NHS Choices

Cancer treatment response may be affected by gut bacteria

NHS Choices - Behind the Headlines -

"Gut bacteria 'boost' cancer therapy," BBC News reports.

The news comes from research into whether people with cancer might respond differently to cancer treatment depending on the bacteria in their gut.

Researchers specifically looked at a type of cancer treatment called immunotherapy.

This involves stimulating the immune system to attack cancerous cells – in this case, by using specially engineered antibodies known as monoclonal antibodies.

Some people respond better to this treatment than others. The researchers wanted to see if the make-up of gut bacteria influenced the outcome of treatment.

The study involved looking at the gut bacteria of 249 people who'd received immunotherapy for different types of cancer, some of whom had also taken antibiotics.

Researchers found gut bacteria differed between people who responded well to immunotherapy and those who didn't.

People who had a positive response tended to have more of a bacteria called Akkermansia muciniphilia.

Transplanting gut bacteria from these people into mice with tumours seemed to improve cancer outcomes in the mice.

The researchers also observed that both people and mice with cancer who'd been given antibiotics tended to have poorer cancer outcomes.

But this research is in its very early stages and the reasons behind these observations are unknown.

We're a long way from being able to say categorically that our gut bacteria directly affect how we respond to treatments, or whether altering the gut bacteria could boost people's responses to immunotherapy.

 

Where did the story come from?

The study was carried out by researchers from a number of research institutions in France, including Gustave Roussy Cancer Campus, Nationale contre le Cancer, Université Paris-Sud and Université Paris-Saclay, as well as the Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College in the US, and Karolinska University Hospital in Sweden.

The researchers were funded by grants from a range of organisations.

The study was published in the peer-reviewed journal Science.

The story was covered well by BBC News, with accurate reporting of the details of the research and appropriate cautions from experts about how we interpret the results.

 

What kind of research was this?

The research involved several studies, including laboratory experiments, that aimed to see whether bacteria present in the gut may affect how people respond to certain types of cancer treatment.

Treatments that target aspects of the immune system, such as specially engineered antibodies know as monoclonal antibodies, can be effective for certain types of cancer, including advanced malignant melanoma or lung cancer.

But the cancers are resistant to these treatments in around two-thirds of people.

Recent animal studies suggest gut bacteria may influence how tumours respond to immunotherapy treatment.

The researchers wanted to see whether gut imbalance as a result of cancer or antibiotic use could affect how people respond to treatment.

They looked at mice with tumours and whether giving antibiotics to people with cancer affected their response to cancer treatment.

These are only very early-stage studies, so there aren't any definitive answers at this stage.

 

What did the research involve?

The researchers first tested how effective 2 types of immunotherapy were in mice with either sarcoma (cancers of bone, muscle and connective tissue) or melanoma (aggressive skin cancer). Some of the mice were also given antibiotics.

They then looked at 249 people with an advanced form of the most common type of lung cancer (non-small cell), cancer of the kidney (renal cell), or cancer of the bladder or ureters (urothelial carcinoma).

The researchers noted whether people had received antibiotics (for example, for a dental infection) either 2 months before or 1 month after starting immunotherapy, and whether this affected their response to immunotherapy.

The researchers then looked at the specific microbes found in the guts of 100 of the people in the study using DNA sequencing.

They also looked at whether mice treated with antibiotics could have an improved response to immunotherapy if they received a stool transplant from people in the study.

 

What were the basic results?

The results of the different studies were as follows:

  • Mice with melanoma or sarcoma that were treated with antibiotics were less likely to survive after immunotherapy compared with those who weren't treated with antibiotics.
  • People who took antibiotics around the time they started immunotherapy had less positive outcomes from their cancer treatment than those who didn't take antibiotics (lower rates of overall survival and lower rates of survival without cancer progression).
  • People who responded well to treatment were more likely to have a particular bacteria called Akkermansia muciniphila in their gut.
  • Mice given stool transplants from people who responded well to immunotherapy had slower-growing tumours than those who had transplants from people who had a poor response.

 

How did the researchers interpret the results?

The researchers concluded the study showed that gut microbes impacted the response people had to cancer treatment.

They acknowledged, however, it wasn't clear exactly how the microbes influenced people's responses to treatment with immunotherapy with monoclonal antibodies.

 

Conclusion

This early-stage study gives us some insights into factors that might influence people's responses to a specific type of cancer treatment (immunotherapy with monoclonal antibodies).

The findings are of interest, but don't have any immediate implications for cancer treatment.

  • We don't know what the conditions that required antibiotic treatment were and whether these could have affected the response to immunotherapy.
  • We don't know whether the antibiotics themselves influenced how well the immunotherapy worked, or whether it was their effect on gut bacteria.
  • We also don't know whether having high levels of particular bacteria improves people's responses to immunotherapy, or whether the immunotherapy somehow influences the levels of specific bacteria.
  • It's unclear whether the findings are more relevant to certain cancers or specific immunotherapies or antibiotic types, or if they're influenced by other patient characteristics.

Further research first needs to clarify whether the gut bacteria directly influences people's responses to immunotherapy, and exactly how this happens.

The next step would be to investigate whether treatment to change the gut bacteria could improve people's responses to cancer treatment.

Overall, it's likely to be some time before we see whether this early study eventually leads to any changes in the way immunotherapy is given.

These findings shouldn't cause any concern for people with cancer who need to take antibiotics.

The risk of not taking the antibiotics you need to treat an infection is likely to be far greater than any potential effect the medicines may have on the cancer or how you respond to treatment.

Links To The Headlines

Gut bacteria 'boost' cancer therapy. BBC News, November 3 2017

Links To Science

Routy B, Le Chatelier E, Derosa L, et al. Gut microbiome influences efficacy of PD-1–based immunotherapy against epithelial tumors. Science. Published online November 2 2017

Could a blood test in middle age predict dementia risk?

NHS Choices - Behind the Headlines -

"Tissue inflammation blood test points to dementia risk," is the headline in The Times.

Researchers in the US say people who have higher measures of inflammation in middle age are likely to have less brain tissue in some parts of their brain in older age.

The differences in brain volume, seen on MRI scans, were also accompanied by small differences in performance on memory tests.

But the study didn't find that people with raised inflammatory measures in middle age were more likely to get dementia, as it wasn't set up to directly measure dementia risk.

Previous research found people with dementia and a smaller brain volume are likely to have higher measures of substances linked to inflammation in their blood.

But it wasn't clear whether the inflammation happened before the dementia, or afterwards.

The association is further complicated by the fact it's normal for people's brains to experience some shrinkage as they get older. And, obviously, not everyone gets dementia as they get older.

While the study is certainly interesting, it doesn't provide any concrete answers.

For example, we don't know how people's inflammatory measures changed over time, or what role factors other than inflammation may have had.

There are steps you can take to reduce your risk of dementia, although these aren't guarantees.

This includes eating a healthy diet, maintaining a healthy weight, exercising regularly, moderating how much alcohol you drink, and quitting smoking if you smoke.

Where did the story come from?

The researchers came from the Johns Hopkins School of Medicine, the Baylor College of Medicine, the University of Minnesota, the Mayo Clinic, and the University of Mississippi Medical Centre, all in the US.

The study was funded by the US National Heart, Lung and Blood Institute, and was published in the peer-reviewed journal Neurology.

The Times and the Mail Online covered the study in reasonably balanced and accurate stories.

Both made it clear in the article (although not in The Times' headline) that the study didn't show a cause and effect relationship between inflammation and dementia.

What kind of research was this?

This was a prospective cohort study.

These types of observational study are good for spotting links between factors – in this case, inflammation and brain volume – but can't prove that one factor causes another.

What did the research involve?

