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NHS Choices

Menopause 'may mix up exercise reward pathways in the brain'

NHS Choices - Behind the Headlines - Fri, 29/07/2016 - 15:30

"Menopause 'crushes your motivation to exercise'," the Mail Online reports. But before you bin your gym card, the study it reports on involved rats, not women.

The female rats were genetically engineered to have either a high or low exercise capacity.

Those who had their ovaries removed to model human menopause showed lower activity on a running wheel over the following 11 weeks compared with those who hadn't.

And surprisingly the rats that had prior high exercise capacity had no protection – in fact, their activity levels declined more than the rats who'd been less active to start with.

The reason seemed to be because lack of oestrogen alters dopamine activity in the brain's motivation and reward centre.

In simplistic terms, dopamine is often described as a "feel-good" chemical and has been linked to many addictive activities, such as gambling.

The findings may give a possible explanation for why some women going through the menopause may feel less motivated to exercise.

But humans aren't genetically engineered rats, and we don't know that our biological mechanisms work in exactly the same way.  

Also, the rats were not given any type of hormone replacement therapy (HRT) to boost oestrogen levels, so these finding may not be applicable for women who choose to have HRT.

Physical activity is recommended at all stages of life, and many postmenopausal women enjoy very active lifestyles.

The best thing for people to do is to follow physical activity recommendations where possible, doing what feels comfortable for them.

Where did the story come from?

The study was carried out by researchers from the University of Missouri and the University of Kansas Medical Center, and received funding from the US National Institutes of Health.

It was published in the peer-reviewed journal, Physiology and Behavior.

The Mail's headline boldly states that the findings directly relate to menopausal women – only hidden well down in the article does it say that it involved rats.

What kind of research was this?

This animal research in genetically engineered rats aimed to see whether those bred to have high exercise capacity are better protected from losing interest in physical activity after they have their ovaries removed, compared with rats bred to have low exercise capacity.

As the researchers say, most people fail to meet physical activity recommendations. Rats bred to have high or low running capacity have also been shown to have different behaviour on a voluntary running wheel.

The researchers think this may be because of differences in dopamine pathways in a brain region called the nucleus accumbens, which control self-motivated activity and reward.  

Oestrogen has been shown to stimulate dopamine receptors and maintain activity in rats.

A loss of oestrogen from the rat's ovaries being removed – modelling human menopause – may be expected to reduce activity. This is what the researchers aimed to examine.

Animal studies can give a good insight into biological mechanisms that may be similar in humans, but we are not genetically engineered rats.

What did the research involve?

The research involved two types of rats – those bred to have either a high or low exercise capacity.

There were 40 female rats in each group, who were then randomised to either have their ovaries removed or a sham operation. 

After one week of recovery they were given access to a voluntary running wheel. Their wheel running was monitored weekly for 11 weeks.

The rats also had other assessments of body composition and blood glucose control. Their brain tissue was examined after death, paying close attention to dopamine activity in the nucleus accumbens.

What were the basic results?

The high exercise capacity rats ran more on the wheel compared with the low capacity rats.

Ovary removal significantly reduced activity in both groups compared with rats who received the sham procedure.

Strangely, while the high capacity rats who had their ovaries removed demonstrated a weekly reduction in the distance they ran on the wheel over the 11 weeks, the low capacity rats with their ovaries removed actually increased the amount they ran each week.

This meant that by the end of the 11 weeks there was no difference in running between the high and low capacity rats who had their ovaries removed. 

Brain examination showed that high capacity rats had greater dopamine activity than the low capacity rats.

Removing the ovaries was associated with increased dopamine blocking in the high capacity rats, but was linked to reduced dopamine blocking in the low capacity rats.

How did the researchers interpret the results?

The researchers concluded that the dopamine system in the brain's nucleus accumbens plays an important role in motivation to run in female rats.

High capacity rats run significantly more than low capacity rats, which is the result of a higher ratio of excitatory to inhibitory dopamine receptors.

The researchers say that despite greater inherent motivation to run, high capacity rats are not protected against the effect that ovary removal has upon dopamine activity.

It reduces the ratio of excitatory to inhibitory dopamine activity, "for which intrinsic fitness does not confer protection".

Conclusion

This research uses an animal model of human menopause – surgically removing the ovaries – to see what effect this would have on rats bred to have either high or low exercise capacity.  

As oestrogen has been shown to have an effect on dopamine activity in the brain's motivation centre, the researchers expected that ovary removal would have an effect on the rats' activity.

However, what was unexpected was that having prior high exercise capacity seemed to give no protection – these rats seemed to decrease their activity much more than rats that had low activity to start with.

These findings could be stretched to explain a possible reason why women who've been through natural or induced menopause (such as having their ovaries removed) may feel less motivated to exercise, particularly if they were very active previously – because of changes in dopamine activity in the brain.

However, humans are obviously not genetically engineered rats running on a wheel. Animal studies can give a good insight into biological mechanisms that may be similar in humans, but we don't know that things work exactly the same.

We also don't know whether these are permanent changes that would persist in the long term, or whether they're only short-term changes around the time of menopause. 

Overall, the findings are of interest, but they do not have any preventative or therapeutic implications.

Physical activity is recommended at all stages of life, and many postmenopausal women enjoy very active lifestyles.

Exercise can be especially important at this time, as it can help boost bone strength, which can weaken during the menopause.

The best thing for people to do is follow physical activity recommendations where possible, doing what feels comfortable for them.

For all adults, including people over 65 who are generally fit and healthy, this is at least 150 minutes of moderate aerobic activity every week (such as cycling or walking) combined with strength exercises that work all muscle groups on two or more days a week. 

Links To The Headlines

How menopause 'crushes your motivation to exercise': Brain changes mean 'many women feel less pleasure and reward from their workout in later life'. Mail Online, July 29 2016

Links To Science

Park YM, Kanaley JA, Padilla J, et al. Effects of intrinsic aerobic capacity and ovariectomy on voluntary wheel running and nucleus accumbens dopamine receptor gene expression. Physiology & Behavior. Published online June 11 2016

Categories: NHS Choices

New weapon in superbug war may be right under our noses

NHS Choices - Behind the Headlines - Thu, 28/07/2016 - 17:40

"Antibiotic resistance: 'snot wars' study yields new class of drugs," BBC News reports.

Researchers studying a type of bacteria found in many people's nostrils have used this knowledge to develop a possible new antibiotic called lugdunin.

While it has not yet been tested in humans, this is a development not to be sniffed at.

Lugdunin was found to eradicate Staphylococcal aureus bacteria, which is carried naturally on the human body, including inside the nostrils.

Staph. aureus wasn't always a concern in most cases, as it usually only caused mild skin infections such as boils. But in recent decades some strains of the bacteria have developed resistance to commonly used antibiotics.

These types of strains are known as methicillin-resistant Staphylococcus aureus (MRSA) and can be challenging to treat. They can also pose a significant threat to people with weakened immune systems.

Researchers found another bacterial strain called Staph. lugdunensis, which lives alongside Staph. aureus and so competes for resources, produces antibacterial enzymes to kill off its competitor – the so-called "snot wars" described by the BBC.

They identified the genetic mechanisms behind this, and from there developed a purified compound called lugdunin that had the same antibacterial activity.

First in human blood samples, and then in rodents and human nasal swabs, they demonstrated that lugdunin can reduce Staph. aureus colonisation.

These are undoubtedly promising findings, but this is early-stage research. There are many testing stages to go.

And Staph. aureus isn't the only resistant microbe out there, so it wouldn't provide the whole answer to antimicrobial resistance – but this research does provide a new avenue for exploration.

Where did the story come from?

The study was carried out by researchers from the University of Tübingen in Germany, and was funded by the German Research Council and the German Center for Infection Research.

It was published in the peer-reviewed journal, Nature.

The UK media's reporting is generally accurate, though headlines talking about a "new class of drugs" may suggest these drugs are already available when they're actually still in the very early stages of development and have not yet been tested in humans.

What kind of research was this?

This laboratory study aimed to develop a new type of antibiotic that prevents Staph. aureus bacterial colonisation.

Antibiotic resistance is a global health problem. A well-known example is methicillin-resistant Staph. aureus (MRSA) – so called because it doesn't respond to methicillin, an old type of penicillin antibiotic.

As the number of infections that do not respond to antibiotics continues to rise, increasingly stronger antibiotics have to be used to treat them.

But this puts us at risk of coming to a point where infections can't be treated, as our strongest antibiotics no longer work.

This means there is an urgent need to develop new antibiotics that can tackle resistant infections – but there is a limit on how quickly they can be developed.

The vast majority of severe infections in people who have weak immune systems or have had major surgery or trauma, for example, are caused by bacteria that are normally carried on the body by healthy people.

Staph. aureus is present in the nose of around a third of the population. 

Bacteria that are naturally present in the body are in constant competition with other types of bacteria.

It has been found some actually produce antibacterial-type substances to kill off the competing bacteria. This is what this research aimed to build on.   

What did the research involve?

The researchers first screened multiple types of Staphylococcal bacteria to see which had antibacterial activity against Staph. aureus.

They found one particular bacterial strain, Staph lugdunensis, was able to prevent growth of Staph aureus.

They investigated the way it did this and identified a cluster of genes called lug, which were responsible for producing a group of antibacterial enzymes.

They then used genetic engineering techniques to amplify the activity of these antibacterial genes to produce a purified compound, which they called lugdunin.

This compound was analysed in the laboratory to confirm its chemical structure and that it had the same antibacterial activity as the original bacteria.

The researchers then moved on to laboratory, animal and human experiments to test how effective it actually was.   

What were the basic results?

When tested in human blood samples in the lab, the researchers found lugdunin had strong antibacterial activity against several resistant bacteria, including MRSA – and this was without causing damage to the human blood cells.

Further analysis showed it seemed to be breaking down the bacteria's energy resources.

Staph. aureus didn't develop resistance to lugdunin, even when repeatedly exposed to low levels of the compound (not enough to kill the bacteria) over the course of 30 days.

They then tested mouse skin infected with Staph. aureus. Mice were treated with lugdunin one to two days after infection. This showed that lugdunin was able to reduce or completely eradicate the bacteria.

They then moved into tests in cotton rats, which are said to be an established animal model for investigating Staph. aureus nasal colonisation.

These animals were infected with both Staph. aureus and the original bacteria, Staph. lugdunensis. This confirmed that production of the antibiotic compound can reduce Staph. aureus colonisation.

This was repeated by testing nasal swabs from 187 hospitalised patients. The researchers found about a third of samples carried Staph. aureus, while 10% carried its opponent, Staph. lugdunensis.

The number of Staph. aureus bacteria present was about six times lower in the swabs also carrying Staph. lugdunensis.

Further tests showed all Staph. aureus were also susceptible to the new compound lugdunin.

How did the researchers interpret the results?

The researchers concluded that, "Lugdunin or lugdunin-producing commensal bacteria could be valuable for preventing staphylococcal infections."

They further say the bacteria naturally carried by humans "should be considered as a source for new antibiotics".

Conclusion

This valuable research has found a possible new avenue in the battle against antibiotic resistance – by harnessing the mechanisms that our own natural bacteria use to compete against other bacteria.

Multi-resistant Staph. aureus bacteria are responsible for many severe infections in hospitalised and immunosuppressed people.

This research found Staph. lugdunensis bacteria produce antibacterial substances, and from this researchers managed to develop a new purified compound that carries these antibacterial properties: lugdunin.

These are undoubtedly promising findings, but it's important not to jump too far ahead. This is currently only an experimental compound in the early stages of development.

Many more stages of testing would be needed before it is better known whether this antibiotic could be effective in humans and how it could be used.

For example, we need to find out whether the antibiotic would be used for just reducing Staph. aureus colonisation on the skin or in the nose, or whether it could actually be given to treat severe infections that have infected the body.

We would also need to know it is safe.

The study has only demonstrated the effects of this compound against Staph. Aureus, not against confirmed MRSA strains, so we don't know if it would definitely combat the well-known superbug.

Staph. aureus aren't the only resistant microbes out there, nor are they responsible for all infections.

This means this single discovery doesn't provide the whole answer to antimicrobial resistance. What it does provide is a new avenue for exploration.

While the possible developments from this research are as yet unknown, there are things you can do to fight antibacterial resistance.

This includes recognising that many simple coughs, colds and tummy upsets are viral and self-limiting. They will likely get better on their own and neither need, nor respond to, antibiotics.

If you are prescribed antibiotics – or any other antimicrobial, for any reason – it is important that you take the full course, even when you start to feel better.

Not taking the full course will expose bacteria to the antibiotic but not kill them off, allowing them to build resistance to it.

Read more about how you can help combat the threat of antibiotic resistance.

Links To The Headlines

Antibiotic resistance: 'Snot wars' study yields new class of drugs. BBC News, July 28 2016

Scientists sniff out new antibiotic – inside the human nose. The Guardian, July 27 2016

Antibiotics that could fight superbugs produced from bacteria in human nose. The Daily Telegraph, July 27 2016

Links To Science

Zipperer A, Konnerth MC, Laux C, et al. Human commensals producing a novel antibiotic impair pathogen colonization. Nature. Published online July 27 2016

Categories: NHS Choices

An hour of exercise a day may compensate for an 'office lifestyle'

NHS Choices - Behind the Headlines - Thu, 28/07/2016 - 16:30

"Office workers must exercise for an hour a day to counter death risk," The Daily Telegraph reports.

A major new study suggests that at least an hour's exercise a day may compensate for the risks of a sedentary lifestyle.

The study, which looked at previous research involving more than a million people, delivered a "bad news, good news" analysis. The bad news is that sitting for long periods may increase the chance of dying earlier. The good news is that doing at least an hour of moderately intense activity (such as cycling or brisk walking) each day may eliminate that risk.

The people in the study who were least active and sat for more than eight hours a day were 59% more likely to have died during the study follow-up than people who exercised most and sat for less than four hours a day. Sitting for longer than four hours a day increased the chance of death for everyone not in the highest activity category. However, people who did the most physical activity did not have an increased risk of death, regardless of how many hours a day they spent sitting.

This type of research cannot prove cause and effect but it certainly seems that daily physical activity brings long-term benefits.

The current activity advice for adults is to do at least 30 minutes of physical activity a day. Increasing that to 60 minutes may be a good idea if you do have a "9-5 office lifestyle".

 

Where did the story come from?

The study was carried out by researchers from institutions in many different countries, including the Norwegian School of Sports Sciences, University of Cambridge, University of Queensland, Oslo University Hospital, Swinburne University of Technology in Melbourne, Sydney University and Harvard Medical School. It received no direct funding.

The study was published in the peer-reviewed journal The Lancet on an open-access basis so it is free to read online (although you need to register).

Some UK media outlets took the study very literally. The Daily Mail tells readers "adults who sit down for at least eight hours every day must do at least an hour's daily exercise to undo all the harm." The study does not prove that exercise will "undo the harm" of sedentary behaviour.

It also ignores the study findings that people who were moderately active for about half an hour to an hour had only a slightly raised risk of death associated with sitting for longer periods. While the advice to exercise more is sound, people might think there's no point in exercising for less than an hour a day, and so give up altogether. It is very much the case that "every little helps" when it comes to exercise.

Experts in sports and exercise medicine were mostly welcoming of the study, describing it as "excellent quality" and "very interesting". However, one expert in evidence based medicine warned of the study's limitations and that it had not sufficiently controlled for factors such as socioeconomic status. 

 

What kind of research was this?

This study was a systematic review and meta-analysis of prospective cohort studies. The researchers went back to the authors of the studies and asked them to re-analyse their data according to a standardised protocol, which allowed them to make direct comparisons between groups.

This is a good way to get a better idea of the relative importance of sitting and physical activity in terms of length of life. However, observational studies cannot tell us whether certain factors (sitting time or physical activity) directly cause another (chances of death). They can only tell us that the factors may be linked. 

 

What did the research involve?

Researchers searched the literature for studies that included information on sitting time, exercise and mortality. They added two studies that had not been published but which had relevant data.

They asked the original study authors to rework their data according to a standardised protocol which divided people into categories of physical activity and sitting time. They then pooled the data to look at how the two factors were linked to length of life. They also looked separately at time spent watching television, and at deaths from cardiovascular disease and cancer.

By applying a standardised protocol, the researchers were able to make direct comparisons across groups according to specific categories of sitting time (less than four hours a day, four to six hours, six to eight hours, and more than eight) and of physical activity. Physical activity was measured by metabolic equivalent of task (MET) hours a week. MET is a measurement of how much energy the body is likely to consume during specific physical activities.

