Utility of clinical trial results for clinical practice.
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Biomedical subjects
Publications and source records attributed to Henry McQuay.
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Previous human imaging studies have revealed a network of brain regions involved in the processing of allodynic pain; this includes prefrontal areas, insula, cingulate cortex, primary and secondary somatosensory cortices and parietal association areas. In this study, the neural correlates of the perceived intensity of allodynic pain in neuropathic pain patients were investigated. In eight patients, dynamic mechanical allodynia was provoked and brain responses recorded using functional magnetic resonance imaging (fMRI). Voxels in which the magnitude of fMRI signal correlated linearly with the ratings of allodynic pain across the group were determined in a whole brain analysis using a general linear model. To ensure that activation reflected only allodynic pain ratings, a nuisance variable containing ratings of ongoing pain was included in the analysis. We found that the magnitude of activation in the caudal anterior insula (cAI) correlates with the perceived intensity of allodynic pain across subjects, independent of the level of ongoing pain. However, the peak of activation in the allodynic condition was located in the rostral portion (rAI). This matches the representation of other clinical pain syndromes, confirmed by a literature review. In contrast, experimental pain in healthy volunteers resides predominantly in the cAI, as shown by the same literature review. Taken together, our data and the literature review suggest a functional segregation of anterior insular cortex.
Of the 4 million annual births in the United States, 2.4 million involve epidural analgesia. Serious adverse events are rare but are important in young women. Robust estimates for the risk of harm are not available. Data for superficial and deep infections, hematoma, and transient and permanent neurologic injury were obtained from studies reporting adverse events with obstetric epidural analgesia, and incidence presented as individual risk for a woman, number of events per million women, and percentage incidence. A total of 1.37 million women received an epidural for childbirth, reported in 27 articles. Most information (85% of women) was in larger (> 10,000 women) studies published after 1990, with risk estimates as follows: epidural hematoma, 1 in 168,000; deep epidural infection, 1 in 145,000; persistent neurologic injury, 1 in 240,000; and transient neurologic injury, 1 in 6,700. Earlier and smaller studies produced significantly higher risk estimates for transient neurologic injury plus injury of unknown duration.
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The aim of this study was to examine whether mean data from categorical pain intensity and visual analogue scales for both pain intensity and relief could be used reliably to derive dichotomous outcome measures for meta-analysis. Individual patient data from randomised controlled trials of single-dose analgesics in acute postoperative pain were used. The methods used were as follows: data from 132 treatments with over 4700 patients were used to calculate mean %maxSPID (categorical pain intensity), %maxVAS-SPID (visual analogue pain intensity) and %maxVAS-TOTPAR (visual analogue pain relief); these were used to derive relationships with the number of patients who achieved at least 50% pain relief (%maxTOTPAR). Good agreement was obtained between the actual number of patients with > 50%maxTOTPAR and the number calculated for all three measures. For SPID, verification included independent data sets. For calculations involving each measure, summing the positive and negative differences between actual and calculated numbers of patients with > 50%maxTOTPAR gave an average difference of less than 0.25 patients per treatment arm. Reports of randomised trials of analgesics frequently describe results of studies in the form of mean derived indices, rather than using discontinuous events, such as number of proportion of patients obtaining at least 50% pain relief. Because mean data inadequately describe information with a non-normal distribution, combining such mean data in systematic reviews may compromise the results. Showing that dichotomous data can reliably be derived from mean SPID, VAS-SPID and VAS-TOTPAR as well as TOTPAR data in previously published acute pain studies makes much more information accessible for meta-analysis.
The objective was to investigate the relationship between pain relief scores produced by placebo and by active interventions in randomised controlled trials (RCTs). Individual patient categorical pain relief scores from 5 placebo-controlled single-dose parallel-group RCTs in acute postoperative pain were used to calculate the percentage of the maximum possible pain relief score (%maxTOTPAR) for the different treatments. One hundred and thirty of the 525 patients in the 5 trials had a placebo. Individual patients' scores with placebo varied from 0 to 100% of the maximum possible pain relief. The proportion who obtained more than 50% of the maximum possible pain relief with placebo varied from 7% to 37% across the trials; with the active drugs the variation was from 5 to 63%. Mean placebo scores were related to the mean score for the active treatments in each study; the higher the mean active score, the higher the mean placebo score. This relationship disappeared when median values were used. Medical folklore has it that the amount of relief obtained with placebo is one-third of the maximum possible (and does not vary), and that one-third of patients respond to placebo. The results show that the amount of relief obtained with placebo varies considerably between patients, that 38% of patients obtained more than 10% of the maximum possible relief, and 16% obtained greater than 50%. In double-blind, randomised parallel-group studies of high quality placebo scores should not vary. Despite these conditions being met the placebo scores did vary. The previous explanation, of a relationship between the mean placebo scores and the mean scores for the active treatments was not supported.
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