Researchers recruited more than 15,000 people aged 45 to 65 for an ongoing study principally intended to look at heart disease risk.

As part of the study, they measured 5 substances linked to inflammation in the participants' blood when they were aged 53 on average.

Twenty-four years later, they selected 1,978 participants to have their brain volume measured by MRI scan and take a word recall memory test.

They then looked at whether higher inflammatory measures were linked to brain volume and memory test performance.

The researchers specifically sought to find out whether age, sex or race might have affected the results, as these have already been linked to dementia risk.

The 5 substances chosen as markers of inflammation were:

  • fibrinogen
  • albumin
  • von Willebrand factor
  • factor VIII
  • white blood cell count

Most of these are linked to blood clotting or the body's response to infection.

The researchers combined people's scores to give an overall inflammatory marker score.

The memory test involved listening to a list of 10 words and recalling as many as possible after a short delay.

The MRI scans looked at total brain volume, as well as analysing specific areas of the brain known to be affected by Alzheimer's disease (AD), such as the hippocampus.

What were the basic results?

People who had higher total inflammatory marker scores in middle age (the average age was 53 at the start of the study) were more likely to have a smaller brain volume in certain areas at the end of the study.

These were:

  • hippocampal volume – the hippocampus is an area of the brain that helps regulate memory
  • occipital volume – the occipital lobe is an area of the brain responsible for visual processing
  • AD signature region volume – an area of the brain previously thought to be smaller in people with Alzheimer's disease; it consists mainly of the cerebrum, which is responsible for higher brain functions

But the people involved in the study did have larger volumes in ventricular parts of the brain (these are cavities in the brain filled with fluid).

Compared with people who didn't have raised levels of any inflammatory markers at the start of the study, those with raised levels on 3 or more markers had smaller hippocampal (4.6% smaller), occipital lobe (5.7% smaller) and AD signature region (5.3% smaller) volumes.

They also did very slightly worse on the memory test, remembering on average 5 words out of 10, compared with 5.5 words for those without inflammatory markers.

The researchers didn't see any link between total brain volume and inflammatory markers.

The association between inflammatory markers and brain volume was stronger in people who had higher markers of inflammation at a younger age, and was weaker in African American participants. There were no differences between the sexes.

How did the researchers interpret the results?

The researchers said their findings "provide support" for an early role for inflammation "in the development of neurodegenerative brain changes associated with late-life cognitive decline, AD [Alzheimer's disease] and other forms of dementia".

Conclusion

Inflammation in the body is a response to injury or disease. But if the body is constantly in an inflammatory state, it can harm blood vessels and lead to heart disease.

This study suggests high levels of inflammation over the long term might also damage the brain.

That's not surprising – what's good for the heart is usually good for the brain, and we already know exercising, avoiding high blood pressure and eating healthily may help protect the brain.

Studies like this will help researchers work out more precisely what's happening in the brain when people experience memory loss or dementia.

But this study has some limitations.

The first and most important is that researchers didn't measure people's brain volume at the start of the study.

This means we don't know whether the results at the end of the study end represent brain shrinkage, or whether some people had always had smaller brain volume in certain areas.

This makes it harder to be sure that differences in inflammatory markers predated the differences in brain volume. This type of study design can't prove cause and effect – and in this case, it can't prove that one situation predated another.

Also, the substances measured may not be very precise measures of inflammation – they're also involved in other physiological processes.

And the study didn't look at whether people with higher inflammatory markers were more likely to get dementia, only at their brain volume and performance in one type of memory test.

We don't know the effect of the smaller brain volume in some areas on those people. The different performance on the memory test was also pretty small.

All in all, it's far too early to say we could ever have a blood test that accurately predicts dementia risk.

Links To The Headlines

Tissue inflammation blood test points to dementia risk. The Times (subscription required), November 2 2017

Inflammation in midlife linked to brain shrinkage later. Mail Online, November 1 2017

Links To Science

Walker KA, Hoogeveen RC, Folsom AR, et al. Midlife systemic inflammatory markers are associated with late-life brain volume. Neurology. Published online November 1 2017

Acid reflux drugs linked to increased stomach cancer risk

NHS Choices - Behind the Headlines -

"A drug commonly used to treat acid reflux is linked to a more than doubled risk of developing stomach cancer," reports The Guardian.

Researchers wanted to investigate whether there's a link between medicines known as proton pump inhibitors (PPIs) and stomach cancer. Widely used PPIs include esomeprazole, lansoprazole, omeprazole, pantoprazole and rabeprazole.

PPIs are used to treat acid reflux and protect the stomach lining, have been linked to stomach cancer before.

But they're also used to treat H. pylori, a bacterial infection that can also cause reflux-like symptoms and is known to raise the risk of stomach cancer. This somewhat complicates the picture.

Researchers from Hong Kong studied 63,397 people who'd been treated for stomach infection with H. pylori bacteria.

Even after the bacteria had been killed, those who took PPIs on a long-term basis were more likely to be diagnosed with stomach cancer in the following 7 to 8 years of follow-up.

Because of the study design, we can't tell if PPIs were the cause of the increased stomach cancer risk. It could also have been down to other factors.

It's important to keep the results in proportion. Long-term use of PPIs was linked to around 4 additional stomach cancers cases per 10,000 people per year.

PPIs are one of the most widely prescribed types of drug. But people who use them shouldn't be particularly concerned by this study: an increase in a very small risk is still a very small risk.

 

Where did the story come from?

The study, published in the peer-reviewed journal Gut, was done by researchers from the University of Hong Kong and University College London. No information about funding was included.

Most of the UK media reports seized on the higher risk figures reported in the study, which applied only to people taking PPIs daily for at least 3 years.

The headlines should have made it clear that while the results suggested a statistically significant increase in risk, this doesn't always translate into a clinically significant increase.

But most articles also included expert comments stating that the absolute risk of cancer was low and the study doesn't prove PPIs are the cause of the risk.

 

What kind of research was this?

This population-based cohort study is a good type of study for looking for links between factors (such as PPIs and stomach cancer), but can't prove that one factor causes the other.

 

What did the research involve?

Researchers identified everyone who'd had successful treatment for H. pylori infection in a Hong Kong database, and followed them for an average of 7 years.

Successful treatment (eradication) is often known as triple therapy, as it involves taking 3 different antibiotics in combination.

The researchers looked at who used PPIs after H. pylori treatment, and who got stomach cancer.

After adjusting their figures to take account of possible confounding factors, they looked at whether people taking PPIs were more likely to get stomach cancer.

The researchers also identified a cohort of 142,460 people taking PPIs who didn't receive triple therapy treatment for H. pylori.
PPIs are used to treat stomach discomfort caused by acid reflux, which could mean that people start taking them because they already have symptoms of stomach cancer.

To avoid overestimating the effect of PPIs, researchers excluded people who'd been prescribed PPIs in the 6 months before a diagnosis of stomach cancer.

Researchers adjusted for age, sex and other illnesses, but were unable to adjust for diet, family history of cancer, and socio-economic status – or adjust properly for alcohol or tobacco use and obesity – because these factors weren't routinely recorded in the database.

 

What were the basic results?

In total, 153 of the 63,397 people in the study got stomach cancer (0.24% of the total):

Those who had a history of successful treatment for H. pylori and used PPIs at least weekly were more likely to be diagnosed with stomach cancer. This group of people had a more than twofold, or 244%, increase in chances of stomach cancer (adjusted hazard ratio [aHR] 2.44, 95% confidence interval [CI] 1.42 to 4.20).

There was no increase in risk for those taking H2RAs (a different type of reflux medication).

The increased risk with PPIs amounted to 4.29 additional cancers per 10,000 people per year (95% CI 1.25 to 9.54).

