Researchers are testing a “radical new theory that multiple sclerosis (MS) is caused by blockages in the veins that drain the brain”, BBC News reported.

This theory was tested in 65 people with MS and several different groups of people without MS (controls). The study found that the blood drainage from the brain and spinal cord in people with MS was reduced compared to people without the condition.

However, as these people already had MS at the beginning of the study, it is difficult to say whether the abnormal drainage was a cause of MS or occurred as a consequence of the disease. A much larger sample of people representing each of the four possible types of MS (disease courses) would need to be examined to confirm the findings.

This is a valuable study, but more research is needed. Any implications for the widespread treatment or prevention of MS are some way off.

 

Where did the story come from?

The research was carried out by Dr Paolo Zamboni and colleagues from the University of Ferrara, Italy. It was funded by the Italian Ministry for University and Scientific Research and by the Foundation Cassa di Risparmio di Ferrara. The study was published in the peer-reviewed Journal of Neurology, Neurosurgery and Psychiatry.

BBC News has reported this research well. However, it did not discuss the main limitation, that researchers cannot known whether abnormal blood drainage is a cause or a consequence of MS.

 

What kind of research was this?

In this cross sectional study, the researchers examined the drainage of blood from the brain (venous outflow) in people with and without MS. Those without MS included healthy subjects and people with neurological conditions other than MS. Previous post-mortems of people with MS have noted that lesions typical of the disease lie in close proximity to the venous system of the brain.

The difficulty with this study design is that it cannot determine causation. It may have been able to demonstrate that the current venous outflow from the brain was impeded in people with MS. However, it cannot establish whether this preceded the development of MS, or whether the physiological changes in the brain as a result of MS caused the current venous flow.

 

What did the research involve?

The study included 65 people diagnosed with MS, who were at various stages/courses of the disease, and 235 control subjects without MS. The controls included 60 healthy people matched by age and sex to the MS group. It also included 82 people who were older than the typical age at which MS develops and who were now unlikely to develop it. The reason for including this older group was that if they had venous abnormalities similar to people with MS, it was less likely that these abnormalities were a cause of the condition.

Other controls included 45 people with neurological diseases other than MS (such as Parkinson’s disease and stroke) and 48 people without neurological disease but who were scheduled for venous examination (venography) for other disease indications. People with diseases that are associated with vascular malformations were excluded from the control group.

Venous drainage of the brain and spinal cord was examined using an ultrasound technique (Doppler). Selected patients also had the blood pressure in their jugular veins measured (the large venous system draining blood from the head).

Although the researchers included controls who were past the normal age of MS development to try to ensure that any venous abnormalities among the cases could be more reliably associated with MS, it is difficult to say whether any abnormalities in the MS group were the cause of MS development, rather than a consequence of the disease.

Another drawback is the small number of people with MS examined. A more reliable way of determining that MS is associated with venous outflow abnormalities from the brain would be to assess a much larger sample.

 

What were the basic results?

People with MS were significantly more likely to have abnormalities in venous drainage from the brain and spinal cord. Further assessment also revealed that, compared to all controls, people with MS had narrowing of the veins draining these areas. This condition is called “cerebrospinal venous insufficiency”. The venous pressure across the narrowed veins was found to be slightly higher than normal for people with MS.

The researchers also note that venous drainage differed between people at different stages and courses of MS (for example, those with relapsing-remitting or secondary progressive courses had different venous abnormalities from those with primary progressive courses). The venous pressure across the narrowed veins was found to be slightly higher than normal.

 

How did the researchers interpret the results?

The authors conclude that multiple sclerosis is strongly associated with cerebrospinal venous insufficiency, which is characterised by abnormal bloodflow and multiple venous narrowings (strictures) of unknown origin.

 

Conclusion

This is valuable research that builds on what is known about the physiological changes that occur in the venous system draining the brain and spinal cord in people with MS. The findings also indicate that there are differences in the venous abnormities in people with the four different disease courses of MS. This suggests that the venous obstruction and its location may have a role in determining the clinical course of MS.

The two principal limitations of these findings are:

• The venous abnormalities were examined at one point in time in people who already had clinical MS. As such, it is not possible to say whether these abnormalities are a cause of MS or are part of the physiological changes in the central nervous venous system that result from MS. It is also possible, as the researchers suggest, that the venous changes could be a side effect of the drugs used in MS.
• The study involved a relatively small number of people with MS (and, therefore, even smaller numbers of people with each disease course). To establish a firmer association between MS and cerebrospinal venous insufficiency, and how this differs in each disease course, larger samples need to be examined.

Although this study has found an association between MS and abnormalities in venous drainage from the brain and spinal cord, it is unclear whether these are a cause or a consequence of disease. More research is needed.

Links To The Headlines

Multiple sclerosis 'blood blockage theory' tested. BBC News, November 27 2009

Links To Science

Zamboni P, Galeotti R, Menegatti E, et al. Chronic cerebrospinal venous insufficiency in patients with multiple sclerosis. J Neurol Neurosurg Psychiatry 2009; 80: 392-399

Last updated: 18.00 BST

Swine flu infection appears to be slowing, with an estimated 46,000 new cases in the past week, down from 53,000 the week before.

However, the latest figures also show there have been 30 further deaths related to the virus in the same period, the largest jump in deaths since swine flu emerged. This takes the UK death total to 242: 163 in England, 43 in Scotland, 23 in Wales and 13 in Northern Ireland.

Hospitalisations also remain high, with 753 people currently receiving hospital treatment. Of these, 154 are in critical care. A large proportion of those in hospital are children under five, a group recently prioritised to receive swine flu vaccinations.

 

New swine flu strain

Testing has confirmed that a handful of Welsh patients have a strain of swine flu that is resistant to Tamiflu, an antiviral medication commonly used to fight the virus. However, the Health Protection Agency (HPA) said the risk to the general healthy population was low and that there was no evidence that the new strain is more virulent than any other type of flu. The resistant virus is still sensitive to the other frontline antiviral drug, Relenza.

Dr Tony Jewell, Chief Medical Officer for Wales, said: “We have stringent processes in place for monitoring for antiviral resistance in the UK.  Identifying these cases shows that our systems are working, so patients should be reassured.”

 

Young children made a priority

Last week Sir Liam Donaldson, the Chief Medical Officer, announced that young children would soon be offered the swine flu vaccine.

Children between the ages of six months and five years have been prioritised based on evidence that they are more likely than other groups to be hospitalised. There have also been high rates of admission to critical care in this age group.

Sir Liam made the announcement at his weekly update and urged everyone who is offered the vaccine to accept it:

“While the risks of serious complications from flu may be small, the impact on those affected can be devastating.

“Protecting those most at risk from the disease will reduce the levels of serious illness and deaths. That’s why we will shortly offer the vaccine to young children”.

Parents of children who are over six months and under five years old should wait to be contacted by their local GP surgery.

 

Vaccinations

Vaccination of people in clinical risk groups is well under way, with an estimated 10m doses of vaccine already distributed. NHS hospitals and GPs are now vaccinating patients facing the greatest risk of complications. Patients will be contacted by their GPs if they fall into one of the at-risk categories.

