A 30-year-old Spanish woman has become the “first transplant patient to receive an organ grown to order in a laboratory”, The Independent reported today. It said the woman’s damaged windpipe had been successfully replaced with a “bioengineered organ”. The organ was grown using her own cells on a donor scaffold, and so she did not need to take drugs to suppress her immune system. Extensive media coverage was given to the operation, which The Times newspaper said could “revolutionise” surgery.

This patient will need to be observed to determine the long term viability of the graft, but the initial results are promising. This technique will now be tried in other patients with similar problems. Further research will need to see if the technique can produce other tissues.

Professor Paolo Macchiarini and colleagues from the Hospital Clinic in Barcelona, as well as other research institutions and universities in Spain and the UK carried out this research. The study was funded by the Ministerio de Sanidad y Consumo, Instituto de Salud Carlos III, Fondo de Investigación Sanitaria, Spain; Charles Courtenay-Cowlin Fund, University of Bristol; UK Arthritis Research Campaign; and the James Tudor Foundation. The study was published in the peer-reviewed medical journal: The Lancet.

This was a case report that described the transplantation of a tissue-engineered trachea (windpipe) into a patient.

The researchers first developed the technique by experimenting on animals. The process involves the construction of a “tissue-engineered windpipe”, which contains cartilage cells (chondrocytes) grown from the subject’s own stem cells and adhered to a donor windpipe scaffold. By using the subject’s own cells, there is less chance that their immune system will reject the graft. The researchers had previously managed to generate short living pieces of trachea in this way, and these had been successfully grafted into animals. Their next step was to attempt to generate a longer piece of living trachea that could be transplanted into a human.

The researchers identified a 30-year old woman who had had various treatments for problems associated with a narrowing of the windpipe leading into her lungs. She had initially suffered from tuberculosis and the condition had eventually led to the removal of part of her windpipe. Scaffolding had then been put in place to hold open the tube leading from the main windpipe to the left lung (bronchus). However, this scaffolding was not well tolerated by the patient’s body, and had to be removed. As a result the bronchus narrowed, her left lung could not function properly and the patient had severe difficulty breathing. As the only remaining option was to remove the whole left lung, an operation associated with complications and a high death rate, the doctors felt she was a suitable test case. They therefore offered to replace the narrowed part of her bronchus with a tissue engineered graft.

A 7cm piece of trachea from a deceased female donor was treated to remove all of the donor’s cells, leaving a tubular cartilage scaffold. The researchers then took bone marrow cells and lining (epithelial) cells from the recipient’s bronchus and grew these in the lab. Bone marrow contains stem cells that can develop into any type of cell. In this case, the researchers grew the bone marrow cells in conditions that would lead to them developing into cartilage cells (chondrocytes). The recipient’s chondrocytes and epithelial cells were then ‘seeded’ onto the donor scaffold and allowed to develop in the lab.

The tracheal graft was then transplanted into the recipient under general anaesthesia. During this procedure, the narrowed part of her bronchus was removed and replaced with a 5cm long piece of the tissue-engineered graft. The patient was monitored after surgery, and tests performed to see if her immune system was producing a response against the donor’s tissue.

What were the results of the study?The researchers produced a living tissue-engineered graft containing cartilage cells generated from the recipient’s own stem cells and grown on a donor trachea scaffold. The inside of this graft tube was also lined with the recipient’s cells.

This graft successfully replaced a part of the narrowed tube leading from the windpipe into the left lung. The recipient did not experience any complications from the surgery, and was able to leave hospital after 10 days. She was then able to resume normal activities, such as walking up two flights of stairs, walking 500m without stopping, and taking care of her children. Her lung function was normal when tested two months after the surgery. She did not show any immune response against the donor tissue up to two months after surgery and did not need drugs to suppress her immune system.

The graft tissue looked healthy when examined using imaging techniques, and by one month did not look any different to normal tracheal tissue. Cells taken by brushing the surface of the graft after four months also looked normal.

The researchers concluded that they could produce a “cellular, tissue-engineered airway” which functions like a normal airway and is free from the risk of rejection. They say their findings suggest that a patient’s own cells, in combination with suitable biological materials, can successfully treat serious medical problems.

This innovative study shows that it is possible to use a patient’s own cells to reduce the risk of graft rejection. The patient will need to be watched to determine the long term viability of this graft, but initial results are promising.

This technique will now be tried in other patients with similar problems. Further research will need to determine whether a similar technique can be used to produce other tissues.

A study has found that “Ginkgo biloba does not prevent dementia” according to the Daily Telegraph today. The newspaper reports that the thousands of elderly people may be “wasting their time”  taking the Chinese herbal supplement to ward off dementia and Alzheimer's.

The newspaper’s story comes from a large, well conducted study in America. This ‘randomised controlled trial’ provides the best evidence to date on the use of Ginkgo biloba supplements by healthy, elderly people to prevent dementia. The study, which followed up 3,000 people for six years, has found no difference in the number of new dementia cases between those taking a fairly standard Ginkgo supplement and those who did not.

Importantly though, this study did not test for changes in the brain that may occur several years before noticeable symptoms of dementia. The researchers will be further investigating effects of Ginkgo in a seperate study, using MRI scans on the brain. Their findings may provide further information on whether Ginkgo has any effect on patients with memory impairment or dementia.

This study was conducted by Dr DeKosky and other investigators..It was funded and supported by the National Centre for Complementary and Alternative Medicine (NCCAM) and other national, charitable and academic institutions.

The Ginkgo biloba tablets and identical placebos were donated by Schwabe Pharmaceuticals. The study was published in the peer-reviewed medical journal, JAMA.

