NHS Choices

Wearing killer high heels could lead to osteoarthritis, study warns

NHS Choices - Behind the Headlines - Fri, 16/01/2015 - 11:30

"Killer heels could lead to osteoarthritis in knees," The Daily Telegraph reports. An analysis of the walking patterns (gait) of 14 women found evidence that walking in high heels puts the knees under additional strain. Over time, this may potentially lead to osteoarthritis: so-called wear and tear arthritis, where damage to a joint causes stiffness and pain.

The main finding was that wearing high heels (3.8cm and 8.3cm were tested) changed the walking gait, especially around the knee joint area.

Hypothetically, the changes in knee dynamics seen in this study could potentially cause strain on the joint, damaging the cartilage inside the knee, thus increasing the possibility of knee osteoarthritis in later life.

However, the study did not keep in touch with participants to see if they went on to develop arthritis, so doesn’t prove any direct evidence that wearing high heels causes more knee osteoarthritis further down the line.

There are many factors linked to developing osteoarthritis in later life, most notably obesity, joint injuries and repetitive stress. Based on this study alone, it is not clear whether footwear is an important additional factor in the mix.

That said, we suspect that wearing high-heels all day, seven days a week, won’t do wonders for your feet.

 

Where did the story come from?

The study was carried out by researchers from Stanford University Medical Center (US) and was funded by the National Institutes for Health.

The study was published in the peer-reviewed medical journal the Journal of Orthopaedic Research.

The UK’s media reporting was factually accurate, although did not highlight any of the limitations of the research. Coverage tended to assume that the study had found a causal link between heel height and osteoarthritis in later life, which was not the case.

 

What kind of research was this?

The research team outline that knee osteoarthritis is about twice as prevalent in women as men and that wearing high-heeled shoes might be contributing to the higher risk in women.

This was an experimental study examining whether high-heeled walking, with and without additional weight, produces gait changes similar to those associated with increased risk of knee osteoarthritis.

The team were testing two theories.

Firstly, that there are significant changes to knee movement and forces during walking that increase in magnitude as heel height increases; and secondly, that the changes to knee movement during walking in high heels are made more extreme by a 20% increase in weight.

The study was set up to tell us whether women walk differently with heels and with added weight. It was not designed to prove that any change would cause more knee damage, specifically osteoarthritis in the future, but this was the research team’s working assumption.

 

What did the research involve?

The research involved 14 healthy female volunteers whose walking pattern – called their gait – was analysed while wearing different footwear. They were comparing “flat athletic shoes” – presumably trainers – with high heels of various heights, 3.8cm (1.5inches) and 8.3cm (3.2 inches). Each participant underwent measurements nine times in total for each shoe. This included walking at three different speeds.

A second part of the study was looking at whether adding weight to the person affected their walking pattern still further. They achieved this by studying the women’s gait with and without them wearing a vest that added 20% to their total body weight. Women with the added weight were tested wearing the different footwear.

The study analysis compared the gait parameters between the different footwear and for the added weight, to look for changes to the women’s normal walking style.

The authors were aware that walking speed affects measures of walking pattern, so performed additional analysis to account for potential differences in walking speed.

 

What were the basic results?

The bottom line was that there were some significant walking pattern changes linked to the two heel heights tested, and the 20% extra weight. For example, when wearing heels, women tended to bend their knees more during specific phases of their walk.

Women walked slower in heels, but weight did not affect walking speed. 

 

How did the researchers interpret the results?

The researchers said that “Many of the changes observed with increasing heel height and weight were similar to those seen with ageing and OA [osteoarthritis] progression,” and that, “This suggests that high heel use, especially in combination with additional weight, may contribute to increased OA risk in women."

 

Conclusion

The main finding of this study was that wearing high heels affected the way women walk compared to flat shoes. Although not a surprise, the study's findings could still be unreliable, as it involved only 14 women. A study of more people would improve confidence in the findings.

The issue that grabbed the headlines was the possibility that this might lead to a higher risk of knee osteoarthritis later in life.

While the study authors do say that “Many of the changes observed with increasing heel height and weight were similar to those seen with ageing and OA [osteoarthritis] progression”, this does not prove cause and effect. The study itself does not provide evidence on whether heels actually cause an increase in joint disease or any kind, only that they affect the way women walk. Other factors, such as how often the women wear heels, what height, at what age they start and stop wearing them and many other factors, could also influence any association between footwear and joint problems in later life. 

There is potentially a different way of assessing the theory that heels may be related to different prevalence of knee osteoarthritis in men and women in later life. You could study knee osteoarthritis rates in men who regularly wear high heels (for example, transvestites and panto performers) to see if they have similar rates of osteoarthritis to similar heel wearers who are women.

Overall, this small study gives researchers more information on the precise gait changes that occur when a woman wears heels, or when they carry added weight. However, the study does not contribute any further understanding about whether wearing heels is causally related to joint problems in later life.

However, there have been reports of an association between “over-wearing” high heels and foot problems such as corns and calluses. Most foot care specialists would recommend saving your killer heels for special occasions, and sticking to flats or trainers for the daily commute. Read more advice about foot care.

Analysis by Bazian. Edited by NHS Choices. Follow Behind the Headlines on Twitter. Join the Healthy Evidence forum.

Links To The Headlines

Killer heels could lead to osteoarthritis in knees, warn scientists. The Daily Telegraph, January 14 2015

How 3.5inch heels could prematurely age your joints: Walking in stilettos this high causes changes to the gait seen in ageing and those with arthritic knees. Mail Online, January 15 2015

Links To Science

Titchenal MR, Asay JL, Favre J, et al. Effects of high heel wear and increased weight on the knee during walking. Journal of Orthopaedic Research. Published online December 22 2014

Categories: NHS Choices

Study finds care home residents 'more likely' to be dehydrated

NHS Choices - Behind the Headlines - Fri, 16/01/2015 - 11:30

"Care home residents five times more likely to be left thirsty," The Independent reports after an analysis of some London hospital admission records found people admitted from care homes were five times more likely to be dehydrated than people coming from their own homes.

Equally serious was the discovery that dehydration at admission was associated with a higher risk of dying while in hospital.

Much of the media seized on anecdotal reports that dehydration was the result of staff restricting access to fluids so residents were less likely to wet themselves during the night or ask to go to the toilet.

But anecdotal reports cannot be proved and, in terms of evidence-based medicine, don't hold high value.

The study did not explore, or provide any hard evidence of, why care home residents are more likely to be dehydrated.

While it would be complacent to discount suspected poor standards of care in certain homes, other factors may also be involved. For example, many people with dementia have reduced thirst and are reluctant to drink.

The truth is we do not yet know what is behind the higher dehydration levels in patients coming from care homes. Finding an explanation is the crucial next step.

 

Where did the story come from?

The study was carried out by researchers from Barnet and Chase Farm NHS Trust (London), the University of Oxford, and the London School of Hygiene and Tropical Medicine.

It was funded by a Wellcome Trust Investigator Award.

The study was published in The Journal of the Royal Society of Medicine, a peer-reviewed medical journal.

The media generally reported the findings of the story accurately, but many fell into the trap of reporting the study authors' speculation as if it was proven fact.

For example, the Daily Mail had the headline, "Lives of care home patients put at risk through lack of water: Staff 'don't want them going to the toilet at night'." This accusation is unproven.

The reasons why patients were dehydrated were not investigated as part of this study. Plausible explanations were put forward by the study’s authors to explain their observations.

They also raised concerns about potential poor care standards, but none of this speculation is based on new evidence. Additional work is needed to find out the reasons behind this worrying statistic.

 

What kind of research was this?

This was a cross-sectional study looking at the risk of dehydration on admission to hospital in older people living in care homes, compared with those who were living in their own home.

The researchers state older people are at a higher risk of dehydration, and dehydration is associated with worse outcomes while in hospital.

They also say mild to moderate dehydration in older people is easily missed, and is often only detected once individuals are admitted to hospital and have their electrolytes measured, revealing sodium imbalances. Abnormally high sodium levels can be a sign of dehydration.

A study like this can tell us whether a person is likely to have been dehydrated on admission to hospital, but it cannot tell us why this was, as there are many possible reasons.

 

What did the research involve?

The study team were granted permission to analyse information already collected on 21,610 people over the age of 65 who were admitted to an NHS hospital in London over a two-year period in January 2011 to December 2013.

The team obtained data on patients' ages, the type of admission (emergency or planned), and whether they lived in a care home or their own home.

They also had information on whether the person was dehydrated when they were admitted to hospital and whether they subsequently died in hospital.

The main analysis looked for links between whether a person was admitted from a care home and dehydration and death.

The team used hypernatraemia (plasma sodium levels of more than 145 mmol/L) to measure dehydration. This measure of sodium levels in the blood is a pretty accurate indicator of whether a person has had enough water or not.

Certain conditions make hypernatraemia more likely, such as prolonged vomiting or diarrhoea, sweating, and high fevers with inadequate replacement of the fluid lost. Some drugs and hormonal conditions can also increase the level of sodium in the blood.

 

What were the basic results?

The results came in two parts. The crude results presented did not take into account any influencing factors (confounders), while the adjusted results did.

But these did not include the reason for the admission, only whether it was planned or an emergency. 

Initial crude findings showed patients admitted from care homes had a 10 times higher prevalence of hypernatraemia than those who lived in their own home (12.0% versus 1.3%, respectively; odds ratio [OR] 10.5, 95% confidence interval [CI] 8.43-13.0).

From this, the research team worked out around one in three cases of dehydration on admission would be avoided if people who lived in care homes were properly hydrated (population attributable fraction 36.0%).

Of note, 61.9% of people in nursing homes suffered from dementia, which can make it challenging for carers to ensure residents are properly hydrated, compared with 14.7% of people in their own homes.

After accounting for age, gender, mode of admission and dementia, the adjusted results found care home residents were around five times more likely to be admitted with hypernatraemia than people who lived in their own homes (adjusted OR 5.32, 95% CI: 3.85-7.37).

Care home residents were also about twice as likely to die while in hospital (adjusted OR: 1.97, 95% CI: 1.59-2.45).

 

How did the researchers interpret the results?

The researchers' interpretation was simple and stark: "Patients admitted to hospital from care homes are commonly dehydrated on admission and, as a result, appear to experience significantly greater risks of in-hospital mortality [death while at hospital]."

 

Conclusion

This research showed older people living in care homes were five times more likely to be admitted to hospital with dehydration than patients who lived in their own homes.

The research team and media expressed great concern this might be a result of poor-quality care in care homes.

While the study was able to show there is a worrying variation in dehydration levels linked to care homes, it was not able to provide evidence to explain these statistics.

There are many possible explanations for these results, many of which are highlighted by the study authors and the media. This study does not provide any direct evidence supporting any of these explanations, which are speculative at this stage.

