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Biomedical subjects

Philippa Shirtcliffe

Publications and source records attributed to Philippa Shirtcliffe.

8 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

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↗
PubMed2002

An inverse correlation between estimated tuberculosis notification rates and asthma symptoms.

BACKGROUND: A recent ecological analysis demonstrated a strong inverse relationship between tuberculosis notification rates and the prevalence of asthma symptoms in 13-14-year-old children as obtained from the International Study of Asthma and Allergies in Childhood (ISAAC). However, the analysis was confined to the 23 countries in which the tuberculosis notification rates were considered to be of sufficient validity. METHODS: A similar analysis was performed using estimated tuberculosis incidence rates obtained from the World Health Organization Global Tuberculosis Programme and asthma symptom prevalence data from ISAAC for both the 6-7 and 13-14 years age groups in 38 and 55 countries, respectively. RESULTS: For the 6-7-year-old children, there was a significant inverse relationship between estimated tuberculosis incidence and the prevalence of key asthma symptoms. However, in the 13-14 year age group, a significant inverse relationship was only demonstrated for 'asthma ever'. CONCLUSION: The present study extends the inverse relationship between tuberculosis rates and asthma prevalence to the 6-7-year-old age group and suggests that the association, if causal, may be stronger at this younger age.

Adolescent↗