The study behind this news report is a large randomised, double-blind, placebo-controlled trial in five academic medical centres across the United States. Researchers were exploring the use of Ginkgo biloba to prevent dementia.

According to the researchers, Ginkgo is prescribed in some countries for preservation of memory, and to date there has been no large, well-run study to investige whether the supplement can in fact prevent the onset of dementia. Researchers set out to investigate whether 240mg of Gingko could reduce the incidence of dementia due to any cause, and in particular due to Alzheimer’s disease.

Between 2000 and 2002 people aged over 75 were contacted through details from voter registration and mailing lists. They were asked to volunteer for this study and were also asked to volunteer a person who would also be willing to be interviewed every six months (a proxy).

Several exclusion criteria applied to people in this study, including current cases of dementia (a score of greater than 0.5 on the Clinical Dementia Rating Scale), people taking warfarin or drugs used to treat dementia, mental disorders (including depression and psychosis), history of bleeding disorders or Parkinson disease, or other abnormal health markers.

Those who were not willing to discontinue over-the-counter Ginkgo biloba for the duration of the study, those taking large doses of vitamin E and those with a known allergy to Ginko biloba were also excluded.

Overall 3069 volunteers took part in this study; most of them had normal cognition and 16% of them (482 people) had mild cognitive impairment.

They were randomised to either Ginkgo biloba or placebo at each medical site. During the course of the study some people withdrew consent or were not available for follow up, so in the end 2874 people were available for analysis. The people receiving treatments and the physicians giving them their treatments were not aware of whether they were using placebos or Ginkgo (i.e. the study was double blind).

The researchers re-interviewed participants every six months for an average of six years, testing cognition and memory and undertaking a full battery of cognitive testing if either the participant or their proxy reported onset of a new cognitive or memory problem.

Those who met the criteria for new-onset dementia (depending on how many of the cognition/memory tests they failed) were sent for more specialist evaluation and brain scanning to confirm the diagnosis.This confirmed the diagnosis and determined which type it was.

Using statistical techniques, the researchers then compared the incidence (number of new cases) of dementia during the study between the Ginkgo group and the placebo group.

What were the results of the study?The average age of participants in this study was 79 years. 54% were men and 46% were women. During the course of the study, 246 people in the placebo group and 277 people in the Ginkgo group were diagnosed with dementia. There was no difference in the rate of total dementia or Alzheimer’s between the two groups.

Of the total dementia cases, the majority (92%) were classified as having Alzheimer’s disease. Whether the person had normal cognition or mild cognitive impairment at the beginning of this study did not appear to affect these results.

There seemed to be a small protective effect on new cases of vascular dementia (dementia caused by damaged blood vessels in the brain), though the number of people in these groups was very small.

The researchers also conclude that the adverse events were similar between Ginkgo and placebo. There were twice as many haemorrhagic strokes in the Ginkgo group (16 vs 8), though the numbers were small and the difference was not statistically significant.

The researchers conclude that the results did not show that Ginkgo is effective in preventing or delaying the onset of dementia or Alzheimer’s disease in those aged over 75 years. The study used a standardised formulation of Gingko biloba and given this, the researchers believe that their results are applicable to other formulations.

This large, randomised, controlled trial provides good, robust evidence that Ginkgo biloba supplements may be of limited use in preventing dementia in generally healthy elderly people.

The design and size of this study mean that confidence in the results is high, and as such this is the best evidence to date of how Ginkgo performs when used to prevent dementia.

The one shortcoming that the researchers highlight is the follow up time of the study, as participants were followed for six years on average. Symptoms of dementia may take many years to become evident, meaning that ‘an effect of Ginkgo biloba, positive or negative, may take many more years to manifest’.

The researchers say that further to this study they are planning to explore the brain function and possible brain changes using MRI scans in a subgroup of participants. This will explore whether or not Ginkgo is associated with  changes preceding clinical symptoms of dementia. The effects of Ginkgo biloba at this level will not be known until the results of this further study are published. 

The shortage of organs available for transplant would not be solved by introducing a new system of “presumed consent” of organ donation, a government appointed taskforce has concluded.

At present, people must “opt in” by specifically placing their names on the Organ Donor Register if they wish to donate organs after death.

The finding sparked widespread media coverage, not least because Gordon Brown, the prime minister, was said to support a move to “presumed consent”.

The report by the Organ Donation Taskforce concluded there were better ways of increasing organ donation rates but said it would revisit the issue of consent in five years time if these did not work.

Why is organ donation important?Around 1,000 people died on the waiting list for an organ transplant in 2007-08. In the same period 3,000 people received a transplant.

The taskforce called this a “desperate situation” and said that people had “died in vain on the waiting list”. It aims to raise the number of registered organ donors from 15 million to 25 million over the next five years. Because of a shortage of organ donors in the UK, there are now more than 8,000 people on the transplant waiting list.

At present, the UK has an opt-in system that means you have to register to be an organ donor. Doctors can only remove organs from people who have registered.

In addition, even if a person has volunteered, it is normal practice for doctors to inform their relatives at the time of their death. If family members oppose donation, a doctor may decide not to proceed.

Registration is with the NHS Organ Donor Register, run by UK Transplant.

What system did the taskforce consider?The taskforce considered, and eventually rejected, a “soft” opt-out system for organ donation, similar to one used in Spain.

Under a “soft” opt-out system, doctors could remove organs from any adult who died unless they had registered their wish not to be a donor. Unlike a compulsory, “hard” system, relatives would still be asked for their agreement.

In addition, and contrary to what is mentioned in some news articles, the system would not technically be one of “presumed consent.” Doctors would not automatically presume consent in all situations.

