Best Evidence Topics

Review or meta-analysis

Isomura T, Suma H, Sato T, Horii T.
Use of Harmonic Scalpel for harvesting arterial conduits in coronary artery bypass.
Euro J Cardiothoracic Surg
1998; 14:101–103.
  • Submitted by:Steven Cowman - SHO Accident and Emergency
  • Institution:Whipps Cross University Hospital
  • Date submitted:14th March 2006
Before CA, i rated this paper: 9/10
1 Objectives and hypotheses
1.1 Are the objectives of the study clearly stated?
  Yes: "To determine whether intravenous aminophylline has an additional bronchodilation effect in adult patients with acute asthma when used in conjunction with inhaled beta-agonists with or without corticosteroids (intravenous, oral and/or inhaled).
2 Design
2.1 Is the study design suitable for the objectives?
  Yes - several randomised controlled trials have previously been published regarding the subject and a meta-analysis of these studies is an appropriate study design.
2.2 Were the search methods used to locate relevant studies comprehensive?
  Yes – A search of the Cochrane Airways Review Group register, a search of the Cochrane Controlled Trials Register, a search of the bibliographies of all available primary studies and reviews, and personal inquiries amongst the authors of primary studies, colleagues within the field and pharmaceutical companies that manufacture methylxanthines to identify any further published trials or unpublished data.
2.3 Was this the right sample to answer the objectives?
  Yes, the search methods used identified several randomised controlled trials directly addressing the question posed in the study's stated objective.
2.4 Is the study large enough to achieve its objectives?
  The study does not mention whether sample size estimates were performed. A total of 17 trials were identified, comprising 739 patients.
2.5 Were all the studies accounted for?
2.6 Were all appropriate outcomes considered?
  Yes, all patient outcomes were considered by the study. In particular the primary outcome was change in peak expiratory flow (PEFR) or change in forced expiratory volume in 1 second (FEV1). Secondary outcomes included: admission to hospital, effect on vital signs, and presence of adverse outcomes.
2.7 Has ethical approval been obtained if appropriate?
3 Measurement and observation
3.1 Is it clear what was measured, how it was measured and what the outcomes were?
  Yes, as covered in 2.6. However, as the author point out, a limitation of this study was the variety of different outcomes used by the different studies, producing a smaller number of studies for subgroup comparisons. The timing of assessments was at 0.5, 1, 12 and 24 hours after drug administration, or as close to them as possible. Few studies provided data at 12 or 24 hours.
3.2 Were explicit methods used to determine which studies to include in the review?
  Yes, the criteria for a study to be considered were:
• Randomised controlled trial
• Adults (>18 years of age) presenting with acute asthma in an acute care setting
• Studies must compare aminophylline + 'standard care' vs. placebo + 'standard care' where 'standard care' always included beta-agonist therapy, plus other agents with or without corticosteroids
• All outcomes were considered (see 2.6)
Exclusion criteria were:
• Patients ventilated at presentation
• Patients who had been in-patients for greater than 24 hours
• Studies which directly compared aminophylline to beta-agonists
3.3 Was the selection of primary studies re-producible and free from bias?
  Studies were identified using a robust search strategy as mentioned above (2.2) using explicit inclusion criteria (3.2). Whilst effort was made to identify unpublished data (no unpublished trials were found) the authors note the possibility that such trials may exist, and hence the possibility of publication or selection bias.
Two independent reviewers assessed the abstracts of identified studies for potential relevance, two independent reviewers then used the full text to select trials for inclusion; disagreements were resolved by an independent third party. It is not mentioned if the reviewers were blinded during selection.
3.4 Was the methodologic quality of the primary studies assessed?
  Two reviewers independently assessed the methodological qualities of the selected trials both by ranking the quality of concealment using the Cochrane approach, and by using the Jadad criteria. Interobserver reliability was measured for both using the kappa statistic, and found no discrepancy for concealment (kappa 1.0) and excellent agreement for Jadad score (kappa 0.81). Again, it is not mentioned if the reviewers were blinded during this process.
3.5 Are the measurements valid?
  Yes, the outcomes in question are clinically relevant and in widespread use.
3.6 Are the measurements reliable?
  Yes, FEV1 perhaps more so than PEFR.
3.7 Are the measurements reproducible?
  Yes, FEV1 perhaps more so than PEFR.