The risk was higher for people taking them long term and daily – an eightfold, or 834%, increase in risk (HR 8.34, 95% CI 2.02 to 34.1).

When comparing rates of stomach cancer between people using PPIs who did and didn't have a history of H. pylori treatment:

The incidence of stomach cancer was 1.0 per 10,000 in people without previous treatment, compared with 8.1 per 10,000 in people who had been treated.

 

How did the researchers interpret the results?

The researchers said: "To our knowledge this is the first study to demonstrate that long-term PPI use, even after H. pylori eradication therapy, is still associated with an increased risk of gastric cancer."

They added: "Physicians should therefore exercise caution when prescribing long-term PPIs to these patients."

 

Conclusion

PPIs are commonly used medicines for acid reflux. This may seem like alarming news for the many people in the UK who take them, but it's important to remember that the overall risk of stomach cancer is still very low.

This study has several limitations that mean we should be cautious about the results:

This type of study can't prove PPIs caused the increased risk of cancer. The increased risk could be down to other factors.

Researchers were unable to adjust their figures to take account of some relevant confounding factors, such as alcohol and tobacco use, as these weren't routinely recorded.

Almost all the patients in the study were Chinese. Asians are known to have a higher risk of developing stomach cancer than other populations, so the results may not be applicable to the general UK population.

But PPIs, like most drugs, do have side effects. They're not usually intended to be taken long term.

If you're taking them regularly, it may be worth discussing with your doctor whether you still need to. There could be alternative treatments that would be of more benefit.

Links To The Headlines

Acid reflux drug linked to more than doubled risk of stomach cancer – study. The Guardian, October 31 2017

Heartburn pills raise chance of developing stomach cancer by eight times. The Sun, November 1 2017

Over-the-counter and prescription acid reflux pills taken by millions 'raise the risk of stomach cancer by up to eight-fold' if they are used regularly. Mail Online, October 31 2017

Links To Science

Cheung KS. Chan EW, Wong AYS, et al. Long-term proton pump inhibitors and risk of gastric cancer development after treatment for Helicobacter pylori: a population-based study. Gut. Published online October 31 2017

Nutrient drink for Alzheimer's has disappointing result in trial

NHS Choices - Behind the Headlines -

A new study investigating the effects of a nutrient drink for Alzheimer's disease has led to very different headlines in the media. While BBC News tells us the "Alzheimer's nutrient drink falters in clinical trial", the Daily Mirror reports the drink "could help stave off Alzheimer's disease, according to scientists".

The trial investigated the effects of Fortasyn Connect – a patented mix of vitamins and minerals, found in the drink Souvenaid – on memory in individuals showing early signs of Alzheimer's disease.

It was hoped those receiving the drink would experience less memory decline than would usually be expected.

Just over 300 participants were given either Souvenaid or a control drink for two years – both looked and tasted the same, so people didn't know which they had. The main aim was to see whether those who drank Souvenaid had better results across a range of memory tests than those who didn't.

The researchers found no difference in this main outcome, but there were some positives in secondary outcomes: those taking the drink had slightly less brain shrinkage and slightly better cognitive scores. However, there was still no difference in the number of people from each group that went on to develop dementia.

Overall, the study provides no evidence that this drink can prevent or slow the progress of dementia.

Regular exercise, a healthy diet, and avoiding drinking heavily and smoking seem to do more to reduce your dementia risk than any nutrient drinks currently available.

 

Where did the story come from?

The study was carried out by researchers from international institutions in Finland, Germany, the Netherlands, Sweden and the US, and was funded by the European Commission 7th Framework Programme. Many of the researchers involved have worked or are currently working for pharmaceutical companies.

The study was published in the peer-reviewed medical journal The Lancet and is free to read online.

There were split reports in the media on this study, with the Mirror and Mail Online claiming the nutrient drink could "stave off dementia".

Thankfully, BBC News provided a more accurate summary, reporting that the trial found no improvements in memory and thinking.

 

What kind of research was this?

This was a double-blinded randomised controlled trial (RCT) investigating the effects of a nutrient drink on brain function in individuals showing early signs of Alzheimer's disease.

The trial, called LipiDiDiet, investigated the benefits of the drink Souvenaid, which contains the Fortasyn Connect multinutrient mix. Earlier studies suggested the drink was well tolerated and may improve certain aspects of memory but didn't slow brain decline overall.

The first part of the LipiDiDiet trial ran for 12 months. This was followed by an optional extension to 24 months, which is what was reported on here.

Double-blind RCTs like this are one of the most reliable ways of assessing the effects of an intervention, as the study design limits the chance that patient characteristics and other confounders are influencing any links.

 

What did the research involve?

The 24-month LipiDiDiet trial was carried out across 11 different sites. Researchers from memory clinics recruited 311 participants, aged 55 to 85 years, who had been diagnosed with "prodromal Alzheimer's disease". This term describes people who have normal cognitive function (as defined by the Mini-Mental State Examination) but are experiencing some memory problems and have some physical changes to the brain associated with early-stage dementia.

Eligible participants were randomised to receive either a placebo drink or the Fortasyn Connect-containing Souvenaid drink (125ml) once a day. None of the participants or assessors knew which individuals were taking the treatment.

Participants took their drinks home and reported consumption in a daily diary. To ensure compliance, motivation and safety, participants were contacted by phone once a month during the first 6 months of the trial and once every 2 months thereafter.

Individuals were assessed at baseline, 6, 12 and 24 months using a battery of neuropsychological tests (NTB) – which tested several aspects of cognitive performance, including written memory and visual memory recall – as well as brain scans. Individuals visited the study nurse or physician every 3 months in the first year and every 6 months in the second year.

The main outcome of interest was change in NTB score over the 24 months. A significant decline in NTB score is often indicative of worsening Alzheimer's.

Other outcomes measured included cognitive change and brain volume. Blood tests were also used to assess the safety of the product.

 

What were the basic results?

The nutrient drink had no effect on the main outcome (change in NTB) at 24 months. The average score change with Fortasyn Connect was -0.028, compared with -0.108 in the placebo group. This gave a between-group difference of 0.098 (95% confidence interval [CI] -0.041 to 0.237), which was not statistically significant.

With regard to the secondary outcomes, there was slightly less reduction in brain volume in the Fortasyn Connect group versus the control group. Overall clinical dementia scores were also slightly worse in the control group than the Fortasyn Connect group. However, there was no significant difference between the number of participants diagnosed with dementia by 24 months, which was 62 people (41%) in the Fortasyn Connect group and 59 (37%) in the placebo group.

Compliance was reported to be high, and there was no difference between groups in the number of adverse events. No serious adverse effects were thought to be related to the drink.

 

How did the researchers interpret the results?

The researchers said: "The intervention had no significant effect on the NTB primary endpoint over 2 years in prodromal Alzheimer's disease. However, cognitive decline in this population was much lower than expected … group differences on secondary endpoints of disease progression measuring cognition and function [and brain shrinkage] were observed.

"Further study of nutritional approaches with larger sample sizes, longer duration, or a primary endpoint more sensitive in this pre-dementia population, is needed."

 

Conclusion

This trial provides valuable evidence about the effects of a nutrient drink, Souvenaid, on memory in individuals with early signs that they may develop Alzheimer's disease.

Importantly, the researchers found no significant effect on the main outcome their study looked at (memory). They did find less brain shrinkage and slightly better cognitive scores in the experimental group, but this still didn't lead to any reduction in the number who were diagnosed with dementia by the end of the study.

This trial therefore provides no evidence that Souvenaid/Fortasyn Connect can help to prevent or slow Alzheimer's developing in people with early signs of cognitive decline.

