NHS Choices - Behind the Headlines

Can exercise offset some of the harms of regular drinking?

"Adults who booze regularly but exercise for five hours a week are no more likely to die than teetotallers," the Mail Online reports.

A study suggests exercise may compensate for some, but certainly not all, of the harms associated with excessive alcohol consumption. This latest study looked at deaths from cancer and cardiovascular disease, as well as premature death in general (usually judged to be dying before the age of 75).

Researchers looked at around 10 years' worth of national survey data from UK adults aged over 40. Unsurprisingly, they found links between all-cause and cancer mortality in inactive people. But they also found increasing levels of physical activity generally removed the association with drinking habits. In fact, occasional drinking was associated with a significant reduction in all-cause mortality for the most active of people.

Although the study had strengths in its large sample size and regular follow-up, we can't be sure that any links observed were solely down to the interaction between alcohol and exercise. For example, people who are physically active may also avoid smoking and consume healthy diets. It is difficult to completely control for such influences when analysing data like this.

While regular exercise may mitigate against some of the harms associated with excessive alcohol consumption it certainly won't make you immune. Many world-class sportspeople, such as George Best and Paul Gascoigne, have had both their careers and lives blighted by drinking.

 

Where did the story come from?

The UK-based study was carried out by an international collaboration of researchers from Canada, Australia, Norway and the UK. The health surveys on which the study was based were commissioned by the Department of Health, UK. Individual study authors also reported receiving funding from the National Health and Medical Research Council and University of Sydney. 

The study was published in the peer-reviewed British Journal of Sports Medicine. 

The media coverage around this topic was generally overly optimistic, highlighting that by exercising, individuals can completely undo the harm caused by excessive alcohol consumption, which is untrue.

In particular, the Mail Online claimed "Adults who booze regularly but exercise for five hours a week are no more likely to die than teetotallers" which could send out the wrong message to the public.

 

What kind of research was this?

This cohort study analysed data from British population-based surveys: Health Survey for England (HSE) and the Scottish Health Survey (SHS) to investigate whether physical activity is able to moderate the risk between alcohol consumption and mortality from cancer and cardiovascular diseases.

Cohort studies like this are useful for assessing suspected links between an exposure and outcome. However, there are potentially other factors that have a role to play in such associations and therefore the study design doesn't allow for confirmation of cause and effect.

 

What did the research involve?

The researchers collected data on 36,370 men and women aged 40 or above from Health Survey for England (1994; 1998; 1999; 2003; 2004; and 2006) and the Scottish Health Survey (1998 and 2003). Among other things, the participants were asked about their current alcohol consumption and physical activity.

Alcohol intake was defined by six categories (UK units/week):

  • never drink (lifetime abstainers)
  • ex-drinkers
  • occasional drinkers (haven't drank anything in past seven days)
  • within (previous) guidelines: <14 units (women) and <21 units (men)
  • hazardous: 14-15 units (women) and 21-19 units (men)
  • harmful: >35 (women) and >49 (men)

Frequency and type of physical activity in the past four weeks was questioned and converted into metabolic equivalent task-hour (MET-hours, which are an estimate of metabolic activity) per week according to national recommendations:

  • inactive (≤7 MET-hours)
  • lower level of active (>7.5 MET-hours)
  • higher level of active (>15 MET-hours)

The surveys were linked to the NHS Central Register for mortality data and the participants were followed up until 2009 (HSE) and 2011 (SHS). There were 5,735 recorded deaths; deaths from cancer and cardiovascular disease were of most interest for this study.

The data was analysed for associations between alcohol consumption and the risk of death from all-causes, cancer and cardiovascular disease. The results were then analysed according to levels of physical activity.

Potential confounders (such as sex, body mass index and smoking status) were controlled for.

 

What were the basic results?

Overall, the study found a direct link between all levels of alcohol consumption and risk of cancer mortality. It also found that increasing levels of physical activity reduced this association with cancer mortality, and also reduced the link with death from any cause.

  • In individuals who reported inactive levels of physical activity (≤7 MET-hours), there was a direct association between alcohol consumption and all-cause mortality.
  • However, in individuals who met the highest level of physical activity recommendations a protective effect of occasional drinking on all-cause mortality was observed (hazard ratio: 0.68; 95% confidence interval (CI): 0.46 to 0.99). It should be noted that this result just skimmed the cut-off point for statistical significance.
  • In this high activity group, there was no link between all-cause mortality and alcohol consumption within guidelines, or even hazardous amounts, but the risk was still increased for those drinking harmful amounts.
  • The risk of death from cancer increased with the amount of alcohol consumed in inactive participants, ranging from a 47% increased risk for those drinking within guidelines to 87% increased risk for those with harmful drinking.
  • In people with higher activity levels (above 7.5 MET hours) there was no significant link between any amount of alcohol consumption and cancer mortality.
  • No association was found between alcohol consumption and mortality from cardiovascular disease, although a protective effect was observed in individuals who reported the lower and higher levels of physical activity (>7.5 MET-hours) and (>15 MET-hours) respectively.

 

How did the researchers interpret the results?

The researchers concluded "we found evidence of a dose–response association between alcohol intake and cancer mortality in inactive participants but not in physically active participants. [Physical activity] slightly attenuates the risk of all-cause mortality up to a hazardous level of drinking."

 

Conclusion

This study aimed to explore whether physical activity is able to moderate the risk between alcohol consumption and mortality from cancer and cardiovascular diseases. It found that increasing levels of physical activity reduced the association for death from both all-causes and cancer.

This study has strengths in its large sample size, comprehensive assessments and long duration of follow-up. The findings are interesting, but there a few points to bear in mind:

  • As the authors mention, cohort studies such as this are unable to confirm cause and effect. Though the researchers have tried to account for various potential health and lifestyle confounding variables, there is the possibility that others are still influencing the results. A notable one is dietary habits which weren't assessed. Also, for example, the former drinkers may have quit due to other health issues which may have introduced bias.
  • The study was unable to look at binge drinking levels of alcohol consumption which would have likely had important health implications.
  • Additionally, there is always the possibility with self-reported surveys that the participants either under or over-reported their drinking habits which can increase the chance of misclassification bias.
  • Though having a large sample size, fewer people reported harmful drinking levels, so links within this category may be less reliable.
  • The study has only looked at the link between alcohol and actually dying from cancer or cardiovascular disease. Links may be different if they looked at associations between alcohol and just being diagnosed with cancer or heart disease, for example.
  • The study is also only representative of adults over the age of 40.

Overall, maintaining a healthy lifestyle seems to be the best bet for reducing the risk of any chronic disease, be it through physical activity, balanced diet or reasonable alcohol consumption.

Current alcohol recommendations for both men and women are to drink no more than 14 units per week.  

Links To The Headlines

How exercise undoes the harm from drinking: Adults who booze regularly but exercise for five hours a week are no more likely to die than teetotallers. Mail Online, September 8 2016

Two hours a week of exercise could offset the dangers of alcohol. The Daily Telegraph, September 8 2016

Exercise can cut risk from alcohol-related diseases, study suggests. The Guardian, September 8 2016

Links To Science

Perreault K, Bauman A, Johnson N, et al. Does physical activity moderate the association between alcohol drinking and all-cause, cancer and cardiovascular diseases mortality? A pooled analysis of eight British population cohorts. British Journal of Sports Medicine. Published online August 31 2016

Fasting diet may help regenerate a diabetic pancreas

"The pancreas can be triggered to regenerate itself through a type of fasting diet, say US researchers," BBC News reports.

Research in mice found a low-calorie diet may help in cases of type 1 and type 2 diabetes.

The pancreas is an organ that uses specialised cells known as beta cells to produce the hormone insulin, which the body uses to break down sugars in the blood (glucose).

In type 1 diabetes the pancreas stops producing insulin. In type 2 diabetes either not enough insulin is produced or cells in the body fail to respond to insulin (insulin resistance).

Mice were fed for four days on a low-calorie, low-protein and low-carbohydrate but high-fat diet, receiving half their normal daily calorie intake on day one, followed by three days of 10% of their normal calorie intake.

Researchers repeated this fast on three occasions, with 10 days of refeeding in between. They then examined the pancreas.

They found in mice modelled to have both type 1 and type 2 diabetes, insulin production was restored, insulin resistance was reduced, and beta cells could be regenerated. Early lab study involving human cell samples showed similar potential.

These are promising results, but further studies are needed to validate these findings in humans.

If you have either type 1 or type 2 diabetes, you shouldn't attempt a fasting diet without first seeking medical advice. A sudden change in your calorie intake could have unpredictable effects and lead to complications.

Where did the story come from?

The study was carried out by researchers from the University of Southern California and the Koch Institute at the Massachusetts Institute of Technology (MIT) in the US, and the IFOM FIRC Institute of Molecular Oncology in Italy.

It was funded by grants from the US National Institutes of Health (NIH) and the US National Institute on Aging (NIA).

The study was published in the peer-reviewed journal, Cell. It's available on an open access basis and is free to read online (PDF, 6.74Mb).

The UK media coverage of the research is generally accurate. BBC News provided useful advice from one of the authors, Dr Longo, who cautioned: "Do not try this [fasting] at home. This is so much more sophisticated than people realise". 

What kind of research was this?

This animal study examined whether a diet mimicking fasting cycles is able to promote the generation of new pancreatic beta cells in a mouse model of diabetes.

Beta cells are found in the pancreas. The cells' primary function is to store and release insulin in response to changes in blood glucose concentration.

In people with diabetes, the beta cells are either destroyed by the person's own immune system (type 1) or are unable to produce a sufficient amount of insulin (type 2).

Beta cells are reported to be highly sensitive to the availability of nutrients. The researchers wanted to see whether prolonged fasting and refeeding could regenerate pancreatic cells.

Animal studies like this one are useful early-stage research to help better our understanding of cellular mechanisms.

However, the human body has complex biology and we're not identical to mice, so further studies would be needed to see whether the same effects are observed in humans.

What did the research involve?

The first phase of the study involved male mice aged 10-16 weeks, some of whom had injections of a chemical to destroy their beta cells to mimic type 1 diabetes. Others were genetically bred to have type 2 diabetes, and normal mice acted as controls.

The researchers put the mice on a four-day fasting regimen consisting of a low-calorie, low-protein, low-carbohydrate and high-fat (FMD) diet.

They were fed 50% of their standard calorie intake on day one, followed by 10% of their normal calorie intake on days two to four.

At the end of the four days, the mice were fed regularly for up to 10 days to ensure they regained their body weight before the next fasting cycle. They underwent three dietary intervention cycles.

Blood glucose measurements were taken regularly. Pancreatic cell samples were taken to look at gene activity and investigate whether there were any changes.

The second phase of the study involved analysing human pancreatic cell samples collected from people with type 1 diabetes. 

Researchers also recruited healthy human adult volunteers without a history of diabetes, who underwent three cycles of a similar five-day fasting regimen. The blood samples from these people were applied to the cultured pancreatic human cells.

What were the basic results?

In the mouse model of type 2 diabetes, after the FMD cycles insulin secretion was restored and insulin resistance was reduced. The FMD cycles seemed to induce beta cell regeneration.

In the mouse model of type 1 diabetes, FMD cycles were able to reduce inflammation and promote changes in the levels of cytokine proteins, which may indicate the restoration of insulin secretion. There was an increase in the proliferation and number of beta cells generating insulin.

The results in the human cell samples suggested similar findings to those seen in mice. FMD cycles – that is, in blood samples from fasted individuals applied to human pancreatic cells in the laboratory – may be able to promote reprogramming of cell lineages and generate insulin in pancreatic islet cells.

How did the researchers interpret the results?

The researchers concluded that, "These results indicate that an FMD promotes the reprogramming of pancreatic cells to restore insulin generation in islets from T1D [type 1 diabetes] patients and reverse both T1D and T2D [type 2 diabetes] phenotypes in mouse models." 

Conclusion

This animal study examined whether a diet mimicking fasting cycles would be able to promote the generation of new insulin-producing pancreatic beta cells in a mouse model of diabetes.

Overall, researchers found in mice models of both type 1 and type 2 diabetes, insulin secretion was restored and insulin resistance and beta cells could be regenerated or have their function restored. Very early laboratory study on human cell samples suggested similar potential.

These results show promise, but further research is needed to validate these findings in humans.

Professor Anne Cooke, professor of immunology at the University of Cambridge, commented: "This is good science and does give promise for the future treatment of diabetes, but we need further studies to see whether this works in people as well as it has in mice."

Don't suddenly try fasting, or any other radical change to your diet, without first consulting the doctor in charge of your care. Sudden changes to your diet could cause complications.

Links To The Headlines

Fasting diet 'regenerates diabetic pancreas'. BBC News, February 24 2017

Hope for millions of diabetics as condition could be reversed with yo-yo starvation diet. Daily Mirror, February 23 2017

Fasting diet could prove the cure for type 2 diabetes. The Times, February 24 2017 (subscription required)

Links To Science

Cheng C, Villani V, Buono R, et al. Fasting-Mimicking Diet Promotes Ngn3-Driven β-Cell Regeneration to Reverse Diabetes. Cell. Published online February 23 2017

Link between herpes in pregnancy and autism is unconfirmed

"'WOMEN infected with herpes while they are pregnant are twice as likely to have a child with autism', " The Sun reports.

The headline is prompted by a study looking at whether maternal infections during pregnancy are associated with the risk of neurological developmental disorders such as autism spectrum disorders (ASDs).

However, The Sun has focused on only one result of a much larger set of findings – none of which were able to confirm the association between maternal infections and autism in children.

The Norwegian study looked at levels of antibodies to several viruses in pregnant women, collecting samples at 18 weeks during pregnancy and after delivery. These antibodies would indicate current or previous infection or immunity following vaccination. They then followed up whether any of the women had children later diagnosed with autism.

It looked at levels of antibodies to the herpes "family" of viruses (HSV-1 and HSV-2), as well as rubella, toxoplasma gondii and cytomegalovirus (a common virus related to chickenpox).

The study initially found no association between any of the levels of antibodies during pregnancy or after delivery, and the development of ASD in boys or girls. When they performed numerous additional analyses, they found that high levels of antibodies to the HSV-2 virus during mid-pregnancy were associated with the development of ASD in boys. However, this was based on just 14 women so it not reliable.

While it is recommended to avoid the herpes virus during pregnancy due to the risks of complications, based on this evidence, autism is not one of these.

 

Where did the story come from?

The study was carried out by researchers from the US and Norway including Columbia University and the University of Oslo. It was funded by grants from the National Institutes of Health, the Jane Botsford Johnson Foundation, the Simons Foundation Autism Research Initiative, the Norwegian Ministry of Health and Care Services, the Norwegian Ministry of Education and Research and the Research Council of Norway.

The study was published in the peer-reviewed journal mSphere on an open-access basis, so the study is free to read online.

Both The Sun and the Mail Online are arguably guilty of scaremongering and inaccuracy in their reporting of the study. They did not point out any of the limitations of the study, in particular that the results are based on such a small number of women that they could have been down to chance.

In contrast, CNN provides useful contrasting opinions from independent experts. Its coverage includes a quote from Dr David Winston Kimberlin, a professor of paediatric infectious diseases, who says "pregnant women should not be worried about HSV-2 (genital herpes) as a cause of autism based upon the findings of this single exploratory research study".

 

What kind of research was this?

This was a case-control study that wanted to look at whether maternal infections during pregnancy are associated with the risk of neurological developmental disorders such as autism spectrum disorders (ASDs).

Autism spectrum disorders are characterised by various degrees of social impairment and deficits in language and communication. The development of the condition is not well understood, but both genetic and environmental factors are thought to play a role.

Infections during pregnancy have been suggested to be a risk factor for the development of several neurological disorders such as ASD in the offspring and this study wanted to explore this hypothesis further. It hoped to understand more about disease severity and whether that was dependent on the time of infection during pregnancy.

Case-control studies are a useful way of better understanding potential links between exposure and outcome for uncommon conditions. However, the study design means that they are more prone to bias so it's important to bear in mind that other factors may have a role to play in the suspected causal relationship.

 

What did the research involve?

This study used data collected as part of the Norwegian Mother and Child Cohort Study, which recruited pregnant mothers, fathers and their children in Norway from 1999 to 2008. The study collected maternal blood samples during week 18 of pregnancy and after delivery. Questionnaires on a variety of health outcomes and conditions were sent to the mothers when their children were three, five and seven.

This Autism Birth Cohort study used data on 442 mothers of children who reported in the questionnaires that their child had been diagnosed with ASD and 464 matched controls (mothers of children without ASD). The controls were matched based on sex, birth month and birth year.