Will the system change?The taskforce recommended that an opt-out system should not be introduced in the immediate future and gave a number of reasons for this decision.

While the taskforce found the public overwhelmingly supported organ donation, it believed there was the possibility that people might be upset by a move to an opt-out system. Ultimately this could lead to a negative view of donation, rather than significantly increasing donation rates.

Also the taskforce identified opportunities to improve donation rates that did not involve changing to an opt-out system.

Spanish officials say that, despite their opt-out system, the most important factor in increasing donation was the organisation and co-ordination of their national transplant system.

The government has proposed a major campaign to help people understand organ donation and the issues around it.The report also recommends a range of changes to the existing system, including the recruitment of around 100 extra donor transplant co-ordinators.

These and existing co-ordinators would be employed centrally by NHS Blood and Transplant rather than by individual NHS trusts. This would standardise employment and training practices across the country, making the system more effective.

Other changes would include a strengthened network of dedicated organ retrieval teams, to be available 24 hours a day. The teams would work closely with the critical care teams in hospitals to retrieve safe high-quality organs for transplant.

The taskforce has recommended reviewing the issue of opt-out systems in 2013, once it is clear whether action to increase the number of donors has been effective.

How can I register as a donor?You can register using the UK Transplant online form or calling on 0845 60 60 400.

If you would like more information to on donation please see the useful links section.

A synthetic hormone injected to “top up tans” is illegal and should not be used, warned The Independent today. Widespread coverage has been given to the news that Melanotan, injected under the skin to encourage the skin to darken, has never been safety tested by any Western government healthcare agency.

The drug is sold online or under the counter at gyms and beauty salons and because the drug is self-injected, there are fears that users are putting themselves at risk of infections such as hepatitis or HIV.

Anyone currently using Melanotan should stop doing so immediately for their own safety. The drug has not been safety tested by the UK medicines safety agency. Users are advised to consult their GP for advice.

Fake tanning lotions and sprays may represent a safer option for those who wish to have tanned skin, but they should be avoided by pregnant women.

Melanotan increases the levels of the pigment melanin in the skin. This pigment is part of the body’s natural response to the sun, and increasing levels of melanin results in skin darkening or tanning. There are two forms available, Melanotan I and II, which are diluted in water before being injected.

All medicines that are used in the UK have to be licensed by a government agency called the Medicines and Healthcare products Regulatory Agency (MHRA). The MHRA ensures that all medicines are effective and safe enough for use before granting them a licence for use.

Melanotan has never been through this licensing process and it is therefore not legal to market or supply this product. The MHRA has issued a warning not to use Melanotan. They are also contacting companies that advertise or supply Melanotan to notify them that it is illegal.

Melanotan is not legal. It has not undergone the stringent safety and effectiveness testing that all medicines have to undergo before they can be licensed for use. This means that the side effects of this treatment are not known. In addition to the possible side effects of Melanotan itself, there are also other potential dangers.

Using non-sterile water to prepare the injections can cause serious blood infections, and sharing needles spreads blood-borne diseases such as HIV and hepatitis. Injections by untrained individuals can cause skin and tissue damage, and might result in permanent or life-threatening injury.

Intentional tanning in the sun or using sunbeds should be avoided as they accelerate skin ageing, and can lead to skin cancer. People should remember to follow Cancer Research UK’s SunSmart rules for sun exposure:

• Spend time in the shade between 11am and 3pm.
• Make sure you never burn.
• Aim to cover up with a t-shirt, hat and sunglasses.
• Remember to take extra care with children.
• Then use factor 15+ sunscreen.

Fake tanning lotions and sprays may represent a safer option for those who want to have tanned skin, but they should be avoided by pregnant women.

I've used Melanotan, what should I do now?You should stop using the products immediately. Consult your GP and tell them if you think you have had an adverse reaction to Melanotan, if you may have used a shared needle, or if you have re-used needles.

Counselling can “double a woman’s chances of surviving breast cancer” according to the Daily Mail today. The newspaper claimed that regular sessions with psychologists also cut the chances of the cancer returning, and affected the length of time it took for the disease to reoccur.

This story comes from a study of 227 women who had surgery for breast cancer. Along with normal care, half of these women also received group counselling sessions with a psychologist every two weeks. These sessions  targeted various issues including stress, lifestyle, and adherence to cancer treatment .

After an average of 11 years participants were followed-up and their survival rates were calculated. Although the study found that the rate at which women died was halved in the counselling group, the way survival rates are calculated means is not the same as the proportion of women who survived being doubled, as the newspaper reports might suggest. However, it does mean that women from the intervention group survived longer on average than those in the control group.

The study highlights the importance of appropriate support for women with breast cancer.

Where did the story come from?Dr Barbara Andersen and colleagues from Ohio State University conducted this research. It was published in the peer-reviewed medical journal, Cancer.

The study was funded by the National Institute of Mental Health, National Cancer Institute, American Cancer Society, Longaberger Company-American Cancer Society, US Army Medical Research Acquisition Activity, Ohio State University Comprehensive Cancer Center, and the Walther Cancer Institute.

What kind of scientific study was this?This was a randomised controlled trial looking at the effects of psychological intervention on survival in women with breast cancer.

The researchers enrolled 227 women aged between 20 and 85 years who had undergone surgery for breast cancer which did not appear to have spread. Women who had certain mental health or medical diagnoses were not eligible to participate.

Participants were interviewed at the start of the study to assess their psychological well being, health and health-related behaviours. After this, women were randomly assigned into two groups. One group  received a psychological intervention, while the other ‘control’ group did not.