MET levels were divided in four groups:

  • less than 2.5 (equivalent to five minutes a day of moderate intensity physical activity)
  • 16 (25 to 35 minutes a day, as recommended by many guidelines)
  • 30 (50 to 65 minutes a day)
  • more than 35.5 (60 to 75 minutes a day)

Researchers took the people who did the most physical activity and had the least sitting time as the baseline, and looked to see how more sitting time affected that, for people in the different categories of physical activity.

The same calculations were repeated using daily hours of TV viewing time, from less than one to five or more.

 

What were the basic results?

For people who did the least physical activity, sitting for more than four hours a day was linked to an increased chance of dying during the study. For these people, sitting for eight hours a day or more increased the chances of death by 27% (hazard ratio (HR) 1.27, 95% confidence interval (CI) 1.22 to 1.32), compared to if they'd been sitting four hours a day or less. Compared to people who did the most exercise and sat for less than four hours a day, they had a 59% increased risk of death (HR 1.59, 95% CI 1.52 to 1.66).

People who were physically active for between half an hour and an hour also had a raised chance of death linked to sitting for eight hours a day compared to four hours a day, of 10% to 12%. But for people who exercised the most, time spent sitting did not increase the risk of death.

High levels of physical activity were clearly linked to lower chance of death. People who did the most activity but sat for eight hours or more were less likely to die than those who did the least activity but sat for four hours or less.

Television viewing time showed similar results, but in this case even the highest amount of physical activity did not cancel the raised risk of watching five hours or more of television. The least active people had a 44% higher risk of death if they watched five or more hours of television, compared to less than one hour (HR 1.44, 95% CI 1.34 to 1.56).

Results were similar when the researchers looked at the chances of dying from cardiovascular disease or cancer.

 

How did the researchers interpret the results?

The researchers concluded: "These results provide further evidence on the benefits of physical activity, particularly in societies where increasing numbers of people have to sit for long hours for work" and suggest the study should be taken into account when public health recommendations are made.

 

Conclusion

This study helps to disentangle the effects of having a sedentary lifestyle and being physically active. Previous studies have had conflicting results, with some saying that sitting for long periods can be counteracted by taking exercise, while others disagreed.

The advantage of this study is that it looks at time spent sitting as well as time spent being physically active, and calculates how both are linked to mortality and to each other.

The study has many strengths, not least its size. It includes data from 1,005,791 people from 16 studies. The researchers applied a standardised protocol and asked study authors to provide re-analysed data. This meant they could pool information and make direct comparisons between groups sub-divided by sitting time and activity levels, to a higher degree of accuracy than would otherwise have been possible.

However, there are limitations. The authors only included English-language papers, so other relevant studies may have been excluded.

The authors tried to account for what is called reverse causation – in this case that illness may have prevented people from being physically active – by including studies of apparently healthy adults. However they admit that this factor was not completely ruled out.

In addition, the data came from participants' own estimates of time spent sitting, watching TV and being physically active. Not only is this reliant on accurate (and honest) self-assessment, it was only measured at one time point, so may not be representative over time.

Although the original studies included controls for most other confounding factors, such as smoking, most did not include socio-economic data, which could have a big impact on the results. For example, watching a lot of television could be linked to being on a low income, or unemployed, which are themselves linked to poor health.

Conversely, going to the gym is expensive, so this type of physical activity may be more common among people who are better-off. That makes it hard to know whether TV watching or exercise are the factor causing the difference in death rates, rather than being a marker for something else.

We know that sedentary lifestyles are linked to poorer health. For many people, work (or travelling to work) involves sitting down for long periods. While some people may be able to change this, for example by using a standing desk or cycling to work, for others it's not so easy. So it's heartening to know that taking exercise and being physically active in your free time may help.

However, it's interesting to note that the levels of activity linked to eliminating the risk of a sedentary lifestyle are higher than those usually recommended. The most active people spent the equivalent of 60 to 75 minutes doing moderately intense physical activity – higher than the usually recommended 30 minutes a day.

It may be that compensating for a desk job requires us to be more physically active than most of us currently manage.

You don't need to join a gym to increase your activity levels. Read more about how you can get fitter for free.

Links To The Headlines

Office workers must exercise for an hour a day to counter death risk. The Daily Telegraph. July 28 2016

Hour's activity 'offsets sedentary day'. BBC News, July 27 2016

One hour of activity needed to offset harmful effects of sitting at a desk. The Guardian, July 27 2016

A desk job could make you 60% more likely to die earlier: Hour's exercise every day is needed to help beat deadly effects of working 9 to 5. Daily Mail, July 28 2016

Links To Science

Ekelund U, Steene-Johannessen J, Brown WJ, et al. Does physical activity attenuate, or even eliminate, the detrimental association of sitting time with mortality? A harmonised meta-analysis of data from more than 1 million men and women. The Lancet. Published online July 27 2016

Categories: NHS Choices

Could a hearing test help diagnose autism in babies?

NHS Choices - Behind the Headlines - Wed, 27/07/2016 - 15:40

"A hearing test is being hailed as a revolutionary technique to spot autism years earlier than current methods can," the Mail Online reports. The test is based on measuring how the inner ear reacts to sound.

But while the test shows promise, the headline is premature. The study the report is based on only looked at boys aged 6 to 17 years old and was not used to diagnose autism spectrum disorder.

In the study, 35 boys with autism and 42 boys the same age without autism had a range of hearing tests.

The first tests measured their ability to detect sounds at different levels and frequencies. All boys had the normal range of hearing.

But other tests used to measure the ear's ability to process and distinguish between similar sounds showed boys with autism had a 25% smaller processing response to sounds in the mid-range.

The researchers say this could make it hard for them to discriminate between sounds – for example, similar vowel sounds in speech.

The processing tests – using a measure called otoacoustic emissions – are regularly used to screen newborn babies.

The hope is they could also be used to look for difficulties in sound processing in line with those found in these boys with autism.

But we don't know whether babies with autism have the same sound processing difficulties, so more work needs to be done before it is confirmed (or not) that such a technique can be used to "diagnose autism" in babies. 

Where did the story come from?

The study was carried out by researchers from the University of Rochester and was funded by the US National Institutes of Health. 

It was published in the peer-reviewed journal, Autism Research.

The Mail Online reporting oversimplified the research, making it sound as if the study simply measured children's ability to hear.

The news story said children with autism "struggled to detect sounds at a frequency of 1-2 kHz".

But, as the study makes clear, all the children could detect a normal range of sounds – it was the ability to process sounds and differentiate between different tones that differed among boys with autism.

The headline also gives the misleading impression that the test had actually been carried out in children with autism, which was not the case. 

What kind of research was this?

This case-control study measured the hearing and sound processing abilities of a group of boys with autism and a group of boys with normal development, matched for age.

Case control studies can show links between factors in one group compared with another – in this case, whether autism is linked to different sound processing ability – but it can't show whether one causes the other.

What did the research involve?

Researchers selected 35 boys aged 6 to 17 with high-functioning autism, and 42 boys matched for age without autism.

Each boy underwent a range of hearing tests – both standard audiometry and tests of cochlear function, which tests how well the ear processes sound.

The researchers looked for differences between the groups. They also looked at whether the results matched up with the boys' verbal or cognitive abilities and the symptoms of boys with autism.

Audiometry screening tests for the ability of the ear to detect sounds at different frequencies, at different decibel levels.

All the boys in the study had to reach a standard level of hearing to be sure any differences were not down to conductive or nervous system hearing loss.

The tests of interest measured the changes to sounds that happen in the ear, which are amplified by the hair cells of the inner ear (cochlear) and can be measured in the ear canal.

These sounds are called otoacoustic emissions (OAEs). An abnormal OAE response can suggest problems with sound processing.

Two types of test were used: one that used two tones close together, and another which used a series of clicks. Boys were tested in both ears.

They were excluded from the study if they had nerve damage or disorders, frequent or persistent ear infections, or other conditions that could affect hearing.

All the boys were tested to check their autism status and IQ before the study.

Researchers looked for differences in OAE results between the groups at different frequencies.

What were the basic results?

In the first test of OAEs, boys with autism had a smaller response to discriminating between two sounds in both ears, compared with the boys without autism, but only at the 1 kilohertz (kHz) frequency, which is in the mid-range of sound.

In the second test of OAEs, boys showed significantly reduced OAE responses to a series of clicks in the right ear, but not in the left ear, across a range of frequencies. When looking at the mid-range 1kHz frequency, both right and left ears showed reduced responses.

The researchers found no correlation between OAE results and either verbal or cognitive abilities.

However, the first OAE test results were related to severity of symptoms in the autism group, with boys with more reduced responses showing more severe symptom scores.

How did the researchers interpret the results?

The researchers said that, "The observed decreases in OAE amplitudes at 1kHz mid-frequency range could cause reduced ability to discriminate between two sounds or impair auditory tuning."

This means children with this hearing problem could have impaired perception and understanding of speech, especially when there is background noise.

The researchers say more work is needed to test younger children and non-speaking children with autism to better understand the role of these hearing tests in autism.

But they suggest these tests might help diagnose children with autism at a much younger stage in the future, allowing them to begin treatment earlier.

Conclusion

Autism is a developmental disorder that affects behaviour and social communication. It's usually diagnosed in children aged around two to four years old.

We know there's a link between the condition and the ability to hear and process sounds – for example, some children with autism are very sensitive to sounds, while others don't respond to them at all.

However, hearing problems seem to be part of autism, rather than a cause of it. This study doesn't mean, for example, that deaf people have autism.

This study is interesting because it found a particular part of the ear, the cochlear, produces different effects in sound processing in children with autism, compared with those without the condition.

It may help us understand how autism starts – for example, whether it happens before birth, when the baby's ears and other organs are still forming.

The study has important limitations, however, meaning the hearing tests used in the study should not be seen as a diagnostic test for autism:

  • Only boys aged 6 to 17 were included in the study. We don't know whether girls or younger children would have the same results.
  • We can only see the average scores from the hearing tests. It's unclear whether all the children without autism had results in the "normal" range. If not, using hearing tests to diagnose autism could mistakenly diagnose children with normal development who have some hearing abnormalities.
  • Similarly, we don't know if all the boys with autism had abnormal hearing test results. If not, hearing tests would not have diagnosed their autism.
  • The researchers say other research into OAEs in autism came up with conflicting results using slightly different methods.
  • We need to see whether repeating the research with the same methods would come up with the same results.
  • We don't know how they recruited the control group of boys and whether they had any other conditions that may have affected the results.

This technique is certainly worth following up, possibly with a cohort study to see if a positive response predicted by the test is actually confirmed in later life by a diagnosis of autism.

Until such research is carried out it is impossible to state with any certainty whether the test will be of practical use.

Links To The Headlines

Could a simple hearing test diagnose autism? Technique 'can spot disorder in children before they start talking'. Mail Online, July 26 2016

Links To Science

Bennetto L, Keith JM, Allen PD, Luebke AE. Children with autism spectrum disorder have reduced otoacoustic emissions at the 1 kHz mid-frequency region. Autism Research. Published online July 12 2016

Categories: NHS Choices

'Netflix and kill?' Binge watching box-sets linked to blood clots

NHS Choices - Behind the Headlines - Tue, 26/07/2016 - 16:30

"Binge watching TV can actually kill you, study finds," The Independent reports in a somewhat exaggerated manner. The Japanese study its report is based on looked at prolonged TV watching and the risk of blood clots, and only found a very weak association.

Researchers were specifically looking at deaths caused by pulmonary embolisms – blockages in the blood vessel that carries blood from the heart to the lungs.

The study included more than 80,000 adults aged between 40 and 79 from Japan. Researchers estimated that people who regularly watched more than five hours of TV a day were two and half times more likely to die of a pulmonary embolism than those who watched less than two and a half hours.

While this may sound alarming it is important to realise that deaths from pulmonary embolisms are rare. Despite the large cohort, only 59 deaths occurred. And a modest increase in a rare risk means the risk remains rare.

The small number of deaths also means that any perceived association could have been the result of chance.

Also, the study design was unable to prove any cause and effect as many other factors may have been involved. That said, there is a growing body of evidence on the risks of sedentary behaviour.

The recommendation from the authors of the study, quoted in the media, that you get up and move around for a few minutes every hour while "binge watching" is sensible. 

It is important to compensate for time spent watching your favourite box sets by exercising regularlyeating a healthy diet and trying to achieve or maintain a healthy weight.

 

Where did the story come from?

The study was carried out by researchers from Osaka University Graduate School and was funded by the Japanese Ministry of Education.

The study was published in the peer-reviewed medical journal Circulation on an open-access basis so you can read it for free online.

Much of the UK media's reporting of the study was as overblown as a season of 24 and did not mention the many limitations of the study. For example, The Independent's headline "Binge watching TV can actually kill you, study finds" is incorrect. The study found no such thing.

It was good to see advice reported in some quarters to ensure you move around for a few minutes each hour.

 

What kind of research was this?

This study used data from a large cohort study to assess the link between the number of hours spent watching the television and the risk of death from pulmonary embolism.

Pulmonary embolism is a when a blood clot gets trapped in the blood vessel that takes blood from the heart to the lungs. It usually follows a clot in one of the leg veins (deep vein thrombosis or DVT) that has travelled through the blood to the heart.

As DVT is associated with prolonged immobility the researchers wanted to know whether watching TV (or, as is increasingly the case, streaming content to a tablet) could be associated with these outcomes.

This cohort study followed participants for a long period of time to draw observations, however, due to the design and the overall rarity of the outcome, the study cannot prove that one directly causes the other.

 

What did the research involve?

The researchers collected data from the Japanese Collaboration Cohort study, which began in 1988 and included adults aged 40 to 79 from 45 regions in Japan.

Participants were excluded if they had incomplete data on time spent watching TV or those with a history of cancer, stroke, myocardial infarction (heart attack), or pulmonary embolism at study start.

Information on potential confounders was collected by a self-administered questionnaire and included:

  • body mass index
  • history of hypertension (high blood pressure) or diabetes
  • smoking status
  • perceived mental stress
  • educational level
  • walking activity
  • sports activity

Participants were categorised according to the time they spent watching television each day, these were:

  • less than two and a half hours
  • between two and a half and five hours
  • five hours or more

The death certificates of participants were examined and the number caused by pulmonary embolism was recorded up to 2009.

Statistical analyses were performed for patients with complete information and were adjusted to take into account the effects of confounding.

 

What were the basic results?

The analysis featured 86,024 participants who were followed, on average, for 19.2 years. During this time 59 deaths from pulmonary embolism were recorded. Nineteen of them occurred in the people who watched TV for less than two and half hours, 27 in the second group, and 13 in the group who watched for five or more hours.

The amount of time spend watching television was associated with increased risk of death from pulmonary embolism.
 
Compared to the first group that watched less than two and a half hours, those who watched television for between two and a half and five hours were not at significantly increased risk death (hazard ratio (HR) 1.7, 95% confidence interval (CI) 0.9 to 3.0).

However, the third group who watched TV for more than five hours a day were two and half times more likely than the lowest duration group to die from pulmonary embolism (HR 2.5, 95% CI 1.2 to 5.3). 

Overall, the data found that each additional two hours of television increased risk by 40% (HR 1.4, 95% CI 1.0 to 1.8).

 

How did the researchers interpret the results?

The researchers conclude: "our prospective cohort study suggests that prolonged television watching is a substantial risk factor for mortality from pulmonary embolism."

 

Conclusion

This study used data from a large Japanese cohort study to assess the link between the number of hours spent watching the television and the risk of death from pulmonary embolism.

The study found that a greater number of hours watching the television increased the risk of death from pulmonary embolism.

The main strength of this study is the very large sample size and long follow-up periods. However, there are a number of limitations:

  • this study design is not able to prove cause and effect, so while there appears to be a link, we cannot be sure the cause of mortality is from television watching
  • even though the researchers attempted to account for relevant health and lifestyle factors such as BMI, smoking and physical activity, this may not be entirely accurate and there is still the possibility of residual confounding from these and other factors
  • despite the large cohort size, death from pulmonary embolism is very rare. These deaths have then been further subdivided by TV category, and statistical comparisons that involve small numbers are less reliable
  • the population was a group of older adults from Japan, the findings may not relate to other age groups or geographical populations
  • mortality from pulmonary embolism was confirmed from death certificates. This is likely to be reliable, but we don't know how many people may have experienced DVT or pulmonary embolism and not died from them 
  • information on the amount of time spent watching television was only collected on one occasion, this may have changed during the follow up period. People may also not be able to estimate with much accuracy how many hours they spent watching the TV, which may vary day to day

This study does however add to the growing evidence on the risks of sedentary behaviour. While much of the research in this area focuses on the relationship between sedentary behaviour and weight, some also suggests sedentary behaviour is independently associated with all-cause mortality, type 2 diabetes and some types of cancer.

