinical trials of etoricoxib that were of at least 6 weeks duration and presented data on cardiovascular thromboembolic events. DATA SOURCES: Six databases including Medline and EMBASE. METHODS: The main outcome measure was cardiovascular thromboembolic events. A secondary analysis was undertaken to identify the presence or absence of predefined features that allowed determination of major cardiovascular events in a clinical trial. RESULTS: There were five studies with a total of 2,919 subjects included in the meta-analysis. There were 7 cardiovascular thromboembolic events in 1,441 patients (0.5%) treated with etoricoxib, and 1 event in 906 patients (0.1%) on placebo. A pooled fixed effect estimate of the absolute risk difference was 0.5% (95% CI 0.1-1.0). The odds ratio for the risk of cardiovascular events with etoricoxib was 1.49 (0.42-5.31). CONCLUSION: The clinical trials of etoricoxib provide limited data on major cardiovascular thromboembolic events as they were neither designed nor powered to assess the potential cardiovascular risks with etoricoxib therapy. However, the limited data that were available provide weak evidence of an increased cardiovascular risk with etoricoxib consistent with a class effect for COX-2 inhibitors.

Cyclooxygenase Inhibitors↗
PubMed2005

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↗
PubMed2005

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↗
PubMed2005

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↗
PubMed2005

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↗