Maternal blood samples had been analysed for levels of immunoglobulin G (IgG) antibodies to Toxoplasma gondii, rubella virus, cytomegalovirus (CMV), herpes simplex virus 1 (HSV-1) and HSV-2. If the IgG antibodies were present, this would indicate that the mother had been infected with the virus at some point in her life. Higher levels or rising levels would suggest current infection or reactivation of the virus. The researchers were able to assess this by comparing the test taken mid-pregnancy with post-pregnancy.

The data was then analysed to see whether there were any links between high levels of infection and the development of ASD in the children. External confounding factors were controlled for including: maternal age at delivery, maternal smoking during pregnancy, parity (number of births) and maternal education.

 

What were the basic results?

Mothers of children with ASD were more likely to be first-time mothers. Most women in each group had antibodies to rubella because of the vaccination programme. Around half of women in each group had antibodies to HSV-1 and CMV. Fewer had antibodies to Toxoplasma (10% of mothers in each group) or HSV-2 (12% in the control group and 13% in the ASD group).

The planned series of tests found no significant differences in the presence of any of the antibodies either during mid-pregnancy or after delivery and subsequent diagnosis of ASD in boys or girls.

The researchers then performed a number of additional unplanned analyses looking at the levels of antibodies to HSV-2 and risk of ASD. When they used a high cut-off level to suggest current infection during mid-pregnancy, they found that boys were more likely to get ASD (odds ratio 2.07, 95% confidence interval 1.06 to 4.06). However, this was based on around 10 women in the ASD group and four in the control group who had "high" levels of 640AU/ml or more (precise figures not provided, our estimates are based on graphs).

With such a small sample group any association could well have been the result of chance.

 

How did the researchers interpret the results?

The researchers concluded: "This is the first study to report an association between maternal anti-HSV-2 antibody levels and risk of ASD in offspring. Our data suggest that the presence of high levels of anti-HSV-2 antibodies at mid-pregnancy increases the risk of ASD in boys.

"We speculate that ASD risk associated with high levels of antibodies to HSV-2 is not specific to HSV-2 but instead reflects the impact of immune activation and inflammation on a vulnerable developing nervous system."

 

Conclusion

This was a Norwegian case-control study that looked at whether maternal infections during pregnancy are associated with the risk of neurological developmental disorders such as autism spectrum disorders (ASDs) in their children.

The study initially found no association between any of the pathogens during pregnancy or after delivery, and the development of ASD in boys or girls.

Further investigations suggested that high levels of HSV-2 virus antibodies during mid-pregnancy were associated with increased risk of the development of ASD in boys.

The researchers suggest that the suspected risk of ASD associated with high levels of virus is not down to the HSV-2 virus itself but the impact of inflammation and the subsequent activation of the immune system on child development during pregnancy

However, while this finding has been widely reported in the media, it is based on just 14 women so is not reliable. Performing repeated unplanned analyses is bound to come up with some association in the end through sheer chance.

It is important that pregnant women do take precautions to prevent herpes infection during pregnancy, especially the third trimester, as there is a risk of passing the virus on to the baby.

More research would be needed to confirm the speculations that herpes infection during pregnancy can increase the risk of autistic spectrum disorder.  

Links To The Headlines

Pregnant women infected with herpes are ‘TWICE as likely to have a baby with autism’. The Sun, February 22 2017

Women who have a flare-up of herpes - or are infected - during early pregnancy are twice as likely to have an autistic child, study warns. Mail Online, February 22 2017

Autism link to herpes during pregnancy may be overstated, experts say. CNN, February 22 2017

Links To Science

Mahic M, Mjaaland S, Bøvelstad HM, et al. Maternal Immunoreactivity to Herpes Simplex Virus 2 and Risk of Autism Spectrum Disorder in Male Offspring. mSphere. Published online February 22 2017

Five-a-day of fruit and veg is good, but '10 is better'

"Forget five a day, eat 10 portions of fruit and veg to cut risk of early death," The Guardian reports.

A major review found people who regularly ate 800g of fruit and veg a day – 10 portions – had a significantly lower risk of chronic diseases, such as heart disease.

Researchers looked at more than 350 studies from around the world that examined the impact of fruit and veg consumption on a range of health outcomes, such as cancer and stroke, as well as premature death.

They found eating more fruit and veg was linked to a lower risk of getting these diseases and dying early when eating up to 800g a day (around 10 portions), or 600g a day for cancer.

The specific types of fruit and veg associated with reducing the risk of developing different diseases were also listed.

So does that mean the 5 A DAY campaign that encourages people to have at least five portions of fruit and veg a day should be updated? Well, as Victoria Taylor of the British Heart Foundation argues: "There is no nutritional benefit in a guideline that is not followed."

Having five portions of fruit and veg a day was chosen by public health campaigners because it was seen as an achievable target for most people.

Dr Alison Tedstone, chief nutritionist at Public Health England, explained to the BBC that, "Whilst consuming more than five portions of fruit and vegetables a day may be desirable ... adding pressure to consume more fruit and vegetables creates an unrealistic expectation." 

Get tips on how to get your 5 A DAY.  

Where did the story come from?

The study was carried out by researchers from various academic and medical institutions in Norway, Imperial College London and Leeds University in the UK, and Harvard University and the Icahn School of Medicine in the US.

The study was funded by Olav og Gerd Meidel Raagholt's Stiftelse for Medisinsk Forskning, the Liaison Committee between the Central Norway Regional Health Authority and the Norwegian University of Science and Technology, and the Imperial College National Institute of Health Research Biomedical Research Centre. The funding body had no input into the design of the study.

The study was published in the peer reviewed International Journal of Epidemiology.

The UK media generally reported the story accurately. Some sources included quotes from independent experts, who explained 5 A DAY may not be the most optimal target, but was chosen for pragmatic reasons. 

What kind of research was this?

This was a systematic review and meta-analysis of studies looking at fruit and veg intake.

The researchers looked at fruit and veg intake and health outcomes, such as coronary heart disease, cardiovascular disease, cancer, stroke and death.

While a meta-analysis is good at summarising all research from a particular area, it's only as good as the studies it includes. Any limitations of the studies included will also be limitations of the meta-analysis.

In this case, all of the studies were prospective cohort studies. This means they are only able to show an association, and can't prove cause and effect.

What did the research involve?

The researchers analysed data from 95 prospective cohort studies that monitored people over time, and looked at fruit and vegetable intake and the risk of various diseases.

The studies were mostly from Europe and the US, but also included research from Asia and Australia. These were large studies, so there was data available for from 226,910 to 2,123,415 people for each analysis.

The relative risks for getting or dying from certain diseases was calculated for:

  • coronary heart disease
  • stroke
  • total cardiovascular disease
  • total cancer
  • all-cause deaths

The researchers looked at how each increase of 200g a day of fruit and vegetables affected the risk of disease and death.

They also estimated the number of early deaths worldwide that may be the result of eating less fruit and veg.

This was based on the assumption that the association between fruit and veg intake and the diseases was causal – in other words, how much fruit and veg a person ate was responsible for whether or not they developed a disease.

They also looked at specific fruit and vegetables and their association with risk.

What were the basic results?

Risk for each disease and death – other than cancer – was reduced with each 200g a day increase in fruit and vegetables up to 800g a day, and 600g a day for cancer.

So eating 800g a day of fruit and vegetables indicated the biggest reduction in risk.

For each 200g a day increase in fruit and veg, the risk of getting each health outcome was decreased by:

  • 8% for coronary heart disease (relative risk [RR] 0.92, 95% confidence interval [CI] 0.90 to 0.94)
  • 16% for stroke (RR 0.84, 95% CI 0.76 to 0.92)
  • 8% for total cardiovascular disease (RR 0.92, 95% CI 0.90 to 0.95)
  • 3% for total cancer (RR 0.97, 95% CI 0.95 to 0.99)
  • 10% for all-cause death (RR 0.90, 95% CI 0.87 to 0.93)

Researchers estimated that globally, a total of 5.6 million early deaths in 2013 were down to eating less than 500g a day of fruit and vegetables.

Researchers estimated that when using 800g a day as the optimal intake of fruit and vegetables, 7.8 million early deaths could have been avoided by people eating this amount.

The following specific fruit and vegetables were found to help reduce the risk of:

  • coronary heart disease – apples or pears, citrus fruit, fruit juices, green leafy vegetables, beta carotene-rich vegetables such as carrots and sweet potato, and vitamin C-rich fruit and vegetables
  • stroke – apples or pears, citrus fruit, green leafy vegetables and pickled vegetables
  • cardiovascular disease – apples or pears, citrus fruit, carrots, green leafy vegetables and non-cruciferous vegetables such as butternut squash
  • total cancer – cruciferous vegetables such as cauliflower and broccoli
  • all cause of death – apples or pears, berries, citrus fruit, cooked or raw vegetables, cruciferous vegetables, potatoes and green leafy vegetables or salads
How did the researchers interpret the results?

The researchers concluded that, "In this meta-analysis of 95 studies (142 publications), reductions in risk of cardiovascular disease and all-cause mortality were observed up to an intake of 800g/day of fruit and vegetables combined, whereas for total cancer no further reductions in risk were observed above 600g/day.

"Inverse associations were observed between intake of apples/pears, citrus fruits, green leafy vegetables/salads and cruciferous vegetables and cardiovascular disease and mortality, and between green-yellow vegetables and cruciferous vegetables and total cancer risk."

They added that, "An estimated 5.6 and 7.8 million premature deaths worldwide in 2013 may be attributable to a fruit and vegetable intake below 500 and 800g/day, respectively, if the observed associations are causal." 

Conclusion

This research supports the idea that the more fruit and veg you eat the better – at least, up to 10 portions (800g) a day.

It also suggests the number of people who die early might be reduced if they were to eat more than the current recommended guideline daily amount.

However, before we take this at face value, there are some important considerations:

  • There are likely to be many confounding factors that may have affected the results. It might be that people who eat a lot of fruit and veg are also more likely to be physically active, consume less alcohol, not smoke and be a healthy weight, or other factors that might mean better health outcomes. It's not just fruit and vegetable intake that influences the risk of getting certain diseases and dying early.
  • The study didn't look at all diseases, such as infectious or respiratory conditions, so it might be the case that eating more fruit and veg than the guideline amount is not beneficial for reducing the risk of developing all diseases.
  • The studies included might have varied in several ways – for example, the country the research was conducted in might have influenced things like the way fruit and vegetables were prepared, the different types of fruit and vegetables available, and other dietary and lifestyle factors.
  • There were few studies looking at the specific types of fruits and vegetables, so it might be there are other fruit and vegetables that are also beneficial but not listed.
  • There were considerable differences between the studies. This means that when you pool their results together, you need to view the results with some caution. This was particularly true for cancer, stroke and all causes of death.
  • As with most studies assessing diet, they are reliant on accurate self-reporting of food intake, and may not take into account changes in diet over time.

Despite these limitations, this was a strong piece of research with good statistical methodology.

If you're in the majority of the UK public who struggle to get their 5 A DAY, current advice may be a more realistic goal to aim for in the short term.

Get more advice and tips on how to make 5 A DAY part of your daily life.  

Links To The Headlines

Forget five a day, eat 10 portions of fruit and veg to cut risk of early death. The Guardian, February 23 2017

Fruit and veg: For a longer life eat 10 a day. BBC News, February 23 2017

Find five-a-day a struggle? Now experts say you should eat ten to reduce the risk of cancer or stroke. Daily Mail, February 23 2017

Forget five-a-day, eat 10 fruit and veg to prevent premature death. Sky News, February 23 2017

Eat 10 fruit and veg a day for a longer life, not five. The Daily Telegraph, February 23 2017

Links To Science

Aune D, Giovannucci E, Boffetta P, et al. Fruit and vegetable intake and the risk of cardiovascular disease, total cancer and all-cause mortality–a systematic review and dose-response meta-analysis of prospective studies. International Journal of Epidemiology. Published online February 22 2017

Exercise 'most proven method' to prevent return of breast cancer

"A half hour stroll a day can help women who've survived breast cancer prevent the killer disease returning," The Sun reports.

A review of recent evidence, carried out by Canadian researchers, was prompted by the fact that many women who undergo treatment for breast cancer are eager to make lifestyle changes that may help reduce the risk of the cancer returning. But there is a great deal of often conflicting advice, so it is hard to make an informed decision.

The researchers' review of evidence found that physical activity had the strongest reported effect on reducing the risk of breast cancer recurring and dying from breast cancer.

Following the recommended 150 minutes of moderate to vigorous exercise or 75 minutes of vigorous exercise per week guidance, as well as two to three weekly sessions of strength training, can help reduce the risk of breast cancer returning and death from the disease.

The effects of treatments such as surgery and chemotherapy can take a toll on motivation to exercise. But clinical guidelines recommend a gradual return to regular exercise.

 

Where did the story come from?

The study was carried out by researchers from the Division of medical Oncology and Hematology, Odette Cancer Centre Sunnybrook Health Sciences Centre, Toronto, Canada.

The researchers did not report any funding for the study and declared no competing interests.

The study was published in the peer-reviewed Canadian Medical Association Journal and is open-access meaning it is free to read online.

The Mail Online and The Sun reported the story very similarly, emphasising the importance of exercise in reducing risk of relapse.

Interestingly, the headline of The Sun was very positive, "brisk 30-minute walk a day 'STOPS killer breast cancer returning'," whereas the Mail Online took a much more pessimistic stance, "boozing, weight gain and failing to exercise INCREASES the risk of breast cancer returning".

It should be pointed out that The Sun's headline is not entirely accurate as we only know that exercise reduces the risk and doesn't actually stop it.

The Sun also quotes one of the authors of the study, Dr. Ellen Warner, who cautions that "some breast cancers have aggressive biology and will recur despite the most meticulous lifestyle behavior … Patients should not be made to feel that inadequate lifestyle changes have led to recurrence of their cancer."

 

What kind of research was this?

This was a review of systematic reviews (and related meta-analyses) and primary research, that aimed to summarise the role of lifestyle factors in the prognosis of women who have had breast cancer.

It aimed to identify which lifestyle changes can be recommended to women in addition to breast cancer treatments, to reduce their risk of future recurrence and death.

This type of review is a good way of summarising research in an area, however findings can only be as reliable as the studies included.

There were a variety of study types included, but most were systematic reviews of individual observational studies, so they were unable to account for all confounding factors and therefore reliability might be variable.

In addition, we don't know whether all relevant studies have been included. This means there is potential for selection bias.

 

What evidence on physical activity did they find?
  • A meta-analysis of 22 cohort studies found that physical activity can reduce the risk of deaths caused by breast cancer by around 40% (hazard ratio [HR] 0.59, 95% confidence interval [CI] 0.45 to 0.78). This is the biggest effect of any lifestyle factor on breast cancer outcomes.
  • At least 150 minutes per week of physical activity is recommended.

 

What evidence on weight management did they find?
  • Weight gain of more than 10% of baseline body weight during or after breast cancer treatment may reduce survival, but the evidence is weak and the result could be due to chance HR 1.17, 95% CI 1.00 to 1.38).
  • Weight gain of less than 10% is not associated with reduced survival.
  • Risk of recurrence of breast cancer may be increased by weight gain, but this is just based on observational studies. Therefore, many other factors could be responsible.
  • Women who are obese or overweight at breast cancer diagnosis have poorer outcomes.
  • It remains unknown whether weight loss has a preventive effect.

 

What evidence on diet did they find?
  • They did not find robust evidence on any diet and risk of recurrence or mortality.
  • Observational studies have not shown any difference between Western-style diets (high in processed grains, processed meats and red meat) and diets high in fruits, vegetables, whole grains and chicken on the rate of breast cancer recurrence.
  • Soy products were not found to increase breast cancer recurrence. There have been claims that, as soy contains phyto-oestrogens (which are similar to the hormone oestrogen), they could stimulate abnormal cell growth. The review actually found soy may reduce cancer risk, although evidence for this is weak.

 

What evidence on smoking did they find?
  • Based on a large observational study of 20,691 women, those who continue to smoke after a breast cancer diagnosis are 72% more likely to die from breast cancer than women who have never smoked (HR 1.72, 95% CI 1.13 to 2.60).
  • There is insufficient evidence on whether quitting smoking after diagnosis has an effect on breast cancer-specific survival, but it will reduce the risk of other cancers, such as lung cancer, and cardiovascular disease such as heart attack and stroke.

 

What evidence on alcohol intake did they find?
  • They could not say whether alcohol consumption affects breast cancer outcomes or not.
  • However, reducing alcohol consumption to one or fewer drinks per day reduces the risk of a new (not recurring) breast cancer.

 

What evidence on vitamin supplementation did they find?
  • Moderate increases in dietary vitamin C or oral supplementation may reduce breast cancer mortality. Randomised controlled trials are needed to confirm this.
  • Most patients would benefit from vitamin D supplementation, at least to optimise bone health.