The way in which the women were randomised aimed to balance characteristics that might affect survival, such as the size of their tumours and whether the cancer had spread to their lymph nodes.

Psychologists provided the psychological intervention, which consisted of four months of weekly group sessions (8-12 women per session), followed by monthly sessions for eight months. The sessions aimed to reduce distress, improve quality of life and mood, improve heath related behaviours and to improve the women’s adherence to their cancer treatment and follow-up programme.

Researchers reassessed all the women’s psychological well being, health and health-related behaviours at four and 12 months into the study, then every six months up to year five, and annually thereafter.

Researchers also asked the women to report any use of antidepressants or anti-anxiety medications, or counselling outside of the intervention. There were no differences between the groups in these factors.

All women had physical examinations every three months for two years and every six months after this. They also had mammograms annually. Any signs or symptoms that suggested a possible recurrence of breast cancer were investigated with laboratory tests, radiologic studies, and biopsies as appropriate.

The researchers recorded any recurrence of breast cancer (either within the breast or in another area), and any deaths from breast cancer or any other cause among participants during follow-up.

They then compared these outcomes (recurrence, death from breast cancer, or death from any cause) in women who received the psychological intervention with outcomes in those who did not receive the intervention.

The researchers adjusted for factors that might affect the outcomes in their analyses, including factors that indicate disease prognosis (such as tumour size), and type of cancer treatment received. They also adjusted for factors that were found to differ between the groups at the start of the study, which were the participant’s “performance status” (a measure of how well they are functioning), and their level of negative mood.

The researchers followed the women for an average (median) of 11 years. In this period about a third of the women experienced a recurrence of their cancer. This broke down into 29 women in the group receiving the psychological intervention and 33 women in the control group that did not receive the intervention.

The researchers also found that;

• On average, recurrences in the intervention group took about 2.8 years to occur (median time to recurrence), compared to 2.2 years in the control group.
• A total of 44 women died from breast cancer during follow-up, 19 women in the psychological intervention group (17%) and 25 women in the control group (22%).
• Among the women who died of breast cancer, the average survival was 6.1 years for those in the intervention group and 4.8 years in the control group.
• The total number of deaths (regardless of cause) was 57. This broke down into 24 women in the psychological intervention group (21%) and 33 women in the control group (27%).
• Average overall survival was 6 years in the psychological intervention group and 5 years in the control group.

When researchers compared the rate at which recurrences, deaths from breast cancer, and deaths from any cause occurred, they found that the psychological intervention roughly halved the rate of occurrence of these outcomes.

The researchers concluded that their psychological intervention could increase survival.

There are a number of points to consider when interpreting this study:

• The measure used to assess death looked at the rate at which women died, and it should not be interpreted as meaning that the proportion of women who died in the intervention group was halved. This can be seen by the fact that 21% in the intervention group died compared with 27% in the control group. The same applies to the rate of recurrence and death from breast cancer.
• The psychological intervention used a number of techniques, and included components aimed at improving health behaviours and adherence to treatment, as well as reducing stress. It is not possible to tell exactly which components might be having an effect, or whether the combination of components is needed to have an effect.
• The study was relatively small, so replication of these findings in a larger study will be necessary to increase confidence in these results.
• The proportion of women over 69 years of age enrolled in the control group was double that in the intervention group (8% versus 4%). Although the analysis was designed to adjust for this difference, the fact that women in the control group were older to begin with could have biased results in favour of the psychological intervention.
• The study was in women with cancer that appeared to be confined to their breast and the local area and had not spread. Therefore their results may not be representative of what would be seen in women with more advanced breast cancer.
  

The study indicates that interventions using several components to target psychological wellbeing, lifestyle and adherence to treatment might be capable of improving survival in women with breast cancer. The findings highlight the importance of appropriate support for women with breast cancer.

Mothers who eat an unhealthy diet in pregnancy may cause their children to over-eat in later life, the BBC's news website reports.

But the study the story is based on was carried out on rats, and its relevance to humans is not clear.

“A high-fat diet in pregnancy may cause changes in the foetal brain that lead to over-eating and obesity early in life,” the website reports. It is based on an animal study that found that when pregnant rats were fed a high-fat diet, their babies, “Ate more, weighed more... and began puberty earlier”.

It’s important to maintain a healthy balanced diet throughout life, including during pregnancy. Pregnant women should follow advice from their doctors and midwives about their diet, as sometimes they may need to eat more or less of certain foods to support the healthy development of their baby.

Where did the story come from?Dr Guo-Qing Chang and colleagues from The Rockefeller University in New York carried out this research. The study was funded by the National Institutes of Health in the US. It was published in the peer-reviewed Journal of Neuroscience.

What kind of scientific study was this?This was an animal study that looked at how a high-fat diet in pregnant rats affected the brains of their offspring. In particular, the researchers were looking at whether the levels of proteins which stimulate the appetite (called orexigenic peptides) were increased in the brains of the offspring because the mothers had eaten a high-fat diet.

The researchers fed half the group of pregnant rats with a high-fat diet (50% fat) and fed the other half with a balanced diet (25% fat) from the sixth day of pregnancy until giving birth (about two weeks). The rats could eat as much of the food as they wanted, whenever they wanted. Three times a week, the researchers measured how much the rats ate, and they were weighed weekly. Overall, throughout their pregnancies, the high-fat and balanced diet rats ate a similar amount of calories and they had similar weights at the time they gave birth.

After the rats gave birth, the babies of the high-fat diet mothers were divided into two, and half were given to the balanced-diet mothers to foster. The other half remained with their mothers, who continued to be fed a high-fat diet until 15 days after the birth. Offspring from high-fat and balanced-diet mothers were followed from the time they were weaned (21 days after birth) until a few weeks after puberty (70 days after birth). Only male offspring were followed up after birth.