The analysis attempted to correct for the finding that people in care homes were slightly older, more likely to be admitted as emergency cases, and far more had dementia. This made a large difference to the relative risk, taking it from 10 times more likely to five times more likely.

This hints at the possibility that people in care homes may be more unwell or have more complex illness and care issues than people who live in their own homes, which may influence their ability to remain hydrated. This is an alternative explanation to the conclusion that the care provided by care homes is inadequate.

The analyses also did not take into account the reason why patients were admitted to hospital, which would have clarified this issue. It is possible these factors (residual confounding) and other unmeasured factors (bias) may still be influencing the results to some degree. 

This type of study is useful in flagging up potential care issues for further investigation by care regulators. In the UK this job falls to the Care Quality Commission (CQC)

The Independent informs us that, "The CQC said ensuring residents get enough food and drink was central to their inspections of care homes," reassuring readers that, "Deputy chief inspector of adult social care in London, Sally Warren, said information on dehydration supplied by Dr Wolff [the author of this study] had been shared with local inspectors."

Analysis by Bazian. Edited by NHS Choices. Follow Behind the Headlines on Twitter. Join the Healthy Evidence forum.

Links To The Headlines

Care home residents five times more likely to be left thirsty, study reveals. The Independent, January 16 2015

Care home staff may leave pensioners dehydrated to stop incontinence, Oxford University warns. The Daily Telegraph, January 16 2015

Lives of care home patients put at risk through lack of water: Staff 'don't want them going to the toilet at night'. Daily Mail, January 16 2015

Scandal of dehydration in care homes exposes neglect. The Times, January 16 2015

Links To Science

Wolff A, Stuckler D, McKee M. Are patients admitted to hospitals from care homes dehydrated? A retrospective analysis of hypernatraemia and in-hospital mortality. The Journal of the Royal Society of Medicine. Published online January 15 2015

Categories: NHS Choices

Inactivity 'twice as deadly' as obesity

NHS Choices - Behind the Headlines - Thu, 15/01/2015 - 11:30

“Lack of exercise is twice as deadly as obesity,” The Daily Telegraph reports. The headline is prompted by a Europe-wide study on obesity, exercise and health outcomes.

Researchers wanted to see how many deaths could theoretically be avoided if inactive people became more active, compared to how many would be avoided if obese people lost weight.

Researchers calculated that if activity levels were increased so that no-one was classed as inactive, then this could reduce early deaths by more than 7%. This compares to avoiding obesity, which could reduce deaths by nearly 4%. In 2008, say the researchers, 676,000 deaths were attributable to physical inactivity, compared with 337,000 deaths attributable to obesity.

This large study also found that among inactive individuals, even small increases in activity may be of benefit, whatever their weight or waist size.

So should we concentrate purely on physical activity and stop worrying about losing weight?

In practice it’s hard to disentangle the two, since exercise, along with diet, helps maintain a healthy weight. Also, obesity is an established risk factor for diseases such as type 2 diabetes, which is best tackled with a combination of diet and exercise.

So it would be a bad idea to ignore the risks of obesity, whatever your levels of physical activity.

 

Where did the story come from?

The study was carried out by researchers from a number of academic centres in Europe, including the Universities of Cambridge, Oxford and London. It was funded by grants from many bodies across Europe, including the EU and in the UK the Department of Health, the Medical Research Council, Cancer Research UK, the Wellcome Trust, the Stroke Association, the British Heart Foundation and the Food Standards Agency.

The study was published in the peer-reviewed American Journal of Clinical Nutrition and has been made available on an open-access basis, so it is free to read online or download as a PDF.

It was covered fairly by the UK media, although the aims and design of the study were more complex than some of the reporting suggests.

 

What kind of research was this?

This was a large cohort study following 334,161 European men and women for an average of about 12 years, looking at levels of physical activity, body mass index (BMI) and waist circumference (a measure of abdominal adiposity) and the risk of early death.  

The researchers say that lack of physical activity has long been associated with an increased risk of death, independent of people’s BMI. Their aim was to find out if either BMI or waist circumference had any influence on the association between physical activity and the risk of early death.

They also compared how many deaths could theoretically be avoided if inactive or obese individuals were more active or non-obese respectively.

 

What did the research involve?

The researchers used data from an ongoing European study (the EPIC study) of more than half a million participants from 23 centres in 10 countries – Sweden, Denmark, Norway, the Netherlands, the UK, France, Germany, Spain, Italy and Greece. They were recruited to the study between 1992 and 2000.

Participants were aged between 25 and 70. Those who reported having heart disease, stroke or cancer at recruitment were excluded from this current analysis, as were those with missing data in areas such as physical activity and lifestyle.

Participants’ height, weight and waist circumference were measured at the start of the study. From this data they were categorised as normal weight (BMI 18.5-24.9), overweight (BMI 25-30) or obese (BMI of 30 or over). For waist circumference researchers considered waist circumference to be high if over 102cm for men and over 88cm for women.

Participants self reported their levels of occupational, recreational and household physical activity, using a validated questionnaire. Levels of physical activity at work were categorised as either sedentary (e.g. office work), standing (e.g. hairdresser, security guard) or physical (e.g. plumber, nurse) or heavy manual work (e.g. bricklayer).

Recreational activity was assessed as the amount of hours per week spent cycling, jogging, swimming and other physical exercise.

The researchers assessed overall activity levels by combining occupational and recreational activity levels. Physical activity was then categorised into four groups:

  • active
  • moderately active
  • moderately inactive
  • inactive

Researchers collected data on participants’ death from all causes between 2008 and 2010 from official records in each country, both at the regional or national level.

They then examined associations between physical activity, obesity, waist circumference (WC) and deaths from all causes. They adjusted their results for sex, smoking, education and alcohol intake.

 

What were the basic results?

The analysis included 116,980 men (average age 52.6 years) and 217,181 women (average age 51.2 years). There were 11,086 deaths among the men and 10,352 deaths among the women.

The risk of early death was reduced by 16-30% in people were who moderately inactive, compared to those who were inactive, whatever their BMI or waist circumference.

In normal weight and overweight people, higher levels of physical activity were associated with a further reduction in risk.

The researchers calculate that avoiding all inactivity could theoretically reduce all-cause mortality by 7.35% (95% confidence interval (CI), 5.88-8.83%).

Avoiding obesity could theoretically reduce all-cause mortality by 3.66% (95% CI, 2.30-5.01%).

 

How did the researchers interpret the results?

The researchers say that the greatest reduction in risk of death was in the moderately inactive groups, compared to those who were totally inactive. This reduction in risk was found across all groups at all levels of BMI and waist size.

Physical inactivity may theoretically be responsible for twice as many deaths as a high BMI, they say.

Efforts to encourage even small increases in activity may be of benefit.

 

Conclusion

This study’s strengths included its large size and long follow-up period. Researchers also took into account a large number of factors (called confounders) that might have influenced the risk of death, such as diet, smoking history and alcohol intake, although it is still possible that both measured and unmeasured confounders influenced mortality rates.

The study had one important limitation. It only measured people’s BMI (calculated by combining their weight and height) and their physical activity once, at the start of the study. It is quite possible that people’s BMI changed over time, and that this would have had an effect on mortality rates. For example, if physical activity helped reduce obesity over time, it is not possible to say that physical activity reduced the risk of mortality, independent of people’s weight.

Also, the calculations on the number of deaths that could be avoided by both reductions in physical inactivity and obesity is hypothetical.

It would be a bad idea to ignore the risks of obesity, whatever your levels of physical activity.

Obesity is an established risk factor for a range of conditions such as diabetes and cardiovascular disease and it is best tackled by both diet and exercise. But no-one would argue with the notion that everyone should be encouraged to increase levels of physical activity, whatever their size.

An ideal way to gradually raise your activity levels is our Couch to 5K programme, which can turn a couch potato into a successful five kilometre runner over the course of nine weeks. 

Analysis by Bazian. Edited by NHS Choices. Follow Behind the Headlines on Twitter. Join the Healthy Evidence forum.

Links To The Headlines

Lack of exercise is twice as deadly as obesity, Cambridge University finds. The Daily Telegraph, January 15 2015

Inactivity 'kills more than obesity'. BBC News, January 15 2015

Physical inactivity kills twice as many as obesity, new study claims. The Independent, January 15 2015

Inactivity 'deadlier than obesity'. Mail Online, January 15 2015

Scientists recommend 20-minute daily walk to avoid premature death. The Guardian, January 14 2015

No exercise kills TWICE as many people as obesity, shock research reveals. Daily Mirror, January 14 2015

Links To Science

Ekelund U, Ward HA, Norat T, et al. Physical activity and all-cause mortality across levels of overall and abdominal adiposity in European men and women: the European Prospective Investigation into Cancer and Nutrition Study (EPIC). The American Journal of Clinical Nutrition. Published online January 14 2015

Categories: NHS Choices

'Hibernation protein' could help repair dementia damage

NHS Choices - Behind the Headlines - Thu, 15/01/2015 - 11:00

"Neurodegenerative diseases have been halted by harnessing the regenerative power of hibernation," BBC News reports. Researchers have identified a protein used by animals coming out of hibernation that can help rebuild damaged brain connections – in mice.

Research found the cooling that occurs in hibernation reduces the number of nerve connections in the brain, but these regrow when an animal warms up.

A protein called RNA-binding motif protein 3 (RBM3) increases during the cooling, and it appears this protein is part of a pathway involved in the regrowth.

When the level of RBM3 was increased without cooling, researchers found the protein protected against the loss of nerve connections in mice with early-stage rodent forms of Alzheimer’s disease and a prion infection similar to Cruetzfeldt-Jakob disease (CJD). The diseases progressed more quickly when the level of RBM3 was lowered.

This same protein is increased in humans when they are given therapeutic hypothermia, where the body temperature is reduced to 34C as a protective treatment after events such as a heart attack.

The hope is that restoring neural connections (synapses) in humans could halt, or even reverse, the effects of dementia and associated neurodegenerative diseases. But this research is still very much in the early stages.

 

Where did the story come from?

The study was carried out by researchers from the University of Leicester and the University of Cambridge, and was funded by the Medical Research Council.

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

On the whole, the media reported the study accurately, but the Mail Online got carried away when they said a drug produced from this research "given in middle age … could keep the brain healthy for longer".

The experiments have only been done in mice so far, and no drug has been developed to target the pathway in humans.

 

What kind of research was this?

This was an animal study that looked at the effects of hibernation on the brain synapses (nerve connections) of mice.

Normally, synapses in the brain go through a process of forming, being removed, and then forming again. Various toxic processes can cause more degeneration, and in some conditions they are not reformed.

This leads to a reduction in the number of synapses, as occurs in conditions such as Alzheimer's disease, which are associated with symptoms such as memory loss and confusion.