4 Presentation of results
4.1 Are the basic data adequately described?
  Yes. Weighted mean differences (WMD) or standardised mean differences (SMD) were given for continuous variables and odds ratios (OR) for dichotomous variables, with 95% confidence intervals for each value given. Where data were not reported clear reasons were given. The data were also presented graphically for ease of comparison.
4.2 Were the differences between studies adequately described?
  Yes. The characteristics of included studies (methods, participants, interventions and outcomes) were clearly presented in table format as an appendix to the study, with the authors' comments and allocation concealment score for each. The Jadad score for each paper was not given.
4.3 Are the results presented clearly, objectively and in sufficient detail to enable readers to make their own judgement?
  Yes, the results were presented objectively and in detail (see 4.1 and 4.2 above).
4.4 Are the results internally consistent, i.e. do the numbers add up properly?
5 Analysis
5.1 Were the results of primary studies combined appropriately?
  Yes. SMD, WMD or OR were calculated as appropriate, with 95% confidence intervals. Pooled estimates were tested for heterogeneity and calculated using the fixed effects model when there was no significant heterogeneity, or the random effects model where significant heterogeneity was found.
5.2 Has a sensitivity analysis been performed?
  Yes, sensitivity analysis was performed using methodological criteria (Cochrane criteria A vs. B or C and Jadad score 3-5 vs. <3) and fixed effects vs. random effects modelling. The results remained unchanged.
Subgroup analysis was performed looking at the effect of severity at presentation (severe asthma being defined as PEFR < 40% expected or < 150L/min or FEV1 <40% expected or < 1 L/min) and corticosteroid administration (vs. none). No differences were found between subgroups. No subgroup analysis was performed examining the effect of the route of beta-agonist administration.
5.3 Were all the important outcomes considered?
  Yes, all outcomes were considered (see 2.6).
5.4 Are the data suitable for analysis?
  Yes, though as mentioned above (3.1) the different outcome measures (FEV1 and PEFR expressed both as % of expected and absolute values) used between trials is a limitation to this study. The 'standard care' given to patients also varied widely between trials, notably the administration of corticosteroids, and the route of administration of beta-agonists. Whilst subgroup analysis was performed to examine the effect of corticosteroid use on the results (see 5.2) none was carried out to examine the effect of the route of beta-agonist administration. The pooled treatment group had lower values for baseline FEV1 and PEFR compared to the pooled control group, though the authors repeated the analysis using adjusted data to compensate for this finding and found the results to be unchanged.
5.5 Are the methods appropriate to the data?
  Yes, appropriate methods were used (see 4.1, 5.1, 5.2 and 5.4).
5.6 Are any statistics correctly performed and interpreted?
  Yes, statistics were performed and interpreted correctly (see 5.5).
6 Discussion
6.1 Are the results discussed in relation to existing knowledge on the subject and study objectives?
  Yes, the discussion places the findings in the light of previous research on the subject and refers to the stated objective. However the stated objective involves examining the use of aminophylline "in conjunction with inhaled beta-agonists", whilst the study itself includes trials using other routes of beta-agonist administration. The differences in the route of beta-agonist administration are not discussed further (see 5.2 and 5.4).
6.2 Is the discussion biased?
  I cannot detect any bias in the discussion. The authors have no conflict of interest and no external funding was supplied.
7 Interpretation
7.1 Are the author's conclusions justified by the data?
  Yes, the assertions made by the authors in their conclusions are supported by the results of this study.
7.2 What level of evidence has this paper presented?
7.3 Does this paper help me to answer my problem?
  This objective of this paper is virtually identical to the problem posed by my three part question, and thus its conclusions are very helpful in answering my question. It is a high-quality systematic review of a number of randomised controlled trials and hence provides a good level of evidence to support my answer. The only caveat is that the inhaled route is the primary route of beta-agonist administration in UK practice, and this study includes several trials using alternative routes of administration. A subgroup analysis looking at the effect of route of beta-agonists administration my have been useful to me; but whilst more specific to my practice would have the drawback of small group sizes.
After CA, i rated this paper: 9/10
8 Implementation
8.1 Can any necessary change be implemented in practice?
  Yes, by the education of healthcare providers (e.g. via local protocols).
8.2 What aids to implementation exist?
  Published guidelines, such as the British Thoracic Society guidelines on the treatment of asthma.
8.3 What barriers to implementation exist?
  None, other than any practical difficulties which may arise in disseminating guidelines to relevant healthcare providers.