 

Conclusion

This was a helpful summary of recent research into how lifestyle changes impact on the risk of breast cancer returning, but it does have some limitations.

Researching lifestyle factors separately is always difficult as they tend to clump together, making it difficult to pick apart individual factors. For example, people who are more physically active tend to have a healthier diet and are less likely to drink excessive amounts of alcohol or smoke.

While the researchers say many studies attempt to make adjustments for these confounding factors, it is difficult to know which studies did this and how successful they were. It is also possible that women who did not exercise were unable to because of adverse effects from their breast cancer treatment.

There is also the fact that lifestyle factors were only looked at after breast cancer diagnosis, when lifestyle before diagnosis might have long term effects.

Still, the conclusion that regular exercise appears to be the best option seems reasonable and appropriate. Aside from cancer prevention, regular exercise can also help reduce the risk of other chronic diseases, such as heart disease.

Read more about the benefits of exercise.

Links To The Headlines

Brisk 30-minute walk a day ‘STOPS killer breast cancer returning’. The Sun, February 21 2017

Boozing, weight gain and failing to exercise INCREASES the risk of breast cancer returning, experts say. Mail Online, February 21 2017

Links To Science

Hamer J, Warner E. Lifestyle modifications for patients with breast cancer to improve prognosis and optimize overall health. Canadian Medical Association Journal. Published online February 21 2017

Long-term daily drinking linked to stiffening of the arteries in men

"Men who drink more than a pint a day over several years are at greater risk of heart attack or stroke," The Sun reports.

A UK study found men who consistently drank more than the recommended limits had signs of stiffening of the arteries, which has been linked to an increased risk of heart disease.

Researchers used data from more than 3,000 British civil servants to examine the link. Participants reported their alcohol intake over a 20-year period.

Stiffness of the arteries was also measured using a device that looks at how pressure waves move through an artery – the faster the pulse wave moves, the stiffer the arteries.

Men who were frequent heavy drinkers across the follow-up period had stiffer arteries compared with frequent moderate drinkers. There were no significant findings seen for women. The reasons for this are unclear.

While the study cannot prove cause and effect, and stiffening of the arteries can have a range of causes, it does highlight the fact alcohol-related harms can affect anyone.

Frequently drinking more than the recommended limits can damage your health.

Learn more about the official alcohol guidelines.

Where did the story come from?

The study was carried out by researchers from University College London and the University of Cambridge.

Funding was provided by the UK Medical Research Council Alcohol and the European Research Council.

The UK Medical Research Council, the British Heart Foundation and the National Institutes of Health supported the Whitehall II study data collection.

The study was published in the peer-reviewed Journal of the American Heart Association on an open access basis, and it's free to read online.

The UK media got itself into a bit of a muddle about whether the study says drinking more than a pint a day, just a pint a day, or even just half a pint a week is linked to cardiovascular disease.

The research suggests drinking more than a pint a day is linked to cardiovascular disease. Men who consumed more than 112g of ethanol, assumed to be seven pints a week, were assessed as putting themselves at risk.

Many media sources have quoted Dr Darragh O'Neill, the study's lead author, who tried to explain his theory about these findings. "Heavier alcohol intake may activate certain enzymes that would lead to collagen accumulation, which could in turn exacerbate the rate of arterial stiffening." 

What kind of research was this?

This prospective cohort study aimed to evaluate the association between alcohol consumption and arterial stiffness. Arterial stiffness has been linked with increased cardiovascular disease risk.

Data from the Whitehall II cohort study, which included British civil servants, was used to find links and hypothesise.

This type of study is good for finding links, but can't prove cause and effect.

What did the research involve?

The study used data from the Whitehall II cohort study. This is an ongoing study that recruited British civil servants between 1985 and 1988.

Participants reported their alcohol consumption at regular intervals (described in the study as phases) over the following 20 years, up to 2007-09.

They were asked to report the number of glasses of wine, pints of beer or cider, and measures of spirits or liqueur they consumed in the week before each assessment. These values were then converted into ethanol volumes.

Participants' long-term drinking patterns over this follow-up were placed in categories.

Long-term drinker type (grams a week in each phase):

  • stable non-drinker – 0g
  • stable moderate drinker – 1-112g
  • stable heavy drinker – more than 112g
  • unstable moderate drinker – between 1g and 112g over more than half the phases, but more than 0g in phase 9
  • unstable heavy drinker – more than 112g across at least half, but not all, of phases 1-9 and more than 0g in phase 9
  • former drinker – 0g at phase 9, but intake more than 0g at any earlier phase

In 2007-09, participants completed repeat pulse wave velocity assessments. This is a measure of arterial stiffness – as waveforms travel faster through less elastic tissue, the higher the pulse wave velocity, the greater the arterial stiffness.

They also had their recent drinker type categorised at this time as:

  • no recent intake – 0g
  • recent moderate – 1-112g
  • recent heavy – more than 112g

Participants had pulse wave velocity measured again four to five years later in 2012-13.

Statistical modelling was used to investigate the link between the different drinker types and the relationship with arterial stiffness, and how this progressed over time.

The model was adjusted for potential confounders, including socioeconomic status, level of exercise, body mass index, blood pressure and cholesterol.

One-third of the full cohort (3,130 adults) had complete data available for analysis. The majority of the full cohort were male (74%) and white.

There were few current smokers, but the majority did not meet the recommended weekly exercise levels set by the World Health Organization. The researchers excluded people with cardiovascular disease.

What were the basic results?

Pulse wave velocity measurements taken at the start of the study period (2007-09) showed men who had a long-term heavy alcohol intake of more than 112g of ethanol a week had significantly stiffer arteries than those who drank moderately. There were no other significant findings at this time.

Over the following five years, all drinker groups showed some progression in their arterial stiffness.

But only male former drinkers showed significant progression compared with those who consistently had a moderate alcohol intake.

After full adjustment for all confounders, no significant links were seen between any of the drinker categories and arterial stiffness for women. It's not clear why this was the case.

How did the researchers interpret the results?

The researchers concluded that, "This work demonstrates that consistently heavy alcohol consumption is associated with higher cardiovascular risk, especially among males, and also provides new insights into the potential impact of changes in drinking levels over time.

"It discusses the additional insights possible when capturing longitudinal consumption patterns in lieu of reliance on recent intake alone." 

Conclusion

This prospective cohort study aimed to look at the relationship between long-term alcohol patterns and stiffness of the arteries as a potential indicator of cardiovascular health.

The researchers found men who were stable heavy drinkers had stiffer arteries compared with stable moderate drinkers.

Male former drinkers also had increasingly stiffer arteries over the following four to five years compared with consistent moderate drinkers. There were no significant findings seen for women at all.

But this study does have limitations:

  • This type of study is not able to prove drinking causes stiffness of the arteries. While the researchers have attempted to adjust for potential confounders, other factors may be responsible for the findings.
  • The study didn't find any significant links for female participants, but this may be because they were under-represented in the sample, at only 23.6%.
  • Data for alcohol consumption was self-reported, and this is subject to bias.
  • Assumptions were used to calculate the ethanol content within the drinks, but this can vary widely between beers and wine.
  • Although the study looked at stiffness of the arteries as a proxy indicator, it didn't assess whether long-term drinking patterns are associated with actual health outcomes, such as high blood pressure, stroke or heart disease.

We all know drinking more than the recommended allowance can damage our health.

To reduce health risks from drinking alcohol, the government advises men and women to not regularly drink more than 14 units a week. If you're drinking this many units, it's better to spread them out over three or more days.

Heavy drinking sessions are known to increase your risk of long-term illnesses, including certain cancers, and also increase your risk of accidents.

Read more about the risks of drinking too much.

Links To The Headlines

Drinking more than a pint a day 'puts men at higher risk of heart attack or stroke'. The Sun, February 21 2017

Just half a pint a week could increase risk of heart disease in men. Daily Mirror, February 20 2017

How just one pint a day can increase the risk of heart disease by prematurely ageing the arteries. Mail Online, February 21 2017

Just half a pint of beer a week increases risk of heart disease - new study. The Daily Telegraph, February 21 2017

Links To Science

O'Neill D, Britton A, Brunner EJ, Bell S. Twenty‐Five‐Year Alcohol Consumption Trajectories and Their Association With Arterial Aging: A Prospective Cohort Study. Journal of the American Heart Association. Published online February 20 2017

Worrying about work out-of-hours 'may be bad for the heart'

"Taking work home can be deadly," the Daily Mail warns.

A small study of London-based office workers found those who reported being frequently troubled by work-related issues had patterns of heart activity associated with stress and anxiety.

Researchers interviewed 195 adults aged between 20 and 62 (70% male) about what they termed work-related rumination.

This was defined as how often a person was troubled by work-related issues when they weren't at work, measured on a scale of one (never/seldom) to five (very often/always).

Based on the responses, the researchers then selected 36 people, 19 of whom were scored as high ruminators (frequent worriers) and 17 who were scored as low ruminators (infrequent worriers). 

On three consecutive weekday evenings, both groups wore a fitness band that combined a heart rate monitor and an accelerometer (a device that tracks physical activity) to look at their heart rate variability.

Heart rate variability is a measurement of the variability over time of the intervals between individual heartbeats. Reduced variability can be the sign of a "fight or flight" stress response being triggered.

Overall, the heart rate patterns suggested that the high ruminators were less relaxed than the low ruminators in the evening.

But despite the Mail's headline, this study certainly doesn't prove work-related thoughts are deadly. Short-term observations of a person's heartbeat cannot predict long-term health outcomes.

Nevertheless, it makes sense that constantly worrying about work can't be good for our mental wellbeing.

Read more about how to combat workplace stress.

Where did the story come from?

The study was carried out by researchers from the University of Surrey in the UK, the University of Pisa in Italy, and Lillehammer University College and Oslo University in Norway.

It was published in the peer-reviewed journal, Frontiers in Human Neuroscience. This is an open access journal, so it's free to read online.

No sources of funding are reported, but some of the authors declared being employees of a commercial company, BioBeats Group Ltd, which holds a patent for the devices used in this study.

While the Daily Mail's and The Sunday Times' reporting of the study was broadly accurate, both newspapers ran somewhat scaremongering headlines: "Taking work home is deadly" (The Sunday Times) and "Taking work home can be deadly" (the Mail). 

What kind of research was this?

This observational study aimed to see whether persistent work-related thoughts could be linked with changes in heart rate.

The researchers discussed the possibility that it's not the stress factor (stressor) itself, such as work, that may cause poor health, but the constant mental awareness of the stressor, even when it's not there.

This is called the theory of perseverative cognition – when individuals continue to experience unwanted mental thoughts related to a stressful situation.

This in turn causes constant physiological arousal, such as tension, sweating and a fast heart rate. Or, in layperson's terms, worrying a lot about something.

The researchers aimed to study this in a small sample of workers. This is useful for exploring the theory, but can't prove that thoughts about work caused the person's heart rate pattern or that, in turn, these changes would actually cause health problems further down the line.

What did the researchers do?

The researchers recruited a sample of individuals working full-time in the financial sector, specifically for the bank BNP Paribas. The data was collected with the help of the healthcare insurance company AXA-PPP.

The full sample included 195 adults aged between 20 and 62 (70% male) who completed a questionnaire on work-related rumination.

Participants answered questions such as, "Are you troubled by work-related issues when not at work?". Responses were on a five-point scale ranging from "very seldom/never" to "very often/always". 

The current study included a small subset of 19 high ruminators (32% female, average age 34) and 17 low ruminators (18% female, average age 33) who had full data available.

They wore a monitor (Microsoft Band v2) paired with an application that measured heart rate.

This collected data on heart rate over three consecutive minutes (followed by a three-minute rest), with accelerometer data measured in 15-second bursts followed by a 45-second rest.

The researchers looked at heart rate data collected between 8pm and 10pm on three consecutive weekday evenings (Monday to Wednesday) when the accelerometer indicated the person was stationary rather than walking or running.

What did they find?

The researchers calculated the root mean square successive differences (RMSSD). This is a mathematical tool that has been well validated in measuring stimulation of the parasympathetic nervous system.

This system is the network of nerves that help the body wind down and relax, as well as regulate the functions of the digestive system.

A low RMSSD score would indicate someone was having problems relaxing in the evening.

Researchers did find RMSSDs were significantly lower in the high ruminators compared with the low ruminators, suggesting that the high ruminators were less relaxed in the evening.

There was no significant difference in the average heart rate between the two groups, and no influence from age or gender. Nor was there any difference in levels of participant activity.  

What did the researchers conclude?

The researchers observed that, as expected, high ruminators had lower heart rate variability than the low ruminators.

They said their findings "may have implications for the design and delivery of interventions to help individuals unwind post work and to manage stress more effectively". 

Conclusions

This research lends support to the theory that people who persistently worry about work may be less relaxed in the evenings compared with those who don't think about work once they've left the office.

However, before we conclude too much from this research, there are several limitations to consider:

  • This is a very small, selective sample of 36 people working for a company involved in banking and financial services. They were part of a much larger cohort and were selected for this sub-study because they were identified as being the highest or lowest ruminators, and furthermore had full data available. They may not be representative of this full cohort, or of the wider population in other areas of work.
  • The questionnaire may not be able to comprehensively assess the person's level of stress around work, or to what extent other health or personal circumstances may contribute to stress.
  • Though the heart rate variability of the high ruminators suggested they were less relaxed, we don't actually know what they were worrying about at the time. It may have been nothing to do with work – in other words, the study doesn't prove work is the cause of these observations. 
  • The measures were only taken on three consecutive evenings – we don't know how representative these heart rate measures are of long-term patterns.
  • Although the researchers say previous studies have linked heart rate variability with cardiovascular disease risk, this study doesn't directly prove that these observations are currently linked to any health problems, or will be in the future.

Nevertheless, it makes sense that being persistently stressed or worrying about work all the time can't be good for our wellbeing, if nothing else.

Technology can make it easier to work from home, but there is also the risk that work activities, or at least concerns about work, can invade our free time and cause both physical and mental distress.

Get advice on how to cope with work-related stress and how to achieve a better work-life balance through improved time management.

Links To The Headlines

Taking work home can be deadly: Staying connected to the office 24/7 'is linked to high stress levels and heart disease'. Daily Mail, February 19 2017

Taking work home is deadly. The Sunday Times, February 19 2017 (subscription required)

Links To Science

Cropley M, Plans D, Morelli D, et al. The Association between Work-Related Rumination and Heart Rate Variability: A Field Study. Frontiers in Human Neuroscience. Published online January 31 2017

Inappropriate antibiotic prescribing by online pharmacies 'reckless'

"Scientists found antibiotics illegally available on 45% of websites they tested," the Mail Online reports.

This headline was prompted by research into 20 online pharmacies selling antibiotics to the UK public.

Researchers looked at whether the online pharmacy was properly registered – and therefore legal – as well as whether they required a prescription before selling the antibiotics and if safety information was provided.

The majority of sellers were not registered and therefore illegal. Most were thought to be based outside the UK, although half did not provide details on where they were based. Almost half did not require a prescription to purchase antibiotics.

The finding that the UK public are buying antibiotics from illegal unregistered prescribers is worrying, particularly when they can choose the specific antibiotic and dose themselves.

Because antibiotics have been overused and prescribed inappropriately, the drugs are losing their effectiveness at treating bacterial infections (antibiotic resistance). The more we use them, the greater the chance bacteria will become resistant to the drugs.

If the ticking timebomb of antibiotic resistance continues, we could end up in a world where previously trivial infections are untreatable.

It's important to use antibiotics in the right way – to use the right medicine, at the right dose, at the right time, for the right duration.

Always consult a GP or another health professional before taking antibiotics, and only take antibiotics and medication that has been specifically prescribed for you.

Where did the story come from?

The study was carried out by researchers from Imperial College Healthcare NHS Trust, the National Institute for Health Research Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance, and the UCL School of Pharmacy, all in the UK.

It was funded by the National Institute for Health Research Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance at Imperial College London, in partnership with Public Health England and Imperial College Healthcare NHS Trust and the Imperial National Institute for Health Research Biomedical Research Centre.

Three authors declared consulting for pharmaceutical companies, but state that the views expressed are their own.

The study was published in the peer-reviewed Journal of Antimicrobial Chemotherapy.

The UK media's reporting of the study was accurate.

Professor Dame Sally Davies, the government's chief medical officer, is quoted in the Mail Online as saying: "Clinicians across the country are making great progress in reducing inappropriate prescriptions, and this cannot be undermined by reckless illegal online pharmacies."

She added: "It is essential that we look after our antibiotics and only use them where clinically appropriate.

"Inappropriate use drives the development of drug-resistant infections, which could halt treatments and operations that we consider routine, such as hip operations, chemotherapy and caesareans." 

What kind of research was this?

This cross-sectional analysis of data aimed to look at the quality and legal status of online pharmacies selling antibiotics to the UK public.

