“A good old belly laugh can help heal leg ulcers,” BBC News has reported. However, the eye-catching claim is only a theory offered by researchers who said the treatment is probably more effective than ultrasound, the treatment they were actually studying.
Their five-year study, which did not look at laughing, was a well-conducted trial, which found that low-dose ultrasound treatment did not speed up the healing of leg ulcers when used alongside standard dressings and compression therapies. Overall, the results of this well-conducted study suggested that 12 weekly treatment sessions of ultrasound did not improve healing time or quality of life.
This negative result, i.e. finding no effect, is itself interesting and important as it can highlight where a potentially costly treatment would provide no benefit if introduced into practice. As low-dose ultrasound is an ineffective treatment, researchers’ future efforts should therefore look at other therapies. Laughing was not discussed in the research, but if it has a rationale as implied in the news reports, perhaps it too should be the subject of a clinical trial.
Where did the story come from?
The study was carried out by researchers from York, the University of York, and the University of Leeds. It was funded by the UK National Institute for Health Research (NIHR) via its Health Technology Assessment Programme and published in the peer-reviewed British Medical Journal.
After its eye-catching headline and introduction, the BBC’s article accurately reported that the study was actually investigating ultrasound and had negative results.
What kind of research was this?
In this randomised controlled trial, the researchers were interested in assessing whether treatment combining standard care with weekly, low-dose, high-frequency therapeutic ultrasound was better than standard care alone for treating venous leg ulcers that were already hard to heal.
The researchers explain that most venous leg ulcers heal within 12 months, but they defined larger ulcers and those that took more than six months to heal as ‘harder to heal’. Some trials have suggested that therapeutic ultrasound can help to heal leg ulcers, but these have mostly been small and varied in the grading of the ulcer, how the ultrasound was applied, or in the treatment that ultrasound was tested against. Here, the researchers set out to conduct a trial that was not limited by these problems or other methodological concerns.
The study was well-reported, and is said to be the largest conducted trial of this type of therapeutic ultrasound for wound healing. Negative results, i.e. finding no effect, are often not as interesting or newsworthy as positive ones, but they are probably equally important as they can protect people from ineffective and unproven therapies.
What did the research involve?
This study was conducted across 11 sites in the UK and one in the Republic of Ireland. It was “pragmatic” in that it set out to test the effect of the ultrasound use in real life situations rather than in a research setting. Between 2006 and 2008, the researchers recruited participants from services led by community and district nurses, community leg ulcer clinics, and hospital outpatient leg ulcer clinics in the 12 urban and rural settings. The trial was known as the VenUS III study, short for the third trial into Venous leg ulcer treatment with Ultrasound.
The researchers recruited 337 participants who had at least one venous leg ulcer for more than six months or an ulcer with an area of 5cm2 or greater, as well as an ankle brachial pressure index of 0.8 or more. The ankle brachial pressure index is a measure of how good the arterial circulation is to the leg. A high ratio suggests that the ulcer is caused by a poor flow of blood returning from the legs through the veins, and is therefore a potential target for this therapy.
Patients were randomised to receive either standard care alone or a weekly administration of low-dose, high-frequency ultrasound therapy for up to 12 weeks, plus standard care. The standard care group received typical low-adherent dressings and four-layer bandaging that offered high compression, reduced compression or no compression, depending on the patient’s tolerance. Bandages were replaced at each weekly visit. Changes to this regimen, if thought appropriate by the treating clinician, were allowed and recorded. The standard care provided was the same treatment usually provided by that local practice. This means that the care could vary between treatment centres.
The researchers were mainly interested in the healing time of the largest eligible leg ulcer. They had six secondary outcomes of interest: the proportion of patients healed by 12 months, change in ulcer size (both as a percentage and as an absolute area), the proportion of time participants were ulcer-free, changes in health-related quality of life and adverse events.
What were the basic results?
There were no significant differences between the groups on any of the outcomes measured. The researchers found:
- Time to healing of the reference leg ulcer was no different.
- After adjustment for baseline ulcer area, baseline ulcer duration, use of compression bandaging, and study centre, there was still no evidence of a difference in healing time (hazard ratio [HR] 0.99 (95% confidence interval [CI] 0.70 to 1.40).
- No significant difference between groups in the proportion of participants with all ulcers healed by 12 months.
- No significant change in ulcer size at four weeks between the treatment groups.
- No difference in time to complete healing of all ulcers. The average (median) time to healing was 328 days with standard care and 365 days with ultrasound - not a significant difference.
- There was also no difference between groups in recurrence rates and quality of life.
How did the researchers interpret the results?
The researchers say they found no evidence that therapeutic low-dose ultrasound delivered once a week improves the healing of venous leg ulcers.
However, the researchers say that rates of ulcer healing differed significantly between treatment centres. This was proportional to the number of participants, suggesting that bigger centres had better outcomes. However, there was no evidence of ultrasound having an effect on healing when analysed by individual centre.
As there was little change in the physical component of Quality of Life scores in either group, and no evidence of a significant change in the mental component summary score over time, the researchers also conclude that ultrasound showed no impact on health-related quality of life.
This research in a real-life situation has produced the important finding that weekly ultrasound treatment appears to have no benefits for ulcer healing time. Nor did it benefit the probability of ulcer having healed at 12 months, or other outcomes relating to hard-to-heal leg ulcers.
It is worth noting a few points that these researchers make:
- There were more adverse events in the ultrasound group than in the standard care group. But as ultrasound is not currently used in practice, it is possible that nurses were more likely to attribute adverse events (such as ulcer deterioration) to the unfamiliar ultrasound treatment. The overall adverse event rate was similar to that in a previous trial, which reported an event rate of about 40%.
- The lack of effect could be explained either by the trial failing to detect an effect that truly existed (due to chance or to methodological problems) or by the dose and frequency of ultrasound therapy used in the trial not accelerating the healing-of-hard to heal venous ulcers.
- The researchers were careful to minimise any sources of bias, and the study had a large sample size. This suggests that the second of their explanations is the likely reason for the lack of effect shown, i.e. that the therapy delivered in this way truly has no effect.
Overall, this well-conducted trial is probably the best evidence yet that this use of ultrasound does not speed up the healing of hard-to-heal leg ulcers. The lead researcher is quoted by BBC News as saying, "They key to care with this group of patients is to stimulate blood flow back up the legs to the heart.” The researcher suggests that “a really hearty chuckle” may help do this. Laughing may well be an alternative way of improving the return of blood from the legs in people with ulcers, but the researchers did not discuss this in their publication of results.
This study is also an example of how small, preliminary research or studies may initially suggest a benefit for a treatment, only for it to not be apparent when the issue is examined in a larger, high-quality study.
Analysis by Bazian
Edited by NHS Website
Links to the headlines
BBC News, 10 March 2011
Daily Mail, 10 March 2011
Links to the science
BMJ 2011; 342:d1092