During follow-up, the rats’ behaviour and physiology were assessed, and their weight and body composition were measured. All the groups of offspring were given access to a balanced diet until day 50, and after this they were given access to both the balanced diet and the high fat diet for 10 days. The researchers looked at the levels of the appetite-stimulating proteins in the rats’ brains during their development. They compared the brains of all the differently fed groups of offspring and investigated how any changes might be occurring.

What were the results of the study? The researchers found that the offspring of mothers that were fed a high-fat diet during pregnancy had higher levels of appetite-stimulating proteins in their brains. This increase started when the offspring were in the womb (from day six of gestation) and lasted up to 15 days after birth. The high-fat diet seemed to stimulate the nerve cells in certain regions of the brain to divide more often, and to develop into cells that produced appetite-stimulating proteins.

The babies of the mothers fed a high-fat diet during and after pregnancy had higher body weights at 30 and 70 days after birth than the babies whose mothers were fed a balanced diet. The offspring of the mothers fed a high-fat diet during and after pregnancy also had higher calorie intake, preferred the high-fat diet to the balanced diet and had higher levels of fats in their blood. By day 70 there were similar changes in the offspring of the mothers fed a high-fat diet during pregnancy which had been fostered to balanced-diet mothers.

What interpretations did the researchers draw from these results? The researchers conclude that the brain changes they saw in the offspring of mothers fed on a high-fat diet, “May have a role in producing the long-term behavioural and physiological changes observed in offspring after weaning”. They suggest that this effect might have contributed to “the increased prevalence of childhood obesity over the past 30 years”.

What does the NHS Knowledge Service make of this study? This study expands on previous work that has shown that in animals such as rats, maternal diet during pregnancy can affect the offspring’s feeding behaviour. Although this work has identified some changes in the brains of the rats that might contribute to this phenomenon, it is not possible to say whether these findings apply to humans.

It is important to maintain a healthy balanced diet both during pregnancy and after the baby is born. Pregnant women will have different dietary requirements to women who are not pregnant, and they may need to eat more or less of certain foods to support the healthy development of their baby. Pregnant women should follow advice from their doctors and midwives about their diet.

British women’s life expectancy “ranks alongside some of the poorest countries in Europe” reported the Daily Telegraph yesterday, suggesting that on average, UK females do not live as long as their counterparts from 25 EU countries.

Their claims were based on research that was actually investigating how long 50-year-olds in each country will live without being affected by disability. In that respect, researchers found that both males and females from the UK live free from disability for significantly longer than the average EU citizen. The study also shows that the UK fared significantly better than Estonia in terms of both life expectancy and years in good health, in contrast to recent reports in other newspapers that Estonian healthcare was rated higher than that in the UK.

As the researchers acknowledge, the study itself has some limitations, meaning its results for whole populations may not be accurately applied to individuals. This study should only be taken as preliminary research into the factors that could be linked to healthy ageing.

This study was conducted by Dr Carol Jagger and colleagues from the University of Leicester, INED in Paris, the Institute of Public Health in Belgium, University Medical Centre Rotterdam in the Netherlands and the French Institute of Health and Medical Research in Montpellier, France. The work was funded by the EU Public Health Programme and published in the peer-reviewed medical journal, the Lancet.

What kind of scientific study was this?This was a large ecological study to explore differences in life expectancy and health during aging for the people in 25 European countries. The researchers wanted to look at a measure of quality of life as a means of estimating the health of a nation, as opposed to simply relying on life expectancy.

To do this researchers used a measure known as ‘healthy life years’ (or HLY), which is the number of further years that a person of a certain age will live free from ‘disability’, as defined by the researchers. For this study researchers looked at life expectancy and HLY from age 50.

Data came from a general population survey, called the Statistics of Income and Living Conditions (SILC) survey, which was initiated by the EU and adopted by the European countries as a way to collect information of this nature. The original purpose of the SILC survey was to investigate possible reasons for HLY differences between countries.

The researchers used disability data from the SILC survey from each country in 2005 to construct an index of ‘healthy life years’. In these surveys, disability had been defined as a long-term (greater than six months) limitation in activity and rated in severity as ‘none’, ‘limited but not severely’ and ‘severely limited’ health. People reporting disability of any severity were not counted in the HLY tally.

They also collected data on life expectancy, GDP, poverty risk for people aged older than 65 years, inequality of income distribution, expenditure on elderly care, unemployment rate, employment rate, age of exit from labour force and level of education. Most of this data had been collected in the respective countries in 2005.

What were the results of the study?The researchers calculated the average life expectancy for 50-year-old males and females across all the countries as of 2005. This was 28.6 years for men and 33.5 years for women, though there was a lot of variability between countries. Life expectancy beyond 50 years was above average for UK males at 29.46 years, while for UK women it was slightly below average compared to the rest of Europe, at 32.69 years.

The researchers also calculated the average number of healthy life years 50-year-olds could expect to live across all countries. Men could expect to live 17.3 disability-free years and women could expect to live 18.1 disability-free years. The figures for the UK were significantly greater than the across-Europe average, namely 19.74 years for men and 20.78 years for women. The 10 newly joined EU countries performed worse than the established 15 countries.

Other factors that were associated with the differences in healthy life year values for men and women included GDPs and expenditure on elderly care. For men only, long-term unemployment rate, life-long learning and low educational attainment were associated with HLY values (positively or negatively). When the researchers repeated their investigation into the potential associated factors within just the 15 established EU countries, they found that none of the factors they included were associated with HLY values.