It aimed to describe the processes for obtaining antibiotics online and look at the approach to promoting and monitoring the use of antimicrobials, including antibiotics, and examine patient safety issues.

Cross-sectional analyses are good at looking at the overall picture at a specific point in time. But they can't show trends over time, so can't tell us if the quality and legality of online pharmacies and the process of obtaining antibiotics online is getting worse or better.

What did the research involve?

This was an exploratory cross-sectional analysis of a representative sample of online pharmacies with the overall aim of understanding the current state of online antibiotic sales in the UK.

A search for "buy antibiotics online" was done on Google and Yahoo, as researchers said these were two of the most popular search engines in the world.

They took 20 websites in total, including the first 10 identified from each search engine, that were in English and selling to consumers within the UK. They then looked to identify the country the website was operating from.

The researchers aimed to understand the state of online antibiotic sales in the UK.

They reviewed the 20 websites by:

  • assessing the quality and legal status of these online pharmacies using registration status as an indication of quality and legal status
  • identifying any Antibiotic Stewardship or patient safety issues 
  • analysing the processes for purchasing online antibiotics, and if these were consumer-driven or prescriber-driven

Consumer-driven was described as whether the customer first selected an antibiotic of their choice to put in their online shopping basket.

Prescriber-driven was when the customer was directed through an online consultation after clicking on a specific illness, and an antibiotic was selected by the online prescriber if required.

What were the basic results?

Of the 20 websites selling antibiotics:

  • 15 were not registered with the necessary bodies – the General Pharmaceutical Council (GPhC) in Great Britain or the UK Medicines and Healthcare products Regulatory Agency (MHRA), who also investigate websites suspected of operating illegally. Of these 15, three were operating from India, two from Cyprus, and the location was unclear for the rest. The five sellers registered with the GPhC and MHRA were all operating from the UK.
  • 16 of the 20 websites were consumer-driven regarding antibiotic choice, dose and duration. This meant people could put the medicine in their shopping basket straight away without having an online consultation or providing a prescription.
  • 9 of the 20 websites did not require a prescription before buying antibiotics.
  • 14 of the 20 websites did provide information before purchase on safety and possible side effects, or when to avoid using antibiotics.

At the end of the study, all online providers found to be illegally selling antibiotics within the UK were reported to the MHRA.

How did the researchers interpret the results?

The researchers concluded: "Wide variation exists among online pharmacies in relation to antibiotic practices, highlighting considerable patient safety and antibiotic stewardship issues.

"Improved education, legislation, regulation and new best practice stewardship guidelines are urgently needed for online antibiotic suppliers."

They added: "In order to promote patient safety and preserve antibiotic therapy, an efficient and operational multidisciplinary taskforce is needed to address the issues we have identified." 

Conclusion

Worryingly, most of the online pharmacies had no evidence of the registration required by current UK and European legislation.

This could be because some of the operators were based outside Europe – but regardless of where they are based, they are still subject to UK legislation if selling to the UK public.

The study raises concerns about the effectiveness of current UK legislation and the regulation of companies selling antibiotics over the internet.

This research does have some limitations, however:

  • Google and Yahoo searches are not identical when different browsers are used or when searches are performed at different times. This means other websites might have been identified at a different time.
  • Illegal sellers might change their name frequently to remain operational, so the same seller might have been identified more than once in this search under different names.
  • The researchers did not proceed to payment in their investigation of the sellers, so extra information on safety or prescribing might have been missed. Websites without information about requiring a prescription might have asked for one at a later stage or refused to prescribe antibiotics.

Aside from the clear safety issues, buying antibiotics online without a prescription can contribute to the growing problem of antibiotic resistance, where antibiotics are no longer effective against infections.

If you think you may need antibiotics, get advice from your GP or pharmacist. Your GP will prescribe medication, including antibiotics, if it is safe and appropriate to do so.

People can help fight the problem of antibiotic resistance by:

  • not buying antibiotics online
  • using antibiotics only when prescribed by a health professional
  • recognising that many coughs and colds, sore throats and stomach upsets are viral and do not need – and will not get better – with antibiotics
  • taking the full course of antibiotics as prescribed, even if you start to feel better
  • never sharing or passing on antibiotics to others

Sourcing antibiotics from a foreign country, especially without consultation with a GP, is not recommended.

Aside from the concerns mentioned above, the safety profile of the drug itself may not match the rigorous UK standards for pharmaceutical manufacturing.  

Links To The Headlines

Web chemists fuelling superbugs crisis by selling antibiotics without prescription and letting patients choose their own dosage. Mail Online, February 17 2017

Online pharmacies illegally handing out antibiotics are fuelling rise of superbugs. The Daily Telegraph, February 17 2017

Links To Science

Boyd SE, Moore LSP, Gilchrist M, et al. Obtaining antibiotics online from within the UK: a cross-sectional study. Journal of Antimicrobial Chemotherapy. Published online February 17 2017

Could brain scans be used to screen for autism?

"Brain scans could identify babies most at risk of developing autism, study shows," The Guardian reports.

Researchers think that looking for distinct changes in infant brains could identify some children with autistic spectrum disorder (ASD).

A small US study used MRI scans to look at the brains of around 150 infants – 106 were thought to be at high risk of developing autism because of their family history. Autism can run in families, with multiple siblings being affected.

This study found some shared signs of unusual brain overgrowth in 15 high-risk infants at 6 and 12 months old. All of the 15 then went on to be diagnosed with ASD at 24 months.

However, 15 children is too small a number to have confidence in these results. If the results could be replicated in larger studies, a screening method could perhaps be created for children thought to be at high risk of the condition.  

Even then, because of the complex nature of ASD, it's likely that further assessment using a combination of behavioural and psychological tests would still be required.

Early signs and symptoms of ASD in preschool children include delayed speech and language development, repetitive behaviour, not responding to their name being called, and little interest in interacting with others.

Visit your GP or health visitor if you're concerned about your child's development.

Where did the story come from?

The study was carried out by researchers from several institutions in the US, including the University of North Carolina, the University of Minnesota and New York University.

It was funded by a grant from the US National Institutes of Health, Autism Speaks and the Simons Foundation.

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

The UK's media coverage on this research was generally poor. The Mail Online in particular reported that "scientists used MRI scan[s] to diagnose [the] condition in hundreds of babies under two years old", which is simply not true. ASD was not diagnosed by the MRI scans, it was diagnosed using traditional methods.

Differences in the MRI brain scans were only seen in 15 children out of 148, and we don't know if these changes are related to ASD or not.

What kind of research was this?

This was a proof of concept study that used brain scans and data from the Infant Brain Imaging Study (IBIS) to investigate whether ASD could be detected in six-month-old children at high risk of the condition before symptoms emerged.

Children with ASD tend to present with symptoms such as problems with social interaction and communication before the age of three.

Previous studies have shown that social deficits characteristic of ASD sometimes emerge in early childhood during the first and second years of life.

Small studies have also suggested there may be brain changes that start before 24 months of age, but these have not been validated.

ASD has been known to run in families. This study wanted to see if brain changes associated with the condition could be detected earlier in children at high risk of developing ASD. They also wanted to know if it could be detected early in children who were at low risk.

What did the research involve?

This analysis used data from the Infant Brain Imaging Study (IBIS), a network study that collected clinical data from four hospitals in the US.

IBIS enrolled children at both high and low risk of ASD. Children were defined as high risk if they had an older sibling clinically diagnosed with ASD.

Infants entered the study at six months of age, and the same children were followed up at 12 and 24 months.

The children were assessed using a brain MRI scan at each of these three time points. The MRI images were used to obtain brain tissue volumes and measurements of the surface area of the brain and cortical thickness.

Further tests measured cognitive development, adaptive functioning and behaviours associated with autism. The assessments were made using the Mullen Scales of Early Learning and the Vineland Scales of Adaptive Behaviour.

Autism-specific assessments included the Autism Diagnostic Interview-Revised, the Autism Diagnostic Observation Scale, and the Symbolic Behaviour Scales of Development Profile.

The final diagnosis of ASD was made by a clinician at 24 months of age using these tools.

This analysis looked at data for 106 high-risk individuals and 42 low-risk children. The researchers analysed the data to see if there were associations between diagnosis of ASD at 24 months and any clinical symptoms earlier in infancy.

What were the basic results?

There were noticeable brain changes in 15 infants below the age of 24 months who went on to be diagnosed with ASD at 24 months.

The changes seen were increased cortical surface area expansion at 6-12 months and brain overgrowth at 12-24 months. The emergence of social deficits characteristic of the condition became apparent during this time period.

There was no difference in total brain volume growth at 6-12 months between the high-risk and low-risk infants.

However, total brain volume growth rate was increased in the high-risk group during the second year of life, when compared with low-risk children. There was no difference between the groups in cortical thickness.

How did the researchers interpret the results?

The researchers concluded: "These findings demonstrate that early brain changes occur during the period in which autistic behaviours are first emerging.

"Our data suggest that very early postnatal hyper expansion of cortical surface areas may have an important role in the development of autism." 

Conclusion

This early-phase research suggests there may be brain changes associated with ASD, and MRI scans could potentially be used to aid earlier diagnosis.

However, we don't know if these changes are present in all children with ASD. Much larger studies would be required to see if this is the case.

The researchers suggest these findings may have implications for the early detection of and intervention for ASD.

However, any such test would need to have a high degree of accuracy to avoid over- or under-diagnosis of ASD in infants. Even if this test was well validated, it would probably be just the start of a process of diagnosis.

Early signs of ASD in preschool children fall into four main categories:

  • problems with spoken language
  • failing to respond to others
  • problems with social interaction
  • unusual behaviour

See your GP or health visitor if your child is showing symptoms of ASD or you're worried about their development.

If appropriate, your GP can refer you to a healthcare professional or team who specialise in diagnosing ASD.

Links To The Headlines

Autism detectable in brain long before symptoms appear. BBC News, February 15 2017

Accurate test for autism? Scientists use MRI scan to diagnose condition in hundreds of babies under 2 years old. Mail Online, February 15 2017

Brain scans could identify babies most at risk of developing autism, study shows. The Guardian, February 15 2017

Links To Science

Cody H, Hongbin Hm Brent G, et al. Early brain development in infants at high risk for autism spectrum disorder. Nature. Published online February 15 2017

'Add vitamin D to food to prevent colds and flu', say researchers

"Adding vitamin D to food would reduce deaths and significantly cut NHS costs," The Guardian reports.

A review of existing data estimates that supplementing food with vitamin D would prevent millions of cold and flu cases, and possibly save lives.

Researchers looked at data from 25 previous studies where vitamin D was compared with a placebo.

The studies explored the effect of vitamin D in preventing acute respiratory tract infections. These are infections of the body's airways, such as colds, flubronchitis and pneumonia. More than 10,000 people were involved in total.

Their analysis suggests daily or weekly vitamin D supplementation was useful in preventing respiratory tract infections. Perhaps unsurprisingly, supplementation was particularly beneficial for people who had very low levels of vitamin D.

The researchers concluded that these results add to the body of evidence that fortifying widely eaten foods with vitamin D would improve public health.

But this opinion is not shared by all experts in the UK. Professor Louis Levy, head of nutrition science at Public Health England (PHE), said: "The evidence on vitamin D and infection is inconsistent, and this study does not provide sufficient evidence to support recommending vitamin D for reducing the risk of respiratory tract infections."

As this debate is ongoing, it would seem sensible to stick to the relatively new guidelines about vitamin D – that is, everyone should consider taking supplements during the winter months.

Where did the story come from?

The study was carried out by researchers from a number of institutions, including Queen Mary University, Winthrop University Hospital in the US, and the Karolinska Institutet in Sweden.

No manufacturers of vitamin D supplements were involved in this research. Funding was provided by the National Institute for Health Research.

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

The findings of this research have been widely covered by the UK media, and the reporting has been accurate.

A number of quotes are provided from experts across all media sources to provide both sides of the argument for vitamin D supplementation and the reaction to this particular review.

The British Medical Journal itself includes an editorial from independent experts arguing that food should not be routinely fortified with vitamin D.

What kind of research was this?

This systematic review and meta-analysis investigated the use of vitamin D supplementation as a way of preventing acute respiratory tract infections such as flu, bronchitis and pneumonia.

This type of review is the best way of gathering all available evidence on a topic – but the findings can only be as reliable as the studies included. The researchers therefore only included high-quality evidence from randomised controlled trials (RCTs).

What did the research involve?

The researchers searched four literature databases and two clinical trial registries to identify RCTs that looked at the overall effect of vitamin D supplementation on risk of acute respiratory tract infection.

To be included in the review, studies had to compare vitamin D3 or D2 with a dummy pill (placebo).

They also had to be double blind, meaning that neither the participant nor the doctor knew which pill they were taking.

Finally, the trial needed to set out to look at the rates of respiratory infection, rather than this being an incidental finding.

The studies included in the analysis were all considered to be high quality according to a validated assessment using the Cochrane risk of bias tool, which assesses bias and skewed reporting.

The primary outcome of the meta-analysis was incidence of acute respiratory tract infection of any location.

When analysing the pooled data, the researchers adjusted for the potential confounding effects of age, sex and duration of the study.

They also performed subgroup analyses, where a data set is split into smaller groups to check for possible patterns, to see if other factors such as asthma and body mass index affected the results.

But the researchers weren't able to analyse the results according to whether people had chronic obstructive airways disease (COPD) or if they had been given a flu vaccine.

What were the basic results?

In total, 25 RCTs from 14 countries, including the UK, were included. These involved a total of 11,321 participants, aged from 0-95 years.

After pooling the findings, vitamin D supplementation was found to reduce the risk of acute respiratory tract infection by 12% (adjusted odds ratio [aOR] 0.88, 95% confidence interval [CI] 0.81 to 0.96).

By splitting the participants into smaller subgroups, a statistically significant protective effect was seen for those who had daily or weekly vitamin D supplementation without large one-off doses (aOR 0.81, 95% CI 0.72 to 0.91) but not for those receiving one or more large one-off doses (aOR 0.97, 95% CI 0.86 to 1.10).

Among those receiving daily or weekly vitamin D, protective effects were stronger for those with lower vitamin D levels at the start of the study and people with asthma. 

There were no serious adverse events or deaths linked to supplementation.

How did the researchers interpret the results?

The researchers concluded: "Our study reports a major new indication for vitamin D supplementation: the prevention of acute respiratory tract infection.

"We also show that people who are very deficient in vitamin D and those receiving daily or weekly supplementation without additional bolus doses experienced particular benefit.

They added: "Our results add to the body of evidence supporting the introduction of public health measures such as food fortification to improve vitamin D status, particularly in settings where profound vitamin D deficiency is common." 

Conclusion

This was a systematic review and meta-analysis investigating the use of vitamin D supplementation as a way of preventing acute respiratory tract infections such as flu, bronchitis and pneumonia.

The study found vitamin D supplementation to be useful in the prevention of acute respiratory tract infection. People who are very deficient in vitamin D and those receiving daily or weekly supplementation without additional large one-off doses had a larger benefit.

This study has both strengths and limitations. It is very well designed and includes high-quality evidence. The researchers made efforts to reduce the risk of bias and investigate possible areas where bias may exist in their study.

They provided the following limitations:

  • Analysis suggests the results may have been subject to some degree of publication bias, so some small trials showing adverse effects of vitamin D may not have been included.
  • The study was not adequately powered to detect effects of vitamin D supplementation in some subgroups, such as people with COPD.
  • Data relating to adherence to supplementation was not available for all participants.

PHE guidelines published in the summer of 2016 recommend adults and children over the age of one should consider taking a daily supplement containing 10 micrograms (mcg) 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.

But PHE currently does not recommend the routine fortification of common foodstuffs with vitamin D.

In the words of Professor Louis Levy, head of nutrition science at PHE: "The evidence on vitamin D and infection is inconsistent, and this study does not provide sufficient evidence to support recommending vitamin D for reducing the risk of respiratory tract infections."

Another way to protect yourself during the winter is to make sure you have the seasonal flu jab if you're vulnerable to the effects of flu.

Read more about who should have the seasonal flu vaccination.

Links To The Headlines

Adding vitamin D to food reduces deaths, say scientists. The Guardian, February 15 2017

Vitamin D pills 'could stop colds or flu'. BBC News, February 16 2017

Put vitamin D in milk and bread: 'Three million people a year would escape colds and flu' if it was added to food. Daily Mail, February 16 2017

Vitamin D pills 'key to beating colds and flu' says study. ITV News, February 16 2017

Vitamin D supplements could prevent colds and flu, according to a new study. Metro, February 16 2017

Links To Science

Martineau AR, Jolliffe DA, Hooper RL, et al. Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data. BMJ. Published online February 15 2017

Heading footballs 'linked to brain damage in professional players'

"As evidence of dementia link to football emerges is it time to stop kids heading the ball?" is the question on the front page of the Daily Mirror.