The main issue considered in this study is the amount of time an individual spends watching television. But people are also sedentary at other times, such as when travelling, sat at a computer, or reading a book. The recommendation is to make sure that you get up and move around for a few minutes every hour.

It is important to compensate for time spent watching your favourite box sets by exercising regularlyeating a healthy diet and trying to achieve or maintain a healthy weight.

Links To The Headlines

Binge watching TV can actually kill you, study finds. The Independent, July 26 2016

How binge watching your favourite box sets could be deadly: More than 2.5 hours in front of the TV raises risk of a clot by 70%. Daily Mail, July 26 2016

Why binge watching your TV box-sets could kill you. The Daily Telegraph, July 26 2016

Netflix and kill warning as watching too much telly can increase risk of dying. Daily Mirror, July 26 2016

TV addicts double risk of blood clots. The Times, July 26 2016 (subscription required)

Links To Science

Shirakawa T, Iso H, Yamagishi K, et al. Watching Television and Risk of Mortality From Pulmonary Embolism Among Japanese Men and Women. Circulation. Published online July 26 2016

Categories: NHS Choices

Smokers who try to quit 'drink less alcohol', too

NHS Choices - Behind the Headlines - Mon, 25/07/2016 - 17:30

"How quitting smoking can be good for your liver: Those who have given up cigarettes 'drink less alcohol too'," the Mail Online reports.

The news follows an analysis of two ongoing studies that aimed to investigate whether people who attempt to stop smoking are more likely than other smokers to report lowering their alcohol consumption.

Those who had attempted to quit smoking within the last week had significantly lower scores on an alcohol intake questionnaire compared with non-quitters.

The same people were also more likely to report they were currently trying to reduce how much alcohol they drank. The main effect seemed to come from a reduction in binge drinking.

It is important to be aware that studies like this are unable to rule out the influence of other potential factors.

It could be the case that some people were advised by their doctor to quit smoking while also reducing their alcohol consumption for health reasons, or were simply on a health kick.

Nevertheless, the links between smoking and excessive alcohol consumption and poor health are well established.

Smoking has long been known as a risk for lung cancer and, as we discussed just last week, smoking is directly linked to seven types of cancer.

Quitting smoking and sticking to the recommended alcohol guidelines should significantly reduce your cancer risk.

Where did the story come from?

The study was carried out by researchers from a number of UK universities, including University College London, the University of Sheffield, King's College London, the University of Bristol, and Newcastle University.

It was funded by the National Institute for Health Research (NIHR) School for Public Health Research (SPHR) and Cancer Research UK.

The study was published in the peer-reviewed journal, BioMed Central (BMC) Public Health. It is available on an open-access basis, so it is free to read online.

Although the tone of the Mail Online headline made it seem like quitting smoking has potential benefits for liver health, this was not proven in this study.

You would need a much longer follow-up period to see if the reduction in alcohol consumption in ex-smokers was a long-term effect. That aside, the main body of the news story provided balanced reporting.

What kind of research was this?

This was a cross-sectional analysis of two ongoing studies: the Smoking Toolkit Study (STS) and the Alcohol Toolkit Study (ATS).

It aimed to investigate whether people who attempt to stop smoking are more likely than other smokers to lower, or at least try to reduce, their alcohol consumption.

Smoking and excessive alcohol consumption are two of the most significant factors that can lead to poor health by triggering chronic diseases such as cancer and heart disease.

The behaviours have a close and complex relationship. As such, they are important public health challenges in the UK.

Research suggests drinking lots of alcohol while also trying to quit smoking makes the quit attempt more likely to fail, one reason being that alcohol can weaken willpower, making a lapse more likely.

As a result, smokers trying to quit are often advised to cut back on alcohol as well, but it is unclear how often they follow this advice.

Cross-sectional studies like this are useful for assessing the relationship between two variables – in this case, quitting smoking and alcohol consumption.

However, the study design cannot confirm the link and say that one has caused the other. 

A longer-term cohort study that followed these people up to see how the two factors changed over time would be one of the best ways to validate these findings and see how they're related.

What did the research involve?

The researchers used data from household surveys conducted as part of two ongoing studies: the Smoking Toolkit Study (STS) and the Alcohol Toolkit Study (ATS), which collected information on smoking, alcohol consumption and related behaviours in England.

They analysed data from 6,287 participants aged 16 and over who had reported smoking tobacco from March 2014 to September 2015.

All the smokers were also asked if they had made a serious attempt to quit smoking, and were classified according to their responses.

The smokers were further classified as light or heavy drinkers. Alcohol consumption was assessed through the Alcohol Use Disorders Identification Test (AUDIT-C), which asked participants about how often they drank.

Information on various socio-demographic, possibly confounding, factors was also collected, including:

  • age
  • sex
  • socio-economic status
  • education level
  • ethnicity
  • disability

The researchers then looked for links between people who had recently attempted to stop smoking and subsequent changes in their alcohol consumption. The results were stratified by socio-demographic factors.

What were the basic results?

Those who attempted to quit smoking within the last week had significantly lower AUDIT-C alcohol scores than those who had not tried to quit. On average their scores were about -0.66 points lower (95% confidence interval [CI] -0.11 to -1.21). 

There was, however, no significant difference in their typical quantity or frequency of drinking.

But those who had attempted to quit smoking in the last week were less likely to binge drink and less likely to be classified as high-risk drinkers (AUDIT-C score of five or more).

The same people who were trying to quit were also more likely to report that they were currently trying to reduce their alcohol consumption.

These analyses were after adjustment for socio-demographic characteristics, which did not differ between quitters and non-quitters.

How did the researchers interpret the results?

The researchers concluded: "Smokers who report a recent attempt to stop are more likely to report lower-risk alcohol consumption, including less frequent binge drinking, after adjusting for socio-demographic characteristics.

"Among smokers with higher-risk alcohol consumption, those who report a last week attempt to stop are more likely to report also a current attempt to cut down on their drinking."

Conclusion

This was a cross-sectional analysis of two ongoing studies that aimed to investigate whether people who attempt to stop smoking are more likely than other smokers to lower, or at least try to reduce, their alcohol consumption.

The researchers found those who attempted to quit smoking within the last week did have lower drinking scores on the AUDIT-C survey compared with smokers who weren't quitting.

The same people were also more likely to report they were currently trying to reduce how much alcohol they drank.

There was no difference in drinking frequency, however – the main effect seemed to be coming from a reduction in binge drinking.

So some participants may have had a drink every day during the week, but still drank less overall in terms of total units consumed.

Despite these results, there are a few points to note:

  • This was an observational study, which cannot prove that the quit attempt has directly caused the reduction in alcohol. Although the researchers attempted to control for potential confounders, there could be other factors that influenced changes in alcohol consumption.
  • As the authors note, it's also not possible to rule out reverse causation – that people with lower alcohol consumption were perhaps more likely to attempt to quit smoking.
  • The self-reporting nature of the surveys could lead to misreporting as a result of possible social pressures, such as stigma attached to both smoking and high alcohol consumption.
  • The study looked at immediate changes in smoking and alcohol consumption (in the last week) but longer-term follow-up would be needed to see if these decisions stuck or whether people reverted to their previous habits.
  • People who are trying to quit smoking may be advised to cut back on alcohol by smoking cessation professionals because of the known association between the two. This study does not inform whether individuals have cut back as a result of the advice of professionals or on their own initiative.

As it stands, people are advised to follow current smoking and alcohol public health recommendations.

If you smoke, the single best thing you can do for your health is to quit smoking. Stopping drinking, or at least cutting down, would be an added bonus your body will welcome.  

Links To The Headlines

How quitting smoking can be good for your LIVER: Those who have given up cigarettes 'drink less alcohol too'. Mail Online, July 22 2016

Links To Science

Brown J, West R, Beard E, et al. Are recent attempts to quit smoking associated with reduced drinking in England? A cross-sectional population survey. BMC Public Health. Published online July 22 2016

Categories: NHS Choices

Alcohol 'a direct cause of seven types of cancer'

NHS Choices - Behind the Headlines - Fri, 22/07/2016 - 15:00

"Even one glass of wine a day raises the risk of cancer: Alarming study reveals booze is linked to at least seven forms of the disease," reports the Mail Online.

The news comes from a review that aimed to summarise data from a range of previous studies to evaluate the strength of evidence that alcohol causes cancer.

The main finding was that existing evidence supports the link between alcohol consumption and cancer at seven sites, including the throat, gullet, liver, colon, rectum and female breast.

The links were said to be strongest for heavy drinking, but this study suggested that even low or moderate drinking may contribute to a significant proportion of cancer cases because of how common this level of drinking is. The study also suggests there's no evidence of a "safe" level of drinking with respect to cancer.

However, it's important to be aware that this review doesn't state how the author identified and assessed the research they've drawn upon. We don't know whether all relevant research has been considered and the conclusions must be considered largely the opinion of this single author.

Nevertheless, the main finding of the link between alcohol and these seven cancers is already well recognised. Recently updated government recommendations state there's no safe level of alcohol consumption, and men and women are advised not to regularly drink more than 14 units a week. This review further supports this advice.

Where did the story come from?

The study was carried out by one researcher from the University of Otago, New Zealand. No external funding was reported.

The study was published in the peer-reviewed scientific journal Addiction. It is available on an open-access basis and is free to read online.

Generally the media coverage of this topic was accurate, although the tone of the reporting tended to suggest this was a new discovery, when the link between alcohol and certain types of cancer is well established.

What kind of research was this?

This was a review which aimed to summarise data from published biological and epidemiological research, and meta-analyses that have pooled data, to evaluate the strength of evidence that alcohol causes cancer.

Alcoholic drinks have been considered potentially carcinogenic (cancer causing) for a while, but there are still concerns about the validity of some observational studies finding links with cancer, and uncertainty about precisely how alcohol causes cancer.

A systematic review is the best way of gathering and summarising the available research around a particular topic area. But in this case the exact methods are not described in the paper and it's not possible to say whether they were systematic.

There's a possibility that some relevant research may have been missed and that this review is giving an incomplete picture of the issue.

What did the research involve?

The author of this review reports drawing upon biological and epidemiological research as well as meta-analyses conducted in the last 10 years by a number of institutions, including the World Cancer Research Fund and American Institute for Cancer Research, the International Agency for Research on Cancer and the Global Burden of Disease Alcohol Group.

The majority of epidemiological research seemed to come from cohort and observational studies.

The research was reviewed and summarised in a narrative format which explored the evidence that alcohol causes cancer, while contrasting this with the notion that alcohol consumption may offer some form of protection from cardiovascular disease.

No methods are provided and the author does not describe how they identified the research, as you would expect from a systematic review.  For example, they do not give the literature databases searched, the search dates, search terms, study inclusion or exclusion criteria, or descriptions of how studies were quality assessed.  

What were the basic results?

There were several findings from this study, the main one being that existing evidence supports the link between alcohol consumption and cancer at seven sites: oropharynx (mouth and throat), larynx (voice box), oesophagus (gullet), liver, colon (bowel), rectum and female breast.

The strength of the association differed by the site of the cancer. It was strongest for the mouth, throat and oesophagus, with the review suggesting that someone who drinks more than 50g of alcohol a day is four to seven times more likely to develop these types of cancer compared to someone who doesn't drink. As the author says, the interaction of smoking with alcohol is also believed to contribute to the risk of these cancers.

The link was comparatively weaker for colorectal, liver and breast cancer. The review suggests someone who drinks more than 50g of alcohol a day is 1.5 times more likely to develop these types of cancer compared to someone who doesn't drink.

For all of these associations there was a dose-response relationship, where increased consumption was linked with an increase in cancer risk. This applied to all types of alcoholic drinks. The highest risks were associated with heavier drinking. There was also some suggestion that the level of risk goes down over time when alcohol consumption stops.

Recent large studies have found uncertain evidence whether low to moderate consumption has a significant effect on total cancer risk. But given that this level of consumption is common in the general population, the author considers that it could still contribute to a significant number of cases.

Furthermore, they say there is no clear threshold of what constitutes a harmful level of alcohol consumption, and therefore no safe level of drinking with respect to cancer.

The author also suggests that confounding factors may be responsible for the protective effect between alcohol consumption and cardiovascular disease that has been found in previous studies. For example, this may be due to the potential bias caused by misclassification of former drinkers as abstainers.

The research went on to report that alcohol is estimated to be responsible for approximately half a million deaths from cancer in 2012 and 5.8% of cancer deaths worldwide, deeming it to be a significant public health burden.

How did the researchers interpret the results?

The author concluded: "There is strong evidence that alcohol causes cancer at seven sites, and probably others. The measured associations exhibit gradients of effect that are biologically plausible, and there is some evidence of reversibility of risk in laryngeal, pharyngeal and liver cancers when consumption ceases."

"The highest risks are associated with the heaviest drinking, but a considerable burden is experienced by drinkers with low to moderate consumption, due to the distribution of drinking in the population."

Conclusion

This narrative review aimed to summarise data from published biological and epidemiological research to discuss the strength of evidence that alcohol causes cancer.

The author gives their main finding as a link between alcohol consumption and cancer at seven sites, and also that the highest risks seem to be associated with heavier drinking. However, they state there's no "safe" drinking threshold and that low to moderate consumption still contributes to a significant number of cancer cases.

The biggest limitation of this review is that it doesn't appear to be systematic. The author provided no methods for how they identified and appraised the research they drew on. Despite referencing a number of large studies and reviews, this study and its conclusions have to be considered largely the opinion of the author following their appraisal of the evidence.

We don't know whether the review has considered all research relevant to the topic and is able to reliably quantify the risks of cancer – overall or at specific sites – associated with alcohol consumption.

An additional limitation to keep in mind is that this data mainly appeared to be from observational studies. These cannot prove cause and effect. The individual studies will likely have varied considerably in the additional health and lifestyle factors they took account of when looking at the links with alcohol. For example, smoking, diet and physical activity are all factors likely to be associated both with level of alcohol consumption and cancer risk.

As the author notes in particular, confounding factors may be responsible for the observed protective effect between alcohol consumption and cardiovascular disease.

Another limitation is that alcohol consumption is likely to be self-reported in the studies analysed, which may be inaccurate and lead to misclassification. For example, a potential bias that the author notes is classifying former drinkers as abstainers.

The author does consider the limitations of these observational findings, saying: "The limitations of cohort studies mean that the true effects may be somewhat weaker or stronger than estimated currently, but are unlikely to be qualitatively different."

But despite the methodological limitations of this review, it does support current understanding around this topic. Cancer Research UK also reports that alcohol can increase risk of these seven cancers and that there is no "safe" alcohol limit.

While we can't give a safe limit to drink when it comes to cancer, people are advised to follow current alcohol recommendations, which are to drink no more than 14 units per week and to spread your drinking over three days or more if you drink as much as 14 units a week.

Links To The Headlines

Even one glass of wine a day raises the risk of cancer: Alarming study reveals booze is linked to at least seven forms of the disease. Mail Online, July 22 2016

Alcohol is a direct cause of seven ​​forms of cancer, finds study. The Guardian, July 22 2016

Alcohol linked to at least seven types of cancer, study says, while 'health benefits are irrelevant'. The Telegraph, July 22 2016

Alcohol raises risk of seven different cancers, experts warn – even just one glass. Daily Mirror, July 22 2016

Alcohol causes seven types of cancer – and probably others, study finds. The Independent, July 22 2016

Links To Science

Connor J. Alcohol consumption as a cause of cancer. Addiction. Published online July 21 2016

Categories: NHS Choices

Eating oily fish 'may boost bowel cancer survival'

NHS Choices - Behind the Headlines - Fri, 22/07/2016 - 13:00

"Oily fish may reduce risk of death from bowel cancer, study suggests," reports The Telegraph.

US research found people with bowel cancer who increased their intake of oily fish after diagnosis were less likely to die from the condition.

Omega-3 fatty acids found in oily fish have been shown to reduce the growth of tumours in a laboratory setting in other studies, so scientists wanted to see whether there's a link between how much oily fish people ate and what happened to them after a diagnosis of bowel cancer.

They followed up 1,659 people with bowel cancer for an average of 10 years. They found people who ate more oily fish were less likely to die of their cancer, but were just as likely to die of other causes.

People who increased their intake of oily fish after diagnosis were less likely to die of their cancer or other causes.

However, the numbers involved may be too small for the results to be completely reliable. The study also can't prove that eating oily fish directly improves bowel cancer survival.

Importantly, people in the study received normal treatment for bowel cancer. The study looked for any additional benefit of eating oily fish.

Current advice is for everyone to eat two portions of oily fish a week, which is similar to the amount of fish found to be beneficial in this study. If the study results are confirmed, they offer another reason to follow this advice.

Where did the story come from?

The study was carried out by researchers from Harvard Medical School, Harvard TH Chan School of Public Health, and Massachusetts Institute of Technology.