The researchers conclude that their study has shown a large variation in ‘remaining years spent free of activity limitations’ in men and women aged 50 years across countries in Europe in 2005.
They say that given that a major target for Europe is that the employment rate for older adults (aged 55 to 64 years) should reach 55% by 2010, HLYs (as an indicator of disability) could be used to assess whether such targets are realistic.

What does the NHS Knowledge Service make of this study?Ecological studies such as this suffer from some weaknesses that should impact on how these results are interpreted.

Firstly, given that the data used in this study is cross-sectional, there is no way to explore the ‘temporal’ link (i.e. time) between associated factors, e.g. unemployment rate, care of the elderly, education and the outcome. It is not possible to know whether these factors are a ‘cause’ of poorer healthy life years.

Secondly, the researchers relied on population-level data to explore these factors, rather than on data from individuals. As it is impossible to extrapolate findings from populations back to individuals, the study cannot prove that the people with lower healthy life years were the same ones with poorer education, healthcare etc.

To make an assumption like this (that what is happening at a population level is also happening at an individual level) is known as the ‘ecological fallacy’, a common weakness of these types of studies. The researchers acknowledge both these and other problems with their research method.

The measurement of HLY values, although more harmonised now following the adoption of the SILC surveys, is still not perfect. Each country would have carried out their surveys slightly differently and bias may be introduced because of this.

People who live in institutions were not included in the SILC surveys and the assumption was made in this study that their health was the same as that of people who were not institutionalised. This is unlikely to be an accurate assumption and a different health profile of this group may have biased the results, though the researchers say that this is unlikely to affect their conclusions.

The researchers themselves say that more data is needed (preferably from individuals) to confirm the associations seen in this study.

Peppermint oil is the most effective treatment for irritable bowel syndrome, according to news reports today. The non-prescription supplement has been shown to be better at easing symptoms than prescribed muscle relaxants or fibre. The results are reported to have been so convincing that an update to national and international treatment guidelines is recommended by researchers. Between five and 20% of the population are believed  to suffer from irritable bowel syndrome (IBS).

This news report is based on a high quality, systematic review that provides good evidence that peppermint oil can be an effective treatment for irritable bowel syndrome. It examined all available studies of peppermint oil, muscle relaxants (or antispasmodics) and fibre used in the treatment of IBS. All three treatments significantly reduced the risk of persistent symptoms (such as abdominal pain and bloating) compared to placebo.

As the studies compared the treatments with placebo and not against each other, it is not possible to conclude which treatment was most effective. However, compared to placebo, peppermint oil had the greatest effect.

Peppermint oil can be bought without prescription from pharmacies.

The researchers searched medical research databases to identify all randomised controlled trials (including foreign language studies) involving adults who met diagnostic criteria for IBS and who had received investigations, if necessary, to exclude an underlying cause. Studies had to compare antispasmodics, fibre or peppermint oil with an inactive placebo drug. They also had to include a follow-up of at least one week with an assessment of cure or improvement of symptoms. The researchers also hand-searched abstracts of conference proceedings for potential studies and looked at reference lists of all selected studies.

The main outcome that the researchers looked for was the efficacy of any of the three treatments compared to placebo on all IBS symptoms or just abdominal pain. The researchers assessed the quality of the trials and results were pooled to give the relative risk of symptoms persisting after treatment.

The 12 trials of fibre had a total of 591 people with IBS. Treatments included bran (five studies), ispaghula husk (six studies) and, in one study, ‘concentrated fibre’. Overall, any fibre treatment reduced the risk of persistent symptoms by 13%, but this result was only of borderline significance (RR 0.87, 95% CI 0.76 to 1.00). The only individual treatment that gave a significant reduction in symptoms was ispaghula.

The 22 trials of antispasmodics included 1,778 people with IBS and used a variety of drugs (12 in total) at different doses. Overall, antispasmodics significantly reduced the risk of persistent symptoms by 32% (RR 0.68, 95% CI 0.57 to 0.81). Of the individual drugs, only hyoscine, cimetropium, pinaverium and otilonium gave consistent significant evidence of benefit.

The four trials of peppermint oil, at different doses, included 392 people with IBS. Across these studies, 26% of those randomised to peppermint oil experienced persistent symptoms compared to 65% of those assigned to placebo. This gave an overall 67% reduction in risk of persistent symptoms when taking peppermint oil (RR 0.43, 95% CI 0.32 to 0.59).

The number of people that would need to be treated to prevent one person from having persistent abdominal symptoms was 2.5 for peppermint, five for antispasmodics and 11 for fibre.

The researchers conclude that antispasmodics, fibre and peppermint oil are all more effective than placebo in the treatment of IBS.

This is a high quality systematic review that looked into all published research of peppermint oil, muscle relaxants (or antispasmodics) and fibre used in the treatment of IBS. The three treatments were all found to reduce the risk of having persistent symptoms (such as abdominal pain and bloating) compared to placebo. However, there are several points to bear in mind:

• The trials included in the review were of variable size, included slightly different patient groups, fulfilling different diagnostic criteria for IBS, different doses and treatment durations, were carried out in different settings (e.g. primary or secondary care), and used different criteria for symptom improvement. In the antispasmodic and peppermint oil trials, heterogeneity (diversity) was demonstrated to be statistically significant, i.e. different methods and results were obtained between trials, which may call into question the validity of combining results of the studies in this way.
• Although peppermint oil was highlighted in the news, as it demonstrated the greatest reduction in risk, it only included four trials with 392 people. This limits the strength of the conclusions that can be drawn from the combination of these studies. However, this is partly countered by the fact that three of the studies were of high quality and there was no statistical heterogeneity when they were combined. This increases the confidence in the finding.
• The authors report that none of the trials state whether the allocation of the treatments was concealed. This means that practitioners may have been aware of whether the active treatment or placebo was being given to participants. It has been found that this type of bias may give an overestimation of treatment effect.
• Adverse effects were not consistently reported across studies, so no firm conclusions can be made about the safety of any of the three treatments.
• The trials have only compared each treatment to inactive placebo, so it cannot be assumed that any one treatment is more effective than the others. 