Healthcare staff dealing with the public are also being vaccinated to help keep medical services running smoothly and to prevent them from passing the virus to patients.

Recently, healthy children aged six months and over to under five years were added to the priority groups. Vaccination of this group will begin shortly. Parents of children of this age should wait to be contacted by their local surgery.

 

Who is a priority for vaccination?

People who are most at risk from swine flu need to be vaccinated first. These groups are, in order of priority:

• People aged between six months and 65 years in the seasonal flu vaccine at-risk groups.
• All pregnant women. The European Medicines Agency has indicated the vaccine can be given to pregnant women regardless of their stage of pregnancy.
• People who live with those whose immune systems are compromised, such as cancer patients or people with HIV/AIDS.
• People aged 65 and over in the seasonal flu vaccine at-risk groups.
• Healthy children aged six months and over to under five years.

Frontline health and social care workers will also be offered the vaccine at the same time as the first clinical at-risk groups. Health and social care workers are both at an increased risk of catching swine flu and of spreading it to other at-risk patients.

 

What are the seasonal flu vaccine at-risk groups?

These are people with:

• chronic respiratory disease, such as chronic obstructive pulmonary disease (COPD),
• chronic heart disease, such as heart failure,
• chronic kidney disease, such as kidney failure,
• chronic liver disease, such as chronic hepatitis,
• chronic neurological disease, such as Parkinson's disease,
• diabetes requiring insulin or oral hypoglycaemic drugs, and
• immunosuppression (a suppressed immune system), due to disease or treatment.

 

Planning assumptions

Revised guidance for planners was issued on October 22. The new guidance is based on the latest scientific understanding of the swine flu virus, drawing on our own experience to date and the southern hemisphere’s experience of winter.

This improved understanding means it is now anticipated that the impact of the virus on the UK is likely to be less severe than previously thought.

The additional information now available confirms earlier guidance that children under 16 are significantly more susceptible to the virus, and up to 30% may fall ill during this second wave.

The worst-case clinical attack rate is revised down from 30% to 12% between October 1 and the end of the normal flu season.  The worst-case hospitalisation rate is now considered to be 35,000 with up to 5,300 requiring critical care over the same period.  The worst case number of deaths is now assumed to be a further 1,000 spread across all age groups.

The threat that swine flu still poses should not, however, be underestimated.

Up to 1.5 million people could still become ill in the peak week. Children under 16 are particularly susceptible to the illness and unfortunately in rare cases healthy children have developed severe complications.

 

Who is at greatest risk of serious complications from swine flu?

Some people are more at risk of complications if they catch swine flu, and need to start taking antivirals as soon as it is confirmed that they have the illness. Doctors may advise some high-risk patients to take antivirals before they have symptoms, if someone close to them has swine flu.

It is already known that people are particularly vulnerable if they have:

• chronic (long-term) lung disease,
• chronic heart disease,
• chronic kidney disease,
• chronic liver disease,
• chronic neurological disease (neurological disorders include motor neurone disease, multiple sclerosis and Parkinson's disease),
• immunosuppression (whether caused by disease or treatment), or diabetes mellitus.

Also at risk are:

• patients who have had drug treatment for asthma in the past three years,
• pregnant women,
• people aged 65 and over, and
• children under five.

 

National Pandemic Flu Service

The National Pandemic Flu Service was launched in July. This online service assesses patients for swine flu and, if required, gives them an authorisation number that can be used to collect antiviral medication.

The system, which can also be accessed by phone, will take the strain off GPs as swine flu spreads. For the moment, it is being used only in England.

“The National Pandemic Flu Service is a new self-care service which will give people with pandemic swine flu symptoms fast access to information and antivirals,” said a Department of Health spokesman.

“This new service will free up GPs, enabling them to deal with other illnesses that need their urgent attention.”

The launch of the system brought important changes to the official advice that is given to people who think they may have swine flu. That advice – and the new system – is supported by the Royal College of General Practitioners.

 

Advice for antivirals

Several newspapers reported that the World Health Organization (WHO) had changed its advice regarding use of antivirals for swine flu. Its advice suggests that while antivirals should always be given in serious cases, they may not always be necessary for otherwise healthy people.

The papers pointed out that this appeared to differ from the approach taken in the UK, where Tamiflu is being widely used.

However, the Department of Health said:
"We believe a safety-first approach of offering antivirals, when required, to everyone remains a sensible and responsible way forward. However, we will keep this policy under review as we learn more about the virus and its effects.

"The WHO recommendations are in fact in line with UK policy on antivirals. We have consistently said that many people with swine flu only get mild symptoms, and they may find bed rest and over-the-counter flu remedies work for them.”

Apple-shaped women face a doubled risk of dementia, according to the Daily Mail.

This news is based on Swedish research that measured the physical dimensions of 1,500 women and followed them for an average of 32 years. Those women with an “apple shape” (broader in the middle than the hips) faced an increased risk of dementia if they lived beyond 70 years.

This study was well designed and collected data over several years. However, the researchers were surprised to find no link between body mass index (BMI) and stroke risk, an association found in other studies. Other results also suggest the findings may have occurred by chance. Overall, this large study has not convincingly shown the link between apple-shaped women and dementia, and raises more questions than it answers. Further research into this area is needed.

 

Where did the story come from?

This research was carried out by Dr Deborah Gustafson and colleagues from the Institute for Neuroscience and Physiology in Sweden. The study was supported by the US National Institutes of Health and the Swedish Research Council. The study was published in the peer-reviewed medical journal Neurology.

Other newspapers reported this research in a similar way to the Daily Mail. The Daily Telegraph also highlighted that the researchers found no link between dementia and high BMI.

 

What kind of research was this?

This was a report of data from a cohort study conducted in Sweden between 1968 and 2000. This research report focuses on the links between physiological measurements and the risk of dementia.

The researchers explain that the relationship between weight and dementia is complex. Higher body fat in middle age and later life is thought to increase dementia risk, but there is also a trend for the elderly to lose weight within a few years of being diagnosed with dementia. The researchers feel that these relationships needed further study.

Given dementia sufferers’ shifts in body fat over time, it was important that this study included analysis of these changes over time. These types of factor can only reliably be analysed using an inception cohort study, which recruits people at the same stage in the development of a disease. In this case, the researchers performed an inception cohort study that recruited only women who had no diagnosis of dementia and followed them over time to see who might develop the condition.

 

What did the research involve?

In this study, called the Prospective Population Study of Women (PPSW), a representative sample of 1,462 women without dementia was recruited in 1968. They ranged in age from 38 to 60 years. At entry into the study, they underwent a range of clinical and psychiatric tests, and had various body measurements taken (weight, height, waist circumference and waist-to-hip ratio). These same tests were performed again in 1974, 1980, 1992 and 2000.