It was funded by grants from the US National Institutes of Health, as well as various charitable foundations.

The study was published in the peer-reviewed journal Gut, owned by BMJ, on an open access basis, so it is free to read online.

The Mail Online headline, saying "A few mouthfuls of oily fish once a week can reduce the risk of dying from bowel cancer by 70%", overstates the importance of the study.

The news story does not make it clear at the start that the study only involved people who had already been diagnosed with bowel cancer, and that the 70% reduced risk is a comparison between people with cancer who did or did not increase their consumption of oily fish. Also, the study cannot prove cause and effect, so it's wrong to say fish can reduce the risk.

The Independent and The Telegraph carried more balanced reports, including cautions about the need to replicate the results in bigger studies.

What kind of research was this?

This was a prospective cohort study of people with bowel cancer. Researchers wanted to see whether their dietary intake of omega-3 fatty acids from oily fish after diagnosis was linked to their survival.

Observational studies like this can spot links between factors – in this case, oily fish consumption and death from bowel cancer – but cannot prove that one causes the other.

What did the research involve?

Researchers followed a group of people with bowel cancer recruited from two much larger cohort studies.

The participants gave information about their diet in questionnaires, and also about their overall lifestyle and health status.

After an average 10 years of follow-up, researchers looked at whether there were links between how much oily fish people ate after their cancer diagnosis and how likely they were to have died from their cancer or other causes.

The researchers used information from two big cohort studies of nurses and other health professionals that have been running for many years in the US. They looked at data collected from 1984 and 1986 until 2012.

Everyone was asked to give detailed information about their health and lifestyle – including diet – every two to four years.

Researchers only looked at information from people in these bigger groups who had been diagnosed with bowel cancer and had completed at least one dietary questionnaire after diagnosis. Both fish and fish oil supplements were included in the assessment.

The researchers ran a series of calculations using the data, looking at people's chances of having died from bowel cancer and death from any cause.

They adjusted the figures to take account of other factors affecting the chances of dying from cancer, including age, ethnic background, exercise and smoking.

They also looked for other factors linked to diet and mortality to see if specific groups of people might benefit more from oily fish.

But the trouble with carrying out so many calculations is you increase the likelihood that some of the results will be down to chance alone.

What were the basic results?

Of the 1,659 people in the study, 561 died during the study. Of these, 169 died directly from their bowel cancer. Other causes of death included cardiovascular disease and other types of cancer.

The researchers said:

  • People who ate at least 0.3g of oily fish a day were 41% less likely to have died of bowel cancer during the study than people who ate less than 0.1g a day. But confidence intervals for these figures overlap with the point of no effect, meaning we cannot be sure this is a true result (hazard ratio [HR] 0.59, 95% confidence interval [CI] 0.35 to 1.01).
  • There was no difference between the groups in the chances of dying from any cause.
  • People who increased the amount of oily fish they ate by at least 0.15g a day were 70% less likely (HR 0.30, 95% CI 0.14 to 0.64) to have died of their cancer than people who did not increase their oily fish consumption by a significant amount (less than 0.02g a day). These people were also slightly less likely to have died of any cause, although the figures overlapped the point of no effect on this measure (HR 0.87, 95% CI 0.62 to 1.21).

The site and stage of the cancer did not appear to influence the results, as there were similar incidences of each severity among people who ate more or less oily fish.

The study showed people who ate more oily fish were also more likely to do physical exercise and less likely to smoke, but they took this into consideration when analysing the results.

How did the researchers interpret the results?

The researchers say their findings show dietary omega-3 fatty acid intake after diagnosis "may lower the risk of colorectal cancer specific mortality".

They also say increasing the amount of oily fish people eat after diagnosis with bowel cancer may "confer additional benefits", although they don't spell out what these benefits are.

They admit "further studies are needed in a larger population" to confirm their findings, and they can't rule out the influence of other dietary or lifestyle factors.

Conclusion

Oily fish have long been thought to have health benefits, especially for heart and circulation. This study suggests they may also be beneficial for people with bowel cancer.

But we should be cautious about the results, as the numbers in the study are quite small for this type of research and the results show a degree of uncertainty.

Finding that one factor (eating oily fish) is linked to another (surviving bowel cancer) is not the same as showing that one causes the other. We know that people in the study who ate more oily fish also exercised more and smoked less.

Although the researchers adjusted their figures to account for these particular factors, this suggests fish-eaters might have been more health conscious generally. That means they might have taken other steps we don't know about to reduce their risk of dying from bowel cancer.

It's also interesting that while the chances of dying from bowel cancer were smaller for people who ate more oily fish, the chances of dying from any cause – including all types of cancer and cardiovascular disease – were the same.

Reading the Mail Online headline, you might think eating oily fish alone can make a huge difference to your chances of surviving bowel cancer.

But it's not obvious from the report that all the people in the study would also have received conventional medical and surgical treatments for their cancer, and uncertainty in the figures means oily fish might actually make very little difference.

For people diagnosed with cancer, eating oily fish may or may not make a difference to their chances of survival. There's certainly no reason why these people should not eat oily fish, but surgical and medical treatments are likely to be much more important for their chances of survival.

For everyone else, the advice is unchanged. Eating two portions of oily fish a week is an important part of a healthy diet.

Links To The Headlines

A few mouthfuls of oily fish once a week 'can reduce the risk of dying from bowel cancer by 70%'. Mail Online, July 19 2016.

Eating oily fish 'cuts risk of death from bowel cancer', research suggests. Independent, July 20 2016.

Oily fish may reduce risk of death from bowel cancer, study suggests. The Telegraph, July 20 2016.

Links To Science

Song M, Zhang X, Meyerhardt JA, et al. Marine ω-3 polyunsaturated fatty acid intake and survival after colorectal cancer diagnosis. Gut. Published online July 19 2016.

Categories: NHS Choices

The new guidelines on vitamin D – what you need to know

NHS Choices - Behind the Headlines - Thu, 21/07/2016 - 13:30

"Experts recommend everyone consider vitamin D supplements over winter," says a headline in today's Daily Mail, while The Guardian urges "Tuck into tuna, salmon and eggs or take vitamin D pills – official health advice".

The headlines were prompted by new advice on vitamin D from Public Health England (PHE), which says that children and adults over the age of one should have 10 micrograms (mcg) of vitamin D every day. This means that some people may want to consider taking a supplement.

The advice is based on recommendations from the government's Scientific Advisory Committee on Nutrition (SACN) following its review of the evidence on vitamin D and health (PDF, 4.2Mb).

How has the new vitamin D advice been reported?

In general the new government advice on vitamin D has been reported accurately.

However, the Guardian's headline, "Tuck into tuna, salmon and eggs or take vitamin D pills – official health advice" is misleading. While it's important to eat these foods as good sources of vitamin D, the advice is to consider taking vitamin D supplements because it is difficult to get enough from food alone.

Meanwhile, the Express headline, "Everyone should take vitamin D: Health chiefs warn millions are at risk of deficiency," overstates the advice. Most people are simply being asked to consider taking supplements.

And, although roughly one in five people has low vitamin D levels, this is not the same as a vitamin D deficiency. It is not accurate to say that millions of people are at risk of deficiency.

What is vitamin D?

Vitamin D helps to control the amount of calcium and phosphate in our bodies. Both are needed for healthy bones, teeth and muscles.

Vitamin D is found naturally in a small number of foods, including oily fish, red meat, liver and egg yolks. It's also found in fortified foods like breakfast cereals and fat spreads.

However, it's difficult for us to get the recommended amount of vitamin D from food alone.

Our main source of vitamin D is from the action of sunlight on our skin. 

See more about vitamin D and sunlight.

What is the new vitamin D advice?

The new advice from PHE is that adults and children over the age of one should consider taking a daily supplement containing 10mcg of vitamin D, particularly during autumn and winter.

People who have a higher risk of vitamin D deficiency are being advised to take a supplement all year round.

SACN's review concluded that these at-risk groups include people whose skin has little or no exposure to the sun, like those in care homes, or people who cover their skin when they are outside.

People with dark skin, from African, African-Caribbean and South Asian backgrounds, may also not get enough vitamin D from sunlight in the summer. They should consider taking a supplement all year round as well.

See more detailed advice on vitamin D.

Is there new vitamin D advice for children too?

Yes. It's recommended that children aged one to four years should have a daily 10mcg vitamin D supplement all year round.

As a precaution, all babies under one year should have a daily 8.5-10mcg vitamin D supplement to make sure they get enough.

However, babies who have more than 500ml (about a pint) of infant formula a day don't need a vitamin D supplement as formula is already fortified.

The government recommends that babies are exclusively breastfed until around six months of age.

See more advice on vitamins for babies and children.

Why are we being advised to take vitamin D supplements?

The government says it has issued new vitamin D recommendations "to ensure that the majority of the UK population has satisfactory vitamin D blood levels throughout the year, in order to protect musculoskeletal health".

The recommendations refer to average intake over a period of time, such as one week, and take account of day-to-day variations in vitamin D intake.

SACN also looked at possible links between vitamin D and non-musculoskeletal conditions, including cancer, multiple sclerosis and cardiovascular disease. They didn't find enough evidence to draw any firm conclusions.

In spring and summer, most of us get enough vitamin D from sunlight on our skin and a healthy, balanced diet.

However, SACN couldn't make any recommendations about how much sunlight people would need to get enough vitamin D because there are a number of factors that can affect how much vitamin D is produced in the skin. So the recommendations assume "minimal sunshine exposure".

During autumn and winter (from October until the end of March) the sun isn't strong enough in the UK to produce vitamin D. That means we have to rely on getting it just from the food we eat. 

Because it's difficult to get enough vitamin D from food alone, many of us risk not getting enough. Taking a supplement helps to keep levels of the vitamin topped up during the colder months.

Where can I get vitamin D supplements?

Vitamin D supplements are widely available from supermarkets and chemists.

Vitamin drops are available for babies. Your health visitor can tell you where to get them. These are available free to low-income families through the Healthy Start scheme.

Links To The Headlines

Tuck into tuna, salmon and eggs or take vitamin D pills – official health advice. The Guardian, July 21 2016

EVERYONE should take Vitamin D: Health chiefs warn millions are at risk of deficiency. Express, July 21 2016

Experts recommend everyone consider vitamin D supplements over winter. Mail Online, July 21 2016

Think vitamin pills are a waste of time? This is the one you really SHOULD take, says the government. The Sun, July 21 2016

Categories: NHS Choices

Chlamydia vaccine research 'shows early progress'

NHS Choices - Behind the Headlines - Wed, 20/07/2016 - 01:00

"Could a nose spray prevent chlamydia?" asks the Daily Mail, one of several media outlets reporting on promising research to develop a vaccine for the sexually transmitted disease (STI).

Canadian researchers found mice treated with an experimental vaccine given as a nasal spray fought off infection with a mouse variant of chlamydia faster.

The laboratory mice also produced fewer bacteria that could pass on the disease, and were less likely to get damaged fallopian tubes as a result of the infection spreading.

Chlamydia trachomatis is one of the most common STIs in the UK, with more than 200,000 cases reported in 2015.

It can be treated with antibiotics, but the infection can spread around the body and lead to long-term health problems, including infertility, if left untreated.

People don't always know they have chlamydia as it doesn't always cause symptoms. This means they don't get treated, and may pass the infection on to partners.

A vaccine that prevented infection or helped the body clear the bacteria quickly would help slow the spread of the disease, and could prevent infertility.

Numerous attempts to create a vaccine since 1957 have failed because of the rapid resistance of chlamydia to the vaccine, unwanted side effects, or even a worse response to chlamydia infection.

While research in animals is a necessary early stage in the development of many vaccines and medicines, what works in mice does not always work in humans.

We need to see more research before we know whether this vaccine will fulfil its promise.

Condom use and regular testing are the best protection against chlamydia.

Where did the story come from?

The study was carried out by researchers from MG DeGroote Institute for Infectious Disease Research, McMaster University and St Joseph's Healthcare, all in Canada.

It was funded by the Canadian Institutes for Health Research. The study was published in the peer-reviewed journal, Vaccine.

The Daily Mail reported the study without mentioning the crucial fact that the research was carried out in mice, not humans.

BBC News did a better job, giving a clear overview of the study and the context of the research.

What kind of research was this?

This was a pre-clinical experimental study carried out with laboratory-bred mice. This type of study usually takes place in the early days of developing a vaccine or medicine.

Mice studies are usually followed by studies in other animals before the vaccine can be tested in a small number of humans to check for safety. Only then can a vaccine be tested in large-scale human trials to see how well it works.

What did the research involve?

Researchers tested a vaccine called BD584 on laboratory-bred mice – half had the vaccine and half a dummy vaccine. They tested the mice for production of anti-chlamydia antibodies.

They infected vaccinated mice with chlamydia bacteria, then tested them to monitor how quickly they fought off the virus and how many of them got a condition called hydrosalpinx, which is blockage of the fallopian tubes caused by infection.

The vaccine included three proteins from the membrane of the chlamydia bacteria thought to be important for enabling the bacteria to infect cells. It was administered as a nasal spray.

Five mice were given the vaccine and five others a dummy vaccine. The mice had blood tests afterwards to check for antibodies specific to chlamydia bacteria. These antibodies were tested in the laboratory to see whether they worked to neutralise bacteria.

Twenty mice (10 vaccinated and 10 controls) were infected with a mouse variant of chlamydia called Chlamydia muridarum.

They then had tests every couple of days to see how much bacteria they were shedding, and for how long.

The researchers compared the response of vaccinated and non-vaccinated mice.

At the end of the study, they checked to see how many mice in each group had signs of blocked fallopian tubes.

What were the basic results?

All mice given the vaccine produced antibodies to chlamydia, while no mice given the dummy vaccine did.

Vaccinated mice shed (produced and released) far less bacteria than unvaccinated mice, with a 95% reduction in bacterial shedding on days five and seven, compared with non-vaccinated mice.

No bacteria were detected in tests of vaccinated mice 32 days after infection, while control mice were still infected.

One of the 10 vaccinated mice showed signs of hydrosalpinx, compared with 8 out of 10 unvaccinated mice.

How did the researchers interpret the results?

The researchers said they showed the vaccine reduced bacterial shedding and the length of infection for mice infected with chlamydia, and that as a result "we speculate that immunisation with BD584 may decrease the transmissibility of chlamydia infections".

They say it also "decreased the rate of hydrosalpinx from 80% to 10%, suggesting that BD584 may reduce infertility".

Both of these factors, they say, show the vaccine "affords a significant degree of protection and could be an effective vaccine for human use".

Conclusion

It's easy to get carried away by headlines about vaccines for common and damaging diseases, but early-stage studies in mice don't always translate into usable vaccines for humans.

People have been trying to find an effective vaccine against chlamydia since the bacteria was discovered in 1957, and research is still being carried out into several different vaccine candidates.

This vaccine may turn out to be effective, but it could become one of the many failed vaccine candidates seen over the years.

This is a small study in just 20 specially bred laboratory mice, and involved a type of chlamydia (Chlamydia muridarum) only mice get.

Much more work will be needed to see whether this experiment can be successfully repeated, and whether the vaccine is safe for use in humans, before we can even look at whether it is effective in preventing Chlamydia trachomatis in humans.

Read more about chlamydia prevention and sexual health.

Links To The Headlines

Could a NOSE SPRAY prevent chlamydia? World's first vaccine for the STD 'is showing promising results'. Mail Online, July 19 2016

Chlamydia vaccine 'shows promise'. BBC News, July 20 2016

Links To Science

Bulira DC, Steven Lianga, S, Leec A, et al. Immunization with chlamydial type III secretion antigens reduces vaginal shedding and prevents fallopian tube pathology following live C. muridarum challenge. Published online June 17 2016

Categories: NHS Choices

'Walk or cycle to work to lose wieght', says study

NHS Choices - Behind the Headlines - Tue, 19/07/2016 - 16:30

"Pedalling the pounds away: Why cycling could be the best way to lose weight," says The Daily Telegraph, reporting on a UK study comparing how different methods of commuting affected obesity levels.

People who cycled to work typically had a lower body mass index (BMI) and body fat than their walking counterparts, according to the study by the London School of Hygiene and Tropical Medicine.

All commuting methods except "car and public transport" showed a significantly lower BMI and body fat percentage for men and women when compared to car-only travellers.

People who used cycling as their main mode of transportation had a BMI that was about 1.7kg/m2 lower than those who mainly travelled by car.

For the average man in the study (age 53 years, height 176cm, weight 86kg) this finding equates to a substantial weight difference of 5kg.

The findings are based on comparing the BMI and body fat percentage of 150,000 UK men and women aged 40 to 69 with their habitual mode of transportation.

The researchers said their findings support the case for programmes to promote commuting by walking and cycling as a means of preventing obesity among mid-life adults.

