Biomedical subjects

D Gavaghan

Publications and source records attributed to D Gavaghan.

7 recordsLinked to original sources

PubMed2001

Using evidence from different sources: an example using paracetamol 1000 mg plus codeine 60 mg.

BACKGROUND: Meta-analysis usually restricts the information pooled, for instance using only randomised, double-blind, placebo-controlled trials. This neglects other types of high quality information. This review explores using different information for the combination of paracetamol 1000 mg and codeine 60 mg in acute postoperative pain. RESULTS: Randomised, double-blind, placebo-controlled trials of paracetamol 1000 mg and codeine 60 mg had an NNT of 2.2 (95% confidence interval 1.7 to 2.9) for at least 50% pain relief over four to six hours in three trials with 197 patients. Computer simulation of randomised trials demonstrated 92% confidence that the simulated NNT was within +/- 0.5 of the underlying value of 2.2 with this number of patients. The result was supported a rational dose-response relationship for different doses of paracetamol and codeine in 17 additional trials with 1,195 patients. Three controlled trials lacking a placebo and with 117 patients treated with of paracetamol 1000 mg and codeine 60 mg had 73% (95%CI 56% to 81%) of patients with at least 50% pain relief, compared with 57% (48% to 66%) in placebo controlled trials. Six trials in acute pain were omitted because of design issues, like the use of different pain measures or multiple dosing regimens. In each paracetamol 1000 mg and codeine 60 mg was shown to be better than placebo or comparators for at least one measure. CONCLUSIONS: Different designs of high quality trials can be used to support limited information used in meta-analysis without recourse to low quality trials that might be biased.

Acetaminophen↗

PubMed2000

Publication and related bias in meta-analysis: power of statistical tests and prevalence in the literature.

Publication and selection biases in meta-analysis are more likely to affect small studies, which also tend to be of lower methodological quality. This may lead to "small-study effects," where the smaller studies in a meta-analysis show larger treatment effects. Small-study effects may also arise because of between-trial heterogeneity. Statistical tests for small-study effects have been proposed, but their validity has been questioned. A set of typical meta-analyses containing 5, 10, 20, and 30 trials was defined based on the characteristics of 78 published meta-analyses identified in a hand search of eight journals from 1993 to 1997. Simulations were performed to assess the power of a weighted regression method and a rank correlation test in the presence of no bias, moderate bias or severe bias. We based evidence of small-study effects on P < 0.1. The power to detect bias increased with increasing numbers of trials. The rank correlation test was less powerful than the regression method. For example, assuming a control group event rate of 20% and no treatment effect, moderate bias was detected with the regression test in 13.7%, 23.5%, 40.1% and 51.6% of meta-analyses with 5, 10, 20 and 30 trials. The corresponding figures for the correlation test were 8.5%, 14.7%, 20.4% and 26.0%, respectively. Severe bias was detected with the regression method in 23.5%, 56.1%, 88.3% and 95.9% of meta-analyses with 5, 10, 20 and 30 trials, as compared to 11.9%, 31.1%, 45.3% and 65.4% with the correlation test. Similar results were obtained in simulations incorporating moderate treatment effects. However the regression method gave false-positive rates which were too high in some situations (large treatment effects, or few events per trial, or all trials of similar sizes). Using the regression method, evidence of small-study effects was present in 21 (26.9%) of the 78 published meta-analyses. Tests for small-study effects should routinely be performed in meta-analysis. Their power is however limited, particularly for moderate amounts of bias or meta-analyses based on a small number of small studies. When evidence of small-study effects is found, careful consideration should be given to possible explanations for these in the reporting of the meta-analysis.

Bias↗

PubMed1997

Deriving dichotomous outcome measures from continuous data in randomised controlled trials of analgesics: verification from independent data.

A previously established relationship for deriving dichotomous from continuous information in randomised controlled trials (RCTs) of analgesics has been tested using an independent data set. Individual patient information from 18 RCTs of parallel-group design in acute postoperative pain (after abdominal, gynaecological and oral surgery) was used to calculate the percentage of the maximum possible pain relief score (%maxTOTPAR) and the proportion of patients with > 50%maxTOTPAR for the different treatments. The relationship between the measures was investigated in 85 treatments with over 3400 patients. In 80 of 85 treatments (94%) agreement between calculated and actual number of patients with > 50%maxTOTPAR was within four patients per treatment and in 72 (85%) was within three (average of 40 patients per treatment, range 21-58 patients). Summing the positive and negative differences between actual and calculated numbers of patients with > 50%maxTOTPAR gave an average difference of 0.30 patients per treatment arm. Reports of RCTs of analgesics frequently describe results of studies in the form of mean derived indices, rather than using discontinuous events, such as number or proportion of patients with 50% pain relief. Because mean data inadequately describe information with a non-normal distribution, combining mean data in systematic reviews may compromise the results. Showing that dichotomous data can reliably be derived from mean data in acute pain studies enables data published as means to be used for quantitative systematic reviews which require data in dichotomous form.