Dementia was diagnosed according to DSM-III-R criteria, a recognised diagnosis method of the American Psychiatric Association. The researchers also included a category for “probable and possible Alzheimer’s dementia”, and diagnosed the sub-types of dementia using recognised criteria and CT scanning where necessary. They particularly looked at a condition called Alzheimer’s dementia with cerebrovascular disease (ADCVD), in which Alzheimer’s was diagnosed in the presence of a history of stroke. Stroke is known to be linked to both dementia and BMI.

The researchers noted whether there was a history of previous heart attack, stroke or diabetes based on the participants’ self-reports. They also conducted blood tests, ECG assessments and assessments of lifestyle factors, including physical activity, alcohol consumption and cigarette smoking. They also asked about level of education and socioeconomic status, which they then defined as working class, middle class or upper class (based on 1968–69 survey responses).

The researchers used all these factors to adjust their analysis in order to minimise the influence of factors linked to dementia. This would increase their ability to detect any link, if one existed, with the weight and fat distribution measures.

The measurements in this study appear to have been carefully conducted, and the study’s findings were well reported.

 

What were the basic results?

Over 32 years, dementia occurred in 161 participants. The average age at diagnosis was 75.6 years (range 48 to 91 years). There were 75 cases of Alzheimer’s, 108 cases of Alzheimer’s in people with previous stroke (ADCVD) and 37 cases of pure vascular dementia.

There was an association between having a waist-to-hip ratio greater than 0.80 at the start of the study (e.g. 80cm waist with 100cm around the hips) and a 2.2-fold higher risk of dementia among surviving participants aged 70 or older. The result reported by the researchers was an odds ratio of 2.22 (95% confidence interval 1.00 to 4.94), meaning that it was only just statistically significant. The other measure of statistical significance, the p-value, was 0.04. This confirmed the borderline significance of the result, as a p-value of less than 0.05 is generally considered significant.

This finding was one of 40 statistical results relating to the relationship between physical factors measured in midlife and late life and dementia. The only other statistically significant result showed that a low BMI or waist circumference in examinations later in life (between the ages of 62 to 92) was associated with an increased risk of dementia. This was consistent with the researchers’ earlier suspicions that the closer a person gets to a diagnosis of dementia, the less likely they are to be overweight.

 

How did the researchers interpret the results?

The researchers say that, in the Swedish women, they observed an approximately twofold increase in the odds of later dementia in those with a high midlife measure of central body fat. They note that this finding is only true for those who survived for 32 years (to at least the age of 70) and who participated in the neuropsychiatric examination.

 

Conclusion

This well-designed study was reported accurately by researchers and news sources. It ran over a long period of time with careful follow-up and measurements. However, only one of the “adiposity” (relating to fat) measurements that the researchers looked at was significant, which suggests that the findings should be treated cautiously. In addition, as the single positive finding was only just statistically significant, it may have occurred by chance alone.

Other cautions are raised by the researchers:

• It is often difficult to diagnose different types of dementia, and the researchers used strict criteria combined with reviews by psychiatrists. However, this review of notes, particularly among those who were lost to follow-up, might have reduced the accuracy of diagnosis.
• There were small numbers of people with the sub-types of dementia, which limits the ability of the researchers to analyse these specific sub-groups.
• The researchers note that, as the study was carried out in a group of Swedish women with similar characteristics (average weight 64.5kg and BMI 24.1), its results may not apply to other more varied groups. They say that, ideally, the study should be repeated in other populations.

Overall, this large study conducted over a long time has not convincingly shown the link between apple-shaped women and dementia, and it raises more questions than it answers. These questions can only be answered through further study.

Links To The Headlines

Apple-shaped women at double risk of dementia. The Daily Mail, November 25 2009

Apple-shaped women 'twice as likely to suffer dementia'. The Daily Telegraph, November 25 2009

Links To Science

Gustafson DR, Bäckman K, Waern M et al. Adiposity indicators and dementia over 32 years in Sweden. Neurology 2009; 73: 1559-1566

Research has shown that “sensations on the skin play a part in how people hear speech,” BBC News reported. It said that the findings could lead to better hearing aids.

This study in 66 people without hearing impairment investigated whether tactile sensation (touch) can aid hearing. The research was based on the principle that when some sounds are spoken, they are accompanied with a short burst of air (“pa” for example, compared to “ba”). In experiments, people had puffs of air directed at their hands or neck while they listened to sounds. Speech that was accompanied by the puffs of air was more accurately interpreted.

The study suggests that, like visual clues, tactile sensations may aid hearing. However, further research would need to establish if a device based on this principal would improve communication for those with impaired hearing.

 

Where did the story come from?

This research was carried out by Bryan Gick from the University of British Columbia in Vancouver and Donald Derrick from New Haven, Connecticut, USA. It was funded by a Discovery Grant from the Natural Sciences and Engineering Council of Canada and by a National Institutes of Health grant.

The study was published in the peer-reviewed science journal Nature.

 

What kind of research was this?

This study investigated whether tactile sensations can affect how sounds are heard. The researchers say that visual cues, such as lip reading, can help people with a hearing impairment to understand speech. In this study, they performed several tests on human volunteers without hearing loss to see if the same was true of the tactile sensation of a puff of air.

The researchers were careful to set up the tests so that the location of the air puff (to the hand or neck, or no puff but sound only) were tested separately. The sound that was produced was also standardised (“pa”, “ba”, “ta” and “da”) and the participants were blindfolded to ensure the results were as reliable as possible.

 

What did the research involve?

The research was carried out in three experimental groups with a total of 66 male and female participants. There were 22 people in each of three experimental groups (hand trial, neck trial and an auditory-only trial). How the participants were recruited, their age and the male and female composition of the groups were not reported.

Before the experiment began, the participants were told that they would experience some background noise and unexpected puffs of air. They sat in a soundproof booth and were told they would hear a series of pairs of sounds (either “pa” and “ba”, or “ta” and “da”). Their task was to identify which of the sounds they heard by pressing a button. They were then blindfolded and listened to the sounds through sound-isolating headphones. The equipment to deliver the tactile stimuli of puffs of air was set up after the participants were blindfolded to conceal the body location of air puffs.

In each of the three groups, half received the “pa”/“ba” pairs of sounds (sounds made with the lips) first and then the “ta”/“da” sounds (sounds made with the tongue on the back of the teeth). The other half heard the sounds the other way around. Within the hand trial and the neck trial groups, the participants listened to 12 sounds (six with air puffs and six without). The auditory trial group listened to 12 sounds without puffs.

In the following test sequence, the participants heard a random assortment of sounds ("pa", "ba", "da" or "ta") either with or without the burst of air. These combinations of interventions left the researchers with 64 sets of results across the “pa”/“ba” and “ta”/“da” groups.

 

What were the basic results?

The researchers say that in the hand-puff experiment, participants got more of the “pa” sounds correct when they had an associated puff of air on the hand than without the puffs. The same was true for the “ta” sound.  Both these sounds are usually associated with a puff of air from the speaker.

The reverse was true for the “ba” and “da” sounds. Fewer participants got the sound correct if these sounds were delivered with a puff of air. These sounds are not normally made when the speaker exhales air.

A similar pattern was seen when air was delivered to the neck. No pattern was seen at all in the auditory-only experiment, which the researchers took to mean that the participants could not hear the airflow or compressor activation.