In 2010, Behind the Headlines reported the findings of an early-stage 12-week study of the same Souvenaid/Fortasyn Connect drink. That study found some changes to verbal recall but, again, no overall effect on cognitive outcomes.

As Dr Doug Brown, director of research at Alzheimer's Society, commented on the present study:

"This trial of Souvenaid did not meet the success criteria that would be needed for developing new drugs, so we cannot be confident of the drink's benefits … we certainly can't conclude that the drink slows progression of Alzheimer's disease.

"People who are worried about their memory should not rush out and buy this drink without first talking to their doctor to find out if it could be suitable for them. There are many causes of memory decline, including normal ageing, so it's important people are investigated for underlying Alzheimer's disease before taking this medical drink, or any kind of treatment."

There's no guaranteed way to prevent dementia – particularly Alzheimer's disease, which doesn't have a fully established cause. However, there are things you can do to try to reduce your risk:

  • eat a healthy, balanced diet
  • exercise regularly
  • lose weight, if necessary
  • only drink alcohol in moderation
  • give up smoking, if applicable

Links To The Headlines

Alzheimer's nutrient drink falters in clinical trial. BBC News, October 31 2017

This drink could help stave off Alzheimer's disease, according to scientists. Daily Mirror, October 31 2017

Could daily £3.50 drink slow Alzheimer's? Nutritional supplement may pause progression of the disease 'before it is too late'. Mail Online, October 31 2017

Links To Science

Soininen H, Solomon A, Visser PJ, et al. 24-month intervention with a specific multinutrient in people with prodromal Alzheimer's disease (LipiDiDiet): a randomised, double-blind, controlled trial. The Lancet Neurology. Published online October 30 2017

Marriage may help lower dementia risk

NHS Choices - Behind the Headlines -

"Marriage and having close friends may help protect against dementia, according to Loughborough University researchers," BBC News reports.

The news comes from a study looking at the link between social relationships and the risk of developing dementia.

The study included a large group of adults aged over 60 who didn't have dementia. They were asked about their marital status and the number of close relationships they had.

Researchers then followed the participants for an average of 6 years to see how many developed dementia.

They found people who weren't married and those with higher loneliness scores had a higher risk of developing dementia.

But this can't prove that being married will protect you against dementia. A combination of many biological, health, lifestyle and environmental factors is likely to influence our risk of developing dementia.

As the causes of some types of dementia – particularly Alzheimer's disease – remain poorly understood, it's difficult to isolate the effect of a single factor like marital status.

It seems more likely that the quality of the marriage and family and social relationships is likely to be the important factor, not just the presence of these relationships.

An unhappy marriage may do little to benefit your wellbeing, and you don't have to be married to have a happy and fulfilling relationship.

Overall, this study does little to further our understanding of the causes of Alzheimer's, but will add to the body of literature looking at how our relationships and social networks are linked to our health.

If you feel lonely and isolated, there are a number of resources you can use to help connect with other people.

 

Where does the study come from?

The study was conducted by researchers at University College London and Loughborough University in the UK, and Universidade Federal de Santa Catarina in Brazil.

The cohort studies informing this research received funding from the UK Economic and Social Research Council, the National Institute for Health Research, and the National Institute on Aging.

It was published in the peer-reviewed Journals of Gerontology: Social Sciences and is available to read free online.

BBC News' reporting of the study was accurate, and included some interesting feedback from independent commentators.

 

What kind of research was this?

This cohort study looked at whether social relationships and loneliness affect the likelihood of a person developing dementia.

But it's difficult to isolate the specific effects of single factors, such as marital status or loneliness, as many different factors may be involved in a person's dementia risk.

 

What did the research involve?

The study used data collected by the English Longitudinal Study of Ageing (ELSA), which the researchers say is a representative sample of people aged 50 and over living in England.

The study began in 2002 with follow-up every 2 years until 2012, resulting in a total of 6 "waves" of results.

Loneliness was first assessed in 2004. People not diagnosed with dementia completed questionnaires about social isolation and the number of close relationships they had.

This included relationships with family and friends, frequency and type of contact, and involvement in social organisations.

Marital status wasn't part of the questionnaire and they were asked about this separately.

An additional short assessment scale produced a loneliness score. Dementia was assessed at follow-up by asking participants whether a doctor had ever diagnosed the condition.

Researchers asked the individual or family to complete a short 16-item questionnaire on the person's cognitive ability compared with how it was 2 years ago (for example, being able to remember different family members).

All follow-up sessions also included cognitive tests used to identify possible cases of dementia.

The researchers looked at the link between social relationships and isolation in 2004 (wave 2) and development of dementia up to 2012-13 (wave 6).

Analyses took account of various confounding factors, including socioeconomic status, educational level, and medical health and disability.

The final analysis included 6,677 participants, who were 66 years old on average at first assessment.

 

What were the basic results?

During an average 6-year follow-up, 3.3% of the sample (220 people) were diagnosed with dementia or had the diagnosis indicated by questionnaires.

Not surprisingly, most of these diagnoses were among participants who were over the age of 80 at the start of the study.

Others factors linked to the development of dementia included heart and vascular disease, impaired mobility, and lower educational levels.

The researchers found people who developed dementia were also less likely to be married, had fewer social relationships, and reported greater loneliness.

In models fully adjusted for other factors, being unmarried was linked to about a doubled risk (hazard ratio [HR] 2.11, 95% confidence interval [CI] 1.52 to 2.92) and a higher loneliness score was linked to about a third higher risk (HR 1.33, 95% CI 1.02 to 1.73).

Having more close relationships was generally associated with a lower risk of dementia.

 

How did the researchers interpret the results?

The researchers concluded: "Dementia risk is associated with loneliness and having fewer close relationships in later life.

"The underlying mechanisms remain to be elucidated, but efforts to enhance older peoples' relationship quality may be relevant to dementia risk."

 

Conclusions

The general findings that marriage and having more social relationships seem to be linked to better health and wellbeing is in line with the results of much previous research.

But there are several important things to keep in mind:

  • Although the study followed people who didn't have dementia at the start of the study, it can't prove that marital status or the number of close relationships directly increased or decreased dementia risk.
  • Biological, health, lifestyle and environmental factors may all influence a person's risk of dementia (particularly the most common form of dementia, Alzheimer's disease, which doesn't have an established cause). Even though the researchers have tried to adjust for different variables, it's still not possible to fully account for all factors or know whether they have an influence.
  • Simply asking someone if they're married or not, or how many relationships they have, can't account for the nature and quality of these relationships. It's likely it's not just marital status that has an impact on health and wellbeing, but whether it's a happy and loving relationship. This type of study simplifies the complex nature of human relationships.
  • Despite the large sample, only a very small proportion of the cohort developed dementia. This means any analysis of such a small sample may not produce reliable risk estimates.
  • The ways dementia was assessed were mixed, and may not give a fully reliable set of cases meeting full diagnostic criteria. Similarly, the study isn't able to analyse by the type of dementia.

The results of this study are of interest, but can't tell us that staying married will prevent dementia.

While the causes of Alzheimer's are unknown, there are more established things you can do to try to reduce your risk of vascular dementia:

  • eating a healthy, balanced diet
  • getting regular exercise
  • losing weight if necessary
  • not smoking
  • drinking alcohol in moderation

There are also organisations and charities that try to help reduce loneliness in older people.

Links To The Headlines

Marriage may protect against dementia. BBC News, October 28 2017

Links To Science

Rafnsson SB, Orrell M, d'Orsi E, et al. Loneliness, Social Integration, and Incident Dementia Over 6 Years: Prospective Findings From the English Longitudinal Study of Ageing. The Journals of Gerontology: Series B. Published online June 27 2017

Afternoon open heart surgery 'leads to fewer complications'

NHS Choices - Behind the Headlines -

"Afternoon heart surgery has lower risk of complications, study suggests," says The Guardian.