The headline was prompted by the results of a small study where post-mortems were carried out on six ex-professional players with a history of dementia.

Researchers found four players had a pattern of brain damage known as chronic traumatic encephalopathy (CTE).

CTE was first identified in boxers and then in athletes who took part in other sports where blows to the head are common, such as American football and wrestling.

The proposed reason for injury was repeated heading of the ball. The researchers estimate a professional footballer playing in positions like central defence or centre forward will head the ball at least 2,000 times over the course of their career.

While these results sound concerning, this was a small descriptive study and hasn't proved repeated headers were the cause of the brain damage seen in the players.

As Dr David Reynolds of Alzheimer's Research UK pointed out, the benefits of regular exercise in terms of dementia prevention may well outweigh any risk, especially for those who play football on a recreational basis.

A large study following up footballers without dementia is now needed to see who develops the condition.

Comparisons can then be made between those with and without dementia, which may be able to identify risk factors like frequency of heading.

As for the question asked by the Daily Mirror, like most headlines that end in a question mark, the answer is likely to be "we don't know". 

Where did the story come from?

The study was carried out by researchers from University College London, Cardiff University and the Cefn Coed Hospital in Swansea.

It was funded by the National Institute for Health Research and the Drake Foundation, a not-for-profit organisation set up in 2014 to fund research into concussion injuries in sport.

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

The study was widely covered in the UK media. While some of the headlines were possibly alarmist, the actual body of the reporting was well balanced.

For example, the Daily Mirror included a column from the lead author of the study, Dr Helen Ling, who said: "It is important to note we studied only a small number of retired footballers with dementia and still do not know how common dementia is among footballers.

"The most pressing question is now to find out if dementia is more common in footballers than in the normal population." 

What kind of research was this?

This was a case series study where a small number of football players who already had dementia were clinically assessed over a long period of time.

Case series are not able to show an association because all the participants already have the condition and there is no comparison group.

This means researchers are not able to account for other possible causes or confounding factors. They are useful types of studies for generating hypotheses that can then be assessed in larger cohort studies.

These larger cohort studies typically involve a large number of people in the population without a condition who are followed up over time to see who develops it. Comparisons can then be made between people with and without the condition.

Cohort studies tend to be large enough to be able to show an association between certain factors – for example, frequent football heading and brain damage – but they cannot prove one factor causes another.

What did the research involve?

Fourteen retired footballers with dementia were regularly clinically assessed by a psychiatrist between 1980 and 2010 until they died. The next of kin of six of the players agreed for them to have a post-mortem brain examination.

In 2015-16 the researchers obtained the following information from the players' medical notes and through interviews with close relatives:

  • football playing career – position and years spent playing
  • other sports
  • military service
  • number and severity of any concussions
  • medical history
  • family history
  • dementia history – age at onset and symptoms
What were the basic results?

Symptoms of dementia began at an average age of 64 years in the retired footballers.

Thirteen had been professional footballers and one was described as a committed amateur. They had started playing football in childhood or their early teens, and on average played for 26 years.

All were reported to have been skilled at heading the ball. Six footballers were reported to have had one concussion each, five of them with loss of consciousness.

These five cases had a post-mortem examination. One of these men was also an amateur boxer.

The post-mortem examinations found all six men had Alzheimer's disease and deposits of a protein called TDP-43, which is found in motor neurone disease (MND).

All six also had some features of CTE. Four of them fulfilled the criteria for CTE diagnosis.

Some of them also had features of other neurological conditions, including vascular dementia, where symptoms occur when the brain is damaged because of problems with blood supply to the brain.

How did the researchers interpret the results?

The researchers made it clear that no firm conclusions could be drawn from this type of study.

They call for "large-scale case-control studies" comparing people who play football with athletes without increased risk of repetitive head impact.

They recommend that repeated clinical assessments over time should include high-tech brain imaging, psychological tests, genetic data and samples of cerebrospinal fluid (CSF).

Conclusion

There is growing concern that repeated concussion in contact sports like American football and rugby increase the risk of CTE, which was first found in boxers.

This study raises questions as to whether less severe but repeated head impacts, such as those sustained by heading a football, could lead to brain damage later in life.

All six of the retired footballers who had a post-mortem showed features of CTE, but the study is not able to show that this was a result of heading footballs.

As CTE can only be diagnosed at post-mortem, it has been difficult to study the progress of the condition with any degree of accuracy.

We don't know how many people develop CTE, whether some people are more genetically susceptible, and what level and type of brain injury is required to cause the development of CTE over time.

The relationship between CTE and development of dementia also remains unclear.

The results of this study are interesting and will hopefully spark much needed larger cohort studies.

In the meantime, it's important to remember exercise is one of the best ways to reduce the risk of dementia.

Read more about the benefits of exercise.

Links To The Headlines

As evidence of dementia link to football emerges is it time to stop kids heading the ball? Daily Mirror, February 15 2017

Football headers 'linked to brain damage'. BBC News, February 15 2017

Footballers could be at risk of dementia from blows to the head, study suggests. The Guardian, February 15 2017

Heading a football raises the risk of dementia: Study of retired footballers finds that it can lead to brain damage. Mail Online, February 15 2017

Links To Science

Ling H, Morris HR, Neal JW, et al. Mixed pathologies including chronic traumatic encephalopathy account for dementia in retired association football (soccer) players. Acta Neuropathologica. Published online February 15 2017

GPs 'failing to prescribe tamoxifen to prevent breast cancer'

"Half of GPs unaware of drug's use [tamoxifen] in cancer prevention," The Guardian reports.

An online survey of GPs found many were unaware of national guidelines recommending the use of tamoxifen for at risk women.

Guidance produced by the National Institute for Health and Care Excellence (NICE) in 2013 recommends women thought to be at high risk of developing breast cancer because they have a family history of the condition should be given the option to take the hormone therapy tamoxifen.

This survey of more than 900 GPs found around half knew tamoxifen can reduce the risk of breast cancer in women who don't currently have cancer but have a high risk because of their family history.

A quarter knew guidelines recommend tamoxifen for those at high risk, and three quarters would be willing to prescribe it to women at high risk.

One important factor not discussed in detail in the media is that tamoxifen is unlicensed for breast cancer prevention. While GPs have the power to prescribe unlicensed drugs if they think they would benefit an individual patient, they are often reluctant to do so.

A commonly reported concern is GPs feel they would be more liable for criticism if a patient developed side effects or complications.

A lot of the numbers being reported by the media are guesswork. A small survey cannot prove half a million women are "missing out" on preventative treatment.

If you're concerned about your family history of breast cancer, the first step is to talk to your GP.

Where did the story come from?

The study was carried out by researchers from the University of Leeds, University College London, Queen Mary University London and the University of Leicester in the UK and Harvard University in the US.

It was funded by Cancer Research UK. The authors declared no conflicts of interest.

The study was published in the peer-reviewed British Journal of General Practice and is open access, meaning it's free to read online.

The story was covered by a number of UK media outlets. While the media accurately reported around half of GPs surveyed were unaware tamoxifen can reduce breast cancer risk, some of the reporting was rather misleading.

The Sun stated that, "500,000 women at higher risk of cancer denied 6p prevention pill because GPs aren't clued up on latest research", a claim echoed in The Daily Telegraph's headline, "Breast cancer pill denied to 500,000 women".

In fact, 500,000 is the approximate number of patients who could hypothetically benefit from the pill. But the study did not report how many women actually received or asked for the pill and were "denied" it. The survey only looked at GP's attitudes and knowledge, not their prescribing history.

This drug isn't licensed for preventative use, so it isn't that surprising GPs aren't prescribing it for this group of patients.

While useful at a population level, the fact tamoxifen is not especially effective at an individual level was not discussed.

As the study itself mentions, for every 42 women taking tamoxifen over the course of 10 years, only one case of breast cancer would be prevented. Or, in other words, the number needed to treat (NNT) for tamoxifen is 42.

What kind of research was this?

This was a cross-sectional survey of GPs practising in the UK in 2016, undertaken online. It aimed to find out GPs' attitudes to prescribing tamoxifen for primary prevention in women at risk of breast cancer.

2013 NICE guidelines on hereditary breast cancer suggest women meeting specific criteria with a high risk of breast cancer may be offered tamoxifen for primary prevention, before cancer has developed. Tamoxifen may also be considered for women with a moderate risk.

However, as NICE highlighted in 2013, tamoxifen was not licensed for primary prevention of breast cancer, and this situation hasn't changed.

As this was a survey of a sample of GPs, it cannot be said to be representative of the views of all GPs in the UK, but does give a good idea of attitudes generally.

What did the research involve?

Researchers approached 13,764 GPs from across the UK, of which 928 completed the survey.

Respondents from Scotland were excluded as they have an agreed care pathway in place for the prescription of tamoxifen.

GPs were randomised to one of four scenarios describing a hypothetical patient at increased risk of breast cancer.

The hypothetical patients were intended to be representative of a typical patient attending a family history clinic.

The scenarios involved a patient at either high lifetime risk (greater than 30% chance of breast cancer) or moderate risk (between 17% and 30% chance of breast cancer).

The GPs were told either they would need to write the first prescription and continue as the main prescriber, or a family history clinician had already written the first prescription and asked the GP to take over as the main prescriber.

They were provided with information about the current UK guidelines, the eligibility criteria for taking tamoxifen, the harms and benefits of the drug, and the typical patient pathway.

The GPs were asked questions around five areas:

  • If they were aware tamoxifen could be used to reduce breast cancer risk in women with a family history of breast cancer, and if they were aware of NICE guidelines.
  • Willingness to prescribe tamoxifen.
  • How comfortable they were discussing the harms and benefits of tamoxifen with a patient, and how comfortable they were managing the patient for the duration of the prescription.
  • Barriers to writing a prescription for the hypothetical patient.
  • GPs reported their age, sex, status within the practice, region of practice and how long they had been qualified.

The responses to the questionnaire were analysed, looking at the effect of cancer risk on the hypothetical patient and who was the initial prescriber (GP themselves or family history clinician).

What were the basic results?

Of the 928 GPs surveyed:

  • 51.7% knew tamoxifen can reduce breast cancer risk and 24.1% were aware of the NICE guidelines
  • 77.4% were willing to prescribe tamoxifen for the hypothetical patient
  • GPs who were told they would be asked to be first prescriber were less willing to prescribe tamoxifen than GPs told they would be asked to continue a prescription initiated by the family history clinician (odds ratio [OR] 0.40, 95% confidence interval CI] = 0.29 to 0.55)
  • no difference in willingness to prescribe based on patient level of risk
  • GPs were less comfortable discussing the harms and benefits of tamoxifen if they were asked to be first prescriber, compared with those told the family history clinician would write the first prescription (OR 0.69, 95% CI= 0.53 to 0.90)
  • GPs aware of the NICE guidelines were more willing to prescribe tamoxifen than those who were not (OR 1.50, 95% CI= 1.02 to 2.19)
How did the researchers interpret the results?

The researchers concluded that, "Initiating tamoxifen prescriptions for preventive therapy in secondary care before asking GPs to continue the patient's care may overcome some prescribing barriers."

They added: "One of the major barriers to implementing the tamoxifen guidelines is the low awareness of its potential to be used as preventive therapy.

"Although cross-sectional surveys do not allow causal inferences, the data suggest increasing awareness of preventive medications could facilitate appropriate prescribing behaviour," they said.

The researchers advised that, "The most common sources of information were training days, GP magazines, and national guidelines. Strategies to promote awareness of tamoxifen for primary prevention should consider ways to target these sources."

Conclusion

This large survey shows around half of GPs surveyed were unaware of the benefits of tamoxifen: namely, that the drug can reduce the risk of breast cancer in women with a family history of the condition. Only around a quarter of GPs surveyed were aware of the current UK guidelines.

Researchers found GPs were more likely to feel comfortable carrying on a prescription initiated by hospital doctors, rather than being the one to take the decision to prescribe.

This is perhaps unsurprising given that the drug is still not licensed for the primary prevention of cancer. NICE currently recommends prescribers need to take full responsibility for their decision to prescribe tamoxifen, and obtain full informed patient consent. Many GPs may not feel sufficiently informed or comfortable about making these decisions themselves.

In light of this, the researchers' conclusions are therefore quite appropriate. They suggest the study indicates a need to provide GPs with information about the official guidelines, as well as benefits and support for GPs in prescribing tamoxifen.

This study does have some limitations, however:

  • The artificial scenarios GPs were given might not reflect real-life patients and situations, and they might respond differently in a real-life situation.
  • The study does not tell us the proportion of patients offered tamoxifen by their GP in real life.
  • The GPs were recruited from an online panel, which not all UK GPs are a member of, so an important group of GPs might have been missed.
  • A small proportion of those initially contacted actually completed the survey. Respondents might not represent the demographics of GPs across the UK, and the results may not be generalisable.

If you're concerned about your family history of breast cancer, the first step is to talk to your GP.

You can also reduce your risk of breast cancer by taking regular exercise, eating a healthy diet, and achieving or maintaining a healthy weight.

Read more about preventing breast cancer.

Links To The Headlines

Half of GPs unaware of drug's use in cancer prevention – study. The Guardian, February 14 2017

Breast cancer pill denied to 500,000 women. The Daily Telegraph, February 14 2017

Cancer pill denied to thousands of women: Doctors are failing to prescribe two daily pills that can slash odds of developing the disease. Daily Mail, February 14 2017

500,000 women at higher risk of cancer denied 6p prevention pill because GPs aren't clued up on latest research. The Sun, February 14 2017

GPs fail to offer women drugs that reduce breast cancer risk. The Times, February 14 2017 (subscription required)

Links To Science

Smith SG, Foy R, McGowan JA, et al. Prescribing tamoxifen in primary care for the prevention of breast cancer: a national online survey of GPs' attitudes. British Journal of General Practice. Published online February 13 2017

Online reviews of health products 'are misleading'

"Don't believe online reviews of health products, they're 'skewed'," the Mail Online reports.

A psychologist compared online reviews of three medical products with results from clinical trials, and found the reviews are skewed towards the positive.

The author of the study, Dr Micheál de Barra, wanted to look into whether people who have had good outcomes from treatments are more likely to go online and give positive reviews than people who have had average or poor outcomes. As such, the product reviews provided by online retailers may be distorted.

The author looked at Amazon.com – the US version of the site – and analysed two cholesterol-reducing products and one weight loss treatment.

In general, he found the extent of cholesterol reduction or weight loss reported by online reviewers was substantially greater than that demonstrated in randomised controlled trials, a more reliable source of evidence on effectiveness.

The research highlights an underlying issue with online reviews, whether they are for health products, films or books. Online reviews are arguably subject to a type of reporting bias in that they are written by people who take the time to write them.

This means it's far more likely that these reviews are written by people who have very strong views, either positive or negative, about a product than people who would score it three out of five stars.

Useful impartial online resources for assessing the effectiveness of medical products and treatments include NHS Evidence, the TRIP Database and the Cochrane Library.

Where did the story come from?

The study was authored by a single researcher from the University of Aberdeen and published in the peer-reviewed journal, Social Science and Medicine.

No sources of financial support are mentioned. The author reports support and advice from four named individuals, but otherwise declares no conflict of interest. 

The UK media's coverage of this study is generally representative, but it would be unfair to single out Amazon or the products discussed as having particularly misleading reviews.

The site and the products just happen to be the ones the author looked at. It's likely other products on other sites have equally skewed reviews.

What kind of research was this?

This study aimed to look into the potential issue of biased reporting by online retailers around the effects of medical treatments.

The author reports how people "often hold unduly positive expectations about the outcomes of medicines and other healthcare products".

He suggests the reason for this could be that people who have had a positive outcome from a treatment are more likely to be vocal about this, compared with people who've had poor to average outcomes.

This means the information available to others through customer reviews on retailers' websites is likely to be distorted in favour of the product.

The author focused on several questions:

  • Whether there is biased online reporting around medical treatments compared with the evidence from clinical trials.
  • Whether there is consistent reporting bias across all treatments targeting the same health problem.
  • Whether those with poor or average outcomes are less likely to report their experience than those who had a positive experience.
What did the researcher do?

The author aimed to see whether the reviews of medical products published by the international online retailer Amazon.com are consistent with outcomes of the same products reported in clinical trials.

If there is no reporting bias, the average outcomes should be more or less the same.

He found three medical products available that met the following criteria:

  • they were genuine medical products
  • they had more than 300 online reviews
  • the reviews contained specific information about the reviewer's health
  • there was high-quality evidence (such as randomised controlled trials) of the products available to check the true clinical effects

The three products that met these criteria were two cholesterol treatments – Benecol Smart Chews Caramels (not available in the UK) and Nature Made CholestOff (a herbal supplement available over the counter) – and a weight loss drug designed to reduce the amount of fat the body takes from food, called Orlistat (also available over the counter under the supervision of a pharmacist). 