Overall, this was a well-designed study which attempted to provide the best possible estimate by using a very large sample from the UK and controlling for key confounders.

However, as this was an observational study it cannot prove cause and effect.

While this study cannot prove the link, it does make sense that those who have a more active lifestyle would be less likely to be overweight.

As it is becoming increasingly difficult to fit exercise into our daily routine, using an active mode of transport to commute can help increase people's physical activity.

Where did the story come from?

The study was carried out by researchers from the London School of Hygiene and Tropical Medicine and was funded by the UK Medical Research Council.

The study was published in the peer-reviewed medical journal: Lancet: Diabetes-Endocrinology.

Its findings were reported accurately in the Telegraph, which included a number of case studies of people who cycle to work and their perceived health benefits.

What kind of research was this?

This was a cross sectional study using data from the UK Biobank, a database set up with the aim of improving the prevention, diagnosis and treatment of a wide range of serious and life-threatening illnesses.

The study aimed to assess the relationship between active commuting and obesity in mid-life.

This type of study is great for examining data collected over a long period, however, while it is possible to show an association, it is not able to prove cause and effect.

What did the research involve?

The researchers used data from the UK Biobank for adults aged 40 to 69, gathered from 22 assessment centres in the UK between 2006 and 2010.

Data was collected for commuting methods which were split into seven groups reflecting the physical exertion required. The categories were:

  • car only
  • car and public transport
  • public transport only
  • car and a mixture of all other methods
  • public transport and active methods (walking, cycling, or both)
  • walking only
  • cycling only
  • cycling and walking

To assess the impact of these commuting methods on obesity the following outcomes were assessed:

  • BMI
  • percentage body fat

These measurements were taken by trained staff.

The relationship was examined using statistical methods and took into account possible confounders, such as income, urban or rural residence, alcohol intake, smoking and leisure physical activity. Data for confounders was self-reported.

What were the basic results?

The analysis included 72,999 men and 83,667 women for the primary outcome of BMI. The most common method of commuting was by car (64% of men, 61% of women), with 23% of men and 24% of women using active transport methods alone or within a mix of methods.

The researchers compared each commuting category to car-only travel.

The greatest difference was found for commuters who travelled by bicycle. After adjusting for confounders, male cyclists had a BMI 1.71kg/m2 lower (95% confidence interval (CI) -1.86 to -1.56), and female cyclists had a BMI 1.65kg/m2 lower (95% CI -1.92 to -1.38) on average than their car-only counterparts.

Percentage body fat was also lowest for cyclists; this was 2.75% lower for men (95% CI -3.03 to -2.48) and 3.26% lower for women (95% CI -3.80 to -2.71).

All commuting methods except "car and public transport" showed significantly lower BMI and percentage body fat for men and women when compared to car travel.

How did the researchers interpret the results?

The researchers conclude: "This study is the first to use UK Biobank data to address the topic of active commuting and obesity and shows robust, independent associations between active commuting and healthier bodyweight and composition.

"These findings support the case for interventions to promote active travel as a population-level policy response for prevention of obesity in mid-life."

Conclusion

This was a cross-sectional study which aimed to assess the link between methods of commuting and obesity in adults.

Overall this was a well-designed study which attempted to provide the best possible estimate by using a very large sample from the UK and controlling for key socioeconomic and lifestyle confounders that could also be associated with BMI and body fat.

However, as this was an observational study it is not possible to prove cause and effect. The limitations are that even when attempts are made, there is always a risk of residual confounding in the model.

Much of the data collected, such as method of commuting and food consumption, was self-reported and this is always subject to bias.

It is possible that the UK Biobank is not representative of the UK population and findings would not be applicable to the general public.

The results also only apply to people from midlife to middle age. You may expect to see similar links in younger adults but this can't be assumed.

It's also worth noting that while the researchers report the difference in BMI between people commuting by car compared with other methods, the proportions of people in the different travel groups who are actually obese is not reported.

The researchers report the average BMI for all men in the study as 27.5 and women at 26.4 – therefore the total sample was on average overweight. However, they do not report the average BMI for people in the different travel categories.

While we cannot be certain from this study that commuting by active methods leads to lower BMI and body fat percentage it would make sense.

With hectic lifestyles it is becoming increasingly difficult to fit exercise into the daily routine so using an active mode of transport to commute helps to increase physical activity time in people of any age.

Links To The Headlines

Pedalling the pounds away: Why cycling could be the best way to lose weight. The Daily Telegraph, July 15 2016

Links To Science

Flint E and Cummins S. Active commuting and obesity in mid-life: cross-sectional, observational evidence from UK Biobank. Lancet Diabetes-Endocrinology. Published online 16 March 2016

 

Categories: NHS Choices

'Nine out of 10 strokes preventable,' claims study

NHS Choices - Behind the Headlines - Mon, 18/07/2016 - 15:45

"Nine out of 10 strokes preventable if people follow 10 health rules," The Daily Telegraph reports.

The news comes from a large study that found the top 10 risk factors for stroke are preventable.

The 10 main risk factors for stroke are:

  • high blood pressure
  • smoking
  • too much alcohol
  • diabetes
  • poor diet
  • lack of exercise
  • high cholesterol
  • heart problems
  • obesity
  • stress

Canadian researchers estimated around 9 out of 10 strokes worldwide, including among people in the UK, could be caused by these risk factors – many of which can be avoided.

Strokes are a major health problem in the UK. Every year, around 110,000 people in England have a stroke. The condition is the third largest cause of death after heart disease and cancer.

This study compared the lifestyles of people who had a stroke with those who had not, involving nearly 27,000 participants from 32 countries.

But the 9 out of 10 figure is only an estimate. We don't know that these risk factors are the definite cause of stroke in the people involved in the study.

Also, much of the study's data is based on self-reported answers, and some answers may be inaccurate.

Nevertheless, the study provides further support for the well-established notion that lifestyle has a bearing on our cardiovascular health, as well as many other chronic diseases.

While we can't change our genetics or risk factors such as age or gender, this study provides further evidence to support the advice that a healthy diet and active lifestyle, not smoking and limiting alcohol intake give us the best chance of reducing our risk of stroke and other chronic diseases.

Where did the story come from?

The study was carried out by researchers from McMaster University and Hamilton Health Sciences in Canada, and various other global institutions that are part of the INTERSTROKE investigators group.

Funding was provided by several sources, including the Canadian Institutes of Health Research, the Heart and Stroke Foundation of Canada, and the Canadian Stroke Network. 

It was published in the peer-reviewed journal, The Lancet.

Media reports of the study were broadly accurate.

What kind of research was this?

This international case-control study aimed to see which preventable risk factors are associated with stroke.

It compared people from around the world who had and hadn't suffered a stroke to see how they differed on risk factors such as smoking, alcohol or high blood pressure.

As the researchers say, stroke is a leading cause of death and disability, making the condition a global health priority.

This study is the second phase of the INTERSTROKE study. The first phase assessed 6,000 people from 22 countries, and identified 10 preventable risk factors.

This second phase aimed to broaden the sample to include around 27,000 people from 32 countries to further look at how risk factors vary in people from different countries, as well as in those who suffer different types of stroke.

What did the research involve?

From 2007-15, the INTERSTROKE study recruited people from 142 centres in 32 different countries worldwide, including low-income and middle-income countries.

Cases were defined as people who had suffered from their first stroke, recruited within five days of the onset of symptoms and within 72 hours of being admitted to hospital.

All cases had to have had a brain scan and to have met clinical criteria for stroke. They included people with stroke caused by a clot (ischaemic) or by a bleed (haemorrhagic).

Age- and gender-matched controls were recruited from the hospital, such as those admitted or attending outpatients for other reasons, or from the community (recruitment not specified). 

Risk factors were assessed by giving structured questionnaires to cases and controls, which were completed by a friend or relative in just over a third of cases where the person who had a stroke developed difficulties with understanding and communication.

These questionnaires covered:

  • history of high blood pressure
  • diabetes
  • physical activity
  • smoking
  • alcohol
  • psychological stress

Medical records or hospital assessments were used to assess previous heart attack, mechanical valve or heart rhythm problems. Blood samples were also taken to assess proteins that bind to fats (apolipoprotein).

The researchers then compared risk factors between the cases and controls.

What were the basic results?

A total of 26,919 people were recruited from the 32 countries – 13,447 cases with stroke and 13,472 controls.

The researchers identified 10 risk factors that were significantly associated with risk of any stroke.

The following were linked with increased risk:

  • high blood pressure (over 140/90mmHg) (odds ratio [OR] 2.98, 95% confidence interval [CI] 2.72 to 3.28)
  • current smoking (OR 1.67, 95% CI 1.49 to 1.87)
  • high alcohol intake (OR 2.09, 95% CI 1.64 to 2.67)
  • high waist-to-hip ratio (OR 1.44, 95% CI 1.27 to 1.64)
  • high apolipoproteins B/A1 ratio (OR 1.84, 95% CI 1.65 to 2.06)
  • diabetes (OR 1.16, 95% CI 1.05 to 2.30)
  • psychosocial factors (INTERHEART stress score) (OR 2.20, 95% CI 1.78 to 2.72)
  • heart factors (combined) (OR 3.17, 95% CI 2.68 to 3.75)

A healthy diet and being active were linked with decreased risk:

  • high diet modified alternative healthy eating index (mAHEI) score indicating healthier cardiovascular diet (OR 0.60, 95% CI 0.53 to 0.67)
  • regular physical activity (OR 0.60, 95% CI 0.52 to 0.70)

When looking at different types of stroke, some factors – such as high blood pressure – were more strongly associated with haemorrhagic stroke, while others – such as smoking, diabetes and blood fats – were more strongly associated with ischaemic stroke.

The researchers calculated that overall, these 10 risk factors could account for 90.7% of all the strokes in the study. That is, if everyone acted on these risk factors, the number of strokes in this sample would plummet by 90%.

How did the researchers interpret the results?

The researchers concluded: "Ten potentially modifiable risk factors are collectively associated with about 90% of stroke in each major region of the world, among ethnic groups, in men and women, and in all ages."

They go on to say their findings "support developing both global and region-specific programmes to prevent stroke".

Conclusion

This valuable research aims to clarify which preventable risk factors are associated with stroke risk – knowledge that could have an effect on addressing this important global health problem.

The study's strengths are that it is based on a large sample size of nearly 27,000 people from 32 countries and of different socioeconomic backgrounds.

The researchers made careful attempts beforehand to calculate how many participants they would need to include to be able to reliably detect differences in risk factors.

There was little missing data across the total sample – for the various different risk factors assessed, only 1% of questionnaires or assessments had missing data.

However, the study has limitations. These include the potential for inaccuracies arising from the self-reported lifestyle and medical questionnaires.

This is particularly a risk for people with stroke for whom the questionnaires were completed by a family member or friend.

Also, certain risk factors, such as past heart attack or problems with heart valves, had to be pooled into one overall category of "heart factors", which makes it difficult to get a reliable indication of what this actually means.

As the researchers also acknowledge, controls may not necessarily be representative of the general population, particularly if most were recruited from hospital departments. The level of recruitment in the community was unclear.

The proportions of strokes that may be attributed to these risk factors are estimates only.

We don't know for definite how much of a contribution they make, and we don't know that these risk factors are the definite cause of stroke in these individuals.

However, the overall finding that medical factors such as high blood pressure, high blood fats and diabetes, and lifestyle factors such as smoking, high alcohol intake, poor diet and low physical activity, are linked with stroke risk is not surprising.

These factors are well known for their association with risk of cardiovascular diseases, as well as certain cancers and other chronic health conditions.  

We may not be able to change our genetics or risk factors such as age or gender, but this study provides further evidence to support advice that we should take care to eat a healthy diet and lead an active lifestyle, avoid smoking and limit our alcohol intake to give us the best chance of reducing our risk of stroke and other long-term diseases. 

Links To The Headlines

Nine out of 10 strokes preventable if people follow 10 health rules. The Daily Telegraph, July 15 2016

Revealed: The top 10 stroke triggers, from obesity to high blood pressure – and how 90% of attacks could be prevented with basic lifestyle changes. Daily Mail, July 16 2016

Links To Science

O'Donnell MJ, Chin SL, Rangarajan S, et al. Global and regional effects of potentially modifiable risk factors associated with acute stroke in 32 countries (INTERSTROKE): a case-control study. The Lancet. Published online July 15 2016

Categories: NHS Choices

Zika virus epidemic to last 'another three years'

NHS Choices - Behind the Headlines - Fri, 15/07/2016 - 15:00

"Zika epidemic to last another three years as 'too late' to control it, say researchers," reports the Telegraph Online.

A team of researchers at Imperial College London aimed to explore the dynamics of the current Zika epidemic in Latin America and used this data to calculate the potential future spread of the virus.

From the analysis in the study, the main predictions were that the current Zika epidemic will largely be over in three years, with seasonal variations based on mosquito populations.

Additionally, once the current epidemic is over, there will be a delay of at least a decade before any more large epidemics of Zika virus. This is because a large percentage of the population will be immune to infection – known as herd immunity.

However, the researchers highlighted the importance of developing new vaccines and testing potential interventions to prevent another epidemic, or at least, contain it quicker than the current outbreak.

As with all modelling studies the results are based on data available and some assumptions. Therefore, it's important to keep in mind the uncertainty that comes with predicting potential future trends of disease.

Where did the story come from?

The study was carried out by researchers from Imperial College London and one from Johns Hopkins University in the US. It was funded by the Medical Research Council, the Bill & Melinda Gates Foundation, the National Institutes of Health, and the UK NIHR Health Protection Research Unit in Modelling Methodology at Imperial College London.

The study was published in the peer-reviewed journal: Science. It is available on an open-access basis, meaning it's free to read online.

Media coverage of this study was widespread and varied. The Telegraph Online reported that "attempts to control the outbreak are now pointless because authorities have missed the chance to prevent the disease exploding," which is not the case.

BBC News was more accurate with its reporting, taking into account that "predicting anything with any degree of certainty was impossible".

What kind of research was this?

This was a modelling study that aimed to explore the trends of the current Zika epidemic and use this data to predict the potential spread of the virus.

Zika virus is a disease mainly spread by mosquitoes, it doesn't naturally occur in the UK. Originally discovered in 1947, the virus received little attention until the 2015 outbreak in Brazil.

Modelling studies such as this help policy makers get an idea of what the potential public health impact of a disease might be. For example, helping them to plan ahead or assist with making recommendations about the control of the disease.

What did the research involve?

The researchers obtained publicly available surveillance data on weekly suspected and laboratory-confirmed Zika cases in Brazil during the 2015-16 outbreak. They used this data to demonstrate the dynamics of the current epidemic and explore how the Zika infection may evolve.

To do this, they used the estimates of "the average number of secondary infections" and "the time between sequential rounds of infection," to calculate the potential future spread of the Zika virus.

In addition, they explored the potential impact of human mobility and the changing age groups which will be affected in the future as immunity develops.

What were the basic results?

The researchers made a number of predictions based on their model.

The headline prediction is that the current epidemic will largely be over in three years, with seasonal variations based on mosquito population. Once the current epidemic is over, herd immunity will lead to a delay of at least a decade before other large epidemics occur.

The average age of infection is predicted to fall in future epidemics, as older people will be more likely to be immune to the Zika virus through past exposure. However, the analysis suggests the risk to pregnant women is unlikely to change.

Although it's difficult to predict the timing of the rounds of epidemics, the analysis suggests future epidemics of Zika virus will typically last for less than six months.

How did the researchers interpret the results?

The researchers concluded the Zika virus is "like Ebola, a public health crisis in which policymakers have had to make decisions in the presence of enormous uncertainty".

However, they recommended that the government response to Zika virus should not mirror Ebola as "Zika and Ebola epidemiology and thus policy options differ fundamentally."

They suggested that the current epidemic "is not containable" and "at best, interventions can mitigate its health impacts".

Despite the warning, they concluded that the current Zika epidemic will run its course naturally, eventually providing "a multiyear window to develop new interventions before further large-scale outbreaks occur."

Conclusion

This modelling study aimed to explore the trends of the current Zika epidemic and use this data to predict the future spread of the virus.

From the analysis, the main predictions were that the current epidemic will largely be over in three years, with seasonal variation based on mosquito populations. Additionally, once the current epidemic is over, there will be a delay of at least a decade before another large Zika virus epidemic.

However, as the researchers acknowledge, with any modelling study the results are based on data available and some assumptions. There is a great deal of uncertainty that comes with predicting potential future trends of disease.

For example, it's difficult to foresee climate change or predict how preventative interventions, mosquito control, or population behaviour may affect their predictions.

Additionally, this analysis was only able to look at trends in Latin America. This means the predictions may not be applicable to other parts of the world, such as Asia, and the figures represent estimates, rather than exact numbers.