Acute Disease↗

PubMed1996

Deriving dichotomous outcome measures from continuous data in randomised controlled trials of analgesics.

Reports of RCTs of analgesics frequently describe results of studies in the form of mean derived indices, rather than using discontinuous events--such as number or proportion of patients with 50% pain relief. Because mean data inadequately describe information with a non-normal distribution, combining mean data in systematic reviews may compromise the results. Showing that dichotomous data can reliably be derived from mean data, at least in acute pain models, indicates that more meaningful overviews or meta-analysis may be possible. This study investigated the relationship between continuous and dichotomous analgesic measures in a set of individual patient data, and then used that relationship to derive dichotomous from continuous information in randomised controlled trials (RCTs) of analgesics. Individual patient information from 13 RCTs of parallel-group and crossover design in acute postoperative pain was used to calculate the percentage of the maximum possible pain relief score (%maxTOTPAR) and the proportion of patients with greater than 50% pain relief (> 50%maxTOTPAR) for the different treatments. The relationship between the measures was investigated in 45 actual treatments and 10,000 treatments simulated using the underlying actual distribution; 1283 patients had 45 separate treatments. Mean %maxTOTPAR correlated with the proportion of patients with > 50%maxTOTPAR (r2 = 0.90). The relationship calculated from all the 45 treatments predicted to within three patients the number of patients with more than 50% pain relief in 42 of 45 treatments, and 98.8% of 10,000 simulated treatments. For seven effective treatments, actual numbers-needed-to-treat (NNT) to achieve > 50%maxTOTPAR compared with placebo were very similar to those derived from calculated data.

Analgesics↗

PubMed1995

Effects of propofol and thiopentone, and benzodiazepine premedication on heart rate variability measured by spectral analysis.

We studied the effects of temazepam premedication and induction of anaesthesia with thiopentone or propofol on the heart rate power spectrum in 47 patients undergoing elective minor surgery. Eighteen patients received temazepam 20 mg orally as premedication. There was a significant reduction in high frequency power and total power, and an increase in the ratio of low to high frequency power after induction of anaesthesia with either propofol or thiopentone. Patients who had received temazepam premedication had significantly greater low frequency, high frequency and total power than those who were not premedicated. There was no significant difference between premedicated and unpremedicated patients in the ratio of low to ventilatory frequency power.

Adult↗

PubMed1994

Effect of methylene blue on the vasodilator action of inhaled nitric oxide in hypoxic sheep.

We have examined the effect of methylene blue 4mg kg-1 on the pulmonary vasodilator action of inhaled nitric oxide (8, 32, 128 and 512 volumes per million) in nine sheep with pulmonary hypertension induced by hypoxia (FlO2 = 0.12). The dose-response to nitric oxide was unchanged by methylene blue, but increased cardiac output was noted (P < 0.01). These results indicate that methylene blue may not inhibit the action of nitric oxide on guanylate cyclase, as suggested previously, and that treatment of methaemoglobinaemia occurring during therapeutic inhalation of nitric oxide with methylene blue may not block the vasodilator effect of nitric oxide on the pulmonary vasculature.

Animals↗

PubMed1990

Epidemiology of shingles.

One thousand and nineteen patients with acute varicella zoster viral infection were referred to the physiotherapy department for treatment between 1978 and 1986. Sixty per cent were women and 40% were men with a mean age of 58 years (range 9-96 years). The prevalence varied between 1.3 and 1.6 per 1000 per annum. The left side was affected in 52% while the right was affected in 48%. The thoracic dermatomes were the most commonly affected (56%) followed by cervical (17%), lumbar (10%), sacral (5%), and the trigeminal nerve was infected in 12%. There was a significant seasonal (P less than 0.001) variation in the prevalence of acute varicella zoster virus infection, most common in the summer and least common in the spring. There was no clustering in time and space so that it is unlikely that the varicella zoster virus is infective or that re-exposure to the virus causes reactivation of the latent virus.

Adolescent↗