IBS has no single identified cause. It is not a pathological condition, i.e. there is no underlying disease process, but the bowel does not function properly, causing discomfort and inconvenience for sufferers. This review provides evidence to support the use of symptomatic treatments such as peppermint oil.

Newspaper reports that a common heart test is 'worthless' in assessing the risk of heart attack are an exaggeration of the research results they are based on.

The Daily Mail says, “An NHS test to assess a patient's risk of heart attack is worthless” and “Simply talking to patients about their symptoms would be be more effective” than using an electrocardiogram, or ECG. (An ECG produces a graph of heart activity from electrical signals in the chest.)

The newspaper has overstated the implications of this well-conducted study commissioned by the NHS. Researchers found that using an ECG did not offer much additional benefit when used alongside a thorough assessment by a doctor, but only in the diagnosis of suspected angina in non-emergency situations.

ECGs remain an invaluable tool in emergency settings for investigating signs of heart ischaemia (lack of oxygen) or heart attack, in addition to a number of other rhythm and conduction abnormalities.

This research was conducted by Doctors Neha Sekhri, Gene Feder and colleagues from Newham University Hospital, University College London, the University of Bristol and Barts and London Queen Mary’s School of Medicine and Dentistry. The study was funded by the National Health Service’s research and development programme, service delivery and organisation. The study was published in the peer-reviewed British Medical Journal.

What kind of scientific study was this?This was a diagnostic cohort study where researchers were investigating the usefulness of the ECG when added to clinical questioning of patients who attend chest pain clinics with suspected angina.

Most chest pain clinics in the UK use ECGs when diagnosing people with suspected angina. Commonly a ‘resting ECG’ (i.e. not during activity) is routinely performed when people present symptoms of angina.

Another form of the test may be given, the ‘exercise ECG’, which records the activity of the heart during exercise (usually while the patient is on a treadmill or exercise bike). The exercise ECG is routinely provided in 59% of chest pain clinics in the UK, according to the researchers.

ECGs are used to investigate whether people are at high risk of coronary heart disease or other heart events. The researchers here questioned whether the resting and exercise ECGs add anything useful to an assessment of this risk for people attending chest pain clinics with new-onset chest pain and no history of heart disease.

People who had been referred by their GP to one of six chest pain clinics in the UK between January 1996 and December 2002 were potentially eligible for this study. From these, patients were included in the study if they met the following criteria:

• They had chest pain and were without a diagnosis of coronary artery disease.
• They did not have missing data.
• They were not of black or ‘unspecified’ ethnicity.

This left a total of 4,848 eligible for this study.

Patients were interviewed by a clinician and details were recorded in a database. Information included age, ethnicity, sex, symptom duration, smoking, history of high blood pressure, diabetes, pulse, systolic blood pressure and descriptions of chest pain. From this clinical data, doctors made a diagnosis of 'angina', 'non-cardiac chest pain' or 'other'.

Resting ECG results were then taken for each patient and recorded in the database as either normal or abnormal. 4,848 of the total cohort had an exercise ECG too, recorded as positive, negative or equivocal for ischaemia (i.e. uncertain). For a proportion of the total patients (1,422 of them) more detailed information was available from an exercise ECG. Patients were followed up until December 2003 and mortality records and records of hospital admissions were collected until then.

Researchers then analysed what factors predicted outcome in these patients, i.e. lifestyle factors and results on ECGs.

Through complex statistical methods, they constructed models that would tell them how well the three types of investigations predicted patient outcome, i.e. basic clinical assessment (discussion with doctor) alone; basic clinical assessment plus resting ECG; and basic clinical assessment plus both resting and exercise ECG (summary results and then detailed results).

By doing this they were investigating whether ECG provides an additional diagnostic benefit on top of the clinical discussion with doctors at presentation.

What were the results of the study?On average, people were followed up for 2.5 years. The smaller groups who also had an exercise ECG were followed up for a slightly shorter time (about 2.2 years). Resting ECGs didn’t add any value to a basic clinical assessment in terms of being able to predict negative outcomes. Exercise ECGs added only a little.

While there was evidence that on their own, abnormal readings on ECGs were able to predict poor outcomes, they didn’t add much to prediction from the basic assessment. 47% of all events during follow-up occurred in people with a negative exercise ECG result, i.e. showing a ‘normal’ result. There were only small differences in the ability of the test to predict outcome when the researchers considered the risk-level of patients at baseline.

What interpretations did the researchers draw from these results?Researchers conclude that ECGs add little incremental value to an assessment of risk of negative cardiac outcome through clinical assessment (i.e. recording history and symptom assessment by a clinician).

They say that these results emphasise the importance of the clinical assessment and the need for more effective means of assessing future risk for these patients. Given that a large number of events occurred in people with ‘normal’ exercise ECGs the researchers say that this emphasises the ‘limitations of using ECGs for risk assessment’.

What does the NHS Knowledge Service make of this study?This large cohort study has shown that, on their own, abnormal ECG results can predict negative cardiovascular outcomes and death in patients with suspected angina. However, it also showed that these tests do not appear to add value towards prognosis when given alongside a thorough clinical assessment.