A similar loss of synapses occurs when animals hibernate, but they are renewed when the animal warms up at the end of hibernation. Previous research found this also happens when rodents are cooled in a laboratory setting.

Researchers found the production of many proteins does not occur at these low temperatures, but some proteins called "cold-shock proteins" are stimulated – one of these is RBM3.

Here, the researchers wanted to further investigate whether this protein plays a role in the regeneration of synapses. They hope it might be key to understanding how we could restart the process of synapse renewal in humans.

 

What did the research involve?

Three groups of mice were studied during hibernation induced in the laboratory setting:

  • normal (wild type) mice – controls
  • mice with a rodent form of Alzheimer's disease
  • mice with a prion disease, similar to Cruetzfeldt-Jakob Disease (CJD)

Some mice were cooled to 16-18C for 45 minutes and then gradually warmed back to their normal body temperature.

Their brains were studied at various stages of the cooling and rewarming process to count the number of synapses and measure the level of RBM3.

Some mice with the prion disease were not cooled so they could be used as a comparison to see if the cooling process had any effect on the course of the disease.

The other mice were also not cooled, but their levels of RBM3 were chemically increased or decreased to see what effect this had on their brains.

 

What were the basic results?

Normal mice and mice with the very early stages of a rodent form of Alzheimer's disease (at two months) and a prion disease (at four and five weeks after infection) lost synapses as they were cooled down, but recovered them as they warmed up.

They also all had increased levels of RBM3 during the cooling stage. These levels of RBM3 stayed elevated for up to three days afterwards.

The prion-infected mice did not succumb to the disease as quickly as mice that had been infected but not cooled.

They survived for seven days longer on average (91 days compared with 84 days). This suggests the cooling process gave some protection against the prion disease.

Mice who had rodent Alzheimer's disease for three months and a prion disease for six weeks (that is, more advanced disease) also lost synapses when they were cooled, but were not able to regrow them on warming up.

They did not have increased levels of RBM3. There was no difference in survival between these prion-infected mice and the prion-infected mice that were not cooled.

In mice where RBM3 levels were artificially reduced, both types of disease worsened more quickly and synapses were lost faster.

Reducing RBM3 levels in mice without these diseases also reduced the number of synapses, and the mice had memory problems.

When RBM3 production was stimulated in one region of the brain (the hippocampus) in mice with prion infection, this reduced the number of synapses that were lost and increased their survival.

 

How did the researchers interpret the results?

The researchers concluded the protein RBM3 is involved in the pathway of synapse regeneration in mice. They found stimulating the protein was protective against synapse loss in mice with a rodent form of Alzheimer's disease and a prion disease. They hope that, with further research, this might be a new avenue for drug development for humans.

 

Conclusion

The researchers have shown how cooling is protective against the loss of synapses in the early stages of rodent forms of Alzheimer's disease and a form of prion disease. Cooling also increased how long prion-infected mice survived.

But cooling was not protective in the later stages of the diseases. The researchers found this may in part be because of the protein RBM3, which is stimulated during cooling. They found levels of RBM3 increased in the early stages of the diseases when the mice were cooled, but did not in the later stages.

Stimulating this protein without cooling the mice also slowed down the loss of synapses and improved survival in mice with a prion infection.

The results also showed the disease processes sped up when RBM3 levels were reduced. The researchers say this indicates RBM3 is likely to be involved in the maintenance of synapse connections under normal conditions, not just during hibernation.

It is already known from other studies that similar increases in RBM3 occur when humans are given therapeutic hypothermia, where the body temperature is reduced to 34C as a protective treatment – for instance, after a heart attack.

It may be the case that if this pathway is stimulated in humans, it could be a new avenue of research for the treatment of neurodegenerative disorders such as Alzheimer's disease.

This is intriguing research, but still very much in its early stages. There is much we don't know about Alzheimer's disease and other related diseases, though there is evidence that taking steps to maintain a healthy blood flow to the brain by taking regular exercise and eating a healthy diet may lower the risk (as well as help prevent heart disease).

Read more about dementia prevention.

Analysis by Bazian. Edited by NHS Choices. Follow Behind the Headlines on Twitter. Join the Healthy Evidence forum.

Links To The Headlines

Hibernating hints at dementia therapy. BBC News, January 15 2015

Do squirrels hold key to preventing Alzheimer's? Breakthrough after scientists discover putting the brain into 'hibernation' could help prevent the devastating disease. Daily Mail, January 14 2015

How hibernating animals could help fight Alzheimer's disease. The Daily Telegraph, January 14 2015

Why hibernating bears could be good news in the fight against dementia. The Independent, January 14 2015

Links To Science

Peretti D, Bastide A, Radford H, et al. RBM3 mediates structural plasticity and protective effects of cooling in neurodegeneration. Nature. Published online January 14 2015

Categories: NHS Choices

Healthy breakfast cereals

NHS Choices - Live Well - Wed, 14/01/2015 - 15:59
Healthy breakfast cereals

With shelves stacked top to bottom with hundreds of brightly coloured boxes competing for your attention, the supermarket aisle of breakfast cereals can sometimes feel like walking through a minefield.

Make the wrong choice and you or your child could end up with a breakfast cereal high in sugar, fat or salt, which if eaten too often can contribute to weight gain and health problems, including tooth decay and high blood pressure.

But whether it's puffed, baked or flaked, cereal can still form part of a healthy balanced diet. We've enlisted dietitian Azmina Govindji to sort the shredded wheat from the chaff to help you make a healthier choice. 

"While it's important to make healthier choices when it comes to breakfast, it's equally just as important to make sure you eat breakfast regularly and that you enjoy it," says Govindji.

What's a healthy breakfast cereal?

For a healthier option, choose breakfast cereals that contain wholegrains and are lower in sugar, fat and salt. Examples include:

  • wholewheat cereal biscuits
  • shredded wholegrain pillows
  • porridge oats

Wholegrains contain fibre and B vitamins, among other nutrients. Fibre helps keep our digestive systems healthy, and research suggests a diet high in fibre may help reduce the risk of developing heart disease and type 2 diabetes.

"Avoid always going for the same brand as manufacturers regularly modify their recipes," says Govindji. "Try looking at the nutrition label, and compare brands so you opt for the healthier version."

Mueslis, which usually contain wholegrains and fruit, are often seen as a healthier option, but check the label first – many can be relatively high in fat, added sugar and, in some cases, salt.

Reading nutrition labels

Food labels can help you choose between brands and avoid breakfast cereals high in sugar, fat and salt. All nutrition information is provided per 100g and "per serving", which can be helpful when comparing one cereal with another.

Some brands also use red, amber and green colour coding on the front of the packet, sometimes known as traffic lights. The more greens on the label, the healthier the choice. Find out more about food labels.

Sugar, fat and salt levels

You can use the per 100g information on the nutrition label to identify breakfast cereals that are:

High in sugar, fat or salt

  • High in sugar: more than 22.5g of total sugars per 100g
  • High in fat: more than 17.5g of fat per 100g
  • High in salt: more than 1.5g of salt per 100g

Low in sugar, fat or salt

  • Low in sugars: 5g of total sugars or less per 100g
  • Low in fat: 3g of saturated fat or less per 100g
  • Low in salt: 0.3g of salt or less per 100g
Serving cereal with milk or yoghurt

Having breakfast cereal is a good opportunity to add calcium to the diet if you serve it with milk or yoghurt. Go for semi-skimmed, 1% or skimmed milk, or lower-fat yoghurt. "Milk and yoghurt are good sources of calcium and protein," says Govindji. Find out what types of milk are suitable for young children.

Adding fruit to cereal

Having cereal is also a good opportunity to get some fruit in the diet. Raisins, dried apricots, bananas and strawberries are popular choices, and can be added to any cereal, depending on your tastes.

"Adding fruit to cereals is a great way to get kids to eat more fruit," says Govindji. "It also helps them enjoy less sugary cereals, as you get sweetness from the fruit."

You could wash down breakfast with a small glass (150ml) of 100% fruit juice, which also counts towards your 5 A DAY.

How many calories should breakfast provide?

A helpful rule of thumb to maintain a healthy weight is to follow the 400-600-600 approach. That means having about:

  • 400kcal for breakfast (including any drinks and accompaniments)
  • 600kcal for lunch (including any drinks and accompaniments)
  • 600kcal for dinner (including any drinks and accompaniments)

That leaves you with just enough left over to enjoy a few healthy drinks and snacks throughout the day. This advice is based on a woman's daily recommended calorie intake of 2,000kcal.

"You might get about 150kcal from a 40g serving of cereal," says Govindji. "You could add a medium sliced banana and 200ml of semi-skimmed milk, which all together would provide about 350kcals. 

"You need fuel in the morning, and starting the day with a filling breakfast can help you avoid reaching for a less healthy mid-morning snack to keep you going until lunch."

'My child is hooked on sugary cereals'

If you want to get your child off sugary cereals, Govindji recommends mixing sugary cereals with similar looking lower-sugar ones. You could then gradually increase the amount of lower-sugar cereal over time to get kids used to them. Or you could let your child pick from a selection of, say, three healthier cereals.

"The fact that your child wants to have breakfast is already a healthy habit," says Govindji. "You don't want to jeopardise that by making breakfast seem suddenly unappealing." 

'I don't have time to sit down for breakfast'

It's a sign of the times that people are increasingly abandoning breakfast cereals, one of the earliest convenience foods, for more convenient "on-the-go" options, such as a breakfast muffin and a latte.

If you're short on time in the morning, how about setting the table the night before? You could also grab a pot of porridge on your way to work or have your cereal when you get in.

"Cereals are still one of the best value breakfasts out there," says Govindji. "A bowl of fortified breakfast cereal with milk gives you more nutrients for your penny when compared to most on-the-go breakfast options."

Find out how to get into breakfast.

Categories: NHS Choices

How therapy and exercise 'may help some with CFS'

NHS Choices - Behind the Headlines - Wed, 14/01/2015 - 12:00

"Chronic fatigue syndrome patients' fear of exercise can hinder treatment," The Guardian reports.

Chronic fatigue syndrome (CFS) is a long-term condition that causes persistent and debilitating fatigue. We do not know what causes the condition and there is no cure, though many people improve over time.

Treatments for CFS aim to reduce symptoms, but some people find certain treatments help, while others don't.

The news coverage is further analysis of a trial from 2011, which investigated four different treatments for CFS.

This study suggested adding either cognitive behavioural therapy (CBT) or graded exercise therapy (GET) to a person's medical care saw some improvements in their symptoms of fatigue and physical function.

CBT is a type of "talking therapy" designed to change patterns of thinking and behaviour, while GET is a structured exercise programme that aims to gradually increase how long a person can carry out a physical activity.

The current analysis assessed a range of possible factors to see whether these might explain how CBT and GET improved symptoms.