Researchers in France were interested in whether the time of day of the operation was carried out affected the rate of complications following a type of open heart surgery known as aortic valve replacement. This involves removing the aortic valve (which controls the flow of blood out of the heart) and replacing it with animal or synthetic tissue.

It has been known for some years that our body clock can have a significant effect on critical biological functions – work in this field won the 2017 Noble Prize for Medicine – so researchers wanted to see if the timing of surgery affected surgical outcomes. Their hypothesis was that as the heart has been conditioned to work harder in the afternoon, performing an aortic valve replacement in the afternoon may reduce the risk of complications.

They found the rate of major cardiovascular complications, such as heart attack and heart failure, was halved among people who had the surgery in the afternoon.

However, this study focused on one hospital, with few surgeons and patients, and one specific type of surgery. It could be the case that it was the different surgical teams, rather than the timing of the surgery, that made the difference.

The results need further investigation through larger studies involving multiple sites, as well as different types of heart surgery.

 

Where did the story come from?

The study was carried out at a single hospital in France by researchers from the University of Lille, the University Hospital CHU Lille, the Institut Pasteur de Lille, and Inserm (U1011 and U1177). It was funded by the Fondation de France, Fédération Française de Cardiologie, Agence Nationale de la Recherche and the CPER-Centre Transdisciplinaire de Recherche sur la Longévité.

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

The UK media headlines reporting this story were very misleading. The Telegraph said: "Surgery is safer in the afternoon," implying that the research had looked at many types of surgery. And BBC News said: "Heart surgery survival chances 'better in the afternoon'," suggesting the research had looked at death rates when, in fact, the study looked at a range of complications. A total of six people died in the study, but there was no significant difference in terms of when they had surgery.

Most of the coverage also talked in general terms about "heart surgery", even though this research only looked at one specific type.

 

What kind of research was this?

This research involved three different types of investigation. Firstly, the researchers looked at a cohort of consecutive people receiving heart valve surgery in one French hospital, comparing the time of day they had surgery with surgery outcomes.

They then used a randomised controlled trial (RCT) to allocate people to a specific time slot – either morning or afternoon.

Finally, they carried out a laboratory study looking at heart tissue samples from people in the trial to examine various biomarkers associated with heart stress.

These are all valid ways of investigating the question at the core of the research. An RCT is the optimal way to look at the specific effects of an intervention (in this case, the time of operation) as randomising the participants to the different groups should get rid of any differences between them that otherwise influence the results. However, the RCT had only a very small number of operations and surgeons.

 

What did the research involve?

The cohort study looked at all consecutive patients (596) needing aortic valve replacement at Lille University Hospital between 2009 and 2015. To be included, people had to:

  • be aged 18 or over
  • have severe aortic stenosis (narrowing of the valve where the heart connects with the aorta, the large artery supplying blood to the rest of the body)
  • have "preserved left ventricular ejection fraction" (meaning their heart otherwise functions well and can still pump blood effectively)

The participants could also be having a coronary artery bypass graft (CABG) at the same time as aortic valve replacement, but people with other types of valve disease or congenital heart disease, or those who had previously had heart surgery, were excluded from the study.

The RCT took place from 2016 to 2017 and involved 88 adults meeting the same criteria, except the operations were limited to those having valve replacement without CABG, and the researchers also excluded people who had diabetes, impaired kidney function, and atrial fibrillation or atrial flutter (heart rhythm problems).

Tissue samples were taken from the first 22 people in the trial, to look at biomarkers in the heart muscle cells. The samples were exposed to conditions where the oxygen supply was reduced and then reinstated to see how the cells behaved.

People in the cohort study were followed up for a period of 500 days after their operation, and those in the RCT were observed until they were discharged from hospital. The main outcome of interest in both cases was major cardiovascular events, which included cardiovascular death, heart attack or hospital admission for heart failure.

 

What were the basic results?

In the cohort study:

  • Four people who had surgery in the morning (1%) and two who had surgery in the afternoon (0.5%) died during their hospital stay. This was not a statistically significant difference.
  • Major adverse cardiac events were less common in the afternoon, occurring in 28 people (9%), compared with 54 people (18%) in the morning group (hazard ratio [HR] 0.50, 95% confidence interval [CI] 0.32 to 0.77).
  • There was no significant difference in rates of cardiovascular death between the groups, but there were fewer cases of acute heart failure in the afternoon group – 14 people (5%) in the morning group and 4 (2%) in the afternoon group (HR 0.36, 95% CI 0.15 to 0.88).

For the smaller group of people involved in the RCT:

  • No patients in either group died during their stay in hospital.
  • Cardiac troponin (a biomarker of heart muscle stress) was higher in the morning group than in the afternoon group.
  • Although there were some between-group differences in various outcomes, such as heart attacks and rhythm problems, these were not statistically significant. This may have been due to the small size of the study.

In the laboratory study:

  • Contraction recovery after the heart muscle was deprived of oxygen and then reoxygenated was better in heart muscle tissue taken from afternoon surgery patients.
  • Further analysis showed the differences may be due to activity of genes involved in the body clock.
How did the researchers interpret the results?

The researchers described the morning-versus-afternoon difference for aortic valve surgery as "clinically significant". They also discussed similar research in other types of heart surgery, such as coronary artery surgery, and noted that the findings were less clear in these other studies.

They suggested that their findings should be investigated further through research based in multiple hospitals rather than at a single site.

 

Conclusion

This study found evidence of an effect that's worth investigating further to see if there are real differences in heart muscle function and risk of complications from heart surgery at different times of the day. However, there were some limitations:

It took place at a single hospital, with a relatively small number of people undergoing operations.

The laboratory study found differences in gene activity that suggested the body clock may play a role in making the heart better able to tolerate loss of oxygen and subsequent re-oxygenation. However, there may be other explanations for these differences. For example, all the operations were performed by only four different surgeons. Variation in post-operation outcomes could have something to do with the surgeons' performances rather than the patients' characteristics.

The research only looked at aortic valve surgery, so we don't know if the same result would be seen for other types of operation.

As one expert – Dr Tim Chico, consultant cardiologist at the University of Sheffield in the UK – pointed out, if what this research suggests is shown to be correct, there would be major implications for the future scheduling of operations, and this could have extensive knock-on effects in terms of staffing and resources across the healthcare service.

That's why further study of this potential effect is very important to ensure we understand the reasons why these differences are seen and what types of surgery they may apply to. At present, this research alone does not answer enough questions to lead to a change in the way operations are organised.

If you have any concerns about an operation you're about to have, you should discuss them with your doctor.

Links To The Headlines

Afternoon heart surgery has lower risk of complications, study suggests. The Guardian, October 26 2017

Heart surgery survival chances 'better in the afternoon'. BBC News, October 27 2017

Surgery is safer in the afternoon because of body's circadian rhythm, study suggests. The Daily Telegraph, October 26 2017

Links To Science

Montaigne D, Marechal X, Modine T, et al. Daytime variation of perioperative myocardial injury in cardiac surgery and its prevention by Rev-Erbα antagonism: a single-centre propensity-matched cohort study and a randomised study. The Lancet. Published online October 26 2017

Report calls for better mental health support in the workplace

NHS Choices - Behind the Headlines -

"Up to 300,000 people with long-term mental health problems have to leave their jobs each year, a report says," writes BBC News. This was just one of the UK media outlets that published the findings of a report looking at the extent of mental ill health in the workplace, and the related economic and social costs.

Most of the media led with headlines stating that 300,000 people with long-term mental health conditions leave work each year – twice the rate of those without mental health conditions.