There are several points to keep in mind when interpreting the results:

• It is important to highlight the fact that abnormal results on the ECGs on their own were able to predict adverse outcomes, so the study findings do not suggest that these tests do not work, only that, for people with suspected angina, they add little to a thorough clinical assessment.
• Predicting long-term risk of cardiovascular outcome is not a straightforward task. The accompanying editorial to this article suggests the results from this study highlight the importance of ensuring that the clinical assessment is thorough in the first place.
• This study was carried out in a select group of patients: those referred by their GPs to chest pain clinics with suspected angina. The results don’t therefore apply to the use of ECG in other settings such as emergency settings or in patients with other presentations.

Patients with suspected angina do not always demonstrate changes on either resting or exercise ECG and therefore thorough clinical assessment on an individual basis is vital when making, or excluding, a diagnosis of angina.

However, the ECG remains an essential investigation for demonstrating signs of heart ischaemia (lack of oxygen, as may be seen during an angina episode) or infarction (heart attack), in addition to a number of other heart rhythm and conduction abnormalities, and should therefore be used in all presentations that are suggestive of chest pain to alert to need for monitoring or urgent treatment.

“The size of your waist is a more important determinant of health than your weight,” The Independent said today. It reported that one of the largest studies conducted into waist size and health found that people with a large waist have a greater likelihood of a premature death - even if they are slim. It said those with a large waist had twice the risk of dying early.

Obesity is often measured using the body mass index (BMI) which is a calculation of an individual’s weight and height. This study of more than 350,000 people highlights that measurements of BMI can be reliably supplemented with waist measurements. The link is already well known and this study may mean that waists are now more commonly measured in general practice.

These researchers say that it is important to consider where fat accumulates as well as how much total fat there is. Their conclusion that it is better to be a pear shape (narrow waists and wide hips) rather than an apple shape (wide waist and narrow hips) should be endorsed.

Dr Tobias Pischon from the German Institute of Human Nutrition in Potsdam-Rehbruecke, Germany, carried out this research with over 40 colleagues from around Europe. The research was supported by grants from several public and private research agencies, cancer societies and foundations. The study was published in the peer-reviewed The New England Journal of Medicine.

In this prospective cohort study, the researchers aimed to clarify the relationship between abdominal obesity, using either measurements of waist circumference or waist–to-hip ratio, with the risk of death.

It is known that these measurements are linked with the risk of disease. International guidelines define abdominal obesity in people who already have a BMI of between 25.0 and 34.9 as:

• a waist circumference of at least 102cm in men and 88cm in women, or
• a waist-to-hip ratio of 1.0 in men and 0.85 in women

The European Prospective Investigation into Cancer and Nutrition (EPIC) study has data on 519,978 men and women between the ages of 25 and 70. These people were enrolled between 1992 and 2000 from the general population of towns or provinces in 10 European countries (Denmark, France, Germany, Greece, Italy, the Netherlands, Norway, Spain, Sweden, and the United Kingdom). The researchers excluded any participants who withdrew from the study and others where there was missing data. After these exclusions, the researchers were left with 359,387 participants for analysis.

The participants had their weight and height measured when they were clothed and not wearing shoes. Waist circumference was measured either at the narrowest circumference of the body or at the midpoint between the lower ribs and the bony part of the hip/pelvis. The participants were then separated into five categories according to their increasing waist circumference. Their hip circumference was measured horizontally at the level of the largest bulge of the hips or over the buttocks. Cause of death was collected from the national cancer registries and death indexes.

The researchers used statistical methods to adjust for a range of factors that could have influenced the results, such as smoking, educational achievement, alcohol consumption and physical activity.

The study ran for 9.7 years during which 14,723 participants (out of about 360,000) died. Men with a BMI of 25.3 and women with a BMI of 24.3 had the lowest risk of death. The participants’ BMI, waist circumference and waist-to-hip ratio were all strongly associated with their risk of death. This was still significant after statistical adjustment for smoking, educational achievement, alcohol consumption and physical activity.

When comparing the chance of dying between the participants with the largest waist circumference and the participants with the smallest, the researchers found that men with the largest waists had nearly double the risk (RR 2.05; 95% CI 1.80 to 2.33) and women had just under double the risk (RR 1.78; 95% CI, 1.56 to 2.04).

BMI remained significantly associated with the risk of death when waist circumference or waist-to-hip ratio were also taken into account (P<0.001), suggesting that both BMI and waist circumference are independent and important indicators of risk.

The researchers say that both “general adiposity [fat] and abdominal adiposity are associated with the risk of death” and that the findings mean that waist circumference or waist-to-hip ratio should be measured in addition to BMI when assessing the risk of death.

The findings from this large study corroborates what has been found in previous studies and confirms what is already generally accepted knowledge. However, one benefit of this study is that it was in a large European population, and so the results can be directly applied to the UK population.

One possible limitation of the study is that the technique of measuring waist circumference is difficult to standardise. It is possible that there is some variation between how the researchers measured it in different parts of the study and this would have led to some inaccuracy in the measurements. For example, the researchers mention that the results in the Greek arm of the study showed systematic differences that could have been explained by the different technique of measurement. However, they were not certain if it was the different measurement technique, if there could have been real differences in the Greek populations waist size or even if the differences had arisen by chance. They say any analysis of the differences between the sub groups, which each have few participants, should be treated with caution.

In general, this is a reliable study which reinforces the use of waist circumference as a measurement for identifying people at higher risk of death. The findings strengthen the advice that people should aim to be a “slim pear” shape rather than a “large apple”.