The findings suggested the treatments could be having an effect at least in part by helping to reduce fear avoidance beliefs, such as worrying exercise would make symptoms worse.

However, this study does have limitations, including the fact the researchers have looked at a lot of different possible factors, and some of the statistical associations may arise by chance.

The researchers aim to use these findings to help them improve these treatments or develop new ones.

As the authors make clear, it is important to note this study did not look at what causes CFS.

 

Where did the story come from?

The study was carried out by researchers from King's College London and other UK universities.

It was funded by the UK Medical Research Council, the Department of Health for England, the Scottish Chief Scientist Office, the Department for Work and Pensions, the National Institute for Health Research (NIHR), the NIHR Biomedical Research Centre for Mental Health at the South London and Maudsley NHS Foundation Trust, and the Institute of Psychiatry, Psychology and Neuroscience at King's College London.

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

The UK news headlines covering this complex study have all tended to miss the point slightly. The headlines either focus on the already published results (The Independent), or talk about "fear of exercise" exacerbating CFS (The Daily Telegraph and the Daily Mail) or hindering treatment (The Guardian).

This study did not look at what causes or "exacerbates" CFS, or hinders treatment. It assessed how CBT and GET might have improved fatigue and physical function.

It found at least part of the treatments' effects seemed to be down to reducing people's "fear avoidance beliefs", such as worrying exercise would make their symptoms worse.

The Daily Telegraph's suggestion that the study says "people suffering from ME [myalgic encephalopathy] should get out of bed and exercise if they want to alleviate their condition" is particularly unhelpful, and feeds the idea that people with CFS are "lazy": this is not the case.

CFS is a serious condition that can cause long-term illness and disability, and it is not reasonable to suggest people with CFS should simply get up and do some exercise.

People living with CFS need to talk to their doctors about what is appropriate for them and, if an exercise programme is recommended as part of their treatment, that this is done in a structured way. If anything, attempting to exercise before the body is ready to can reverse the rehabilitation process.

 

What kind of research was this?

This was an analysis of data from a randomised controlled trial of different treatments for CFS, which attempted to investigate how these treatments might work.

The trial was called PACE (adaptive Pacing, graded Activity and Cognitive behaviour therapy; a randomised Evaluation trial). It compared four different treatments in 641 people with CFS:

  • specialist medical care alone
  • specialist medical care with adaptive pacing therapy, which involves balancing periods of activity with periods of rest
  • specialist medical care with cognitive behaviour therapy (CBT)
  • specialist medical care with graded exercise therapy (GET)

These treatments are described in more detail in our analysis of this study from 2011.

It found adding CBT or GET to medical care gave moderate improvements in physical function and fatigue compared with medical care alone.

In this study, researchers wanted to see if they could identify what factors (mediators) CBT and GET might be influencing to give rise to these improvements.

The researchers had planned these "secondary" analyses of the PACE trial in advance, so they were able to collect all the relevant data they needed during the trial.

This is a more robust approach than carrying out ad hoc analyses after the study is completed. These secondary analyses tend to be used to generate hypotheses that can be further investigated in future studies.

 

What did the research involve?

The researchers carried out analyses of the PACE trial data to identify possible mediators (factors than can influence the effectiveness of treatments).

This essentially involved looking at whether the effects of CBT or GET were still statistically significant if the researchers adjusted for the potential mediators in their analyses.

The idea is that if CBT or GET work by changing one or more of the mediators, adjusting the analyses to essentially "remove" changes in these mediators will also reduce or remove the effects of CBT or GET on the outcomes.

They also looked at the effect of CBT and GET on these mediators, and the relationship between the mediators and the outcomes.

At the start and various other points during the PACE trial, the researchers measured certain factors they thought could be potential mediators.

Most of these mediators were measured using the Cognitive Behavioural Responses Questionnaire (CBRQ), while a few were measured using specific tests.

These factors included the level of participants':

  • fear avoidance beliefs – such as being afraid exercising would make symptoms worse
  • symptom focusing – thinking a lot about symptoms
  • catastrophising – such as believing they would never feel right again
  • embarrassment avoidance beliefs – such as being embarrassed by symptoms
  • damage beliefs – such as the belief that symptoms show they are damaging themselves
  • avoidance or resting behaviour – such as staying in bed to control symptoms
  • all-or-nothing behaviour – behaviour characterised by periods of high activity and subsequent long periods of resting
  • self-efficacy – feelings of control over symptoms and the disease
  • sleep problems – measured using the Jenkins Sleep Scale
  • anxiety and depression – measured using the Hospital Anxiety and Depression Scale (HADS)
  • fitness and perceived exertion – measured using a step test
  • walking ability – measured as the maximum distance a person could walk in six minutes

For their analyses, the researchers took into account the participants' level of these mediators 12 weeks into the trial. The exception was the walk test, which was assessed at 24 weeks.

The researchers also looked for mediators of the effect of CBT and GET at 52 weeks. These outcomes were measured using the physical function subscale of the Short Form (SF)-36 and the Chalder Fatigue Scale respectively.

Individuals with missing data were excluded from the analyses. The researchers also adjusted for a range of potential confounders in their analyses.

 

What were the basic results?

The researchers found fear avoidance beliefs appeared to be the strongest mediator of the effects of both CBT and GET on physical function and fatigue compared with specialist medical care. It seemed to account for up to 60% of their effect on these outcomes.

For GET, adjusting for participants' increase in exercise tolerance (how far they could walk in six minutes) substantially reduced the effects of GET, but not CBT.

A number of other factors also seemed to be mediators of CBT or GET (compared with specialist medical care alone or adaptive pacing therapy), but the effects tended to be smaller. Fitness and perceived exertion did not appear to be mediating the effects of treatment.

 

How did the researchers interpret the results?

The researchers concluded fear avoidance beliefs were the most important mediators of the effects of CBT and GET.

They say that: "Changes in both beliefs and behaviour mediated the effects of both CBT and GET, but more so for GET."

 

Conclusion

This study has tried to pick apart how cognitive behavioural therapy (CBT) and graduated exercise therapy (GET) affected fatigue and physical function in the PACE randomised controlled trial (RCT).

Its findings suggest this could partly be a result of CBT and GET reducing fear avoidance beliefs, such as the fear that exercise would make symptoms worse. But these treatments were less effective in cases where fear avoidance beliefs remained.

The researchers also identified other factors (mediators) that seemed to be playing a role, such as GET increasing the maximum distance an individual could walk in the six-minute walk test.

This study benefits from being a pre-planned analysis of an RCT, as well as the fact the treatments, mediators and outcomes occurred one after the other. The latter means it is possible the treatments are influencing the mediators, which are then influencing outcomes.

The study only measured some potential mediators, and the authors note they could not rule out the possibility unmeasured factors are influencing the results. They did adjust for a range of confounders to try to reduce this chance, however.

Another potential limitation was the main analysis excluded participants with missing data. This is appropriate if those with missing data are missing at random, but if particular types of people – such as those for whom the treatments are not working as well – are more likely to be missing data, this can bias the results.

The researchers did a separate analysis that included incomplete data to look at whether this might be a problem, and this did not differ very much from the original analysis. This suggested missing data was not having a large effect.

The analyses also only included mediators and outcomes assessed at one point, although they were measured multiple times. The authors say they are analysing this additional data, as well as looking at the mediators together, rather than singly. They say the multiple analyses may have made it more likely some of their significant findings were down to chance.

Overall, this analysis has given researchers an idea of how CBT and GET could have been having an effect in the PACE trial. They hope this knowledge could help them improve these treatments or develop new ones. Any new or adapted treatments will need to be tested in RCTs to know how effective and safe they are.


Analysis by Bazian. Edited by NHS Choices. Follow Behind the Headlines on Twitter. Join the Healthy Evidence forum.

Links To The Headlines

Chronic fatigue syndrome patients' fear of exercise can hinder treatment. The Guardian, January 14 2015

Chronic fatigue victims 'suffer fear of exercise': Patients are anxious activities such as walking could aggravate the condition. Daily Mail, January 14 2015

Sufferers of chronic fatigue syndrome 'can benefit from exercise'. The Independent, January 14 2015

ME: fear of exercise exacerbates chronic fatigue syndrome, say researchers. The Daily Telegraph, January 14 2015

Links To Science

Chalder T, Goldsmith KA, White PD, et al. Rehabilitative therapies for chronic fatigue syndrome: a secondary mediation analysis of the PACE trial. The Lancet Psychiatry. Published online January 13 2015

Categories: NHS Choices

Under-80 cancer deaths 'eliminated by 2050' claim

NHS Choices - Behind the Headlines - Wed, 14/01/2015 - 09:54

“Cancer deaths will be eliminated for all under 80 by 2050,” The Independent reports. This is the optimistic prediction contained in a paper written by specialists in pharmacy from University College London (UCL).

The paper is an opinion piece (PDF, 2.1Mb) that points out that deaths from the most common cancers have fallen by nearly a third in the last two decades. This is due to factors such as the decline in smoking, more effective early diagnosis, and better drug and surgical treatments. However, it argues that a further reduction in death rates requires more advances in areas such as screening, genetic testing, cancer awareness programmes and innovative treatments.

It claims that further advances in prevention are needed, including the use of aspirin to reduce the risk of colorectal cancer and more effective treatment for late-stage cancers, so that people with advanced diseases can continue to live fulfilling lives.

In particular, it says that "winning the cancer war" depends on reforming a healthcare culture that discourages the reporting of "minor" symptoms that can indicate a serious disease, since all cancers are most effectively treated at an early stage.

To play “devil’s advocate”, you could argue that while certain trends are improving, such as a reduction in smokers, others are worsening, such as the number of people who are now obese. And, as a recent study found that we discussed last year, the UK is now one of the leading countries when it comes to the number of obesity-related cancers, such as bowel cancer.

Our advice is not to be complacent. It is unlikely that a cure for cancer will be available in the near future. Therefore, core cancer prevention recommendations, such as avoiding smoking, taking regular exercise and eating a healthy diet, remained unchanged. 

 

Where does the report come from?

The report has been researched and written by academics from the School of Pharmacy at UCL. It is unclear whether the report has been peer-reviewed. The study was funded by Boots UK.

There is a potential conflict of interest as several of the measures suggested for improving prevention, early detection and treatments revolve around community pharmacists. While community pharmacists, such as Boots, do provide an essential service, they are not charities.

 

What type of study is it?

The study is a narrative review. This is a type of study that usually gives a comprehensive overview of a topic, rather than addressing a specific question, such as how effective a treatment is for a particular condition.

It does not report on how the search for literature was carried out or how it was decided which studies were relevant to include. Because of this, it is not a systematic review, where all of the relevant evidence is included based on pre-specified criteria. This means there could be gaps in the evidence that is presented.

 

What are the figures?