The loss to the economy was estimated to be up to £99 billion a year, including lost productivity output, the cost of providing benefits and healthcare costs.

 

What is the basis for these news stories?

They are based on a report, "Thriving at Work: a review of mental health and employers", commissioned by Prime Minister Theresa May in January 2017.

It was written by Lord Dennis Stevenson (mental health campaigner and former HBOS chief) and Paul Farmer (chief executive of the mental health charity Mind), and was jointly published by the Department of Health and the Department for Work and Pensions. It includes research by audit firm Deloitte on costs to employers and the state.

The report is free to download from the government's website.

The prime minister welcomed the publication and said she wanted the recommendations to be implemented.

 

What were the main findings?

The 88-page report looked at the extent of the problem of poor mental health in the workplace and its associated costs. It examined case studies of good practice and makes recommendations for employers in both the public and private sector, and for the government, to improve the situation.

Key findings include:

  • Around 15% of people in work have symptoms of a mental health condition.
  • Around 6% of people with a long-term mental health condition lose their job each quarter – amounting to 300,000 people each year – compared with 4% of those with a physical health condition.

The authors say that everyone – not just people with long-term mental health conditions – has a mental health status, which can move between "thriving at work" to "struggling at work".

Some of those struggling will be off sick. However, the report stresses that people with mental health conditions can still thrive at work if given the right support.

The key effects of mental ill health include:

  • people being off work sick (absenteeism)
  • people being at work but unable to work effectively (so-called "presenteeism")
  • increased workload for the rest of the workforce
  • increased turnover of the workforce
  • lack of career progression for people with mental health conditions

The costs to employers are estimated at:

  • £8 billion for absenteeism
  • £17-26 billion for lost productivity from presenteeism
  • £8 billion for staff turnover

Costs varied widely between different private sector industries and were higher for the public sector.

What does the report recommend?

It says that all employers of any size in the UK should adopt six "core standards" for improving mental health at work:

  1. Produce, implement and communicate a "mental health at work" plan.
  2. Develop mental health awareness among employees.
  3. Encourage open conversations about mental health and the support available when employees are struggling.
  4. Provide employees with good working conditions.
  5. Promote effective people management.
  6. Routinely monitor employee mental health and wellbeing.

These recommendations are based on best practice or evidence, and the authors state there is a "pressing need" for more robust evidence about what works to support improved mental health at work.

In addition, they say public sector employers – such as the NHS, civil service and education service – and private sector employers with more than 500 employees should adopt "enhanced" standards to:

  • increase transparency and accountability through internal and external reporting
  • demonstrate accountability
  • improve the disclosure process
  • ensure provision of tailored in-house mental health support and signposting to clinical help

Recommendations for the government include introducing legal changes to enhance protection for people with mental health conditions and the development of a more flexible model for statutory sick pay, to help people return to work gradually.

The authors conclude: "At a time when there is a national focus on productivity, the inescapable conclusion is that it is massively in the interest of both employers and Government to prioritise and invest far more in improving mental health. The UK can ill-afford the productivity cost of this poor mental health."

 

What does this mean for you?

Many people go through periods of mental ill health that make it more difficult for them to work. For some, this is a short-term problem and they can continue at work, or return to work after sickness absence, with appropriate support.

Many people with longer-term mental health problems can also continue working, or return to work after absence, although the report suggests some people struggle or are unable to do so.

It stresses that people with long-term mental health conditions are able to work and should be supported to continue to do so by their employers.

Under the Equality Act (2010), your employer has a legal duty to make "reasonable adjustments" to your work.

Depending on your circumstances, you might like to ask about:

  • flexible hours – for instance, you might like to return to work part-time, or start later in the day if you're sleepy from medication in the mornings
  • support from a colleague in the short or long term
  • a place you can go for a break when needed

Returning to the workplace after a mental health issue can be daunting at first, but research suggests it usually has a positive effect on wellbeing in the long run.

Read more advice about Returning to work after mental health issues.

Links To The Headlines

Mental health sees 300,000 people leave their jobs each year. BBC News, October 26 2017

Mental health problems are forcing thousands in UK out of work – report. The Guardian, October 26 2017

More than 300,000 UK workers laid off each year due to long-term mental health problems, finds report. The Independent, October 26 2017

Employers should accept sick notes for the mentally ill, major report finds. The Daily Telegraph, October 26 2017

300,000 people lose jobs over mental health every year – report. Sky News, October 26 2017

Report reveals 300,000 people lose jobs over mental health each year. ITV News, October 26 2017

Links To Science

 

Blood-thinning drugs may reduce dementia risk in people with irregular heartbeats

NHS Choices - Behind the Headlines -

"Common blood thinning drugs halve the risk of dementia for patients who have an irregular heartbeat," reports the Mail Online.

Researchers in Sweden used the country's health registry data to assess whether people with a condition called atrial fibrillation were less likely to get dementia if they took drugs like warfarin.

Atrial fibrillation (AF) is a heart condition that causes an irregular and often abnormally fast heartbeat. This can make the blood more likely to clot, which can lead to a stroke.

Most people with AF are prescribed anticoagulant drugs, which reduce the blood's ability to clot.

Anticoagulants are often referred to as "blood-thinning drugs", but this is technically incorrect as they don't affect the density of blood.

People with AF are also at more risk of dementia, probably because of a build-up of tiny clots in the small blood vessels of the brain.

This study showed people with AF who were prescribed anticoagulants within a month of diagnosis had a 29% lower risk of getting dementia, compared with those not given the prescription.

But because of the type of study, the researchers can't prove that anticoagulants are the reason for the reduced risk.

Still, as the researchers point out, the possible reduction in dementia risk is another reason to keep taking anticoagulant drugs if you're prescribed them.

You shouldn't take anticoagulants if you're not at risk of blood clots as they can increase your risk of bleeding.

Where did the story come from?

The study was carried out by researchers at Danderyds University Hospital in Stockholm, Sweden.

It was published in the peer-reviewed European Heart Journal on an open access basis, making it free to read online.

Among the UK media, only the Sun pointed out that the study can't prove cause and effect. The Sun's headline described anticoagulant treatment as a "2p Alzheimer's buster", which is unfortunate – the type of dementia likely to be most affected by blood clots is not Alzheimer's disease, but vascular dementia.

All the media used the more impressive 48% risk reduction figure from the study, which came from looking at people who took the drugs for most of the time, compared with people who never took them.

The more usual scientific standard is to use an intention to treat analysis of the figures, which gives a risk reduction of 29%.

Finally, The Guardian's headline could have made it clearer that any reported dementia risk reduction only applied to people diagnosed with atrial fibrillation and not the population at large.

What kind of research was this?

This retrospective cohort study used data from Swedish health registries.

This type of study can help researchers spot patterns and links between factors (in this case anticoagulant drugs and dementia) but can't prove that one thing (the drugs) causes another (the lower dementia risk).

That's because researchers can't rule out the effect of confounding factors that may influence the results.

What did the research involve?

Researchers looked at the records of all patients diagnosed with AF in Sweden from 2006 to 2014, excluding those who already had dementia.

They looked at who was prescribed anticoagulants within 30 days of diagnosis and who was diagnosed with dementia during an average of around 3 years of follow-up.

After adjusting for confounding factors, they calculated the risk of stroke for people with or without anticoagulant prescriptions.

The researchers used a statistical technique called propensity scoring to try to even out confounding factors of why some people did and others didn't take anticoagulants despite all having a diagnosis of AF.

This is a suitable step to take, as compliance problems (not taking medication as instructed) are a known issue in some AF patients. They say this allowed them to make matched comparisons between the groups.