As the author says, it's likely that many other treatments would also have met these criteria, but these were the first three identified.

He included a total of 908 reviews of the two cholesterol products where the reviewers also provided information on changes in blood cholesterol levels.

These were compared with the size of the effects reported in a systematic review of clinical trials.

There were 767 reviews of Orlistat included – a specific weight change was reported in about a third of these.

A recent systematic review was identified for comparison, which included two clinical trials of this drug.

What did he find?

For the cholesterol products, the author found the blood cholesterol reductions reported by online reviewers were significantly greater than those reported in clinical trials.

For example, Benecol users reported a 45mg/dl reduction in cholesterol, compared with a range of 9.28-24mg/dl reduction reported in trials.

Similarly, the weight loss reported by Orlistat reviewers was significantly greater than in the clinical trial participants (specific kg loss not reported in the study).

The author calculated that the "reputational distortion" (the perceived benefit) for the three products was three to six times greater than the actual size of the benefit gained from the treatment.

When looking at the one- to five-star grading system, on average, reviews that were shared had 0.55 more positive stars than those that weren't shared.

What did the researcher conclude?

The author concluded that, "People with good treatment outcomes are more inclined to share information about their treatment, which distorts the information available to others.

"People who rely on word of mouth reputation, electronic or real life, are likely to develop unduly positive expectations." 

Conclusions

This unique study suggests that, in general, online medical product reviews may give a distorted and enhanced perception of the effectiveness of the product compared with that actually demonstrated in randomised controlled trials.

The author discusses potential theories around this. For example, it may reflect the fact people are more likely to post a review if they found something good than if the benefit they found was not that remarkable or there was no benefit at all.

He also suggests people may not wish to dwell on prior periods of ill health, whereas a positive recovery is something they may want to share with others.

People who remain in poorer health could also have lower mood and be less inclined to engage in sharing information about their health.

But, as the author acknowledges, in the case of raised cholesterol this theory doesn't provide the whole answer because the condition doesn't cause as many obvious health problems.

However, it's important to note a few points:

  • Fraudulent or fake reviews are rare and were not found in the data reviewed in this study. The benefits reported may have been greater than those found in clinical trials, but they were still reporting the same effect: lower cholesterol or weight loss.
  • Around 90-100% of reviews are thought to be reliable, or at least written in "good faith" and not in an attempt to mislead people.
  • People who achieve big results with certain products may be the exception rather than the rule, and most people may be more likely to see average results.
  • We don't have any information about other lifestyle changes or medical treatments people may also have been using. For example, those people achieving greater weight loss with Orlistat may also have been making diet and physical activity changes.
  • This study has not singled out Amazon or these three specific products. As the author says, he could have looked at many other products, but these just happened to be the first three that met the criteria. There are many other general or brand-specific online retailers that provide customer reviews of their products, so the focus should not just be on Amazon.

While not as user-friendly as Amazon, sites such as NHS EvidenceTRIP Database and the Cochrane Library provide impartial and unbiased assessments of medical products and treatments.

When it comes to lowering your cholesterol or trying to lose weight, it's advised that you follow official diet and physical activity guidelines.

Links To The Headlines

Don't believe online reviews of health products, they're 'skewed' and 'misleading', study concludes. Mail Online, February 10 2017

Amazon weight loss product reviews 'positively misleading' customers, say researchers. The Independent, February 10 2017

Links To Science

De Barra M. Reporting bias inflates the reputation of medical treatments: A comparison of outcomes in clinical trials and online product reviews. Social Science & Medicine. Published online February 10 2017

Four-in-one pill 'effective' for high blood pressure

"Four-in-one 'miracle' pill to cure high blood pressure," is the headline on Mail Online.

This is based on early research from Australia looking at the effect of a four-in-one "quadpill" on high blood pressure.

The idea behind the quadpill is that by combining four hypertension drugs at a much lower dose than they are normally used, you still get a beneficial effect, but you minimise the risk of side effects.

In a small study involving only 18 people, the quadpill was compared to placebo (a dummy treatment).

While they were taking the drug all 18 people had a greater reduction in blood pressure compared with when they were taking the placebo.

While the prospect of a blood pressure-lowering drug with fewer side effects is exciting, it is important to remember that this was a very small study.

As only 18 people took the drug for just four weeks, and the quadpill was not compared to full strength blood pressure pills, we don't know yet if it is a "miracle" or just a useful option.

All adults over 40 are advised to have their blood pressure checked at least every five years. Getting this done is easy and could save your life.

 

Where did the story come from?

The proof-of-concept study was carried out by researchers from various institutions across Australia, including the University of Sydney, as well as John Hopkins Bloomberg School of Public Health, US, and Imperial College, UK.

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

The study was funded by various sources, including National Health and Medical Research Council (NHMRC) fellowships and a range of pharmaceutical companies. The authors declare the funder had no role in any aspect of the study.

The UK's media generally reported the story accurately, if a little overexcitedly. The Sun's report that the drug was "100 per cent effective at tackling high blood pressure" is a bit misleading, as blood pressure was reduced to a controlled level on just one measure.

And Mail Online's claim that this was a "miracle drug" is hyperbolic.

The idea that this was early exploratory research seemed to be largely overlooked by the media.

 

What kind of research was this?

This was a randomised controlled trial (RCT) of patients who had untreated moderate to high blood pressure, aiming to see if a combination pill – quadpill – of four blood pressure-lowering drugs (each at a lower dose than normal) would be effective and safe, compared to a placebo drug.

An RCT is good as you can see the effects of an intervention – in this case the quadpill – on reducing blood pressure.

As a crossover trial, everyone had the chance of receiving four weeks of treatment and four weeks of placebo (with a two-week break in between), without evaluators being aware of the order treatment was given

The researchers also included a systematic review of the literature in order to look at the existing studies into effectiveness of just one blood pressure drug given at a quarter strength. This was useful in judging whether theirs was a one-off finding and to see what the average side-effect rates for the component drugs compared to a placebo were.

 

What did the research involve?

Researchers randomised 21 adults, of whom 18 completed the trial. These people had untreated high blood pressure. They carried out a double-blind randomised controlled trial, comparing a quadpill (a pill containing four blood pressure reducing drugs, each at a quarter of their usual strength) and a placebo.

The participants were randomly allocated to either the quadpill or a placebo for four weeks. This treatment was followed by a two-week "washout" (no pill taken), then the other treatment was taken for four weeks (participants taking placebo for the first four weeks took the quadpill for the final four weeks and vice versa).

At four weeks, the researchers looked at the reduction in mean 24-hour systolic blood pressure (the highest pressure when your heart beats and pushes blood around your body) while carrying out normal daily activities.

They also looked at reduction in mean 24-hour diastolic blood pressure (the lowest pressure when your heart relaxes between beats), as well as daytime and nighttime diastolic blood pressure, at four weeks.

Blood pressure recorded in the researchers' office was also examined.

Controlled blood pressure was considered to be less than 135/85mm Hg for the 24-hour blood pressure, and less than 140/90mm Hg for office blood pressure.

Researchers also looked at adverse events of taking the quadpill compared to placebo.

A systematic review was also done, looking at the effectiveness and side effects of taking either one or two blood pressure-reducing pills (rather than four) at a quarter of the usual strength, compared to a placebo.

 

What were the basic results?

24-hour blood pressure less than 135/85mm Hg (the threshold for controlled blood pressure) was achieved by 15 of 18 participants on the quadpill compared with seven of 18 on placebo (relative risk [RR] 2.14, 95% confidence interval [CI] 1.25 to 3.65).

All 18 participants achieved office systolic and diastolic blood pressure less than 140/90mm Hg (the threshold for controlled blood pressure) while on the quadpill, compared with six of 18 on placebo (relative risk 3.01, 95% confidence interval (CI) 1.54 to 5.89).

  • The difference in mean 24-hour systolic blood pressure between quadpill and placebo was 18.7mm Hg (95% (CI) 14.3 to 23.0).
  • The difference in mean 24-hour diastolic blood pressure between quadpill and placebo was 14.2mm Hg (95% CI 11.5 to 16.9).
  • The difference in mean office systolic blood pressure between quadpill and placebo was 22.4mm Hg (95% CI 16.5 to 28.3).
  • The difference in mean office diastolic blood pressure between quadpill and placebo was 13.1mm Hg (95% CI 8.9 to 17.3).

There were no serious adverse events reported.

The systematic review found 36 trials with one drug at a quarter dose and six trials of two drugs at a quarter dose, against a placebo. No increase in side effects was found compared with a placebo, indicating the advantages of a single pill with low doses of multiple blood pressure-lowering drugs.

 

How did the researchers interpret the results?

The researchers conclude that "the findings of our small trial in the context of previous randomised evidence suggest that the benefits of quarter-dose therapy could be additive across classes and might confer a clinically important reduction in blood pressure".

They add that "further examination of the quadpill concept is needed to investigate effectiveness against usual treatment options and longer-term tolerability".

 

Conclusion

The findings of this early-stage study suggest that a quadpill might be an effective way of lowering blood pressure. It might also show fewer side effects associated with taking blood pressure tablets at higher doses, such as dizziness, diarrhoea, or a cough.

There are some limitations to the study:

  • There were only 18 people included in the study. A bigger trial needs to be undertaken to find out what the results would look like if the quadpill was widely used in the population.
  • The study was undertaken in an Australian setting where medication and monitoring of blood pressure might differ – therefore results might not be generalisable to other settings.
  • People in the study took the quadpill for just four weeks. The medication needs to be taken for longer in order to see long-term effectiveness and possible side effects.
  • The "controlled" level of blood pressure the researchers used did not mean that participants had an ideal blood pressure, just that their blood pressure was no longer considered high.

This is an early-stage trial. Changes to advice on blood pressure medication won't happen immediately, but this approach appears to be promising and further larger trials, hopefully against existing single therapies, could provide stronger evidence.

Ways you can combat high blood pressure, as well as other chronic diseases, include:

Read more about preventing high blood pressure.

Links To The Headlines

Four-in-one 'miracle' pill to cure high blood pressure: Every patient given treatment during trial saw their hypertension drop to healthy levels. Mail Online, February 10 2017

Four-in-one pill is ‘100 per cent effective, SLASHING blood pressure and cutting heart attack risk’. The Sun, February 10 2017

Links To Science

Chow CK, Thakklar J, Bennett A, et al. Quarter-dose quadruple combination therapy for initial treatment of hypertension: placebo-controlled, crossover, randomised trial and systematic review. The Lancet. Published online February 9 2017

'Antibiotics, not surgery, best for child appendicitis' says study

"Operating on children with acute appendicitis may be unnecessary in many of cases," the Mail Online reports.

The headline is a little misleading as the researchers were specifically looking at a type of appendicitis known as "appendix mass". This is where a lump develops inside the appendix.

The most common treatment approach for an appendix mass is to treat it first with antibiotics and then use surgery to remove the appendix to stop the problem from reoccurring.

In this study, researchers wanted to see if the second stage of surgical treatment was actually required.

The study included over 100 children from the UK, Sweden and New Zealand with appendicitis treated with antibiotics and found that later removal of the appendix could be avoided in many cases.

While the risk of complications following surgery is low, they can be serious. So if a condition can be treated without resorting to surgery,  this is usually for the best. 

This was a well-designed trial including over 100 children. But it does have some limitations, such as the short follow-up period (one year) for detecting the risk of recurrent appendicitis.

However, the findings of the trial are interesting and useful for clinicians and parents faced with a decision about treating this type of appendicitis: antibiotics followed by active surveillance, or antibiotics followed by surgery?

Guidelines for these sorts of issues are never set in stone. So it could be the case that this evidence will "add to the mix" for evolving theories of best practice for treatment.

 

Where did the story come from?

The study was carried out by researchers from the University of Southampton and was funded by the BUPA Foundation. The study was published in the peer-reviewed medical journal The Lancet.

Mail Online has provided an accurate report of the trial and also included the details of other studies that have been done around treatment options for appendicitis.

As mentioned, the headline did not mention "appendix mass", but this is understandable as the phrase would mean little to most people.

 

What kind of research was this?

This was a randomised controlled trial (RCT) that compared the "interval" removal (surgical removal of the appendix following antibiotic treatment) of the appendix with active observation in children who had previously received non-operative treatment for appendicitis with a lump on the appendix (appendix mass).

Appendicitis is the most common general surgical emergency in children. Around 9% of children have an appendix mass that is treated with antibiotics as the risk of complications from surgery can be high.

However as the appendix is still in place it is possible that the child could have recurrent problems.

According to a 2009 survey of paediatric surgeons in the UK, it was reported that 68% routinely recommend removal of the appendix for all children after non-operative treatment of an appendix mass.

However, a systematic review published in 2011 suggested that the risk of recurrence after successful non-operative treatment of an appendix mass in children was 20%, and the incidence of complications after surgery was 3%.

 

What did the research involve?

The researchers recruited children to take part in the CHildren's INterval Appendicectomy (CHINA) study from 19 specialist paediatric surgery centres, 17 in the UK, one in Sweden, and one in New Zealand.

Children included were aged 3 to 15 years and had successful non-operative treatment for acute appendicitis with a mass. Children were excluded from the study if they had existing gastrointestinal disease, another medical condition or an immune system problem.

The included children were randomly assigned to either receive interval appendectomy (removal of the appendix), where they were followed up at an outpatient clinic at around six weeks after surgery and again at one year after randomisation.

The other group of children went under active observation where they were reviewed every three months in the outpatient clinic for one year after randomisation.

The two main outcomes of interest were the proportion of children that developed acute appendicitis or recurrent appendix mass within one year following previous successful treatment in the active observation group, and the occurrence of severe complications related to interval appendectomy.

 

What were the basic results?

A total of 106 children were included in the trial, 52 children were assigned to interval appendectomy and 54 to active observation, (average age 8.5 years).

Following randomisation only 44 children in the interval appendectomy group had surgery and two children in the active observation group became ineligible after randomisation.

During the follow-up period six children (12%, 95% confidence interval [CI] 5 to 23) in the active observation group had recurrent acute appendicitis and three children (6%, 95% CI 1 to 17) in the interval appendectomy group had severe complications.

The severe complications related to interval appendectomy in three children were:

  • one child had a hernia where the surgery was performed
  • two children had a wound infection

Of the active observation group, 12 (23%) of these children underwent appendectomy during the follow-up period.

 

How did the researchers interpret the results?

The researchers conclude: "More than three-quarters of children could avoid appendectomy during early follow-up after successful non-operative treatment of an appendix mass. Although the risk of complications after interval appendectomy is low, complications can be severe. Adoption of a wait-and-see approach, reserving appendicectomy for those who develop recurrence or recurrent symptoms, results in fewer days in hospital, fewer days away from normal daily activity, and is cheaper than routine interval appendicectomy. These high-quality data will allow clinicians, parents, and children to make an evidence-based decision regarding the justification for interval appendicectomy."

 

Conclusion

This was a randomised controlled trial (RCT) that compared the removal of the appendix with active observation in children who had previously received non-operative treatment for an appendix mass.

The researchers found that appendectomy could be avoided in many cases.

Perhaps actively keeping an eye on the child's symptoms and only operating on those that develop appendicitis could be an approach worth considering.

This was a well-designed trial and efforts were made to reduce the risk of bias. For example, allocation to groups was concealed at the point of assignment. The trial was also performed at multiple centres, which increases the generalisability of the findings.

However there are also limitations.

  • Due to the interventions being compared blinding was not possible in this trial, but objective outcomes were assessed as far as possible.
  • As no formal definition of appendicitis or of a mass was used, the diagnosis was made by the surgeon in charge of the child’s care – this can be subject to bias as each surgeon's opinion is subjective.
  • The active observation group was followed up for only one year, which may not have been long enough to get a true estimate of the risk of recurrent appendicitis.

The findings of this trial are interesting as there have been some confusion over the benefits of interval appendectomy and provides useful information for parents and surgeons faced with this decision.

Read more about the treatment options for appendicitis.

Links To The Headlines

Why removing your child's appendix could be a waste of time: Study finds that antibiotics could be just as effective. Mail Online, February 9 2017

Links To Science

Hall NJ, Eaton S, Stanton MP, et al. Active observation versus interval appendicectomy after successful non-operative treatment of an appendix mass in children (CHINA study): an open-label, randomised controlled trial. The Lancet – Gastroenterology & Hepatology. Published online February 6 2017

Switching to wholegrains may boost metabolism

"Eating more wholegrain foods can help to speed up weight loss, scientists claim," the Daily Mail reports.

Researchers found that people who ate a diet high in wholegrains absorbed less energy from food than people who ate a similar diet, but with refined grains (such as white flour).