The basic UK figures provided are:

  • 325,000 new cases of cancer in 2013
  • 150,000 deaths from cancer in 2013

The incidence of cancer increases with age. The yearly risk is:

  • 1 in 5,000 in people aged 20 or less
  • 1 in 100 for people in their 50s 
  • 1 in 30 for people over 65

In 2011, nearly half of new cases were in people aged 70 or over, and more than half of the deaths were in people over the age of 75.

As cancer is more common in old age, the ageing UK population means that the incidence of cancer is higher than at any time in history. However, despite the increased number of cases, the death rate is improving. For example, deaths from the "top four cancers" (breast, lungbowel and prostate) have fallen by 30% in the last 20 years.

The authors highlight the following factors that have contributed to this improvement:

  • reduced smoking
  • more effective early diagnosis
  • better cancer treatments

What changes are proposed to improve cancer prevention?

The authors suggest:

  • improving access to weight management programmes, such as through local pharmacies
  • continuing smoking cessation services
  • better screening for "pre-cancers", such as bowel polyps
  • testing for genetic vulnerabilities, such as being a BRCA gene carrier
  • improving access to immunisations, such as HPV and Hep B vaccination
  • reducing the risk of bowel cancer by encouraging people in their 50s to take low-dose aspirin

 

What measures do they say could improve cancer survival rates?

The report says that there is room to improve the number of cancers that are identified at an earlier stage when there is more chance of a cure. They quote an estimate that 5,000-10,000 lives could be saved if the UK had the same rate as “the best in the world”. A component of this would be improving awareness of early symptoms and encouraging people to see a healthcare professional, including a community pharmacist.

They support continued research into more effective methods for diagnosis and better treatments. They also suggest improvements in supportive care provided for people with more advanced and metastatic cancers (cancers that have spread) or survivors who have long-term side effects as a result of the cancer treatments.

 

Conclusion

Most of the recommendations in this paper are already part of cancer prevention strategy and best practice guidelines.

The advice that all people over 50 should take aspirin is controversial. While there is some evidence of a protective effect, as we discussed last year, this has to be balanced against side effects such as peptic ulcers and bleeding from the stomach, particularly in older people. It's important to see your GP before deciding to take aspirin regularly.

This review could be considered to be over-optimistic. Recommendations regarding cancer prevention remain unchanged.

Analysis by Bazian. Edited by NHS Choices. Follow Behind the Headlines on Twitter. Join the Healthy Evidence forum.

Links To The Headlines

Cancer deaths will be eliminated for all under 80 by 2050, new research predicts. The Independent, January 14 2015

Under-80s cancer deaths 'eradicated within 30 years': Death rates from most common cancers will continue to drop, report claims. Mail Online, January 14 2015

How cancer death rates have dropped since 1991. The Daily Telegraph, January 14 2015

Cancer deaths under 80 ‘will be eradicated’. The Times, January 14 2015

Categories: NHS Choices

Napping 'key' to babies' memory and learning

NHS Choices - Behind the Headlines - Tue, 13/01/2015 - 14:30

"The key to learning and memory in early life is a lengthy nap, say scientists," BBC News reports.

The scientists were interested in babies' abilities to remember activities and events.

They carried out a study involving 216 babies, who took part in trials to see whether napping affected their memory for a new activity.

The babies first watched the researchers taking a mitten off a hand puppet, shaking it, and putting it back on. Half had a nap shortly afterwards and half did not.

Babies who had the nap were able to mimic more of the activities when they played with the hand puppet four hours later. This was also true when the babies were tested 24 hours after being shown the puppets. This may suggest napping shortly after a new activity or event helps to consolidate that memory.

The researchers speculate sleep may help "strengthen" the impact of recent memories as they are stored in the hippocampus, an area of the brain associated with long-term memory retention.

The study suggests napping is important for memory in babies. While sleep is important for memory in adults, this study was only in infants, so you can't use it as an excuse if caught napping at work.

 

Where did the story come from?

The study was carried out by researchers from the Ruhr University Bochum in Germany and the University of Sheffield.

It was funded by a grant from the Deutsche Forschungsgemeinschaft (German Research Foundation).

The study was published in the peer-reviewed journal, Proceedings of the National Academy of Sciences USA (PNAS).

In general, BBC News reported the story accurately, but its headline doesn't make it clear that the research is in babies.

 

What kind of research was this?

This was a randomised controlled trial assessing whether napping shortly after being taught a new activity influences how well babies remember how to do that activity.

Previous studies assessing sleep and memory in babies have mostly been observational, and could not determine whether the sleep patterns might be directly influencing memory.

This study overcomes this by directly assessing the impact of napping on developing a specific memory in a controlled experiment.

Randomly allocating the babies into groups is the best way of ensuring the groups are well balanced and the only thing differing between them is whether or not they had a nap.

 

What did the research involve?

The researchers enrolled babies aged six months or a year old. The babies were randomly allocated to have a nap or no nap after being taught a new activity involving playing with hand puppets.

They were then tested to see if they could remember and repeat the activity, either four hours later (experiment one) or 24 hours later (experiment two). The researchers then assessed whether the babies who had naps remembered the activity better.

The activity involved the researchers showing the babies a hand puppet wearing a mitten with a bell in it. The researcher removed the mitten from the puppet and shook it to ring the bell to draw attention to the mitten. They then replaced the mitten.

This was all done out of the babies' reach and repeated three times for the year-old babies and six times for the six month olds.

The test involved showing the baby the puppet again, but this time within arm's reach. The researchers recorded if the baby removed the puppet's mitten, attempted to shake the mitten, and attempted to replace the mitten within 90 seconds of being shown the puppet.

The babies scored one point for each of the three actions they tried to replicate. The researchers and parents did not verbally or physically encourage the babies to remove the mitten, and the bell in the mitten had been removed so its sound did not prompt the babies to grab the mitten.

For the "nap" group, the researchers scheduled the activity to occur just before they were about to have a nap. For the "no nap" group, it was scheduled for just after they had had a nap, so they would not be due to have another nap in the next four hours.

A nap was considered as at least 30 minutes of uninterrupted sleep, and the babies wore small motion detectors to see if they were awake or asleep. Caregivers also recorded the babies' sleep patterns. The researchers used both of these sources to assess nap timing and duration.

In the study, caregivers were told not to influence their baby's sleep patterns for the study, and babies whose sleep patterns were not compatible with the group they were assigned to were excluded. This may have unbalanced the groups. Another group of babies were excluded for various reasons, such as tester error.

In their first experiment, the researchers compared the nap and no nap groups with babies who had not been shown the hand puppet activity, but just tested to see what they did naturally when shown the hand puppet.

In total, 120 babies took part in experiment one (test at four hours after hand puppet activity), and 96 babies took part in experiment two (test at 24 hours after hand puppet activity).

They looked at whether nap timing had an impact on how well the baby performed. 

 

What were the basic results?

The researchers found the babies who took naps shortly after the hand puppet activity were better able to remember it after four and 24 hours.

 

How did the researchers interpret the results?

The researchers say that to their knowledge, this is the first evidence sleep enhances the ability of babies to retain memories of new behaviours in their first year of life.

 

Conclusion

This study suggests napping shortly after an event may help babies up to the age of one to remember those events.

The study was well designed. The design means differences seen between the groups should be attributable to the naps and not other factors.

The fact some babies were excluded – for example, if they did not have naps as intended – might lead to some imbalances in the groups that could influence results. However, it is difficult to tell if this is the case.

The main assessors of the babies' performance were not blinded as to which group they were in, and therefore could theoretically have influenced results consciously or subconsciously.

However, an independent assessor who was blinded to the groups carried out an assessment of half of the test sessions and showed a high level of agreement with the main assessor. This showed assessor bias was not likely to explain the findings.

Sleep is important for brain function and memory in older children and adults, and this study supports a similar role in younger children.

There are no official UK guidelines on exactly how much sleep babies and children get. One rough guide is babies aged around 12 months need around 2.5 hours of sleep during the day and 11.5 hours a night. Read more about How much sleep do kids need?

Analysis by Bazian. Edited by NHS Choices. Follow Behind the Headlines on Twitter. Join the Healthy Evidence forum.

Links To The Headlines

Regular naps are 'key to learning'. BBC News, January 13 2015

Links To Science

Seehagen S, Konrad C, Herbert JS, et al. Timely sleep facilitates declarative memory consolidation in infants. PNAS. Published online January 12 2015

Categories: NHS Choices

Could brain protein help people 'sleep off' the flu?

NHS Choices - Behind the Headlines - Tue, 13/01/2015 - 11:55

"Scientists…believe that a nasal spray could be produced which boosts a protein so sufferers could sleep off the flu," The Daily Telegraph reports.

As yet, the research has been confined to assessing the role of one protein – in mice.

The paper reports on complex research in mice on a protein called AcPb, which researchers thought could be playing a role in regulating normal sleep and the body's response to flu infection.

They found mice genetically engineered to lack the protein could not catch up on sleep as well after sleep deprivation.

Also, while normal mice slept more if they were infected with an adapted flu virus, the mice lacking AcPb slept less. They also showed worse signs of the flu and were more likely to die as a result of the infection.

The researchers have shown if you remove the AcPb protein, mice don't fight the flu virus as well. This does not necessarily mean giving mice more of the protein would make them fight it better.

While the news suggests there may be a possibility of an effective flu treatment, we are a long way off knowing whether this is the case. 

Differences between the species may mean the normal role of the protein may not be exactly the same in humans. We also don't know if giving humans (or indeed mice) extra doses of the protein would be safe or effective.

When it comes to flu, prevention is better than (the non-existent) cure. Check to see if you need the flu jab, and always maintain good hygiene if you're unwell.

 

Where did the story come from?

The study was carried out by researchers from the University of Washington and Washington State University Spokane. It was funded by the US National Institutes of Health.

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

The Telegraph overemphasises the implications of this animal research for humans. This in part seems to be prompted by the scientists envisaging a "nasal spray" of the protein to treat humans – something that has not been developed or tested in this study.

The Telegraph says that, "The protein will also fight the H1N1 bird flu strain, which swept across the world in the 2009 pandemic". This mouse research did use an adapted strain of H1N1 flu virus – and it was an H1N1 flu virus that caused so-called "swine flu" (not bird flu).

But this is very early-stage research, and we have no idea whether it will result in useful treatments for seasonal flu, let alone any future potential flu pandemic.

 

What kind of research was this?

This was an animal study in mice, looking at the role of a protein called AcPb on sleep and the body's response to the flu virus.

The researchers wanted to test what role the AcPb protein plays in a pathway (a chain of biochemical events) that affects how our bodies regulate our sleep while we are well and during infection. AcPb is primarily found in the brain.

Animal experiments such as these are used when researchers could not carry out similar studies in humans because of ethical and safety concerns.