They also tested anticoagulant use with unconnected outcomes like falls, flu, diabetes and chronic obstructive pulmonary disorders (COPD).

They said that if anticoagulants were linked to any of them, this would indicate there may be an underlying confounding factor they hadn't accounted for.

This would mean they wouldn't be confident making any association between anticoagulants and dementia risk.

What were the basic results?

The researchers found:

  • 26,210 of the 444,106 people in the study group got dementia – a rate of 1.73 dementia cases per 100 people each year
  • people who'd started anticoagulants shortly after AF diagnosis were 29% less likely to get dementia (hazard ratio [HR] 0.71, 95% confidence interval [CI] 0.69 to 0.74)
  • there was no difference between rates of dementia when directly comparing older anticoagulants like warfarin with newer types, such as clopidogrel
  • people who had anticoagulant prescriptions 80% of the time were 48% less likely to get dementia than people who never had anticoagulant prescriptions (HR 0.52, 95% CI 0.5 to 0.55)
  • there was no association between anticoagulants and falls or flu

Anticoagulant use slightly increased the risk of diabetes and COPD, but as this association was in the opposite direction from that for dementia, the researchers remained confident in their results.

They also found that people prescribed anticoagulants were likely to be younger and healthier.

Apart from not taking anticoagulants, the factors most closely linked to chances of getting dementia were older age, Parkinson's disease and alcohol abuse.

How did the researchers interpret the results?

The researchers said their results "strongly suggest that oral anticoagulation treatment protects against dementia in atrial fibrillation" and that "early initiation of anticoagulant treatment in patients with AF could be of value" to prevent dementia.

Conclusion

If you've been diagnosed with AF and prescribed anticoagulant treatments such as warfarin or clopidogrel, we already know they protect you against having a stroke. This study suggests they may also help protect you against dementia.

Cutting the risk of dementia for people who have a raised risk from AF would be an exciting step forward.

Unfortunately, we can't tell from this study whether the protection against dementia was down to the anticoagulants because of the possible effect of unmeasured confounding factors.

Usually, we'd want to see a randomised controlled trial (RCT) to follow this study to find out if anticoagulant drugs really do have that effect.

But because people with AF are usually prescribed anticoagulants to reduce their risk of stroke, it wouldn't be ethical to do an RCT, as it would leave people unprotected against stroke when a known preventative treatment is available.

Because of the difficulties of carrying out a proper trial, we'll need to see more studies of the kind done here, in different populations, to see whether the results hold true.

It would be useful if future studies have clearer information about which confounding factors are being taken into account.

There are a few things we don't know from this study.

  • The researchers were unable to differentiate between types of AF. Some people have just 1 episode of AF that doesn't return or goes away with treatment, while others have persistent AF that happens all the time. The type of AF may affect both dementia risk and whether you're prescribed anticoagulants.
  • We also don't know which types of dementia people were diagnosed with. AF may be more strongly linked to vascular dementia than Alzheimer's disease. But we don't know for sure which type of dementia might be helped by taking anticoagulants.

You can reduce your risk of vascular dementia by avoiding conditions such as type 2 diabetes and high blood pressure, which can be triggered by smoking and obesity.

When it comes to dementia prevention, it's often the case that what's good for the heart is also good for the brain.

Links To The Headlines

Blood-thinning drugs 'can reduce risk of dementia by up to 48%'. The Guardian, October 25 2017

Common blood thinning drugs halve the risk of dementia for patients who have an irregular heartbeat. Mail Online, October 25 2017

Giving Brits 2p-a-day blood-thinning drugs could SLASH dementia risk by up to 50 per cent, study reveals. The Sun, October 25 2017

Links To Science

Friberg L, Rosenqvist M. Less dementia with oral anticoagulation in atrial fibrillation. European Heart Journal. Published online October 24 2017

New genetic variants associated with breast cancer identified

NHS Choices - Behind the Headlines -

"Do you have one of the 180 breast cancer genes? One in five women has a variant that raises her risk of the condition by a third" is the rather inaccurate headline in the Mail Online.

The story covers 2 new studies looking for genetic variations known as single nucleotide polymorphisms (SNPs).

These are small variations in our DNA, some of which are associated with an increased risk of developing a disease – in this case, breast cancer.

While the Mail Online's headline suggests the "breast cancer genes" have been pinpointed, this is not the case.

In most cases, the genetic variations identified by the researchers simply signpost regions in the DNA (loci) where the genes that affect breast cancer risk are likely to be located.

This is not the same as identifying specific genes or discovering why they increase the risk of breast cancer.

The individual variations identified are only associated with small increases in risk, and many women will carry them.

This is very different from the mutations in the BRCA1 or BRCA2 genes, which cause breast cancer – these are rare and have a bigger impact on risk.

These findings are useful steps towards understanding more about which genes influence breast cancer risk.

But while they may eventually pave the way towards more targeted screening strategies, the research is still at a relatively early stage.

You can't change the genes you're born with, but there are things you can do to reduce your risk of getting many types of cancer, such as quitting smoking if you smoke, taking regular exercise, maintaining a healthy weight, and drinking alcohol in moderation.

Where did the story come from?

The headlines are actually based on 2 related research papers.

One study looked at breast cancer as a whole, and the second, smaller, study looked at a specific type of breast cancer known as oestrogen receptor negative breast cancer.

Together, the 2 studies looked at data on 275,000 women.

This analysis focuses on the first, larger study.

The study was carried out by researchers from several international institutions, including the University of Cambridge in the UK and the University of Washington School of Public Health in the US.

It was published in the peer-reviewed journal Nature.

The study was funded by a large number of organisations, including charities, educational institutions and government agencies.

Some of the media headlines covering this study are misleading. For example, the Sun suggests that, "More women [are] at risk due to discovery of further cancer causing gene mutations".

This poorly worded headline suggests women's level of risk has somehow risen.

The study has helped us understand more about women's risk, but their risk hasn't changed: it's the same.

And hopefully as we learn more about the genetics of breast cancer we may be able to find ways to reduce this risk.

The study also didn't identify "180 breast cancer genes". The results just signpost where in the DNA these genes are likely to be.

What kind of research was this?

This study is what's known as a genome-wide association study. This involved studying the human genome – the complete set of DNA present in a human.

The researchers looked at small variations in DNA. These variations are known as single nucleotide polymorphisms (SNPs, pronounced "snips").

Most SNPs don't affect a person's health or characteristics. But they can help researchers find genes that affect people's risk of disease.

Some SNPs are more common in people who have a specific condition (such as breast cancer) than those without the condition.

This indicates that the regions of DNA surrounding these SNPs are likely to contain genes that are contributing to these diseases.

What did the research involve?

The researchers analysed data from 78 genome-wide studies: 67 European and 12 Asian ones.

The studies included data on the DNA of about 256,000 women, about 137,000 of whom had breast cancer.

The researchers analysed information on around 21 million genetic variations.

What were the basic results?

The main finding was the identification of SNPs in 65 new regions of DNA (loci) associated with an increased risk of breast cancer.

The researchers then carried out various analyses to look at which genes lay nearby and could be responsible for the links found.

They found almost 700 genes of interest, including some already known to be involved in breast cancer.

How did the researchers interpret the results?

The researchers concluded: "These results provide further insight into genetic susceptibility to breast cancer, and will improve the use of genetic risk scores for individualised screening and prevention."

Conclusion

This large analysis of data has identified 65 more SNPs associated with an increased risk of developing breast cancer.

These variations hadn't previously been associated with overall breast cancer risk.

A second, smaller study published at the same time identified another 7 variations specifically associated with an increased risk of oestrogen receptor negative breast cancer, a type of breast cancer that's notoriously hard to treat.

In total, these studies bring the number of SNPs associated with breast cancer to about 180.