 

How did the researchers interpret the results?

The researchers say that their findings support the theory that human appreciation of voice and language combines information from touch with sound in much the same way as vision and sound, as has been previously been shown.

 

Conclusion

The results of this experimental study suggest that the sensation of air being blown on the hands or neck can help people interpret a selection of sounds.

Although theses participants did not have a hearing impairment, the study raises the possibility that the sensation of touch may help those who have hearing loss distinguish these pairs of sounds. A hearing aid that uses touch has not yet been developed, so as yet it is unknown how useful this new finding will be in improving communication for people with hearing impairments.

Links To The Headlines

Humans 'hear' through their skin. BBC News, November 26 2009

How our skin helps us hear. Daily Express, November 26 2009

Links To Science

Gick B, Derrick D. Aero-tactile integration in speech perception. Nature, November 26 2009; 462

“The government's maximum daily salt intake target has been set too high for people to avoid unnecessary stroke and heart deaths,” the BBC reported. Newspapers also said that cutting the amount of salt in your diet by a teaspoon (5g) a day can reduce your chances of having a stroke.

This news is based on a large, high-quality review of salt intake and cardiovascular disease, which found that higher intake of salt was associated with a 23% increase in the risk of stroke. The advice to cut intake by 5g a day is based on an estimate that people in the West eat 10g a day. This cut would bring people into line with the World Health Organization’s recommended 5g a day.

The important point for individuals is that too much salt is bad for you and increases the risk of health problems. Although the UK has a recommended salt intake of 6g a day, this is the maximum recommended amount and eating less would do no harm. In fact, the Food Standards Agency (FSA) states, “there is little or no evidence that having a low intake of salt has a negative effect on health.”

 

Where did the story come from?

This research was carried out by Pasquale Stazzullo and colleagues from the University of Naples and University of Warwick. The study was supported by an EC grant, and the publication is reported as not necessarily reflecting the position of WHO. The study was published in the peer-reviewed British Medical Journal.

An editorial states that the evidence that salt raises blood pressure is now indisputable and calls for a reduction in salt intake.

Generally, the study has been accurately reported. It states that average daily salt consumption in Western countries is about 10g, and that reducing this by about 5g (one teaspoon) to roughly the WHO target of 5g a day could reduce the risk of stroke. The study does not criticise the FSA’s recommended level for salt of 6g a day, nor does it compare the FSA and WHO targets.

 

What kind of research was this?

This systematic review and meta-analysis investigated the relationship between salt intake and stroke and cardiovascular disease.

A systematic review aims to combine the findings of all available previous studies on a subject, and is the most effective and respected type of study for examining the current evidence on a particular issue. By necessity, the studies included in the review were observational studies, as due to the health implications it would be unfeasible and unethical to experiment with people’s salt intake.

There are inherent drawbacks to pooling observational studies. Even a well-designed systematic review has limitations as the included studies are likely to have slightly different methods, follow-up and measurement of outcome and exposure, and not all of them may have accounted for all possible confounders.

 

What did the research involve?

To find appropriate studies for the review, the researchers conducted a search of several medical databases for cohort (group) studies published between 1966 and 2008. The studies all assessed salt intake at their beginning and recorded incidences of either stroke or total cardiovascular disease (the outcome) at least three years later.

A total of 13 studies (out of a possible 3,246 publications) met the inclusion criteria and were suitable for meta-analysis. Details were collected on the studies’ populations, their methods of assessing and categorising salt intake, follow-up, and outcomes assessed (stroke and cardiovascular disease). Some studies reported only stroke outcomes while others looked only at total cardiovascular events or deaths. A combined risk ratio was calculated, using statistical methods to take into account differences between the studies.

The review was particularly thorough and well executed, and the researchers had specific inclusion criteria to ensure that studies had a minimum follow-up, specified a cardiovascular outcome and had categorised salt intake. All studies were also assessed for quality. These steps limited the chances of introducing errors because of differences between the studies, and allowed the researchers to look at the effects of the different methods that were used.

For example, how salt intake was measured varied considerably and included 24-hour dietary recall, food frequency questionnaire, 24-hour urine excretion and questionnaire. Risk was also reported differently. For example, some studies gave the number of events for each salt exposure category, while others specifically reported differences in event rate per 100mmol/day difference in salt intake. Attempts to account for these differences were made in the combined analysis.

 

What were the basic results?

The 13 studies involved a total of 177,025 participants, and follow-up varied between 3.5 and 19 years. During this time, there were over 11,000 vascular events (such as stroke or heart attack).

Higher salt intake was associated with a 23% increased risk of stroke (relative risk [RR] 1.23, 95% confidence interval [CI] 1.06 to 1.43). There was no increased risk of cardiovascular disease as a whole with higher salt intake, although when one study with outlying results (highly different findings from all the other studies) was excluded, there was a borderline significant increased risk (RR 1.17, 95% CI 1.02 to 1.34). The relationships between stroke and cardiovascular outcome were reported to be stronger with a greater difference in salt intake and with longer follow-up.

 

How did the researchers interpret the results?

The researchers conclude that high salt intake is associated with significantly increased risk of stroke and total cardiovascular disease.

In addition, they argue that, as salt intake was imprecisely measured in most studies, the effects “are likely to be underestimated”. They say these findings support the requirement for a “substantial population reduction in salt intake for the prevention of cardiovascular disease”.

 

Conclusion

This well-conducted review examined a collectively large population for the relationship between salt intake and stroke and cardiovascular disease. In addition, it collected detailed information from each individual study on its methods, findings and quality, and attempted to take into account the differences between these in its analysis.

However, the review does have some inherent limitations:

• Although the researchers attempted to include only studies where participants had a definite prior salt exposure and a later cardiovascular outcome, there were some differences between the studies, particularly in their length of follow-up and how they assessed salt exposure and risk.
• In the meta-analysis, there was calculated to be significant heterogeneity between studies indicating differences between them in their results, which could be due to the different methods used. Although all studies showed a trend towards increased risk of stroke with higher salt intake, the relationship was only significant in four individual studies. Only three out of ten individual studies found a significant increased risk of cardiovascular disease. However, when the results are combined in meta-analysis, the trend across studies leads to a significant increased risk.
• It is also probable that a person’s day-to-day salt intake can vary considerably. As only a single measurement of salt levels was taken, either through 24-hour urine excretion or a food frequency questionnaire, this cannot be reliably accounted for.
• There were a number of possible confounders that were not taken into account in the different studies but which may have affected the relationships. For example, few studies analysed men and women separately. The confounders that the studies took into account also varied and included blood pressure, BMI, age, diabetes, smoking, cholesterol and alcohol.
• It is not clear how or if the participants were tested for cardiovascular disease at the beginning of all the studies. This would be necessary to establish whether the outcome (CVD) definitely followed the exposure (salt).

It should be noted that 5g of salt a day is the WHO recommendation, while the UK recommendation is 6g a day. Although this research supports a move to reduce current UK salt intake, it does not criticise the UK salt limit, nor does it compare the FSA and WHO recommendations directly or suggest what the daily intake should be.