Other animals are similar enough to humans to help researchers get an insight into how our bodies work. But there are differences between different species, and not all findings in rats or mice will be representative of what happens in humans.

Researchers therefore ideally need to go on to test their hypotheses from animal studies in humans.

 

What did the research involve?

The researchers looked at how mice genetically engineered to lack the AcPb protein differed from normal mice.

They tested their responses to sleep deprivation at different time points, and also to a form of the human H1N1 flu virus adapted to infect mice.

 

What were the basic results?

When normal mice were deprived of sleep at any time, they "caught up" on that sleep later. Mice genetically engineered to lack the AcPb protein (AcPb "knockout" mice) were less able to catch up on sleep after sleep deprivation.

Levels of the AcPb protein naturally fluctuate during the day, and the extent to which the AcPb knockout mice were able to catch up on sleep depended on exactly where in this fluctuation cycle they were.

When exposed to the flu virus, normal mice slept more than they normally did, but AcPb knockout mice slept less than they normally would, and also less than normal mice.

The knockout mice also suffered from the effects of the flu on their body temperature and activity, and were more likely than normal mice to die after exposure to the flu virus.

 

How did the researchers interpret the results?

The researchers concluded the AcPb protein plays a role in regulating sleep and the body's defences against viral attack.

 

Conclusion

This complex study suggests the AcPb protein is playing a role in regulating normal sleep and the response to flu infection in mice.

At this stage, the implications of this research for humans are unclear, as differences between the species may mean the results would not be exactly the same in humans.

While The Telegraph suggests this "could finally lead to an effective treatment for the [flu], which until now has eluded experts", we are a long way off knowing whether this is the case.

What the researchers have shown – in mice – is if you remove this protein, mice don't fight the virus as well. This does not necessarily mean giving mice more of the protein would make them fight it better. It also doesn't mean giving more of the protein wouldn't have side effects.

Overall, this research is at a very early stage, with much more animal research needed before we know if we are closer to a flu treatment.

There is currently no cure for the flu, so the most effective weapon against it is prevention, such as good basic hygiene procedures and the flu jab.

The jab is recommended for people who are at risk of developing serious complications if they catch the flu, such as the over 65s, pregnant women, and people with a serious long-term illness.

Read about the influenza vaccination and who should get it.

Analysis by Bazian. Edited by NHS Choices. Follow Behind the Headlines on Twitter. Join the Healthy Evidence forum.

Links To The Headlines

Treatment for flu possible as scientists find healing protein. The Daily Telegraph, January 12 2015

Links To Science

Davis CJ, Dunbrasky D, Oonk M, et al. The neuron-specific interleukin-1 receptor accessory protein is required for homeostatic sleep and sleep responses to influenza viral challenge in mice. Brain, Behavior and Immunity. Published online November 4 2014

Categories: NHS Choices

Blood test may tell you the 'best' way to quit smoking

NHS Choices - Behind the Headlines - Mon, 12/01/2015 - 11:40

“A blood test could help people choose a stop-smoking strategy that would give them the best chance of quitting,” BBC News reports. The test measures how quickly an individual breaks down nicotine inside their body, which is known as the nicotine-metabolite ratio (NMR).

Researchers wanted to see whether people with “normal” and “slow” NMR responded differently to stop smoking treatments, and if the blood test could eventually be used as an aid to help guide people to the best treatments to help them quit smoking.

They first tested people and categorised them as slow or normal metabolisers of nicotine. These people were then randomised to an 11-week treatment plan of a placebo, nicotine patches or the stop smoking drug varenicline. All treatments were given in addition to behavioural counselling.

Overall, they found that varenicline was more effective at helping a “normal metaboliser” to quit than patches. For slower metabolisers, there was no difference in the effectiveness of the two treatments, but they tended to get more side effects with varenicline.

Importantly, quit rates were only different after the 11-week treatment. A significant proportion started smoking again six or 12 months later. Therefore, how to maintain quit rates in the longer term is an issue that needs to be resolved.

There are multiple methods available that can help you quit smoking. If one doesn’t work out for you, then you can always try another one.

 

Were did the story come from?

The study was carried out by researchers from the University of Pennsylvania and other institutions in the US and Canada. Funding was provided by the National Institutes of Health, Canadian Institutes of Health Research, Abramson Cancer Center, Centre for Addiction and Mental Health Foundation, and Pennsylvania Department of Health.

A number of the researchers had received grants from the pharmaceutical company Pfizer, which manufactures and sells varenicline. This arguably represents a conflict of interest (which was made clear in the study).

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

The UK media accurately reported the findings of the study.

 

What kind of research was this?

This was a randomised controlled trial aiming to see whether a new biological marker could help pick the most appropriate method of stopping smoking for someone.

The researchers say that there is considerable variability in a person’s treatment response and side effects to different treatments for tobacco dependence. This provides a strong incentive to try to find biomarkers that may indicate the optimal treatment for a particular individual. In this study, they identified a genetically-informed biomarker of nicotine clearance – the ratio of two breakdown products of nicotine (3ʹ-hydroxycotinine and cotinine). They referred to this as the nicotine-metabolite ratio (NMR).

In this study, people were assigned to placebo, nicotine patch or varenicline (all in addition to behavioural counselling) and they looked at how good the NMR was at predicting the response to each treatment.

 

What did the research involve?

The research included 1,246 smokers. They excluded people using e-cigarettes, taking other smoking treatments, with a history of substance misuse or other significant medical problems. At enrolment, all provided blood samples for testing of their NMR. Based on their NMR results, they were categorised as either “slow” or “normal” metabolisers of nicotine (based on a pre-defined cut-off level).

The smokers were randomised to three groups, stratified by their NMR status, to ensure they had an even number of slow and normal metabolisers in each group. All groups also received behavioural counselling. The participants were divided as such:

  • placebo patch and placebo pill (408 people)
  • nicotine patch and placebo pill (418 people)
  • placebo patch and varenicline pill (420 people)

Treatment was given double-blind, with neither researchers nor investigators aware of treatment allocation or NMR status. The stop smoking treatment period lasted 11 weeks.

The main endpoint was seven-day point prevalence abstinence at 11 weeks, which was defined as no self-reported smoking (“not even a puff” as the study put it) for at least seven days before the telephone assessment, with in-person verification (by carbon monoxide levels). Participants lost to follow-up were considered smokers. Later follow-ups at six and 12 months were also conducted. The main aim was to compare the efficacy of a nicotine patch with varenicline by NMR group (normal metabolisers vs. low metabolisers).

 

What were the basic results?

At the end of the 11-week treatment, slow metabolisers had quit rates of 17.2% using a placebo, 27.7% using a nicotine patch and 30.4% using varenicline.

Normal metabolisers had quit rates of 18.6% using placebo, 22.5% using nicotine patch and 38.5% using varenicline.

From these results, varenicline was significantly more effective than the nicotine patch for normal metabolisers. Their odds of abstinence with varenicline were more than double that compared with the nicotine patch (odds ratio [OR] 2.17, 95% confidence interval [CI] 1.38 to 3.42). Slow metabolisers were no more likely to achieve abstinence with varenicline than the nicotine patch (OR 1.13, 0.74 to 1.71).

Among normal metabolisers, the number of people needing to enter the stop smoking programme to achieve one case of abstinence (the number needed to treat or NNT) 11 weeks later was 26 using nicotine patches and just 4.9 with varenicline.

For slow metabolisers, the NNT was not much different: 10.3 for nicotine patch and 8.1 for varenicline.

The researchers also found that slow metabolisers were significantly more likely than normal metabolisers to have more severe side effects when taking varenicline compared to placebo.

 

How did the researchers interpret the results?

The researchers conclude that “Treating normal metabolisers with varenicline and slow metabolisers with nicotine patch could optimise quit rates while minimising side effects”.

 

Conclusion

This is a well-conducted randomised controlled trial, which found that use of the nicotine-metabolite ratio (NMR) may be helpful in indicating which stop smoking treatment may be best for different people. For those with a normal NMR, varenicline was more effective than a nicotine patch. For slower metabolisers, there was no significant difference in the effectiveness of the two treatments, but they tended to get more side effects with varenicline.

The study benefits from its large size, double-blind design and high follow-up rates.

However, there are still questions to be answered. For example, the difference in abstinence rates between varenicline and nicotine patch for normal metabolisers was significant at the end of 11-week treatment. But by six months, abstinence rates had generally deteriorated across all treatment groups and for both slow and normal metabolisers. Abstinence rates for normal metabolisers given varenicline were still significantly higher than those given nicotine patch at six months, but this difference was no longer significant at the 12-month follow-up.

How to maintain quit rates in the longer term after cessation of treatment still appears to be an issue that needs resolving, regardless of treatment or nicotine metabolism type.

Overall, the research is promising. Whether the NMR is something that will ever be brought into wider use when deciding on the most appropriate smoking cessation therapy is not currently known. Even if it is, other factors are also still likely to guide treatment decisions, such as individual preference or previously tried treatments.

What the study does highlight is that there are multiple methods available you can use to quit smoking. These range from nicotine replacement products such as patches or gum and medication such as varenicline and bupropion (Zyban). While currently unlicensed as a stop smoking treatment (and with little direct scientific evidence of their effectiveness), many people have found that e-cigarettes can help them quit or cut down smoking.

The important thing is not to get discouraged if your first attempt at quitting smoking is unsuccessful. Try a different method, as this could be better suited to you.

Analysis by Bazian. Edited by NHS Choices. Follow Behind the Headlines on Twitter. Join the Healthy Evidence forum.

Links To The Headlines

Blood test to help smokers 'find best way to quit'. BBC News, January 12 2015

Quit smoking success 'predictable'. Mail Online, January 12 2015

Ability to quit smoking 'predictable'. ITV News, January 12 2015

Links To Science

Lerman C, Schnoll RA, Hawk LW, et al. Use of the nicotine metabolite ratio as a genetically informed biomarker of response to nicotine patch or varenicline for smoking cessation: a randomised, double-blind placebo-controlled trial. The Lancet Respiratory Medicine. Published online January 11 2015

Categories: NHS Choices

Does contraceptive jab make HIV more likely?

NHS Choices - Behind the Headlines - Mon, 12/01/2015 - 11:05

"Contraceptive injections moderately increase a woman's risk of becoming infected with HIV," The Guardian reports.

The headline was prompted by an analysis of 12 studies that looked at whether the use of hormonal contraception, such as the oral contraceptive pill, increases the risk of contracting HIV.

All of the studies involved were conducted in sub-Saharan Africa in low- and middle-income countries.

Researchers found a link between a common injectable form of contraception called depot medroxyprogesterone acetate (Depo-Provera) and the risk of HIV. No link was found with other types of hormonal contraception.