The study included 81 men and women in the US, who were each allocated to eat a wholegrain or refined grain diet for six weeks, after a two week run-in period of eating no wholegrain. All food and drink was provided during the study.

People provided stool samples, gave blood samples, and had their metabolic rate tested. On the latter, researchers were interested in what is known as the resting metabolic rate (RMR), which is the amount of energy the body burns during rest. RMR is sometime used as a benchmark for how efficiently the metabolism is working.

People who ate the wholegrain diet were found to pass more stools (poo). They also had a higher RMR: although this difference was so small it could have been down to chance. These two factors combined amounted to an average difference in energy balance between the two groups of about 92 calories a day.

Assuming people didn't eat more to make up the difference, the study authors said, this would amount to a weight loss of about 2.5kg over a year.

If this modest amount of weight loss doesn't seem inspiring, wholegrain foods include more micronutrients than refined grains, and may improve digestion and reduce the risk of bowel cancer.

 

Where did the story come from?

The study was carried out by researchers from Tufts University, the University of Minnesota, and the Bell Institute of Health and Nutrition, in the US. It was funded by the Bell Institute of Health and Nutrition. The study was published in the peer-reviewed The American Journal of Clinical Nutrition.

Mail Online concentrated on the findings that a wholegrain diet may speed up metabolism, rather than the effects on stools, saying rather coyly that the wholegrain group "absorbed fewer calories in their digestive systems".

A more accurate, if less palatable, headline would have been "Wholegrains make you poo more".

The report also focused on white versus brown rice, although the study said most of the grain consumed in the study was from wheat, rather than rice.

 

What kind of research was this?

This was a randomised controlled trial. Although people in the study weren't told whether they were on a wholegrain or refined grain diet, they would have been able to see whether they were eating, say, wholegrain or white bread – so the study was not blinded.

This type of study is a good way of looking at the effects of an intervention such as a diet, especially when (as in this case) all food was provided.

 

What did the research involve?

Researchers recruited 49 men and 32 women, all aged 40 to 65. All the women were postmenopausal. They were supplied with all food and drink for an eight-week period. For the first two weeks they ate an identical low-fibre diet, then were randomly allocated to a diet similar in nutrients, except that one group ate wholegrain and the other refined grain.

The wholegrain diet included an average 207g of wholegrain daily, including 40g dietary fibre. The refined grain diet included no wholegrain and an average 21g of dietary fibre.

People gave stool samples after two weeks and eight weeks that were collected in separate containers over a 72-hour period and stored chilled until transported to the laboratory. They also had blood tests, tests of metabolic rate, and filled in questionnaires about their appetite, feelings of hunger and satisfaction with their diet. Researchers compared test results taken at weeks two and eight of the study, between the two groups.

The diet was designed to keep their weight steady, not to lead to weight loss or gain. People were excluded from the study for a range of reasons, including if:

  • their weight had fluctuated over the past year
  • they had certain diseases, including cancer or gastrointestinal disease
  • they took medicines affecting appetite or digestion
  • they took supplements (except calcium and vitamin D)
  • they had recently taken antibiotics
  • they drank two or more alcoholic drinks per day

The researchers looked at a wide range of confounding factors that they thought could be affected by wholegrain diet, including people's digestion, metabolic rate, appetite, gut bacteria and the body's regulation of glucose.

Study results were adjusted for people's age, sex and body mass index (BMI). Researchers also looked at the effect of daily adherence to the diet (ie whether people stuck to the diet, or ate other things as well) on the results.

 

What were the basic results?

After six weeks of the diet, people who ate the wholegrain diet:

  • passed more stool, with a higher total energy content, than those who ate the refined grain diet (an additional 96 calories/day, plus or minus 18 calories)
  • had a resting metabolic rate that burned 48 calories a day more (plus or minus 23 calories) than those who ate the refined grain diet. However, this finding did not hold true when the researchers excluded people who did not stick to the diet
  • after adjusting for other factors, the combined average daily energy loss for people eating a wholegrain diet was 92 calories a day, or 108 calories a day if you only look at people who stuck to the diet
  • the study found no effect on control of glucose in the blood, and no differences in appetite, hunger, satisfaction with diet or eating behaviour

 

How did the researchers interpret the results?

The researchers said they’d found "new evidence of energetic benefits" if you replace refined grain with wholegrain in the diet.

"We showed that dietary substitution of wholegrains for refined grains conferred favourable energetic benefits that were primarily attributable to a greater energy excretion in the stool," they said.

 

Conclusion

The suggestion that you can lose weight by simply swapping refined grains like white bread and rice for wholegrains like wholemeal bread and brown rice is attractive if you're planning to shift a few pounds. But there are some things to remember before relying on the study results:

  • People didn't lose weight during the study. Indeed, it was designed to make sure they didn't lose or gain weight, with a dietitian adjusting their daily calories if they started to gain or lose weight.
  • The daily extra amount of calories that the researchers estimate people in the wholegrain group lost is modest – the equivalent of two small ginger nut biscuits, or a matchbox-sized piece of cheddar cheese. Relying on this alone is unlikely to help you lose significant amounts of weight, especially as it would be easy to eat that much extra food each day without realising.
  • Some of the results, such as the effects on metabolic rate, were on the border of being too small to be reliable.

However, we already know that wholegrain foods provide more micronutrients and that the fibre they contain may help digestion. Choosing wholegrain over refined grain foods is a healthy choice.

While they may not automatically melt away the weight, wholegrain foods are a good choice as part of a balanced weight loss diet, such as the NHS Choices weight loss plan.

Links To The Headlines

Swapping white rice for its brown alternative speeds up weight loss and is the equivalent of a 30 minute brisk walk. Daily Mail, February 9 2017

Links To Science

Karl JP, Meydani M, Barnett JB, et al. Substituting whole grains for refined grains in a 6-wk randomized trial favorably affects energy-balance metrics in healthy men and postmenopausal women. The American Journal of Clinical Nutrition. Published online February 8 2017

Shift work and heavy lifting may make it harder to get pregnant

“Shift work and physically demanding jobs linked to lower fertility in women” Sky News reports. A small US study found a link between both activities and a reduction in both the number and quality of a woman’s eggs.

An important fact to highlight from the start, which has somewhat been overlooked in media reports, is the study recruited only women who were seeking IVF treatment for fertility problems. So any results may not be representative of women in general.

The study found that those who worked outside of normal office hours produced fewer mature eggs when stimulated during hormone treatment. They also found that women who sometimes or often did heavy lifting or physically demanding work produced fewer mature eggs.

As the numbers involved were quite small (only 36 of 313 women who had IVF worked evening, night or rotating shifts) they may not be reliable.

The study cannot show that shift work or physically demanding work was the reason why women produced fewer mature eggs. Techniques for harvesting the eggs may also have changed over the course of the 11 year study, which may have affected the results.

If you are undergoing IVF treatment and you have the luxury of choosing the type and timing of your work, then it may be a good idea to ask for a “9 to 5ish” shift and ask to be excused from heavy lifting.

Otherwise, following standard advice about protecting your fertility would seem to be the best option if you are trying for a baby.

 

Where did the story come from?

The study was carried out by researchers from Harvard TH Chan School of Public Health and Harvard Medical School and was funded by the US National Institutes of Health. The study was published in the peer-reviewed journal Occupational Environmental Medicine on an open access basis, so it’s free to read online.

Most of the UK media took the research at face value, telling readers that shift work or heavy physical work would make it harder for them to get pregnant. Headline writers also failed to make clear that the study involved women actively seeking treatment for fertility problems.

Sky News also said that women’s “ovarian reserve” - a measure of how many eggs she will be able to release in her lifetime - was lower in women who did heavy work, but the study results don’t bear this out. Several news outlets repeat advice from a UK paediatrician who tells women to “stick to the day job and leave the lifting to their partner”. Arguably his comments are patronising, inaccurate (lifting was measured at work, not at home) and probably impractical for many women, and not backed up by the research.

 

What kind of research was this?

This was a cohort study of women seeking in vitro fertilisation treatment (IVF) using their own eggs, at fertility centres in the US. The researchers wanted to see if their working circumstances were linked to their hormones levels, follicles (egg sacs) and numbers of eggs produced during treatment.

Cohort studies can suggest links between factors, but cannot show whether one (in this case working shifts or doing physically-demanding work) directly acts on another (hormones, follicles or eggs).

 

What did the research involve?

Researchers asked 581 women seeking IVF treatment between 2004 and 2015 to fill in a questionnaire about their employment. Of these, 107 women (18%) were excluded as they did not complete a questionnaire. One other women was excluded as her body mass index information was unavailable. The remaining 473 women had their ovarian reserve (current supply of eggs) measured by ultrasound and hormone levels measured in blood tests.

Of these women, 313 completed at least one cycle of IVF. Researchers recorded the numbers of eggs retrieved, and the numbers of mature eggs (ready to be fertilised).

After adjusting for some confounding factors, they looked to see if employment factors were linked to fertility measures.

In the questionnaires, women were asked if they lifted or moved heavy objects never, sometimes or often, in their work. Researchers combined the responses into “never” and “sometimes or often” when reporting the results.

Women were asked if their typical work shift was day, evening, night or rotating. Researchers combined the responses into “day” and all the other responses. Women were also asked if their level of physical exertion at work was light (ie office job), medium (involving lifting light loads or frequent walking), or heavy (heavy manual labour).

Ovarian reserve was measured as total antrial follicle count (AFC), which measures the numbers of undeveloped eggs in follicles in the ovary, and levels of follicle stimulating hormone (FSH), which stimulates egg development in the follicles.

Ovarian response was measured as the number of eggs that could be retrieved from the ovaries by doctors, following ovarian stimulation with injected hormones (the standard IVF procedure). The doctors categorised the eggs to see how many were “mature”, or suitable for fertilisation.

Researchers took account of the following confounding factors:

  • age
  • body mass index (BMI)
  • education level
  • infertility diagnosis (male, female or unexplained)

 

What were the basic results?

Shift work, moving heavy objects and physical exertion were not linked to ovarian reserve, after taking account of confounding factors. Although the researchers said in their introduction that women who did heavy lifting had a lower AFC count, this difference was so small it could have been down to chance.

The main finding was that numbers of mature eggs retrieved during IVF treatment varied according to work factors:

  • Women who sometimes or often lifted heavy objects at work produced an average 8.3 mature eggs (95% confidence interval (CI) 7.7 to 9) compared to 9.7 (95% CI 9.1 to 10.3) for women who never lifted heavy objects at work.
  • Women whose level of physical exertion at work was moderate to heavy produced an average 8.1 mature eggs (95% CI 7.3 to 9.1) compared to 9.4 (95% CI 8.9 to 10) for women whose level of exertion was low.
  • Women who worked evening, night or rotating shifts produced an average 7 mature eggs (95% CI 5.8 to 8.4) compared to 9.3 (95% CI 8.9 to 9.8) for women who worked days.

 

How did the researchers interpret the results?

The researchers said “women working non-day shifts and those who had more physically demanding jobs” produced fewer mature eggs during IVF treatment. They say their results “provide insight into possible mechanisms linking these occupational exposures with decreased fecundity”. Fecundity means the biological potential for fertility, as measured by eggs and hormones. 

 

Conclusion

Many factors affect a couple’s ability to get pregnant, and the numbers of mature eggs produced by the woman is one of them. This study seems to have found a link between physically demanding work, shift work, and egg production.

However, the study has many limitations.

All the women were seeking IVF treatment, so already knew they had a fertility problem. The numbers of mature eggs, used in the study to calculate the women’s potential for fertility, were counted after extraction during IVF treatment. It’s not clear whether these findings would have applied to women releasing eggs naturally (eggs are usually released one at a time), or to women without known fertility problems.

The study took place over a long period of time, from 2004 to 2015. Techniques for egg retrieval have improved over this time which may have affected results.

Shift work and physically demanding work may be a marker for other lifestyle or health factors not measured in this study. For a start, we don’t know the length of women’s working hours, or their salaries, their household income, financial pressures or other illnesses. All of these could affect women’s health and fertility potential.

The study is relatively small. Although more than 500 women were recruited, we only have information about working conditions and egg retrieval - the main result - for 313 women. Of these, 186 said they sometimes or often lifted heavy loads at work, 106 said they did physically demanding work and 36 said they worked evening, night or rotational shifts.

Finally, although the researchers say their research provides insight into possible mechanisms for reduced fertility, it doesn’t explain how shift work or physically demanding work might actually affect a woman’s fertile egg production. Lack of an obvious mechanism makes it less likely that the link is down to cause and effect.

If you’re trying to get pregnant, it makes sense to ensure you are as healthy as possible, and that you’re taking the supplements you need (such as folic acid).

If you’ve been trying for a year or more and have not become pregnant, see your GP. Your GP can do tests to help identify possible fertility problems, and provide advice on the next steps. 

Read more about fertility tests.

Links To The Headlines

Shift work and physically demanding jobs linked to lower fertility in women – study. Sky News, February 8 2017

How hormone fluctuations caused by working night shifts could make it harder for women to conceive. Daily Mail, February 8 2017

Shift work and heavy lifting may reduce women’s fertility, study finds. The Independent, February 8 2017

Women who work nightshift may be damaging fertility, as study shows they have fewer eggs. The Daily Telegraph, February 7 2017

Links To Science

Mínguez-Alarcón L, Souter I, Williams PL, et al. Occupational factors and markers of ovarian reserve and response among women at a fertility centre. Occupational and Environmental Medicine. Published online February 6 2017

Long-term vaping 'far safer than smoking' says 'landmark' study

"Vaping has been endorsed by health experts after the first long-term study of its effects in ex-smokers," ITV News reports.

E-cigarettes contain nicotine but not many of the harmful substances produced by smoking tobacco, such as tar or carbon monoxide. However, there has been debate about exactly how safe their long-term use is.

The study, involving 181 smokers or ex-smokers, has been described as "landmark" as it is thought to be the first (or at least one of the first) looking at long-term vaping outcomes in "real world" users. Previous studies of this kind have mainly relied on laboratory equipment, or animal research, to estimate the long-term effects of e-cigarettes.

The volunteers completed questionnaires and provided breath, saliva and urine samples. The researchers found significantly lower levels of toxic chemicals and cancer-causing substances (carcinogens) in the samples of those of former smokers who had been using e-cigarettes or nicotine replacement therapy (NRT) compared to current smokers.

Another noted result is that current smokers who may be trying to reduce their risk of harm by switching between e-cigarettes and normal cigarettes may be saving money, but doing little for their health. "Combination users" still had very high levels of toxins and carcinogens

This study provides evidence that e-cigarettes and NRT can reduce harm to smokers by reducing exposure to toxic chemicals. The evidence would also seem to support Public Health England’s 2015 report that “E-cigarettes are 95% less harmful than tobacco”.

 

Where did the story come from?

The study was carried out by researchers from a number of institutions, including University College London, and the Roswell Park Cancer Institute and Centers for Disease Control and Prevention (both in the US). Funding was provided by Cancer Research UK.

The study was published in the peer-reviewed journal: Annals of Internal Medicine.

There has been much discussion over the benefits of vaping over conventional smoking methods and this is the first long-term study assessing these effects. In general the findings have been reported accurately in the UK media; however none of the limitations, as described by the researchers themselves, have been mentioned.

The Daily Mirror included a quote from professor Kevin Fenton, national director of health and wellbeing at Public Health England, who added: "This study provides further evidence that switching to e-cigarettes can significantly reduce harm to smokers, with greatly reduced exposure to carcinogens and toxins."

 

What kind of research was this?

This was a cross-sectional study that drew comparisons on exposure to nicotine and other tobacco-related toxins and carcinogens in the following groups:

  • current cigarette smokers who only smoked cigarettes
  • current cigarette smokers who also used e-cigarettes
  • current cigarette smokers who also use other forms of nicotine replacement therapies (NRT), such as skin patches or gum
  • former smokers who were now using only e-cigarettes
  • former smokers who were now using only NRT

Limitations to this study design include the possibility of recall bias as participants provide information about their smoking habits through a questionnaire. There is also the possibility of residual confounding from other unmeasured factors so findings may not be entirely accurate.

What did the research involve?

The researchers recruited participants from Greater London by placing advertisements in newspapers and online, posters in pharmacies and though marketing companies.

To be able to join the study participants had to be either:

  • a current smoker, who has smoked an average of five or more cigarettes per day for at least six months
  • a former smoker, who has stopped using tobacco products for at least six months

Researchers aimed to assess the effects of long-term use of non-combustible nicotine delivery – that is NRT or e-cigarettes – for a minimum of six months. They compared:

  • current smokers of cigarettes only
  • combination smokers – cigarette smokers also using an e-cigarette or NRT
  • former smokers using e-cigarettes-only or NRT-only

Participants were asked to visit a laboratory after not eating, drinking, or using combustible cigarettes or other nicotine products for an hour before their visit. During the appointment the participants filled in a questionnaire including questions on sociodemographic and smoking characteristics.