Although these are interesting findings, there are a few points to bear in mind:

  • The variations investigated in this type of study don't usually cause the increase in risk. Instead, they usually lie near a gene that's actually affecting the risk. Researchers have started to look for these genes, but as yet we can't say this specific piece of research "found 180 breast cancer genes".
  • The individual variations identified are only associated with small increases in risk, and many women will carry them. This is very different from the mutations in the BRCA1 or BRCA2 genes that cause breast cancer – these are rare and have a bigger impact on risk.
  • The researchers and some of the news sources suggest that this study's findings could help with the early detection and prevention of breast cancer. While this may be the case in the longer term, it's still early days when it comes to using this data for recommending preventative treatment like mastectomy.

Professor Karen Vousden, chief scientist at Cancer Research UK commented: "The results, gathered from around the world, help pinpoint the genetic changes linked to a women's risk of breast cancer.

"Learning which women are at higher risk of breast cancer could help identify who may benefit from earlier screening, and spare women at a lower risk from having to attend screening if it's unlikely to benefit them."

Links To The Headlines

Breast cancer study uncovers new genetic variants for increased risk. The Guardian, October 23 2017

Scientists find some of the genetic variants responsible for increasing womens' chance of breast cancer. The Independent, October 23 2017

Do you have one of the 180 breast cancer genes? One in five women has a variant that raises her risk of the condition by a third. Mail Online, October 23 2017

Links To Science

Michailidou K, Lindström S, Dennis J, et al. Association analysis identifies 65 new breast cancer risk loci. Nature. Published online October 23 2017

Milne RL, Kuchenbaecker KB, Michailidou K, et al. Identification of ten variants associated with risk of estrogen-receptor-negative breast cancer. Nature Genetics. Published online October 23 2017

Eating mushrooms at breakfast may help you feel fuller

NHS Choices - Behind the Headlines -

"Starting the day with mushrooms could help you shed pounds from your waistline, new research has found," the Mail Online reports.

US researchers wanted to see if regularly eating mushrooms for breakfast makes you feel fuller.

Satiety or feeling full can be an important part of a successful weight loss plan, as regular snacking due to hunger pangs can make it harder to stick to a daily calorie allowance.

The researchers carried out a small study in a group of people from a US university. The participants ate either a mushroom sandwich or a minced beef sandwich each day for breakfast for 10 days, then for another 10 days ate the opposite.

Those who ate mushrooms reported feeling fuller in the hour or so afterwards – but this didn’t alter their overall energy intake during the study period.

The researchers give one possible explanation for why people felt fuller after eating mushrooms. Because the protein content of the meals had to be the same, people had to eat a bigger sandwich with a much larger volume of mushrooms to match the amount of protein in the minced beef sandwich.

The study also mentioned that mushrooms are higher in fibre than minced beef and fibre helps you feel more full.

Effects on weight weren't measured in this short-term study, so claims that mushrooms can help you lose weight are unproven.

 

Where does the study come from?

The study was conducted by researchers from the University of Minnesota in the US and published in the peer-reviewed journal Appetite.

Interestingly, the study was supported by a grant from the Mushroom Council. The Council is a US organisation funded by mushroom producers; its aims include persuading people to buy and eat mushrooms.

The Mail has taken a bit of a leap saying that new research has found starting the day with mushrooms could help you shed pounds from your waistline – the study didn't look at weight and found little evidence that eating mushrooms altered overall energy intake.

The website's reporting that mushrooms make you feel fuller than bacon or sausages is also unsupported. The study didn’t directly compare mushrooms with either food source. It only looked at minced beef sandwiches.

 

What kind of research was this?

This was a randomised controlled crossover trial which aimed to compare the effects of consuming mushrooms or meat for breakfast, for 10 days each.

In a crossover trial each person acts as their own control as they receive both interventions in random order. This type of trial is often used to increase the sample size.

The researchers carried out this study because it's been suggested that mushrooms make you feel fuller than meat but this hadn’t been examined in matched studies.

Increasing understanding of the foods that satiate our appetite is one possible approach towards fighting obesity, but there is only so much that a small short-term food study can tell us.

 

What were the basic results?

The study included 32 healthy adults recruited via flyers placed on the University of Minnesota campus.

The researchers excluded smokers, people who'd had weight gain or loss of more than 10 pounds in the past three months, those who ate more than three servings of fibre-rich food a day, people who took supplements other than a multivitamin, and people who did vigorous endurance exercise.

The study involved eating mushrooms for breakfast (452 grams each day) for 10 days and meat for 10 days, in either order, with a 10 day break in between.

At the start of each 10-day period the participants attended the test centre. They completed a visual analogue scale (VAS) where they rated between 0 and 10 how hungry they were. A VAS is typically a 10cm line and participants are asked to mark their response on the line (going from left to right).

They were then given a breakfast meal of a sandwich containing either roasted mushrooms or lean beef mince, along with a muffin, egg and two cheese slices.

The mushroom and meat sandwiches were matched for protein and energy content.

The participants completed the VAS 15, 30, 45, 60 and 120 minutes after eating and were also offered a pizza 180 minutes after the start of the session.

They were then given either raw mushrooms or beef mince to take home and eat for a further 10 days. They were also given VAS questionnaires to take home and complete, and asked to complete a food diary of all food and drink on days 2 and 10.

 

What do the researchers conclude?

The main finding was that on the VAS people reported feeling less hungry and more full after eating mushrooms than after eating meat, though they didn't eat any less at lunchtime.

There were no differences in the food eaten by the participants on the day before each test period, but on day 2 the participants ate more fibre after eating mushrooms. There were no differences by day 10.

There was, no difference in overall energy intake over each 10 day period.

 

What do the researchers conclude?

The researchers suggest: "There may be a benefit to consumers to substitute mushrooms for meat in some meals or replace some of the meat content of meals with mushrooms to increase vegetable and fiber intake as well as protein from sustainable non-animal sources."

 

Conclusions

Though of interest, this study doesn't provide strong evidence that you should eat mushrooms if you want to lose weight.

The study has a number of limitations:

  • It's a short-term study that didn't look at effects on weight. It showed that people reported feeling fuller after eating mushrooms, but there were few signs this actually led to them eating less.
  • As the researchers openly acknowledge, there could be other explanations for the findings. To match the protein content in mince required a much larger volume of mushrooms, and therefore a larger sandwich that would have taken more time and effort to chew. This could have led to people reporting feeling fuller.
  • The study only looked at mushrooms compared to meat – people might report feeling fuller after eating other foods for breakfast such as beans, eggs or avocados.
  • Though the researchers tried to monitor compliance, people may not have completely adhered to the diets. The researchers also acknowledged several errors on the take-home VAS printouts, including having nowhere to record feelings 180 min after eating the mushrooms or mince.
  • This was a small specific sample of people recruited from a US university campus. The findings may not the same in other groups.

Even if mushrooms do have some wonder ingredient, it's unlikely, as the authors themselves say, that most people would choose to eat such a high volume of mushrooms each day – or similarly that people would choose to eat mince day after day.

Regular activity and a healthy balanced diet remain the best ways to achieve and maintain a healthy weight. A balanced diet involves eating a variety of foods, not relying on a single food item. 

Links To The Headlines

Order mushrooms for breakfast if you want to lose weight: Eating fungi instead of sausages and bacon helps you feel fuller for longer. Mail Online, October 20 2017

If you’re trying to lose or maintain weight, try having mushrooms for breakfast. Metro, October 22 2017

Links To Science

Hess JM, Wang Q, Kraft C, Slavin JL. Impact of Agaricus bisporus mushroom consumption on satiety and food intake. Appetite. Published online June 21 2017

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