But these results do not prove the depot injection directly increases the risk of HIV. The studies included varied in their design and methods, and have several potential sources of bias.

Any link could be down to behavioural patterns rather than medical reasons. For example, women who know they have an effective long-term contraceptive may forget about the risks of sexually transmitted infections.

Hormonal contraception, including injections or oral tablets, can be an extremely effective form of contraception. But it won't protect you against sexually transmitted infections.

It is worth discussing with your health professional and making sure you are using the method that is most effective, convenient and safest for you, depending on your circumstances.  

 

Where did the story come from?

The study was carried out by researchers from the University of California and received no financial support.

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

The Mail Online correctly reports the main findings of this study, but would benefit from highlighting that the findings do not prove a causal association between the depot injection and HIV risk, a point clearly made by the researchers in the original publication.

The Guardian's reporting of the study is more measured and highlights how for women in poorer countries, an unwanted pregnancy may pose a greater threat to health and wellbeing than HIV. Rates of maternal death occurring during or shortly after pregnancy remain high in many sub-Saharan countries.

 

What kind of research was this?

This was a systematic review that aimed to search the global literature to find studies examining whether the use of hormonal contraception, such as the oral contraceptive pill or contraceptive injections, increase the risk of contracting HIV.

The researchers say previous study into whether there could be an associated risk has been inconsistent. They pooled the results of different studies in a meta-analysis.

A systematic review and meta-analysis is the best way of identifying and looking at all evidence that has addressed the particular question of interest.

But this type of research is always going to have some limitations reflecting the strength and quality of the underlying studies being reviewed.

It is unlikely a trial would be conducted that would allocate women to hormonal contraception or not, purely to see if this increased their risk of getting HIV.

Instead, the studies are likely to be observational or trials that have primarily been investigating other things.

This means there is potential that associations are being influenced by confounders. In short, other factors linked to contraceptive use, such as lifestyle behaviours, are themselves influencing the risk of HIV, rather than contraceptives directly. 

 

What did the research involve?

The researchers built on the findings of a previous 2012 World Health Organization (WHO) review.

For the current review, they searched one literature database for English-language articles published from December 2011 onwards that included the terms "hormonal contraception", "HIV/acquisition", "injectables", "progestin", and "oral contraceptive pills".

They included studies that assessed hormonal contraceptives, included women without HIV at the study start, and were prospective in nature (following people over time).

Eligible studies were also required to have followed up at least 70% of their participants, have adjusted at least for a woman's age and condom use (to try to minimise confounding from these factors), and been conducted in a low- or middle-income country.

Separate researchers individually assessed the methods and quality of the eligible studies, and extracted data.

 

What were the basic results?

A total of 12 studies met the criteria for being included. All of these studies were conducted in low- or middle-income African countries.

These studies included large numbers of women, from between 400 to more than 8,000, and lasted between one and three years.

What were the studies investigating?

Three of the 12 studies included were observational studies designed specifically to examine any connection between contraception and HIV, while the other studies included women taking part in trials investigating interventions for HIV prevention.

Who was involved in the studies?

Most of the the 12 studies included looked at women aged 25 to 40 in the general population, while two looked specifically at women at high risk of HIV (commercial sex workers or women whose partner was HIV positive).

What contraceptives did the studies examine?

Some of the studies looked at women taking oral hormonal contraception (either combined pill or progestogen only).

In some the women were taking the injectable progestogen depot medroxyprogesterone acetate, and in the remaining studies the women were taking another type of injectable progestogen (norethisterone enanthate).

Most trials compared these hormonal types of contraception with a non-hormonal method of contraception, or with no method of contraception at all.

What were the specific results for the contraceptive injection?

Pooled results of 10 studies of depot medroxyprogesterone acetate found it was associated with a 40% increased risk of HIV (hazard ratio (HR) 1.40, 95% confidence interval (CI) 1.16 to 1.69).

This risk was slightly lower when restricted to only the studies of women in the general population (pooled HR 1.31, 95% CI 1.10 to 1.57) rather than those at high risk of contracting HIV.

There was no evidence of an increased risk of HIV in women taking the other injectable progestogen, norethisterone enanthate (pooled HR 1.10, 0.88 to 1.37); nor was there any increased of HIV risk found from the use of oral contraceptive pills (HR 1.00, 0.86 to 1.16).

 

How did the researchers interpret the results?

The researchers concluded their findings "show a moderate increased risk of HIV acquisition for all women using depot medroxyprogesterone acetate, with a smaller increase in risk for women in the general population.

"Whether the risks of HIV observed in our study would merit complete withdrawal of depot medroxyprogesterone acetate needs to be balanced against the known benefits of a highly effective contraceptive."

 

Conclusion

This is a well-conducted systematic review that tried to identify all studies investigating the possible link between hormonal contraceptive use and HIV.

It did not find an association between HIV risk and oral hormonal contraceptive use, nor with one type of injectable progestogen contraceptive.

But it did find an increased risk of HIV in studies where women used a commonly used injectable form of contraception called depot medroxyprogesterone acetate.

The review had strict inclusion criteria, but the possibility of selection bias and confounding from other factors still cannot be ruled out.

Only three out of the 12 studies directly set out to look at whether hormonal contraceptive use was linked to HIV. And these were still observational studies, meaning the women chose their method of contraception.

The other nine studies were not designed to look for this association.

As women in all of the 12 studies included chose their method of contraception, this could mean there are other differences – such as health and lifestyle – between the women who chose to use this type of contraception and those who chose to use non-hormonal methods. So the contraception may not have been the sole or direct cause of the link.

Two of the studies also included high-risk women, such as commercial sex workers or women whose partner was HIV positive. Exclusion of these studies decreased the association between depot contraceptive injection use and HIV, although the link remained statistically significant.

As the researchers themselves acknowledge, the studies can't say whether the association between hormonal contraception and HIV is "causal". And this is crucial to bear in mind when looking at this review.

Other limitations of this research
  • As the authors also say, it is difficult for them to be sure of the timing of contraception use in relation to subsequent HIV infection.
  • Although the studies included contraceptive methods that are used in the UK, none of these studies were UK-based and all were conducted in sub-Saharan Africa. The prevalence of HIV in these countries is much higher than it is the UK, so the baseline risk of contracting HIV is already much higher than it would be in the UK. The 40% risk increase with the depot injection is a relative increase of what would comparatively be a very small baseline risk in the UK.

Contraceptive injections such as Depo-Provera are extremely effective – estimated to have a failure rate of less than 1 in 330. But they provide no protection against sexually transmitted infections.

Only barrier methods such as condoms protect against HIV and other sexually transmitted infections, such as chlamydia and genital warts.

Talk to your GP if you're unsure you're using the most effective and convenient contraceptive for you. 

Analysis by Bazian. Edited by NHS Choices. Follow Behind the Headlines on Twitter. Join the Healthy Evidence forum.

Links To The Headlines

Contraceptive injection raises risk of HIV, research warns. The Guardian, January 9 2015

Women on the contraceptive jab have a greater risk of contracting HIV than those using other forms of birth control or NONE at all. Mail Online, January 9 2015

Links To Science

Ralph LJ, McCoy SI, Shu K, et al. Hormonal contraceptive use and women's risk of HIV acquisition: a meta-analysis of observational studies. The Lancet Infectious Diseases. Published online January 9 2015

Categories: NHS Choices

'Bionic' spinal implant helped paralysed rats walk

NHS Choices - Behind the Headlines - Fri, 09/01/2015 - 12:00

"Elastic implant 'restores movement' in paralysed rats," BBC News reports after researchers developed an implant that can be used to treat damaged spinal cords in rats.

The spinal cord, which is present in all mammals, is a bundle of nerves that runs from the brain through the spine, before branching off to different parts of the body.

It is the main "communication route" the brain uses to control the body, so damage usually results in some degree of paralysis or sensory loss, depending on the extent of the injury.

This promising research developed a novel spinal cord implant that has been able to restore movement in paralysed rats. The implant is made of a flexible material that is able to integrate and move with the spinal cord.

This overcomes problems found with previously tested rigid and inflexible implants, which have caused inflammation and quickly stopped working.

The implant works by delivering both electrical and chemical signals, and enabled the rats to walk again for the six weeks of testing.

However, the research is mainly "proof of concept" at this stage, showing the technique works in animals – at least in the short term. It remains to be seen whether implants are safe and effective at restoring movement in people with paralysis. 

 

Where did the story come from?

The study was carried out by researchers from École Polytechnique Fédérale de Lausanne in Switzerland and other institutions in Switzerland, Russia, Italy and the US.

Financial support was provided by various organisations, including the Bertarelli Foundation, the International Paraplegic Foundation, and the European Research Council.

It was published in the peer-reviewed journal, Science Magazine. 

Of all the UK coverage, BBC News reported the research most accurately, and included quotes about the promising nature of the research, but also due caution about the long timeline ahead before it is known whether such implants could be used in people.

Other headlines, such as that in The Times, arguably offer premature hope of a new treatment that can help the paralysed walk again. 

 

What kind of research was this?

This animal research aimed to develop a new flexible spinal implant to restore movement after a spinal cord injury.

Implants are just one of the ways medical science is exploring how to help people who have spine injuries regain sensation and movement.

In the past, electrical implants for the spinal cord encountered problems because spinal cord tissue is soft and flexible, while the implants of old were often rigid and inflexible.

The researchers expected implants with mechanical properties matching those of the host tissue would work better and for longer.

Here, they designed and developed a new soft electrical implant, which has the shape and elasticity of the dura mater, the outermost layer of the protective membranes (meninges) that cover the brain and spinal cord.

The device was tested in paralysed rats. Animal studies are a valuable first step in the development of treatments that may one day be used in people.

However, the road ahead is a long one in terms of developing the treatment for testing in people, hopefully followed by trials of its safety and effectiveness.

 

What did the research involve?

The researchers developed a silicone implant they called electronic dura mater, or e-dura. This implant has interconnecting channels that transmit electrical signals and can also deliver drugs. It was made for surgical insertion just beneath the dura mater layer.

They first tested the long-term functionality of this soft implant compared with conventional stiff implants. Long-term meant testing the device for six weeks.

Each type of implant was inserted into the lower part of the spinal cord of healthy rats. The rats were then assessed using specialised movement recordings, and the rats with the soft spinal implant were able to behave and move as normal.

However, rats with the stiff implants started to demonstrate problems with their movement one to two weeks after surgery, which only deteriorated further up to six weeks.

When examining the rats' spinal cords after the implants were removed at six weeks, the researchers found rats with the stiff implants displayed significant deformity and inflammation in the spinal cord. None of these adverse effects were observed in those who had the soft implant.

They followed this with a series of further tests of the mechanics and functioning of the soft implant, both in the laboratory using a model of spinal cord tissue and in further tests in healthy rats.

The researchers also examined the ability of e-dura to restore movement after spinal cord injury.