The important finding of this study for individuals is that too much salt is bad for you and increases your risk of stroke and cardiovascular problems. The UK’s 6g daily salt allowance is the maximum recommended level, and eating less than this would do no harm. In fact, the FSA says, “there is little or no evidence that having a low intake of salt has a negative effect on health.”

Links To The Headlines

Hidden salt killing 40,000 a year. Daily Express, November 25 2009

Daily salt intake allowances 'were set too high'. BBC News, November 25 2009

Just 1 teaspoon less salt a day cuts health risk at a stroke. Daily Mirror, November 25 2009

Cut salt by a teaspoon a day to save yourself from a stroke, experts say. Daily Mail, November 25 2009

Links To Science

Strazzullo P, D’Elia L, Kandala B-B, Cappuccio FP. Salt intake, stroke, and cardiovascular disease: meta-analysis of prospective studies. BMJ 2009; 339: b4567

Lawrence J Appel. The case for population-wide salt reduction gets stronger. BMJ 2009; 339: b4980

 

“An ancient herbal mint tea from Brazil is as effective at delivering pain relief as commercial medicine,” according to The Guardian.

The news comes from a study into Hyptis crenata, a Brazilian herb that is distilled in water to make a tea-type drink. Scientists gave mice an extract of the plant and looked at their pain response, which seemed to be reduced by the extract. The study has not yet been fully published or presented, so its results should be seen as very preliminary. Also, the current implications of this animal research are very limited, and as yet there is no definite evidence of pain-relieving effects in humans.

Should future research find pain-relieving properties for humans, the chemicals responsible might be extracted and developed into a medicine. However, developing medicines is a long and complex process, and issues of safety, effectiveness, cost and how they compare to existing medicines must all be considered.

 

Where did the story come from?

These news reports are based on a forthcoming conference presentation by Graciela Silva Rocha of Newcastle University, who was the lead researcher in this study. The presentation will be given as part of the 2nd International Symposium on Medicinal and Nutraceutical Plants in New Delhi, India, and is scheduled to appear in the society’s journal, Acta Horticulturae.

As this research has not yet been published, full details of its methods and findings are not available. Some details are available from a press release from Newcastle University, and a powerpoint presentation describing some of the research. This appraisal is based on these sources. The final presentation given at the Symposium in India may differ.

 

What kind of research was this?

This research looked at the potential pain-killing properties of the plant Hyptis crenata, a type of mint that grows in western Brazil.

The researchers say that it is widely used as a traditional medicine in the area, but that it has not yet been pharmacologically researched. They say that this species of plant (Hyptis) has been reported to have therapeutic properties, such as relieving pain and fighting inflammation and cancer. Several drugs that are used today, including aspirin, originate from plants that were used for medicinal purposes in the past.

Before the research began, a survey had been conducted in 20 Brazilian people to assess their beliefs about the plant’s effects. Some of the respondents used the plant to deal with pain, most commonly by brewed into tea. A small sample of subjective opinions can be used to initially point towards a possible area for research, but it does need to be followed up by rigorous scientific testing.

The current research was an animal study which examined the pain-relieving effects of H. crenata in mice and attempted to identify the chemical components of the plant behind this action. Although studies in animals can be valuable early research, the results may not be directly applicable to humans. In addition, this study has not yet been fully published and, therefore, has not been through the peer-review process. Until it is fully published, it should be treated with caution.

 

What did the research involve?

Mice in a laboratory were given different concentrations of H. crenata, which was presumably administered as a “tea”, though this is not specifically reported. Infrared heat was then applied to the hind paw and the researchers timed how long it took for the mice to withdraw from the heat.

The researchers then compared these results to those when the mice were given an anti-inflammatory drug (indomethacin) or plain water. The study did not report what period of time elapsed between administration of the tea and the application of the heat, or how many times the test was repeated. In a second set of tests, the researchers injected the irritant acetic acid into the abdomens of the mice and counted the number of contortions they performed.

Studies in mice that involve proxy measures of pain may not be directly applicable to humans.

As a final part of the experiment, the researchers analysed H. crenata in the laboratory to see whether it contained compounds similar to salicylic acid, the active compound in aspirin.

 

What were the basic results?

The presentation reports that the pain-relieving effects of H. crenata increased over a 24-hour period following administration of either low dose (15mg/kg) or high dose (150mg/kg). This effect was found to be similar to that of the anti-inflammatory drug indomethacin, while plain water had no effect. Comparable results were seen in the experiments in which the mice were injected with acetic acid.

The researchers found that H. crenata did not contain salicylic acid.

 

How did the researchers interpret the results?

The researchers conclude that Hyptis crenata has pain-relieving properties which are effective at low and high dose. They say that future aims are to discover the active pain-relieving compounds in the plant and to understand the pain-relieving mechanisms involved.

 

Conclusion

This study appears to have very limited applications at present. Testing a sample of mice for degrees of pain relief using proxy measures does not show direct evidence of the effects on pain in humans. Although the report says that the pain-relieving effects were similar to those of the anti-inflammatory drug tested, there is no direct evidence to show that this would be the case in humans.

However, it is likely that Brazilian mint (Hyptis crenata) will be subject to further research, as chemicals derived from plants have been used as the basis of some breakthrough medications such as aspirin and digoxin. Even if these tests show promise, creating a medicine using its active ingredients could be a long and complex process, involving years of development, testing and safety checks. The research would also have to address whether such a drug would be any safer or more effective or cheaper than established painkillers such as aspirin and paracetamol.

It should also be noted that the study was on a Brazilian plant Hyptis crenata and not a cup of normal mint tea, as some headlines have implied.

Links To The Headlines

Cup of mint tea is an effective painkiller. BBC News, November 24 2009

Brazilian Mint reduces pain 'as effectively as leading drugs'. The Daily Telegraph, November 24 2009

Brazilian mint tea 'as effective as pain-relief drugs'. The Guardian, November 25 2009

Links To Science

Got a pain? – Have a cup of Brazilian mint. Newcastle University, November 25 2009

A blazing row with your boss “may be good for your heart”, according to the Daily Mail. The newspaper also said that male workers who do not complain about unfair treatment double their risk of a heart attack.

The news is based on Swedish research that suggests there is a link between passive behaviour during workplace conflict and a risk of heart disease. However, the research has a number of limitations, including using very simple methods to assess the impact of complex factors, such as smoking and drinking. The study was also small and did not assess important factors including diet.

These limitations mean that this study cannot prove that a passive way of coping with conflict at work increases the risk of heart disease, nor does the study identify the best coping style. It is not advisable to shout at your boss on the basis of this research (even if you are right).

 

Where did the story come from?

This research was conducted by Dr Costanze Leineweber from the Stress Research Institute at the University of Stockholm and colleagues from other research centres in Sweden and the UK. The research was funded by the Swedish Council for Working Life and Social Research and the Academy of Finland. The study was published in the peer-reviewed Journal of Epidemiology and Community Health.