Links To The Headlines

Zika epidemic to last another three years as 'too late' to control it, say researchers. The Daily Telegraph, July 14, 2016

Zika epidemic will end in three years, study suggests. BBC News, July 14 2016

Zika epidemic could burn itself out in three years as people become immune say experts. Mirror Online, July 14 2016

Is the Zika epidemic nearly over? Disease to burn out in the next 2 years because it 'will have run out of people to infect'. Mail Online, July 15 2016

Zika epidemic has peaked and may run its course within 18 months, say experts. The Guardian, July 14 2016

Links To Science

Ferguson NM, Cucunuba ZM, Dorigatti I, et al. Countering Zika in Latin America. Science. Published online July 14 2016

Categories: NHS Choices

Obesity 'now a leading cause of death; especially in men'

NHS Choices - Behind the Headlines - Thu, 14/07/2016 - 14:25

"Being overweight or obese puts men at a greater risk of dying prematurely than women," BBC News reports.

A survey of global trends found obesity was now second only to smoking as a cause of premature death in Europe. A study of almost 4 million people from 32 countries showed that being overweight (as well as being underweight) increases the risk of dying early, compared to people with a healthy weight. This is usually defined as having a body mass index (BMI) of between 18.5 and 24.9.

The study was designed to calculate the impact of BMI on chances of death in four geographical regions, free from the effects of confounding factors such as smoking or existing chronic disease.

Researchers calculated that, in Europe, 1 in 7 (14%) premature deaths could be prevented if people were a healthy weight, rather than overweight or obese. Men who were overweight were more likely to die early than women who were overweight.

The study does not prove that obesity causes early death, only that people who are overweight or obese are more likely to die earlier. Other factors such as diet, exercise, socioeconomic status and ethnicity may have an effect on people's individual risk, as well as their BMI.

That said, it does cast doubt on previous claims that it is possible to be "fat and fit", while also adding to evidence that a healthy weight plays an important role in the chances of living a long and healthy life.

 

Where did the story come from?

The study was carried out by over 500 researchers from more than 300 institutions in 32 countries. It was co-ordinated by researchers at the University of Cambridge and was funded by grants from organisations including the UK Medical Research Council, British Heart Foundation, Cancer Research UK, National Institute of Health Research and US National Institutes of Health.

The study was published in the peer-reviewed journal The Lancet on an open-access basis, so it's free to read online.

The story was widely covered in the UK media, with reasonably accurate reports.

Several articles quoted figures supplied by researchers in The Lancet's press release, which are not included in the main body of the report. While these figures (which look at the chances of death for men and women at different ages and different BMI levels) may well be true, they are not included in the main study, so we cannot verify their accuracy.

 

What kind of research was this?

This was a meta-analysis of 239 cohort studies, carried out in four continents (Asia, Australia and New Zealand, Europe, and North America).

Meta-analyses pool data from lots of smaller studies, to give a more reliable overall figure. Cohort studies are good for showing links between factors (in this case BMI and death) but cannot show that one causes another.

 

What did the research involve?

A big group of researchers (more than 500 people) agreed to analyse large prospective studies of more than 100,000 people, which included data about BMI and mortality (death).

They excluded people who had ever smoked, people who'd been diagnosed with a chronic illness, and people who died in the first five years of the study. They then calculated the chances of having died during the study, for people in nine BMI categories, from very underweight to very obese.

Study centres on four continents used standardised analysis methods to ensure the results were as comparable as possible. They included studies with information about weight, height, age and sex, from a general population (not a group of patients with a particular disease), with records of deaths, and more than five years of follow up.

They deliberately excluded from their analysis all people in the studies whose records showed they had ever smoked, been diagnosed with a chronic disease or who died in the first five years. They also excluded people aged under 20 or over 90 at the start of the studies, or with a BMI under 15 or over 60 (the healthy range of BMI according to the World Health Organization (WHO) is 18.5 to 24.9).

The exclusion of people with chronic illness, who died within five years, or who had smoked, was because these things have an effect on people's BMI and can skew the results. For example, people who smoke often have a lower BMI, but are at increased risk of dying early, so that can mask the effect of a higher BMI.

Researchers then pulled together all the information to calculate the chances of death at different BMI levels, in different geographical regions and for different ages and sexes.

 

What were the basic results?

Researchers looked at the records of more than 10.6 million people from 239 studies, then narrowed their research down to 3.95 million people from 189 studies, after excluding smokers and people with chronic disease or who died within five years.

The pooled data showed that people with a BMI of 20 to 25 had the lowest chance of death. People with a BMI lower or higher than this had an increased chance of death. For overweight or obese people in Europe and east Asia, every additional five BMI points was linked to an additional 39% increase in their risk of death (hazard ratio (HR) 1.39, 95% confidence interval (CI) 1.34 to 1.43); the relative risk (RR) was slightly lower in the US and Australia.

Other notable results were:

  • Men had a higher risk of death from every additional five BMI points compared to women, (HR 1.51 (95% CI 1.46 to 1.56) for men; HR 1.30 (95% CI 1.26 to 1.33) for women).
  • The increased risk of death linked to overweight or obesity was stronger at younger ages. The increased RR of death for every additional five BMI points over 25 was 52% for people aged 35 to 49 (HR 1.52, 95% CI 1.47 to 1.56), but 21% for people aged 70 to 89 (HR 1.21, 95% CI 1.17 to 1.25).
  • Deaths from heart disease, stroke and respiratory disease were strongly increased for people with a BMI over 25, and death from cancer was moderately increased.
  • The amount of excess deaths that might be attributed to overweight or obesity varied a lot by region, from 19% in North America to only 5% in east Asia.

 

How did the researchers interpret the results?

The researchers say their results "challenge previous suggestions that overweight (25 to less than 30kg/m2) and grade 1 obesity (30 to less than 35kg/m2) are not associated with higher mortality, bypassing speculation" that excess fat might actually protect people who are otherwise healthy.

They say the size and rigour of their study provide a better estimate of the link between overweight and obesity than previous studies, which have been unable to adjust their figures fully to take account of the effects of smoking or pre-existing illness. They say their study supports efforts to combat overweight and obesity at all levels, worldwide.

 

Conclusion

The effect of being overweight or obese on length of life has been discussed a lot in recent years, mainly because of studies which seemed to show people might live longer if they have a BMI in the overweight range, and that even moderate obesity did not raise the risk of death.

However, this study suggests the previous findings were due to confounding factors – such as smoking and pre-existing diseases – which masked the link between BMI and length of life. The overall conclusion is that weight does matter, especially for men and younger people, who seem most affected by the link between BMI and early death.

The study has a number of strengths, including the vast amounts of data from a wide geographical area, and the researchers' use of a standardized protocol to exclude factors they thought might have confounded the results.

However, the use of BMI as a measure does exclude other factors that might have been important – for example, the fat to muscle ratio or the distribution of fat. People who carry fat around their waist (as many men do) are thought to be at higher risk of health problems than people who carry fat on their hips (as many women do).

Using BMI alone also means we don't know about people's overall health-related habits. For example, high BMI could be a sign of doing little exercise, or eating an unhealthy diet, both of which are likely to shorten life.

This means we cannot say that higher BMI is a cause of early death. But the study results make a strong case for higher BMI being linked to early death, across several geographical regions, among men and women, and at all levels of BMI.

It's worth noting that being underweight is also strongly linked to higher chances of dying early. The researchers found that even those at the lower end of the WHO's "healthy" spectrum – with a BMI of 18.5 to less than 20 – were at increased risk compared to people with a BMI of 20 to 25.

Whether or not BMI is directly linked to length of life, it makes sense to aim for a healthy weight, through eating a healthy balanced diet and taking regular exercise.

Links To The Headlines

Obesity 'puts men at greater risk of early death'. BBC News, July 14 2016

Obesity causes premature death, concludes study of studies. The Guardian, July 13 2016

Obesity is three times as deadly for men than women. The Daily Telegraph, July 13 2016

Being obese DOES increase the likelihood you'll die early – and that risk increases with every extra pound of weight. Mail Online, July 14 2016

Links To Science

The Global BMI Mortality Collaboration. Body-mass index and all-cause mortality: individual-participant-data meta-analysis of 239 prospective studies in four continents. The Lancet. Published online July 13 2016

Categories: NHS Choices

Pomegranate compound 'could combat' complications of ageing

NHS Choices - Behind the Headlines - Wed, 13/07/2016 - 15:00

"Pomegranates slow down the ageing process by prompting cells to recycle and rebuild themselves, a study shows," The Daily Telegraph reports. But before you rush to stock up on the "food of the gods", the study in question only involved worms and rodents.

Compounds called urolithins are produced by bacteria in the gut when breaking down food such as pomegranates, nuts and berries. The researchers found that one of them in particular, urolithin A, increased the lifespan of roundworms by a half. They also improved muscle function in rodents (specifically, mice and rats).

Urolithin A seemed to improve ageing muscles by having an influence on the cells' mitochondria. These biological components are often described as a cell's battery as it is the part of the cell that converts food into energy. During the ageing process, there is gradual decline in mitochondrial function. The findings suggested that urolithin A causes cells to get rid of these damaged mitochondria and in turn, increase production of healthy mitochondria to replace them.

Whether similar results would be found for humans is not known, though clinical trials are now under way, with results expected in 2017.

Rather than just waiting until then, older people can improve muscle strength, as well as heart and lung health, through regular exercise. Read more about the importance of exercise as you get older.

 

Where did the story come from?

The study was carried out by researchers from the Ecole Polytechnique Fédérale de Lausanne and Amazentis SA biotechnical company, both in Switzerland. It was funded by the polytechnique and the Commission for Technology and Innovation. There is a potential conflict of interest as some of the authors work for Amazentis, a drug company that produces urolithin A.

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

Both the Daily Mail and the Telegraph wrote that it was not guaranteed that everyone might benefit from pomegranates, as some people do not convert the compounds into urolithins. While it is true that previous research found that some people do not produce urolithins, we still do not know if urolithins are beneficial for humans (only worms and rodents at the moment).

 

What kind of research was this?

This was a laboratory study that investigated the effects of compounds called urolithins on roundworms, mice and rats.

Urolithins are produced by gut bacteria from natural compounds called ellagitannins that are found in pomegranates, nuts and berries. The ellagitannins are first converted to ellagic acid in the stomach, and then gut bacteria finish the process. There appears to be variability between humans as to how many urolithins are produced, with some people not producing any at all.

Previous laboratory research has suggested that urolithins might have anti-cancer and anti-inflammatory properties, but their exact mechanism of action was not known. This study looked at the effect of different urolithins, including urolithin A, urolithin B and urolithin C on muscle function in roundworms, mice and rats. Whilst this can provide some insights into the effects of urolithins, the findings may not be directly applicable to humans.

 

What did the research involve?

The researchers fed roundworms different urolithins or ellagic acid from birth until they died and compared the results with roundworms fed a control diet. They then performed several experiments to determine how the urolithins affected the mitochondria, a part of each cell that transforms food into energy.

Follow-up studies were performed on mice and rats using urolithin A, as this had shown the most promise in the roundworm studies. The rodents were given urolithin A or a control for between six weeks and eight months. Muscle mass, body weight, running endurance and activity levels were compared. In the molecular analysis of muscles, the researchers looked at the level of mitochondrial turnover and function.

 

What were the basic results?

Urolithin A increased the lifespan of roundworms by 45% compared with control. Feeding roundworms ellagic acid had no effect on lifespan.

Muscle function in mice was improved with urolithin A. Feeding 16-month-old mice urolithin A daily for eight months resulted in a 9% increase in grip strength with no change in muscle mass. The mice also spontaneously exercised 57% more than the control mice. In another mouse experiment, urolithin A given for six weeks increased running endurance by 42%. In rats, six weeks of urolithin A increased running capacity by 65%.

The improved muscle function appeared to be due to urolithin A causing cells to eliminate damaged mitochondria and increase production of healthy mitochondria.

 

How did the researchers interpret the results?

The researchers concluded that urolithin A is likely to improve the quality of muscle cells for rodents. They say that this "holds promise for further development in humans as an innovative approach for improving mitochondrial and muscle function". In their press release they informed us that clinical trials in humans have begun, with results expected in 2017.

 

Conclusion

This was a mixed animal study that aimed to investigate the effect of compounds called urolithins first in roundworms and then rodents. Urolithins are formed during the breakdown of ellagitannins, which are found in pomegranates, nuts and berries. It was not known whether urolithins were just a waste product, or if they had any beneficial effects.

The study found that one of the urolithins in particular, urolithin A, seems to improve muscle function in rodents. We do not know conclusively why, but the results suggested this was due to improving the quality of the mitochondria by increasing the rate of destruction of damaged mitochondria and increasing production of healthy mitochondria.

Studies like this are useful early-stage research for getting an indication of biological processes and how things may work in humans, however, we are not identical and findings can't necessarily be extrapolated.

We now eagerly await the results of the clinical trials that are now under way to see if there are similar positive effects in humans, and also to assess the safety and required dosage.

Exercise recommendations for older adults (aged 65 or above) are broadly the same as for all adults, and recommend at least 150 minutes a week of activity, combining both aerobic and muscle-strengthening activities.  

Links To The Headlines

Discovery of pomegranate's anti-ageing molecule is a 'milestone'. The Daily Telegraph, July 11 2016

Are pomegranates a fountain of youth? Fruit contains 'miracle' ingredient that strengthens ageing muscles and extends life. Mail Online, July 11 2016

Pomegranate could help you live longer. The Times, July 12 2016 (subscription required)

Pomegranate by-product boosts muscles and may fight ageing. New Scientist, July 11 2016

Links To Science

Ryu D, Mouchiroud L, Andreux PA, et al. Urolithin A induces mitophagy and prolongs lifespan in C. elegans and increases muscle function in rodents. Nature Medicine. Published online July 11 2016

Categories: NHS Choices

'Secret ginger gene' may increase skin cancer risk for millions

NHS Choices - Behind the Headlines - Wed, 13/07/2016 - 12:30

"People can carry a 'silent' red hair gene that raises their risk of sun-related skin cancer, experts warn," BBC News reports.

Research suggests that carrying just one copy of a variant of the MC1R gene (having two copies causes red hair) increases skin cancer risk, even for people without red hair.

The variant is called an R allele, people who have two R allele variants tend to have ginger hair, pale skin, freckles and burn easily in the sun. These people are known to be at higher risk of skin cancer; both non-melanoma and melanoma.

However, many people have one R allele variant (some reports claim 25% of the UK population are carriers), which doesn't necessarily produce red hair. Researchers wanted to look at the DNA of skin cancers to see whether there was a difference at a genetic level between cells from people with R alleles and those without.

They found more genetic mutations in tumours from people with one or two R allele variants.

They report little difference between mutation levels with one R allele or two R alleles – meaning that people with one R allele who don't have ginger hair could be at the same raised risk of skin cancer.

The study reinforces that point that people of all hair types and skin colour are at risk of skin cancer; not just pale white people with red hair. People often forget that reggae legend Bob Marley died of skin cancer aged just 36. 

Where did the story come from?

The study was carried out by researchers from the Wellcome Trust Sanger Institute, Universidad Nacional Autonoma de Mexico, Boston University School of Medicine, Cambridge Biomedical Campus, Royal College of Surgeons in Ireland, Yale University School of Medicine and the University of Leeds and was funded by Cancer Research UK and the Wellcome Trust.

The study was published in the peer-reviewed journal Nature Communications, on an open-access basis, meaning it is free to read online.

Most of the UK media focused on the increased risk of skin cancer for people with the "hidden ginger" gene, although there was a tendency to overstate the reliability of the findings.

The Daily Mail says that "Carrying the 'ginger gene' is as dangerous as 21 years of sun exposure as it raises the risk of deadly skin cancer." But the researchers say that other factors, such as the likelihood of people trying to avoid sunburn (people with darker hair and /or complexion may spend more time in the sun), may have confounded their results.

The Guardian and BBC News provided the best overviews of the study and included useful discussions of the implications of the results.

 

What kind of research was this?

This is a cohort study, which examined cells from tumours removed from 405 people diagnosed with melanoma skin cancer (the more dangerous type). Researchers wanted to know whether the R allele gene variant influenced the numbers of mutations in cell DNA from these cancers. They hope this will help them understand the way these cancers develop.

Cohort studies can show links between factors, but they cannot show whether one factor (in this case, presence of the MC1R R allele) causes another (the number of DNA mutations found in cells).

 

What did the research involve?

Researchers analysed the DNA of tumour samples from 405 people diagnosed with melanoma skin cancer. They checked whether the samples had one or two R allele gene variants, then measured the numbers of DNA mutations from the six main classes of mutation.