Breath, saliva, and urine samples were taken, which were assessed for levels of nicotine and other carcinogenic or toxic chemicals.

This included tobacco specific nitrosamines (TSNAs), which are one of the most important carcinogens in tobacco formed from nicotine. They also looked at a class of toxins called volatile organic compounds (VOCs) such as acrylamide and cyanide-releasing acrylonitrile. 

Analyses were adjusted for smoking history, sociodemographic variables, physical health and subjective wellbeing.

What were the basic results?

A total of 181 participants were included in the study.

Significantly lower levels of cancer causing chemicals, TSNAs and VOCs were found in samples from former smokers using e-cigarettes only or NRT only, compared with current smokers. Their levels were lower than both those who smoked cigarettes only, or smokers using either e-cigarette or NRT alongside cigarettes.

Former smokers using e-cigarettes only had significantly lower levels of the toxic chemical NNAL (a by-product of exposure to TSNAs) than all other groups. This was equivalent to a 97% reduction compared with the levels of cigarette-only users.

Current smokers of combustible cigarettes only, and current smokers also using NRT or e–cigarettes, had similar levels of the tobacco-related toxins and carcinogens.

Looking at nicotine, levels in urine samples were broadly similar across groups. There was though some variation in salvia levels, with e-cigarette-only users, and those using NRT while continuing to smoke cigarettes had slightly lower nicotine levels than other groups.  

 

How did the researchers interpret the results?

The researchers conclude: "Former smokers with long-term e-cigarette-only or NRT-only use may obtain roughly similar levels of nicotine compared with smokers of combustible cigarettes only, but results varied. Long-term NRT-only and e-cigarette-only use, but not dual use of NRTs or e-cigarettes with combustible cigarettes, is associated with substantially reduced levels of measured carcinogens and toxins relative to smoking only combustible cigarettes".

 

Conclusion

This cross-sectional study aimed to assess whether there are differences in levels of nicotine and toxic chemicals in cigarette smokers, and former or current smokers who are also long-term users of e-cigarettes or NRT.

E-cigarettes are designed for users to inhale nicotine without most of the harmful effects of smoking. There has been much discussion over the benefits of vaping over conventional smoking methods and this is the first long-term study assessing these effects.

The main findings are not that surprising – former smokers who have now switched to using e-cigarettes or NRT only have significantly lower levels of toxins than those who continue to smoke regular cigarettes.

However, the study has limitations.

  • while attempts were made to control for confounders, it is possible that other unmeasured factors are influencing the results
  • this was a self-selected sample and therefore findings may not be generalisable to the whole population of former or current smokers
  • indirect exposure to cigarette smoking could not be accounted for in this research
  • the study is not able to assess the comparative effectiveness of NRT or e-cigarettes as aids to smoking cessation

The findings of this study do appear to reassure that use of e-cigarettes and nicotine replacement therapy – while continuing to provide nicotine – can reduce exposure to toxic chemicals that can lead to cancer in cigarette smokers.

However, this is only if you completely stop smoking – using e-cigarettes or NRT while continuing to smoke won’t help.

Smokers who want to stop smoking can get help from NHS stop smoking services, which can reduce their risk of smoking-related disease and death.

Read more about stop smoking services in your area.

Links To The Headlines

Vaping is 'far safer' than smoking cigarettes. ITV News, February 7 2017

E-cigarettes 'are much safer than normal cigarettes, with a very low risk' says study. Daily Mirror, February 7 2017

Vaping dubbed ‘very low risk’ and less toxic than tobacco in first major study into e-cigarettes. The Sun, February 7 2017

E-cigarettes ‘much safer than smoking tobacco’. The Times, February 7 2017

Links To Science

Shahab L, Goniewicz ML, Blount BC, et al. Nicotine, Carcinogen, and Toxin Exposure in Long-Term E-Cigarette and Nicotine Replacement Therapy Users: A Cross-sectional Study. Annals of Internal Medicine. Published online February 7 2017

Harnessing 'brute force' could be key to creating new antibiotics

"Antibiotics 'seen using brute force to kill bugs'',"BBC News reports. The hope is that researchers could replicate the effect to create new antibiotics that could help combat the continuing threat of antibiotic resistance.

The BBC reports on an early stage laboratory study investigating how our strongest antibacterial drugs target and destroy "hard to kill" bacteria such as the "superbug" methicillin-resistant Staphylococcus aureus (MRSA).

The answer lies in how well the drug can bind (stick) to target protein molecules on the bacterial surface membrane. When there is sufficient binding across the membrane, this exerts a level of mechanical force that causes the membrane to literally break apart and the cell is destroyed. One way of picturing this process is somebody ripping apart a bag of frozen peas spreading the contents everywhere.

The researchers hope that further study will be able to build on these findings and develop new or modified antibiotics that have better ability to interact with targets on the surface membrane and so destroy the bacteria.

With increasing numbers of bacteria developing resistance to drugs, it is a major public health concern whereby we could reach a point where some infections become untreatable.

So further developments from this study are eagerly awaited.  

 

Where did the story come from?

The study was carried out by researchers from University College London, the Royal Free Hospital, the University of Cambridge, and other institutions in Kenya, Australia and Switzerland. The study received funding from various sources including the EPSRC Interdisciplinary Research Centre in Nanotechnology and EPSRC Grand Challenge in Nanotechnology for Healthcare.

The study was published in the peer-reviewed scientific journal Nature: Scientific Reports and the article is free to read online.

The UK’s media reporting of the study was accurate.

 

What kind of research was this?

This was a laboratory study looking at the mechanisms by which antibiotics target and destroy multi-resistant bacteria – bacteria resistant to more than antibiotics.

As the researchers say, the increase in the number of bacteria that are developing resistance to antibiotics is a major health concern. To tackle this there is a need to develop new antibiotics or new mechanisms to combat infection.

This study centred on some of the strongest antibiotics that are normally reserved to treat severe bacterial infections that are resistant to other antibiotics, such as methicillin-resistant staphylococcus aureus (MRSA) – methicillin was an early penicillin antibiotic).

It looked at the way they bind to specific protein targets on the bacteria and the force exerted to kill the bacteria. 

 

What did the researchers do?

The research involved studying how four strong antibiotics bind to protein targets on both susceptible bacteria and multi-resistant bacteria.

The four antibiotics were vancomycin, oritavancin, ristomycin and chloroeremomycin. Vancomycin is often the "last resort" antibiotic used to treat severe MRSA infections and clostridium difficile bowel infections.

Oritavancin is a new antibiotic used to treat complicated skin and soft tissue infections. The latter two are not currently licensed antibiotics.

Researchers measured signals that indicated the level of mechanical stress or force exerted at the cell surface when antibiotics bound to the membrane targets. They looked at the effects of different antibiotics and concentrations of antibiotic.

 

What did they find?

When the antibiotics bind to the protein targets on the bacterial membrane they produce a mechanical strain that increases with the number of bound targets – that is, as the antibiotic dose or concentration increases.

At a particular strain they weaken the overall strength of the cell membrane, making it unable to resist the osmotic pressure coming from inside the cell. This causes the bacteria to eventually break apart and die.

The researchers found the way in which the four different antibiotics bind to membrane targets of susceptible (non-resistant) bacteria was the same. However, there was significant difference in the mechanical force they exerted on the resistant bacterial targets.

Notably they found the binding force of oritavancin was 11,000 times stronger than that of vancomycin. 

 

What did the researchers conclude?

The researchers conclude: "Using an exactly solvable model, which takes into account the solvent and membrane effects, we demonstrate that drug-target interactions are strengthened by pronounced polyvalent interactions catalysed by the surface itself".

They suggest the findings "further enhance our understanding of antibiotic mode of action and will enable development of more effective therapies".

 

Conclusions

This laboratory study furthers understanding of the mechanisms by which antibacterial drugs target and destroy bacteria.

The answer seems to lie in how effectively the drug can bind to target molecules on the bacterial surface membrane. When the force of this binding exerts sufficient mechanical strain on the cell surface, then the bacteria breaks apart and is destroyed.

It shows that the strongest antibacterials that we have, such as vancomycin, are currently not infallible.

That we could reach a point where we have bacterial infections that not even the strongest antibiotics are able to fight is a major public health concern. It is hoped that further research will be able to build on these findings and develop new or modified antibacterials that have better ability to interact with the bacterial surface membrane and so destroy the cells.

Lead researcher Dr Jospeh Ndieyira is quoted in BBC News as saying: "No-one has really thought about antibiotics using mechanical forces to kill their targets before. This will help us create a new generation of antibiotics to tackle multi-drug resistant bacterial infections, now recognised as one of the greatest global threats in modern healthcare."

You can help combat the threat of antibiotic resistance yourself by:

  • recognising that most coughs, colds and stomach bugs are viral and do not need antibiotics
  • if prescribed antibiotics, always take them exactly as prescribed and take the full course, even if you start to feel better
  • never share them with anyone

Links To The Headlines

Antibiotics 'seen using brute force to kill bugs'. BBC News, February 4 2017

Scientists 'supercharge' antibiotics to tear superbugs apart: Study hailed as groundbreaking amid race to combat drug resistance. Mail Online, February 3 2017

Links To Science

Ndieyira JW, Bailey J, Patil SB, et al. Surface mediated cooperative interactions of drugs enhance mechanical forces for antibiotic action. Scientific Reports. Published online February 3 2017

Does eating liquorice in pregnancy raise the risk of ADHD?

"Avoid liquorice while pregnant: Scientists find one of its ingredients can affect a child's IQ, memory and even cause ADHD," the Mail Online reports.

Researchers found eating liquorice in pregnancy is linked to a range of developmental issues.

The news is based on Finnish research on almost 400 young adolescents with an average age of 12.5.

Liquorice consumption is thought to be higher in Finland than in the UK thanks to the popularity of salmiakki, a popular salty liquorice snack.

Researchers found girls whose mothers had consumed high amounts of liquorice during pregnancy were more likely to go through puberty at a younger age.

And girls and boys whose mothers consumed high amounts scored seven points lower on intelligence tests, and higher for attention deficit hyperactivity disorder (ADHD).

But, as with many other diet studies, the picture is too complex for us to assume a direct cause and effect relationship.

The component in liquorice thought to cause damage is called glycyrrhizin. But it's also found in a range of other foods, drinks and medicines.

Only liquorice intake was measured in the study, so the actual level of glycyrrhizin the women ate is merely an estimate.

Many other factors influence cognitive development, and it's not clear if the researchers fully adjusted for all possible factors.

There are currently no UK guidelines suggesting pregnant women should avoid all liquorice.

But, as a precaution, it's advised pregnant women avoid the herbal remedy liquorice root, as it has a particularly high concentration of glycyrrhizin.

Where did the story come from?

The study was carried out by researchers from the University of Helsinki in Finland.

It was funded by a range of academic and governmental institutions, including the Academy of Finland, the National Doctoral Programme of Psychology, and the Finnish Ministry of Education and Culture. The sponsor had no role in the study design.

The study was published in the peer-reviewed American Journal of Epidemiology on an open access basis, so it's free to read online. The authors declared no conflicts of interest.

The Mail generally covered the study accurately, acknowledging that the results need to be interpreted with caution as researchers "said it was impossible to say whether it was directly responsible for the development of a child".

But, as is so often the case, the headline let the story down with the unproven statement that, "Scientists find one of its [liquorice's] ingredients [glycyrrhizin] can affect a child's IQ, memory and even cause ADHD".

What kind of research was this?

This was a longitudinal cohort study of Finnish mothers and children.

The study previously looked at the children when they were eight years old and found those whose mothers reported high liquorice consumption during pregnancy scored lower on tests of intelligence and memory, and had a higher risk of behavioural problems.

The researchers aimed to follow up on this cohort of children again, now with a mean age of 12.5 years, to explore associations with puberty maturation and cognitive and behavioural factors.

A cohort study can show links between factors – in this case, liquorice consumption in pregnancy and later outcomes in childhood and adolescence – but cannot show that one factor causes another.

What did the research involve?

The study looked at 378 children born in 1998, now with a mean age of 12.5 years, whose mothers had either consumed large amounts of glycyrrhizin, a natural constituent of liquorice, of more than 500mg a week, or a low amount of less than 249mg a week.

While on the maternity ward, mothers reported the brand and how much liquorice they ate on a weekly basis during pregnancy. The researchers used this amount to calculate the quantity of glycyrrhizin consumed a week in mg.

Of the 378 children, 327 children were exposed to low amounts of glycyrrhizin in the womb and 51 were exposed to high amounts.

At follow-up, children were assessed for:

  • stages and signs of puberty, based on three measures of growth and development – this included height, weight, body mass index (BMI) for age, and the difference between current and expected adult height; the researchers also looked at Tanner staging for pubertal stage and the Pubertal Development Scale, both well-validated ways of measuring pubertal development
  • cognition – based on tests of intelligence, memory and learning, social perception, attention and executive function
  • psychiatric problems – based on their mother's completion of the Child Behaviour Checklist
  • neuroendocrine function – studying how hormones like cortisol could affect the function of the nervous system and, in turn, other functions, such as the metabolism

Confounding variables were adjusted for, including:

  • child's age
  • educational level of either parent
  • maternal age and BMI
  • maternal smoking and alcohol intake
  • coffee, tea and chocolate consumption
  • stress during pregnancy
What were the basic results?

Girls whose mothers consumed high amounts of liquorice during pregnancy, compared with those whose mothers consumed low amounts:

  • were 3cm taller on average (mean difference [MD] 0.4 standard deviations [SD], 95% confidence interval [CI] 0.1 to 0.8)
  • were 8kg heavier on average (MD 0.6 SD, 95% CI 0.2 to 1.9)
  • had BMIs 2.2 higher (MD 0.6 SD, 95% CI 0.2 to 0.9)
  • 37.9% scored "development definitely under way" on the Pubertal Development Scale Score, compared with 10.4%

For boys, there were no consistent associations between maternal liquorice consumption during pregnancy and pubertal maturation at this age.

Girls and boys whose mothers consumed high amounts of liquorice during pregnancy, compared with those whose mothers consumed low amounts:

  • scored seven points lower on tests of intelligence quotient on a scale of 100 points (95% CI 3.1 to 11.2)
  • had threefold greater odds of attention deficit hyperactivity disorder (ADHD) problems (95% CI 1.4 to 7.7)

No difference was found in cortisol levels.

How did the researchers interpret the results?

The authors concluded that, "Nutritional recommendations of various expert organisations do not mention glycyrrhizin use during pregnancy.

"The present findings suggest that pregnant women should be informed that consumption of liquorice and other food products containing glycyrrhizin may be associated with harm for their developing offspring." 

Conclusion

This study provides evidence of some link between how much liquorice a pregnant woman eats and earlier puberty in girls, but not boys.

It also shows some association between pregnant women eating liquorice and their children scoring lower for intelligence and being more likely to have ADHD.

However, this study has some limitations to consider:

  • Glycyrrhizin is found in other food products, such as chewing gum, sweets, cookies, ice creams, herbal teas, and herbal and traditional medicines, as well as alcoholic and non-alcoholic drinks.
  • The amount of these products the women ate was not reported, which means their intake of glycyrrhizin may not have been measured accurately.
  • Although the study accounted for some confounding variables, there are other factors that might have affected the results that were not reported – for example, income or social class.
  • The study was carried out on healthy babies all born in Helsinki, Finland. People in this region may consume larger amounts of liquorice than people in other countries, especially a salty liquorice called salmiakki, so the results may not be generalisable to women in the UK or elsewhere.
  • There were only 51 children in the group who had mothers who consumed large amounts of liquorice. This is a fairly low number, and a bigger study may have shown less difference between the groups.

There are currently no UK guidelines suggesting pregnant women should avoid all liquorice.

But, as a precaution, it's advised they avoid the herbal remedy liquorice root, as it contains high levels of the active ingredient glycyrrhizin.

There's also evidence that all people – not just pregnant women – should avoid regularly eating very high levels of liquorice of more than 57g (two ounces) a day for more than two weeks as this could lead to potentially serious health problems, such as increased blood pressure and an irregular heart rhythm (arrhythmia).

Read more advice about healthy eating in pregnancy and what foods to avoid in pregnancy.  

Links To The Headlines

Avoid liquorice while pregnant: Scientists find one of its ingredients can affect a child's IQ, memory and even cause ADHD. Mail Online, February 3 2017

Links To Science

Räikkönen K, Martikainen S, Pesonen A, et al. Maternal Licorice Consumption During Pregnancy and Pubertal, Cognitive, and Psychiatric Outcomes in Children. American Journal of Epidemiology. Published online February 3 2017

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