The story was covered by the Daily Mail, Daily Express and The Independent. The Express and Mail did not mention any of the limitations to this study, while The Independent said that no conclusions can be drawn about women.

 

What kind of research was this?

This was an analysis of data collected as part of the WOLF Stockholm study, a larger prospective cohort study looking at the health of people aged 19 to 70 working in Stockholm. This subanalysis of the WOLF study looked at whether using “covert coping” to deal with unfair treatment at work affects the risk of developing heart disease. The researchers defined covert coping as a person not showing that they feel unfairly treated.

This type of study (a prospective cohort) is the best way of looking at factors that cannot be controlled by researchers. However, the study must still be conducted in a careful way and should take into account factors that may affect results and the differences between comparison groups.

 

What did the research involve?

Between 1992 and 1995, the WOLF cohort study enrolled people who worked in the Stockholm area, assessing a number of factors including employees’ coping styles. This subsequent study followed participants until 2003, using national registers to identify any participants who had been hospitalised due to a heart attack or had died from heart disease.

Assessments of coping style involved a questionnaire that asked how participants usually reacted to unfair treatment or conflict within the workplace, both from superiors and workmates. The participants indicated how often they felt they used covert coping techniques or experienced negative effects that could be associated with these techniques including letting things pass without saying anything, going away, feeling bad (e.g. developing a headache or stomach ache), and getting into a bad mood at home. Their answers were used to assign them a covert coping score, and to split them into low (bottom 25%), high (top 25%) or medium (remaining 50%) scoring groups.

The current analysis only looked at the 2,755 male participants (average age 41.5 years) who had not been hospitalised for a heart attack before the study, and for whom complete data were available. The researchers looked at whether there was a relationship between how the participants coped with unfair treatment at work and their risk of heart attack or death from heart disease. They took into account factors that could affect results (confounders), such as the men’s age, socioeconomic factors (e.g. education), risk behaviours (e.g. smoking and alcohol problems), job strain including recent workplace conflicts, and biological risk factors such as diabetes, blood pressure, BMI and blood cholesterol.

Although it is appropriate to take into account factors that could affect results, this study assessed many of them using simple yes or no questions (e.g. “Have you sought help in the last 10 years because of drinking problems”, “Have you experienced conflicts in the workplace in the past 12 months”, and smoking status). Using such simple analysis methods when adjusting for these factors may not fully remove their influence. Relying on hospital records to identify heart disease based only on hospitalisation for heart attack or death from heart disease may miss some people with heart disease.

 

What were the basic results?

Men with more covert coping behaviour were more likely to be older, have lower income and poorer education, and less likely to have supervisory status in their job. There were also differences in their perceived job demands and they felt they had less ability to make decisions at work.

During the study, 47 men were hospitalised for a heart attack or died from heart disease. The researchers found that the more the men used covert coping behaviours and had related negative effects, the greater their risk of being hospitalised for a heart attack or dying of heart disease.

The researchers then performed their analyses having adjusted for all their measured confounders. They found that there was a just-significant association when comparing only men with high covert coping scores and men with low scores (hazard ratio 2.29, 95% confidence interval 1.00 to 5.29).

When analyses were restricted to just the covert coping behaviours (silently letting things pass or going away), the association between increasing behavioural score and risk of heart disease was significant. It remained significant even after adjusting for all potential confounders.

 

How did the researchers interpret the results?

The researchers concluded that their study showed that “covert coping is strongly related to increased risk of [hospitalisation or death due to] cardiovascular disease”.

 

Conclusion

This study suggests that there is a link between coping style at work and risk of heart disease. However, the study has a number of limitations:

• The results seen could be due to the influence of confounders. Although the researchers tried to take into account factors that could affect results, many of these factors were assessed using simple yes or no questions or through the participants’ self-reports. Quantitative factors (e.g. blood pressure, cholesterol and BMI) were measured, but only on one occasion. Using such simple analyses to take into account and adjust for these factors may not accurately measure their impact or fully remove their effects.
• Other unmeasured factors could also have a confounding effect. These include diet, depression or anxiety.
• This study identified heart disease only through records of hospitalisation for heart attack or death from heart disease. This may have missed some people with heart disease.
• Results of this all-male study may not apply to women.
• The study was relatively small and had a relatively short follow-up. Only 47 men had had heart disease events by the end of the study. This small number of events reduces the reliability of the results.
• The study carried out multiple statistical tests, which increases the possibility that a significant difference will be found by chance.
• The authors note that they only decided to analyse the two coping behaviours (silently letting things pass or going away) separately to the effects (feeling bad or getting into a bad temper at home) after they saw the results of an analysis of each item individually. They say that these results should be treated with caution and need confirmation from other studies.
• The authors also note that their study does not suggest what a healthy coping strategy might be, and say that they found no association between the open (“active”) coping strategies they assessed and heart attacks or cardiac death.

Overall, this study by itself does not provide robust evidence that a covert coping style directly increases the risk of heart disease. Its results will need to be assessed in the light of other research.

Links To The Headlines

Having a row at work could be GOOD for your heart, new research shows. Daily Mail, November 24 2009

Heart attack risk for men who keep quiet about unfair treatment at work, Daily Express, November 24 2009

Stressed at work? Shout at your boss. The Independent, November 24 2009

Links To Science

Leineweber C, Westerlund H, Theorell T et al. Covert coping with unfair treatment at work and risk of incident myocardial infarction and cardiac death among men: prospective cohort study. J Epidemiol Community Health 2009

“Having children could slow down the progression of multiple sclerosis (MS),” The Independent reported. It said researchers have found that, compared to women with MS who have never had children, those who had children after the onset of the disease were 39% less likely to have progressed to a stage where they needed assistance when walking 100m.

This research looked at the medical records of women attending an MS clinic in Belgium. The study has a number of limitations. For example, rather than childbirth slowing down the progress of MS, an alternative explanation of the results is that women who have less severe MS are more likely to decide to have children than those who have a faster-progressing disease.

Due to the study's limitations, it does not provide conclusive evidence of the effects of pregnancy on the long-term progression of MS. Larger studies that examine this question are needed.

 

Where did the story come from?

The research was carried out by Dr M B D’hooghe and colleagues from the National MS Centre (Nationaal MS Centrum) in Belgium and other research centres in Belgium and the Netherlands. No sources of funding were reported for the study, and the researchers declared that they had no conflicts of interest. The study was published in the peer-reviewed Journal of Neurology, Neurosurgery and Psychiatry.

This study was reported accurately by the BBC News website and The Independent. However, the BBC gave a more balanced report as it also provided important information about the study’s limitations.

 

What kind of research was this?

This study investigated how childbirth affects multiple sclerosis (MS) in the long term. Some previous studies have suggested that the risk of relapse in MS might reduce during pregnancy but then increase in the three months after giving birth. The researchers report that the long-term effects of pregnancy on MS progression are not clear.

The study was cross sectional, which means that the data were collected at one point in time. The data were collected from medical records, which allowed the researchers to identify when MS was first diagnosed, its severity over time, and details of any pregnancies the women had. As this data was not collected specifically for this study, there is a greater possibility that some of the information may be inaccurate or missing. A study that was set up to collect specific data prospectively would have been preferable.