The numbers of mutations were compared within the six classes, and overall, and they calculated the size of the difference in terms of how many years of sun exposure they could represent.

Researchers used samples taken from two separate patient groups. For all patients, they were able to adjust figures to take account of people's age, sex and where the sample was taken from (the initial tumour or a secondary tumour). For 132 people (one of the groups) they could also take account of factors including which centre the patient had been treated at and clinical characteristics of the tumour.

In addition to the primary research question, the researchers also did some laboratory tests on cell lines, to see whether the R allele variants affected cell activity associated with DNA repair.

 

What were the basic results?

Tumours from people with one or two R allele variants had a 42% higher level of DNA mutations, compared to people without R allele variants (95% confidence interval 15% to 76%).

Importantly, there was little difference in the levels of mutation seen among people with one R allele compared to two R alleles. This might mean that people without the tell-tale ginger hair and freckles associated with two R alleles are at the same skin cancer risk, but without knowing it.

Cell cultures in the laboratory showed reduced DNA repair activity in cells with R allele variants.

 

How did the researchers interpret the results?

Researchers said the increase in one type of DNA mutation found among R allele variant carriers was comparable to what you might see after an additional 21 years of ageing.

They said the finding that one or two R alleles had similar effects on DNA mutations "suggests that the majority of persons with one R allele, who do not have a red hair/sun sensitivity phenotype, may still be highly susceptible to the mutagenic effects of UV light." In other words, even if they don't have red hair or burn easily, sunlight may still influence their DNA to mutate.

However, they warned there are other factors to consider: "It has been suggested that red haired, sun-sensitive individuals are more likely to practice sun avoidance, a factor that confounds ready interpretation of the association between mutation count and number of R alleles".

So if people with red hair are more likely to avoid the sun, people without red hair but with an R allele variant may pick up more DNA mutations because they are exposed to more sun.

 

Conclusion

The study adds more weight to the importance of using sun protection to avoid skin cancer. We already know that people with red hair and freckles who burn easily are at increased risk of skin cancer.

This study suggests other people may also have a higher risk, without knowing it. Taking sensible sun protection measures makes good sense for everyone.

The findings are also useful for researchers, as they add to our understanding about how certain genetic traits affect the development of skin cancer. If DNA repair is reduced in people with some gene variants, sun damage may not be the only thing affecting their chances of getting skin cancer.

The study has limitations due to the type of research. It cannot tell us that these gene variants directly cause skin cancer, although it seems likely they are involved in some way. It's important to remember that not everyone in the study carried these gene variants – around half did not have R alleles, but they did have skin cancer. So while R alleles may raise the risk of skin cancer, the lack of an R allele gene variant does not mean you won't get it.

It's worth noting that the confidence interval for the increase in DNA mutations is quite wide, making it difficult to be precise about the increased level of mutation. This means the reported "21 years of ageing" comparison might not be accurate.

Whatever your hair colour, eye colour and skin colour, the advice on protecting your skin from the harmful effects of the sun remains the same.

Links To The Headlines

Hidden red hair gene a skin cancer risk. BBC News, July 12 2016

Scientists closer to understanding why red hair genes increase skin cancer risk. The Guardian, July 12 2016

Beware the silent ginger gene: Even brunettes and blondes can carry 'red-head gene' which is as dangerous to skin as 21 YEARS of sun exposure. Daily Mail, July 13 2016

Millions of 'secret gingers' carry the gene which raises risk of skin cancer. The Daily Telegraph, July 13 2016

People with a ‘hidden’ ginger hair gene are officially more at risk of getting skin cancer. The Sun, July 12 2016

Hidden ginger gene puts 25% at greater risk of skin cancer. The Times, July 13 2016 (subscription required)

Links To Science

Daniela Robles-Espinoz C, Roberts NH, Chen S, et al. Germline MC1R status influences somatic mutation burden in melanoma. Nature Communications. Published online July 12 2016

Categories: NHS Choices

Pregnancy supplements 'don’t help, just take vit D and folic acid'

NHS Choices - Behind the Headlines - Tue, 12/07/2016 - 17:30

"Pregnancy multivitamins are a waste of money because most mothers-to-be do not need them, according to researchers," BBC News reports.

A new report found that only the use of vitamin D and folic acid in pregnancy was supported by the evidence. Whereas expensive multivitamin supplements (often costing around £15 for a month's dose) that combine a wide range of vitamins and supplements, were assessed as being "unlikely to be needed and are an unnecessary expense".

This report summarises a number of systematic reviews and trials on vitamin supplementation in pregnancy. However the report is lacking any explanations of the formal methods used to search and assess the evidence. So we cannot say this is a comprehensive review that assessed all evidence relevant to the use of supplements during pregnancy.

That said, the report chimes with the current official UK advice that women should take 400 micrograms of folic acid each day, from before pregnancy up to 12 weeks, and 10 micrograms of vitamin D daily throughout pregnancy and breastfeeding.

Folic acid is known to reduce the risks of birth defects such as spina bifida and vitamin D may help boost both the mother's and baby's bone and muscle health.
 
Read more about what vitamins and supplements are recommended during pregnancy.

Where did the story come from?

This was a report in the Drug and Therapeutics Bulletin, part of the BMJ publishing group. The article on vitamin supplementation in pregnancy does not specifically state its authors, their affiliations, or any sources of funding.

This report received wide media coverage in the UK. All media stories mention the current recommendations for pregnant women, but none discuss the reliability of the study, which appears to be a non-systematic review.

Some sources carry a quote from Dr Carrie Ruxton, a dietitian and spokeswoman for trade body the Health Supplements Information Service, who says: "Evidence from the national diet and nutrition survey shows that few women eat the right diet … the role of food supplements is simply to combat dietary gaps".

You could make the case that £15 a month would be better spent of buying cheap, healthy food, as an alternative method of plugging those gaps. Read more about healthy eating in pregnancy.

 

What kind of research was this?

This was a non-systematic review which summarised the current UK guidance for vitamin supplementation in pregnancy and the evidence it is based on.

As there are no methods provided in this report, we can't be sure the arguments for or against the current guidelines are a good representation of all available evidence. A systematic review including good quality randomised controlled trials would be the best way to form judgements on whether supplementation is worthwhile, however this may be considered unethical in pregnancy. 

 

What did the research involve?

Researchers reviewed studies looking at vitamin supplementation in pregnancy and assessed these against guidelines in the UK. The supplements of interest were:

  • folic acid
  • vitamin D
  • iron
  • vitamins A/C/E
  • multivitamins

They provide details of UK guidance from the National Institute of Health and Care Excellence (NICE) for folic acid, vitamin D and vitamin A, however no guidance is given for the other supplements.

The researchers give a summary of their findings for each of the supplements, indicating whether they were based on trial or observational data and the number of people included in the analysis.

The authors did not describe their study inclusion and exclusion criteria, or clearly set out methods. For example, they did not give information on which literature databases they searched, the search dates, search terms, or a description of how studies were quality-assessed and considered for inclusion. 

 

What were the basic results?

NICE recommends women should take 400 micrograms of folic acid each day, from before pregnancy until the end of the first trimester (first 12 weeks), and 10 micrograms of vitamin D daily throughout pregnancy and while breastfeeding. No other supplements are recommended for routine use.

The researchers' findings confirmed NICE recommendations:

  • Folic acid (400 micrograms) should be taken when trying to conceive and for the first 12 weeks of pregnancy to protect against neural tube defects (NTD), such as spina bifida, in babies. A higher dose of 5 milligrams is suggested for women at higher risk of NTD (e.g. a previous baby with NTD or family history). A systematic review including 6,708 births found that folate reduced risk of neural tube defects (risk ratio (RR) 0.31, 95% confidence interval (CI) 0.17 to 0.58).
  • Vitamin D (10 micrograms) is recommended throughout pregnancy and breastfeeding. It is thought this helps the baby's bone formation. A number of systematic reviews were reported by the authors, those based on trial data found that a higher concentration of vitamin D was found in the umbilical cord samples of those taking supplements. Some systematic reviews of observational studies have found a possible link between low vitamin D levels and pregnancy or type 2 diabetes, but this link may have been due to confounding. Others have found inconsistent or no effects on other outcomes such as pre-eclampsia, preterm birth or low birthweight baby. 
  • There is no evidence to suggest a need for vitamin supplementation in well nourished women. Vitamin A supplementation should be avoided during pregnancy as it may cause birth defects. Systematic reviews of vitamin C and E have found no evidence of a benefit in the mother or baby. Studies of multivitamins have mostly been carried out in low income countries and so the results can't easily be applied to the UK.
  • There is also no evidence for routine iron supplementation in all pregnant women as this may cause stomach irritation and constipation or diarrhoea. Pregnant women with low haemoglobin levels need to be investigated and treated as indicated.

 

How did the researchers interpret the results?

The researchers summarise their findings, saying: "Of the supplements routinely offered to pregnant women in the UK, folic acid has the strongest evidence base".

They go on to say: "the evidence for vitamin D supplementation for all pregnant women is less clear cut, with little randomised controlled trial evidence supporting an effect on clinical outcomes. Nevertheless, a dose of 10µg vitamin D daily is recommended throughout pregnancy and breastfeeding (with a higher dose suggested for some women). For other vitamin supplements, the evidence does not show clear benefit for clinical outcomes for most women who are well nourished. Women should also be advised to avoid taking vitamin A supplements during pregnancy."

They concluded by saying that the primary focus should be on promoting a healthy diet and improving the use of folic acid supplements, which have a poor uptake, particularly among those from lower income families.

 

Conclusion

This report aimed to assess the current UK guidance for vitamin supplementation in pregnancy and the evidence on which it is based.

Overall the findings are in line with the current recommendations. However, this study cannot be assumed to be a comprehensive systematic review on the effectiveness and safety of vitamins during pregnancy.  There is lack of detail on any formal methods and we don't know if the researchers assessed all available evidence on the supplements or whether they have cherry picked ones that fit in with the recommendations. 

The researchers suggest a further limitation that many of the studies investigating vitamin supplementation have been carried out in low income countries or among undernourished populations, which does not represent the general population in the UK.

The bottom line here is that the current guideline recommendations have been set for a reason and will have been underpinned by a systematic review and careful appraisal of all relevant research on the issue. This article – though perhaps not systematic – does provide supportive data that those recommendations are doing a good job.

Eating a good, balanced diet during pregnancy, along with folic acid and vitamin D supplements ensures the best possible health for the mother and unborn child.

Read more about diet and the use of supplements during pregnancy.

Links To The Headlines

Pregnancy multivitamins 'are a waste of money'. BBC News, July 12 2016

Pregnant women wasting money on vitamin supplements, study says. The Guardian, July 11 2016

Pregnant women who take vitamins to boost their baby's health 'are wasting their money' as there is no evidence they boost health. Daily Mail, July 12 2016

Multivitamins for pregnant women are a waste of money, say experts. The Daily Telegraph, July 11 2016

Vitamin pills for pregnant women are 'pointless waste of money' say doctors. Daily Mirror, July 11 2016

Links To Science

Drug and Therapeutic Bulletin. Vitamin supplementation in pregnancy. July 2016

Categories: NHS Choices

Thumb sucking and nail biting not key to preventing child allergies

NHS Choices - Behind the Headlines - Mon, 11/07/2016 - 17:30

"Children who suck their thumbs and bite their nails suffer fewer allergies, study finds," The Daily Telegraph reports.

Researchers have reported a link between these common childhood habits and a lower rate of positive allergy tests; with the important exceptions of hay fever and asthma.

The researchers were interested in what is known as the "hygiene hypothesis". The idea that a level of exposure to germs during early childhood may actually be a good thing as it helps "train" the immune system. And a trained immune system may be less likely to mistake harmless substances, such as pollen, as a threat and trigger an allergic reaction.

Thumb sucking and nail biting are plausible candidates for exposing young children to germs in their immediate environment.

This study involved asking the parents of young children about thumb sucking and nail biting behaviours, and then giving the child allergy skin tests from the age of 13 to 32.

Despite the headlines, the results were not that impressive. Overall, the study found 38% of children who sucked their thumb or bit their nails had a skin reaction compared with 49% who didn't have these habits.

The results were quite mixed, with no clear links to the habits individually, to individual allergic substances – and importantly no links at all with asthma or hay fever.

There's no known way to "train" your child's immune system. Probably the best thing is just to encourage regular play as normal – with other children, indoors and outdoors – while making sure they wash their hands regularly.

 

Where did the story come from?

The study was carried out by three researchers from University of Otago in New Zealand, and McMaster University and St Joseph's Healthcare, in Canada. Funding was provided by the New Zealand Health Research Council, and one author was also supported by an Otago Medical Research Foundation-Kellier Charitable Trust Summer Scholarship.

The study was published in the peer-reviewed medical journal Pediatrics on an open-access basis so you can download a PDF of the study for free.

The Daily Telegraph and Daily Mail report the findings at face value – that these habits do reduce a child's risk of allergies – without considering the many limitations or the paucity of the reported benefits.

 

What kind of research was this?

This was a cohort study which aimed to see whether parental reports of their child's thumb sucking and nail biting were linked with allergies in adulthood.

The "hygiene hypothesis" is the theory that it's a good thing for children to be exposed to varied microbes because this may reduce their risk of developing allergies. Thumb sucking and nail biting – habits of up to a quarter of young children – could transfer more germs on the hands into the mouth, so the researchers' theory was that these habits could reduce risk of asthma, hay fever and other allergies.

The problem with cohort studies is that they can't prove cause and effect between one exposure and an outcome – especially with subjective reports such as how often a parent reports their child puts their fingers in their mouth.

 

What did the research involve?

This study used data collected as part of The Dunedin Multidisciplinary Health and Development Study – a population-based birth cohort study involving 1,037 children born in the New Zealand city of Dunedin in 1972–73.

Parents were asked about their child's thumb sucking and nail biting habits when they were 5, 7, 9 and 11 years of age. They were asked if the statements "frequently sucks their finger/thumb" or "frequently bites their nails" applied to their child "not at all", "somewhat" or "certainly". Children were considered to suck their thumbs or bite their nails if their parents reported "certainly" at least once.

Sensitivity to allergens was tested by skin prick tests of various allergic substances (including dust mites, grass, animal fur, wool) carried out at 13 and then 32 years of age. Allergic sensitivity was defined as having a reaction to one or more of the tested substances.

Children were considered to have asthma if they "reported a diagnosis of asthma and had compatible symptoms or treatment in the previous 12 months" when aged nine. They were considered to have hay fever if this was reported at age 13 or 32 years.

When looking at the relationship between thumb sucking and nail biting and these various allergies they took account of potential confounders, including:

  • gender
  • whether they were breast fed
  • parental allergies and smoking history
  • socioeconomic status
  • cat or dog ownership
  • how many other children were in the house

 

What were the basic results?

Just under a third of the children (317, 31%) were reported by their parents to "certainly" either suck their thumb or bite their nails. Overall 45% of the children showed a reaction to at least one of the allergic substances aged 13.

However, the prevalence of allergic sensitivity was significantly lower among children with reported thumb sucking or nail biting (38%) compared to those without these habits (49%). The lowest prevalence was among those with both these habits (31%).

Overall, when adjusted for confounders, thumb sucking or nail biting were linked with over a third reduced odds of having an allergic sensitivity at age 13 (odds ratio (OR) 0.64, 95% confidence interval (CI) 0.45 to 0.91) and age 32 (OR 0.62, 95% CI 0.45 to 0.86).

However, while links were significant for either habit, when looking at each habit alone they remained significant for thumb sucking, but not for nail biting, at age 13. At age 32, there was no link with either habit individually.

When looking at specific allergic substances, rather than all of them together, links were only significant for house dust mite age 32, not for any specific substances at 13, or any others age 32.

There were no links between thumb sucking or nail biting and asthma or hay fever at any age.

 

How did the researchers interpret the results?

The researchers conclude: "Children who suck their thumbs or bite their nails are less likely to have atopic sensitization in childhood and adulthood."

 

Conclusion

This study does not provide good evidence that thumb sucking or nail biting have any effect on a child's likelihood of developing allergies.

Overall the results give a mixed picture. Although children who sucked their thumb or bit their nails were slightly less likely to have a reaction to the skin tests, when the habits were looked at individually only thumb sucking was linked to a skin test reaction at 13 – and neither habit individually for skin tests at 32.

There were also no clear links for any specific allergic reaction – and no links at all with reported asthma or hay fever. So this doesn't give a clear answer of whether these habits are linked with allergy risk or not.