 

What did the research involve?

The researchers used data from the medical records of 330 women attending their MS clinic. The women had had MS for an average of 18 years. The researchers grouped the women into those who did not have children (80 women), those who had children before they developed MS (170 women), those who had children after they developed MS (61 women), and those who had children before and after they developed MS (19 women).

The researchers were interested in when the women reached a specific level of MS severity. The scale they used to measure MS severity was the Expanded Disability Status Scale (EDSS), which ranges from zero (normal neurological function) to 10 (death from MS). The level the researchers were interested in was EDSS 6, which signifies a level of disability where the women needed assistance (e.g. with a cane) for at least part of a 100 metre walk.

The researchers compared how long it took the groups of women who had children at differing time points to reach EDSS 6 compared to women with no children. In this analysis, the researchers took into account the time when the women’s MS began.

Another analysis compared all women who had children with those without, as it can be difficult to say exactly when the biological process that results in MS starts. The researchers also specifically looked at women who developed MS before the age of 30, as these women were more likely to give birth after that age.

 

What were the basic results?

The women had MS for an average of 18 years, at which point just over half (55%) the women had reached the EDSS 6 level of severity. The proportion of each group that reached EDSS 6 was:

• 52% of the women who did not have children.
• 59% of those who had children before they developed MS.
• 51% of those who had children after they developed MS.
• 37% of those who had children before and after they developed MS.

The researchers found that women who had children after the onset of their MS tended to take longer to reach EDSS 6 than those who had no children. Some of this effect was due to the age at which the groups developed MS, but the difference was still significant even after this was taken into account (hazard ratio [HR] 0.61, 95% confidence interval [CI] 0.37 to 0.99). Women who had children at any time also took longer to reach EDSS 6 than women who did not have children (hazard ratio [HR] 0.66, 95% confidence interval [CI] 0.47 to 0.95).

Similar results were found when the researchers assessed only women who developed MS before the age of 30. However, the difference between the four groups did not reach statistical significance. This may have been due to the smaller number of women in this analysis.

 

How did the researchers interpret the results?

The researchers conclude that their results “seem to support a possible favourable long-term effect of childbirth on the course of MS”, but that the results could be biased.

 

Conclusion

This research has a number of limitations that reduce the reliability of its results:

• As the authors acknowledge, they cannot exclude the possibility that women who have less severe MS are more likely to have children than those who have more severe MS. If this is the case, the severity of MS would affect the likelihood of having a baby, rather than childbirth affecting the severity of MS. The researchers did not have detailed information about how the severity of MS progressed over time or about the women’s reasons for not becoming pregnant, which could help them to determine whether this was the case.
• The women’s age at the onset of the disease also seemed to affect the results, as taking this into account reduced the size of the observed effect. To remove this problem, the researchers carried out analyses only in women who developed MS before the age of 30. Although these analyses still showed a trend towards a longer time to EDSS 6 in women who had children after the onset of MS, this effect was no longer significant. This may have been due to the smaller number of women in this analysis. These results will need to be confirmed in another study.
• The study was relatively small, which may reduce the reliability of its results. This small size may explain the wide confidence intervals around the hazard ratios, suggesting that these findings are not particularly robust.
• Medical records, from which this study obtained its data, are not always completely accurate and don’t always give the complete story. For example, women may have first gone to the clinic at different stages in their development of MS, and there may have been discrepancies in how the severity of their MS was assessed.
• The study did not take into account what treatments the women were receiving. The researchers say that immune system treatments for MS have only gradually come into use over the past 10 years, and for most of the study period would not have been used by the majority of the participants.
• Not all the women that were assessed had reached EDSS 6, and the results may have been different if all the women had been followed until they reached this stage.

Due to these limitations, this study does not provide conclusive evidence about the effects of pregnancy on the long-term progression of MS. Further studies will need to look at this question. These studies will preferably involve a group of women of similar ages shortly after they develop MS and will follow them up over time to monitor the severity of their MS.

Links To The Headlines

Giving birth could slow MS. The Independent, November 24 2009

MS progress slowed by giving birth, Belgian doctors say. BBC News, November 24 2009

 

Links To Science

D’hooghe MB, Nagels G, Uitdehaag BMJ. Long-term effects of childbirth in MS. J Neurol Neurosurg Psychiatry 2009 

“Fad diets make you fat,” according to the Daily Express, which said that many quick fixes for obesity are “doomed to end in failure”.

The claim was based on a conference presentation being given by Professor Chris Hawkey, president of the British Society of Gastroenterology. The newspaper quotes a press release on his talk, which says that people should avoid extreme food regimes based on “theory rather than evidence”. These include only eating grapefruit and  the Victorian practice of chewing each mouthful of food 32 times.

While people may turn to extreme diets to lose weight, the most well-established way to maintain both good health and an ideal body weight is to adopt a balanced diet, take regular exercise, not smoke and limit alcohol consumption.  

 

What is the basis for these current reports?

Professor Chris Hawkey is speaking today at GASTRO 2009, an annual international conference on gastroenterology, the field of medicine concerned with the stomach, intestines and other organs related to digestion. Professor Hawkey is the president of the British Society of Gastroenterology (BSG) and a professor of gastroenterology at the University of Nottingham.

Professor Hawkey’s presentation focuses on the fact that, despite the rise in popularity of diets and extreme food regimes, the obesity problem appears to be getting worse. He also states that balanced eating is more important than some of the “quirky” practices being adopted in the name of keeping slim and healthy.

To illustrate his point, Professor Hawkey focusses on “food fads of yesterday and today”, discussing how habits in eating and dieting have changed through time and particularly how some diets quickly rise in popularity but then fade into obscurity. He also presents the findings from a recent survey commissioned by the BSG which examined public attitudes towards food and diet.

 

What examples does he draw on?

The press release detailing Professor Hawkey’s presentation mentions several food fads. In the available summary of his talk, it is not clear whether he will discuss the scientific evidence to support or disprove them, or whether they are solely included for context. More detail will be available when the conference is over and any transcripts and related research papers are made available.

The food fads discussed by Professor Hawkey include:

• Fruitarian diets based on the belief that fruit was man’s original diet in the Garden of Eden.
• The Hollywood Grapefruit Diet, which is based on the claim that grapefruit contains an enzyme that can burn body fat.
• Consuming apple or cider vinegar before a meal to counteract alkaline substances in the diet.
• The Atkins Diet, which is based on the idea that diets that are low in carbohydrates may have a nutritional advantage because they encourage the body to burn more calories. As an interesting aside, Professor Hawkey notes that, at its peak, about 9% of all Americans followed the Atkins diet until the death of its founder, which was thought be linked to his diet.
• The Max Gerson Diet, which included rectally administered hydrogen peroxide and daily consumption of an extract of raw calf liver. He claimed his diet could cure cancer and other chronic illnesses.