Further important limitations include:

  • The subjective nature of the parental reports. Parents were asked whether their child "not at all", "somewhat" or "certainly" sucked their thumb or bit their nails. The researchers then compared children for whom the parents replied "certainly" with the other children. However, there is likely to be a wide range and frequency of habits among children for whom parents give the different responses. For example, a child who sucked their thumb every now and again – some parents could call this "somewhat" while others could say "certainly" because they see them do it.
  • The skin tests may indicate sensitivity but it's difficult to tell from this how much the individual child would be affected by allergies. Links with actual diagnosis of asthma or hay fever would have been more notable findings – though even then, it could be questioned whether the children meeting the study definition of asthma at age nine actually had a medically-confirmed diagnosis. Eczema is another notable exception of an allergy that was not examined in this study.
  • Even though the researchers tried to take account of various potential confounders, it is difficult to prove direct cause and effect between the habit and allergy because other health, lifestyle and environmental factors could still be having an influence.
  • The study was conducted in a population of children born more than 40 years ago. Health, lifestyle, environmental factors and medical care could also have changed considerably over this time meaning these results can't be applied to children today.
  • Also when considering generalisability – this was a sample from a single New Zealand city. Environmental factors and allergy prevalence may also be considerably different there compared to the UK.

Thumb sucking or nail biting are common childhood habits. Most children grow out of them and they are only usually considered a problem requiring treatment if they persist once a child has started school.  

Links To The Headlines

Children who suck their thumbs and bite their nails suffer fewer allergies, study finds. The Daily Telegraph, July 11 2016

Children who bite their nails or suck their thumb cut their risk of developing an allergy as an adult by a fifth. Daily Mail, July 11 2016

Thumb-suckers and nail-biters have fewer allergies. BBC News, July 11 2016 

Links To Science

Lynch SL, Sears MR, Hancox RJ. Thumb-Sucking, Nail-Biting, and Atopic Sensitization, Asthma, and Hay Fever. Pediatrics. Published online July 11 2016

Categories: NHS Choices

Could an obscure type of herpes virus trigger female infertility?

NHS Choices - Behind the Headlines - Fri, 08/07/2016 - 17:30

"Obscure virus may be cause of unexplained infertility," The Independent reports.

Italian researchers found copies of the HHV-6A virus – a type of herpes virus – in the womb lining of 43% of women with unexplained infertility compared to 0% in women with a history of successful pregnancy.

This small study analysed cells from the womb linings of 30 women with unexplained infertility and 36 women who'd had one successful pregnancy. Researchers found the HHV-6A virus in cells from almost half the women with unexplained infertility but none of the women who'd had babies had the HHV-6A virus.

There was also some difference in their levels of certain immune system molecules, which the researchers suggest could affect the ability to sustain a pregnancy – but this is only speculation.

Most people are infected with HHV-6 viruses in early childhood. These viruses (there's an A and B type), cause a usually mild childhood rash called roseola. Like other herpes viruses, they then live in the body and remain inactive for many years. However, reactivated forms of the virus have been linked by different researchers, in recent years, to more than 50 different conditions, ranging from amnesia to uveitis. Its impact on health outcomes remains uncertain. 

Ultimately, this is very early-stage research that leaves many questions unanswered and further studies are needed to find out whether HHV-6A really is a cause of infertility, and if so, whether treating the virus with antivirals would improve the chances of a successful conception.

 

Where did the story come from?

The study was carried out by researchers from the University of Geneva, University of Ferrara and Human Reproduction Centre Brunico Hospital and was funded by Regione Emila Romagna.

The study was published in the peer-reviewed journal PLOS One, an open-access journal, and is free to read online.

The Independent provides the most accurate summary of the study. Other news sources don't do as well.

The Mail Online's story, while basically accurate, may raise hopes of a cure before the cause of unexplained fertility is established.

The Times says: "Almost half of women with unexplained fertility problems are infected with a mysterious virus," although we don't know whether the proportion of women found to have HHV-6A infection in this small study would hold true of all women with unexplained infertility.

The Daily Telegraph has a bizarre headline which urges people to "Be careful who you kiss," on the basis that the virus may be passed on by saliva, despite the fact that most people are infected as toddlers.

The Telegraph's story also says unexplained primary infertility means "the inability ever to bear a child", when it actually means that a woman has been unable to become pregnant after one year or more of trying, without any obvious cause.

 

What kind of research was this?

This was an Italian cohort study, in which researchers took cells from the womb linings of women with and without infertility to look for DNA from HHV-6 viruses. HHV-6 (human herpes virus 6) is a virus that most people are infected with in childhood and then lies dormant in the body. It was discovered in 1986 and little is known about the role it may play in regards to human health.

Reactivation of the virus has been associated with various diseases, including immune and inflammatory conditions. Previous research has suggested the female genital and reproductive system could be a site for the virus to become reactivated and this was the basis for this research.

Cohort studies can show differences between groups, and links between one factor (in this case viral infection) and another (infertility) but they cannot prove that one causes the other.

 

What did the research involve?

The research involved analyzing womb samples taken from 30 women who'd attended a clinic for infertility treatment, for whom no obvious cause of infertility had been found. These women were reportedly taking part in a randomised trial, though no further information on this is given. They were compared with another group of 36 women who'd had at least one child, who were within the same age range. The recruitment of the control cohort, or why they had womb samples taken, is unclear. 

They took samples of cells from the womb lining of each woman, during the same phase of the menstrual period. They analysed cells for the presence of HHV-6A and the linked HHV-6B virus, both in the cells and in the blood supply.

In further studies, researchers looked at how the cells infected with HHV-6A behaved and whether this was different from cells not infected with HHV-6A. They also looked at other factors such as hormone levels.

 

What were the basic results?

The researchers found:

  • similar numbers of women with and without infertility had HHV-6B DNA in their blood cells (8 infertile, 10 fertile)
  • no women with or without infertility had HHV-6B DNA in their womb lining cells
  • no women with or without infertility had HHV-6A DNA in their blood
  • 13 women (43%) with infertility had HHV-6A DNA in womb lining cells compared to none without infertility

In further research, they found that women with HHV-6A DNA in womb lining cells also had higher levels of one type of reproductive hormone (estradiol), and different levels of certain immune system signalling molecules compared to women without HHV-6A DNA, both in infertile and fertile women. 

 

How did the researchers interpret the results?

The researchers say: "further studies are required to confirm the association," but "our study indicates that HHV-6A infection might be an important factor in female primary unexplained infertility."

They suggest the reactivated virus in the womb might trigger changes to the immune system that promote "a dysfunctional uterine environment," or in other words, conditions in the womb that are unsuitable for pregnancy.

 

Conclusion

Unexplained infertility causes distress for thousands of couples trying for a baby. It can be hard to accept that doctors can find no reason for a couple's inability to get pregnant, and many couples spend a lot of time and money trying fertility treatments.

Finding a potential cause for unexplained infertility could raise a lot of people's hopes. This study has interesting results, but it was very small and needs to be replicated on a larger scale to be sure the results hold true. We also need to remember that this study cannot show causation – it can't tell us whether the virus is a cause of infertility, only that it seems to be more common in women with infertility not otherwise explained.

Having said that, these women had unexplained infertility and there is still a lot that we don't know about them. The researchers say that they didn't have endometriosis, any problems with ovulation or any structural abnormalities of the reproductive system.

However, we don't know any more than that, such as exploration of male factors for infertility, how long the woman/couple had been trying to conceive, prior miscarriages, or the success of future fertility treatment. We also know nothing about the control group – such as how they were recruited or why womb samples were taken – other than that they'd had a baby. They may have had problems conceiving themselves for all we know.

Overall, it can't be said that the women with infertility problems and HHV-6A would necessarily be less likely to become pregnant or have a successful outcome from assisted reproduction.

Even if we did find out that HHV-6A was responsible for some cases of infertility, that is not the same as being able to cure the condition. A range of antiviral drugs have been used to treat other conditions linked to HHV-6A reactivation, but none have been developed specifically for this virus and we don't know if they would be helpful in treating infertility.

Sadly, a lot more research is needed before we know whether half of unexplained infertility, as claimed by some news sources, could be treated by targeting this virus.  

Links To The Headlines

Obscure virus may be cause of unexplained infertility. The Independent, July 7 2016

Is this why some women are infertile? Chicken pox-style virus that lurks in the womb 'may be to blame'. Mail Online, July 7 2016

Careful who you kiss: virus found in saliva associated with unexplained infertility. The Daily Telegraph, July 7 2016

Mysterious virus found in half of infertile women. The Times, July 8 2016 (subscription required)

Links To Science

Marci R, Gentili V, Bortolotti D, et al. Presence of HHV-6A in Endometrial Epithelial Cells from Women with Primary Unexplained Infertility. PLOS One. Published online July 1 2016

Categories: NHS Choices

1 in 8 advanced prostate cancers may be linked to faulty genes

NHS Choices - Behind the Headlines - Fri, 08/07/2016 - 12:28

"Nearly one in eight men who develop [advanced] prostate cancer carry mutations in genes which repair damage to DNA," The Daily Telegraph reports.

One of the difficulties in detecting and treating prostate cancer is that some cancers spread rapidly around the body (metastatic cancers) causing illness and death, while others grow very slowly within the prostate (localised cancers) and may never cause problems. There is currently no reliable test for showing which type of prostate cancer a man will get.

This study found that mutations in 16 genes linked to DNA repair were more common among 692 men with metastatic cancer compared to those with localised prostate cancer. This could suggest a way forward for treatment as scientists already know that men with metastatic prostate cancer and DNA repair gene mutations respond well to certain types of cancer therapy.

Research we discussed in 2015 suggests that a type of drug called olaparib, licensed for the use of ovarian cancer, may also help slow the progress of these types of gene-associated prostate cancers.

The researchers further suggest that, because DNA repair genes tend to run in families, causing breast, ovarian and pancreatic cancers as well as prostate cancer, a test might also enable men's relatives to know their own risk.

However, screening is another issue that would warrant careful consideration of the possible benefits and harms.        

Where did the story come from?

The study was carried out by researchers from the University of Washington, Fred Hutchinson Cancer Research Center, Institute of Cancer Research and Royal Marsden Hospital, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College, Prostate Cancer Clinical Trials Consortium, University of Michigan, Howard Hughes Medical Institute and Dana–Farber Cancer Institute.

Funding was provided by grants from institutions including Stand Up To Cancer, US National Institutes for Health and Department of Defense and Prostate Cancer UK.

Some of the authors reported commercial relationships with a number of pharmaceutical companies which manufacture prostate cancer drugs.

The study was published in the peer-reviewed New England Medical Journal. 

Much of the UK media seemed to miss the point of the story – that mutated DNA repair genes, including BRCA1 and BRCA2, are more common among men with advanced (metastatic) prostate cancer than localised prostate cancer.

The Daily Telegraph said that "nearly one in eight men who develop prostate cancer" carry mutations to DNA repair genes, which is not correct. The figure refers only to men in the study with metastatic cancer – men with localised cancer had a much lower rate of DNA repair gene mutation, at 4.6%. The Daily Mail made the same error, saying the "faulty BRCA2 gene is linked to 1 in 20 cases of the disease in men," without explaining that this referred only to metastatic cancer.

BBC News correctly identified the figures as relating only to metastatic prostate cancer and explained the significance of the study.

The distinction is important as sometimes localised prostate cancer is slow-growing so it does not pose an immediate threat to health (in some cases, no threat at all). This means the treatment plan is entirely different than for metastatic prostate cancer.

 

What kind of research was this?

This was a case series study, in which researchers analysed the DNA of 692 men with metastatic prostate cancer (advanced cancer that's spread to other parts of the body). They wanted to see how common it was for these men to have mutations in one of the genes known to be important for DNA repair, and then compare this to men with localised forms of the disease.

This type of study is useful to find how common something is within a specific group, but it is not a reliable way of comparing groups, because we don't know if there are factors affecting the other groups that might skew the results. Also, it can't tell us whether something (in this case a gene mutation) directly and independently causes something else (prostate cancer); only how many people with prostate cancer have a gene mutation.

 

What did the research involve?

Researchers analysed DNA from saliva or blood taken from 692 men who had been diagnosed with metastatic prostate cancer, from seven hospitals in the UK and US. Their DNA was analysed to check for the presence of variants among 20 genes known to affect DNA repair.

They compared their results to data from other studies of men with localised prostate cancer, and to databases of people not diagnosed with any cancer, to see whether these mutations were more common in men with metastatic cancer.

The men studied were not selected on any grounds other than their diagnosis – for example, their age, family history or initial prostate cancer risk score – because the researchers wanted to get an overview of how big a role gene mutations played in all metastatic prostate cancer. However, they went on to look at whether these factors affected the likelihood of having a gene mutation. 

The groups used for comparison of genetic data were:

  • a study of 499 men with prostate cancer that had not spread from the prostate
  • a database of 53,105 people without a cancer diagnosis

Researchers analysed the data for likelihood of having any mutation among the 20 genes studied, for mutations of specific genes, and for external factors that might have affected the results.

 

What were the basic results?

Of the 692 men with metastatic prostate cancer:

  • 82 (11.8%) had at least one mutation in a DNA repair gene.
  • 37 (44% of all mutations, 5.3% of the sample) had a BRCA2 gene mutation (a mutation also linked to breast and ovarian cancer in women).
  • 15 other gene mutations were identified, but these were less prevalent (including BRACA1, 6 men, 7% of all mutations, 1% of the sample). 
  • There was no difference between the numbers of men with and without DNA repair gene mutations who had a close relative with prostate cancer (22% for both groups). But 71% of men with these mutations had a close relative with another type of cancer, compared to 50% of men without these mutations.
  • Age at diagnosis did not affect the chances of having DNA repair gene mutations.
  • Men with a DNA repair gene mutation tended to have a higher prostate cancer risk score at diagnosis, but the numbers were too small to be sure of this result.

Comparing with other groups, 4.6% of men in the localised prostate cancer study had a DNA repair gene mutation, and 2.7% of people without a known cancer diagnosis.

The chances of having a DNA repair gene mutation were five times higher among men with metastatic prostate cancer, compared to people without cancer (odds ratio 5.0, 95% confidence interval 3.9 to 6.3).

 

How did the researchers interpret the results?

The researchers said their findings have "several important clinical implications." They say that their findings of higher levels of DNA repair mutations among men with metastatic prostate cancer provides a "clear treatment pathway in accordance with precision medicine strategies," because men with metastatic cancer and these mutations can be treated with specific treatments.

They also say that identifying these gene mutations provides useful information for male and female relatives, who can be counselled about their own cancer risk.

 

Conclusion

Much of modern cancer treatment is aimed at finding the right treatment for the right person, and this type of genetic research may help doctors to target treatments at the people who are most likely to benefit from them.

It's not news that mutations in DNA repair genes like BRCA2 are linked to an increased risk of prostate cancer, although we are still some way from understanding how that link works. But the finding that these mutations seem to be much more common in men whose cancer has spread around the body is interesting.

Doctors have long wanted a test that could identify which prostate cancers are more likely to spread, and this genetic test could potentially add to the information that helps pinpoint that risk.

A class of medication known as poly ADP ribose polymerase (PARP) inhibitors has proved useful in treating other types of cancer associated with mutations in DNA repair genes. Further research to explore this avenue of potential treatment would be useful.

The study has important limitations. Different methods of DNA analysis were used in different hospitals, which might have affected the results. More importantly, there was no direct comparison group, so researchers were unable to balance or match men with metastatic cancer with men with localised prostate cancer of the same age or with the same family history, to get an unbiased comparison between the two groups.

The study used to compare rates of gene mutations in men with localised prostate cancer included mainly men with higher risk cancers, which means it may not be representative of all men with localised prostate cancer. This would affect the usefulness of the gene test in spotting men with cancer likely to spread.

The researchers' call for men with prostate cancer to be tested so their relatives can then be counselled about their risk of cancer raises questions. Not all people with DNA repair gene mutations like BRCA1 and BRCA2 go on to get cancer, although the mutations do raise the risk of cancer.

Wider testing could put people into a position where they had to decide whether to take drastic preventive action (as actress Angelina Jolie famously chose to do by having her breasts and ovaries removed) or live with the risk.

Links To The Headlines

Genes which raise risk of prostate cancer discovered by scientists. The Daily Telegraph, July 6 2016

Prostate cancer: Test for inherited risk. BBC News, July 6 2016

'Angelina Jolie gene' may also cause prostate cancer: Faulty BRCA2 is linked to 1 in 20 cases of the disease in men. Daily Mail, July 7 2016

'Angelina Jolie' gene which triggers breast cancer may also cause prostate cancer. Daily Mirror, June 6 2016

DNA test to identify best prostate cancer treatment. The Times, July 7 2016 (subscription required)

Links To Science

Pritchard CC, Mateo J, Walsh MF, et al. Inherited DNA-Repair Gene Mutations in Men with Metastatic Prostate Cancer. The New England Journal of Medicine. Published online July 6 2016

Categories: NHS Choices

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