Professor Hawkey is quoted as saying that “the main problem facing society is not the content of our diet but its quantity and consequent obesity.” He discusses his idea of a “Feed the World” approach to weight reduction, where consumers would purchase a 15% reduced portion of food for the same price as a full-size portion and the cost difference would go to famine relief. He speculates that “frustrated idealism” may lie beneath eating disorders. An exposé of the myths behind some of these fads will be welcome in this context.

 

What did the the survey on diet find?

Research commissioned by the British Society of Gastroenterology found that:

• One in 20 (5%) women would try the Atkins diet to lose weight.
• Only 2% of British people think the Atkins diet is good for their health.
• One in five (21%) Londoners would try weight-loss pills to lose weight.
• Only 65% of women would increase their exercise levels if trying to lose weight.
• Nearly one in 10 (9%) British people think a diet with a high fish content is bad for their health.

The figures come from an online survey of 1,959 adults conducted by YouGov research company in September 2009.

 

What is the bottom line?

There are numerous well-documented benefits associated with a healthy, balanced diet. These include preventing long-term illnesses, increasing lifespan and improving cardiovascular health. Consuming a healthy diet, doing regular exercise, not smoking and limiting alcohol are the most well-established ways of maintaining both good health and a healthy body weight.

Links To The Headlines

Could fad diets be making the obesity epidemic worse? Daily Mail, November 23 2009

Modern 'superdiets' based on myths, says expert. The Daily Telegraph, November 23 2009

Superdiets? They're just a fairytale, says top doctor. The Guardian, November 23 2009

Fad diets: why they make you fat. Daily Express, November 23 2009

“Children should be allowed to play in the dirt because being too clean can impair the skin’s ability to heal itself,” The Daily Telegraph reported. It said scientists have found that common bacteria on the skin’s surface can “dampen down overactive immune responses, which can lead to rashes or cause cuts and bruises to become swollen and painful”.

This news report is based on research in human skin cells and mice. Researchers found that some non-harmful bacteria that live on the skin play an important role in regulating inflammation. These intriguing findings improve our understanding of the complex reactions that occur when cells are infected or injured.

While the newspaper suggests that the findings are directly relevant to children’s health, this was not investigated by the researchers, though they did suggest their results may have some application in the management of inflammatory skin disorders. At this early stage, however, this is speculation and much more research is needed.

 

Where did the story come from?

The study was carried out by Dr Yuping Lai and colleagues from the University of California and other academic institutions across the USA. The research was funded by the National Institutes of Health and was published in the peer-reviewed medical journal Nature Medicine.

The Daily Telegraph has given a good report of the research, although the focus on children’s health may lead readers to misinterpret the study’s methods. This was laboratory research and included some studies in live mice in which injury was induced.

The findings pave the way for future studies of these complex chemical responses in humans, particularly those with inflammatory skin disorders.

 

What kind of research was this?

This laboratory study was carried out in mice and human tissue. It investigated whether chemicals produced by the bacteria Staphylococcus epidermidis could inhibit skin inflammation.

In a normal immune response to infection or injury, there needs to be a balance between rapidly responding to the immune challenge (which involves some inflammation) and unnecessary inflammation. S. epidermidis is commonly present on the skin and in most people does not cause disease. In people with weakened immune systems, these bacteria can sometimes cause illness.

The researchers state that finding out how such bacteria exist on the skin without causing inflammatory responses could help them understand whether these bacteria have a role in immune responses in general.

 

What did the research involve?

The researchers treated human skin cells with a range of chemicals that are involved in the inflammatory response. They found that a chemical called poly(I:C) initiated the greatest inflammatory response. They then pre-treated some skin cells with a chemical produced by S. epidermidis to see whether it had any effect on the inflammation reactions that poly(I:C) induced.

Similar experiments were repeated in live mice, where patches on the ears were pre-treated with the bacterial by-product and then exposed to poly(I:C). The cells’ responses when exposed to other inflammation-inducing chemicals (lipopolysaccharide or phorbol 12-myristate 13-acetate) were also assessed.

The researchers then analysed whether other staphylococcal strains produced this bacterial by-product and if it had a similar effect on inflammatory processes.

The second set of experiments investigated how this bacterial by-product works. To study this, the researchers induced injury in mice that were genetically modified to be missing certain receptors in their cells (called toll-like receptors 3 or TLR3). These receptors are involved in initiating an immune response.

The researchers then assessed the effects of pre-treatment with S. epidermidis in these mice compared with the response in normal mice. Several other experiments explored in more depth TLR3 and inflammation, and how the substances produced by S. epidermidis can prevent this.

 

What were the basic results?

Pre-treatment of cells with the bacterial by-product (both in culture and in live mice) reduced the inflammatory response caused by poly(I:C). The researchers say this shows that “a product of S. epidermidis functions as a selected suppressor” of the inflammation induced by poly(I:C). It does this ultimately by inhibiting certain receptors called TLR3. They say a range of staphylococcal bacteria produce this by-product.

Pre-treating mice that were genetically modified to lack the TLR3 receptors with the chemical produced by S. epidermidis did not reduce inflammation, confirming that the TLR3 receptors are the target of the chemical. Other TLR receptors (TLR2) were also found to be important.

The chemical that suppressed inflammation in the skin cells was identified as Lipoteichoic acid (LTA), a major component in the cell wall of these types of bacteria. These LTAs had an opposite effect (i.e. they induced inflammatory responses) on other immune cells called macrophages, monocytes and mast cells.

 

How did the researchers interpret the results?

The researchers say that this study confirms the important role of TLR3 receptors in detecting injury to the skin and that LTAs produced by certain staphylococcal bacteria can inhibit the inflammatory response. They say that the skin is frequently exposed to the LTAs produced by bacteria and that S. epidermidis “may benefit the host by dampening unwanted inflammation”.

 

Conclusion

This laboratory study sheds light on some of the complex processes involved in the skin’s response to injury. Inflammation is an important response to immune challenges, such as infection and injury, but skin conditions such as psoriasis and eczema are associated with hyperinflammatory reactions (excessive inflammation).

This research suggests that bacteria such as S. epidermidis play an important role in regulating the inflammatory response. The researchers speculate that chemicals produced by this type of bacteria may moderate inflammation from injury and control inflammatory skin disorders. They also highlight the crucial point that any treatment that reduces the detrimental effects of inflammation would have to do so without increasing the risk of wound infection. This balance has yet to be established.

Despite the news reports, this study did not investigate how playing in the dirt might affect children’s immune systems. This interpretation is not surprising and there are theories suggesting that a lack of exposure to some germs early in life can adversely affect the immune system. However, this study was in the laboratory and it is too soon to say that the findings apply directly to children.

This is interesting research that will lead to further work in humans. Until the role of these chemicals has been studied further, the direct relevance to healthy adults or children or for treatment of people with inflammatory skin disorders is unclear.

Links To The Headlines

Children should be allowed to play in the dirt, new research suggests. The Daily Telegraph, November 23 2009
 

Links To Science

Lai Y, Di Nardo A, Nakatsuji T et al. Commensal bacteria regulate Toll-like receptor 3–dependent inflammation after skin injury. Nature Medicine November 22 2009 (advance online publication)