The rats received a spinal cord injury that led to permanent paralysis of both hind legs. The e-dura implant was then surgically inserted in the spinal cord, and drug therapy and electrical stimulation were delivered through the electrode to see how it worked. 

 

What were the basic results?

Most of the results in the publication relate to the initial developmental stages of the device. When it came to the paralysed rats, relatively little was said.

However, what the researchers did say is the combination of electrical and chemical stimulation through the implant enabled the paralysed rats to move both of their hind legs again and walk, apparently as normal (though this isn't specifically stated).

The e-dura implant was able to bring about these effects for the six-week period it was tested. 

 

How did the researchers interpret the results?

The researchers concluded they have developed a soft implant that shows long-term biointegration and functioning with the spinal cord.

The implants met the demanding mechanical properties of the spinal tissue, with a limited inflammatory reaction that has been seen with other implants.

When used in paralysed rats, the implant allowed for electrical and chemical stimulation to restore movement deficits over an extended period of time.

 

Conclusion

This is promising research that demonstrates how a new spinal cord implant has been able to restore movement in paralysed rats.

The e-dura implant is a breakthrough in that it overcomes a lot of the problems presented by previous rigid and inflexible implants. Instead, it is made of a flexible material that is able to integrate with spinal cord tissue.

The study demonstrated long-term functionality in rats and few side effects over the six-week testing period.

Rats given a serious spinal cord injury, who were consequently permanently paralysed, were able to walk again after the implant was surgically placed in their spinal cord. The implant works by delivering both electrical and chemical signals.

However, this research is still in the very early stages. While the findings are promising, there is a long way to go before we know whether these implants can be developed to successfully help humans with spinal injuries.

If the implants were developed for human testing, they would need to go through several stages of safety and effectiveness testing to see whether they worked at restoring movement in paralysed people.

It also needs to be seen how they would function in the much longer term, beyond just a few weeks.

Loss of movement is only one of the ways a person can be affected by permanent paralysis of both legs.

We do not know whether this implant would have any effect on loss of bladder, bowel or sexual function, for example.

These effects can have as much of a detrimental effect on quality of life as loss of physical movement.

But, overall, this is promising early-stage research and future developments are awaited with anticipation.

Analysis by Bazian. Edited by NHS Choices. Follow Behind the Headlines on Twitter. Join the Healthy Evidence forum.

Links To The Headlines

Elastic implant 'restores movement' in paralysed rats. BBC News, January 9 2015

'Cyborg' spinal implant could help paralysed walk again. The Daily Telegraph, January 8 2015

The tiny ribbon that could help the paralysed walk again: 'Cyborg' implant can delivers electric shocks and drugs directly to the spine and even read brain activity. Mail Online, January 9 2015

Links To Science

Minev IR, Musienko P, Hirsch A, et al. Electronic dura mater for long-term multimodal neural interfaces. Science. Published online January 9 2015

Categories: NHS Choices

How 'baby talk' may give infants a cognitive boost

NHS Choices - Behind the Headlines - Fri, 09/01/2015 - 10:30

"Say 'mama'! Talking to babies boosts their ability to make friends and learn,” the Mail Online reports. In a review, two American psychologists argue that even very young infants respond to speech and that "baby talk" is essential for their development.

It is important to stress that a review of this sort is not the same as fresh evidence.

The review must largely be considered to be the authors’ opinion based on the studies they have looked at. The methods and quality of these underlying studies informing this review are also unknown, so we cannot say how solid this evidence is.

That said, the authors’ arguments would chime with most parents’ instinctive beliefs: regularly talking to your baby is a “good thing”. Regularly talking to your baby is likely to have many benefits, not least in helping their understanding of speech and strengthening the bond between parent and baby.

However, whether talking to your baby has greater effects on their learning capacity or ability to make friends in the future is something that cannot be proven by this review.

 

Where did the story come from?

The study was written by two psychologists from New York University and Northwestern University in the US. The work was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health, and the National Science Foundation. It was published in the peer-reviewed scientific journal Cell.

The Mail Online reports the review accurately, but doesn’t recognise the important limitations of this review in relation to its absent methods, which means it must largely be considered to be the authors’ opinions.

 

What kind of research was this?

This was a narrative review discussing a selection of evidence about the effects of exposure to human speech during the first year of a baby’s life. They discuss how this affects not only their speech and language development, but potentially their cognitive ability and social capacity as well.

The authors provide no methods for their review. This does not appear to be a systematic review, where the authors have systematically searched the global literature to identify all evidence related to this topic. It is not known how the authors selected the studies they chose to discuss, and whether other relevant evidence was left out. Therefore, this review must largely be considered to be the opinion of the authors.

While we find the possibility highly unlikely, this sort of unsystematic review may have been subject to what is known as “cherry-picking” – where evidence that does not support the authors’ arguments is deliberately ignored.

 

What do the authors discuss?

The researchers say it has been thought that listening to speech is mainly beneficial for infants in helping them to develop language. However, they say that new evidence suggests that benefits lie beyond just language acquisition. 

They say that from the first months of life, listening to speech promotes the acquisition of fundamental psychological processes, including:

  • pattern learning – the ability to recognise both visual and verbal patterns, such as “ma-ma-ma”
  • the formation of object categories – the ability to place external objects into categories, such as being able to tell the difference between a white van and a white sheep
  • identifying people to communicate with
  • acquiring knowledge about social interactions
  • development of social cognition – the ability to interpret, recognise and respond appropriately to other peoples’ feelings and emotions

They also discuss the idea that as babies grow, they specifically favour human speech over other vocalisations, such as laughing or sneezing. They discuss the different nerve cell responses to human speech compared with other sounds, and how speech particularly activates certain areas of the brain. The researchers then go on to discuss the more intricate patterns of how babies learn the rules and patterns of speech as they grow, such as understanding repetitive sequences of different syllables.

The authors present findings of some experiments that aim to see how speech helps babies to learn object categorisation. Babies aged three to 12 months viewed different objects (such as animals) accompanied by listening to either speech or sounds/tones. This found that those listening to speech were better able to categorise similar objects than those who had heard only tones accompanying the objects.

The discussion then turned to how speech may enable babies to identify “potential communicative partners”. That is, they develop the knowledge to treat people and objects differently (for example smiling and making sounds at people). Babies also develop an understanding of how speech conveys information and intentions, even if they cannot understand what is being conveyed. 

 

What do the authors conclude?

The authors conclude: “Before infants begin talking, they are listening to speech. We have proposed that even before infants can understand the meaning of the speech that surrounds them, listening to speech transforms infants’ acquisition of core cognitive capacities […]. What begins as a natural preference for listening to speech actually provides infants with a powerful natural mechanism for learning rapidly about the objects, events and people that populate their world”.

They say that further research is needed into the range of cognitive and social processes that are and are not facilitated by speech, and the mechanisms underlying this.

 

Conclusion

This is an interesting narrative review that challenges the belief that speaking to babies is only beneficial in terms of their own speech and language acquisition. The discussion presents what they describe as new evidence, suggesting that the benefits may extend far beyond this. They argue that speaking to babies may have benefits in terms of developing their cognitive abilities, such as the tests where accompanying speech helped babies better categorise objects. The review suggested that it may enhance their social capacity, such as recognising people to talk to and understanding the nature of speech and how it conveys thoughts and intentions.

Much of this discussion is plausible, but the limitations of this review must be noted. The authors provide no methods on how they have searched for, reviewed and selected the evidence they discuss. We don’t know whether all evidence relevant to the topic has been considered, or whether a biased account has been given. Therefore, this review must largely be considered to be the authors’ opinions based on the studies that they have looked at. The methods and quality of these underlying studies informing this review are also unknown, so we cannot say how solid the evidence is.

It makes sense that regularly talking to your baby is beneficial, not least by helping their understanding of speech and strengthening the bond between the two of you.

There is also evidence that babies born into “speech-poor” environments, where they do not receive regular exposure to spoken language, may have delayed development.

However, whether talking to your baby will turn them into a new Mozart or Einstein, or make them super-popular in later life, cannot be proven by this review.

Analysis by Bazian. Edited by NHS Choices. Follow Behind the Headlines on Twitter. Join the Healthy Evidence forum.

Links To The Headlines

Say 'mama'! Talking to babies boosts their ability to make friends and learn, psychologists claim. Mail Online, January 8 2015

Links To Science

Vouloumanos A, Waxman SR. Listen up! Speech is for thinking during infancy. Trends in Cognitive Sciences. Published online November 7 2014

Categories: NHS Choices

Can eating like a Viking 'reduce obesity risks'?

NHS Choices - Behind the Headlines - Thu, 08/01/2015 - 12:15

"A Nordic diet could reduce the dangers of being overweight, a study suggests," The Daily Telegraph reports. The headline comes from the results of a small randomised controlled trial.

Half the people in the trial were put on the Nordic diet, which consists of wholegrain products, vegetables, root vegetables, berries, fruit, low-fat dairy products, rapeseed oil, and three servings of fish a week.

The other half acted as a control group and ate a diet of low-fibre grain products, butter-based spreads, and a limited intake of fish.

Researchers found people on the Nordic diet developed reduced activity (expression) in 128 genes associated with inflammation of their abdominal fat compared with controls.

Inflammation may cause some of the adverse health effects associated with being overweight, such as insulin resistance, which is a risk factor for type 2 diabetes.

However, changes in gene expression are not the same as proven changes in clinical outcomes. The study did not find any correlation between these changes in gene expression and clinical measurements of risk factors, such as blood pressure or cholesterol. 

Nevertheless, it is plausible that the Nordic diet has a protective effect – it is relatively similar to the Mediterranean diet (with a bit more herring and a bit less pasta), which has been associated with a reduced risk of chronic diseases.

 

Where did the story come from?

The study was carried out by researchers from a number of academic institutions in Finland, Norway, Sweden, Iceland and Denmark.

Funding came from several sources in these countries, including research foundations and academic institutes. Several commercial companies provided food products for the study participants.

The study was published in the peer-reviewed American Journal of Clinical Nutrition.

The Daily Telegraph and the Mail Online's coverage was accurate, but both overstated the results of the study, failing to point out that research into gene activity alone is not enough to show the health benefits of a diet.

 

What kind of research was this?

This was a randomised controlled trial, which is the best way to determine the effects of an intervention.

The trial was designed to look at whether a Nordic diet had an effect on the activity of genes in abdominal fat just beneath the skin (adipose tissue) in obese people.

It also aimed to see whether any changes in gene expression were associated with clinical and biochemical effects.

In previous research, "dysfunctional adipose tissue" had been proposed as an important link between obesity and its adverse health effects, such as insulin resistance and an unhealthy balance of blood fats.

However, little is known about how diet influences adipose tissue inflammation at the molecular level.

 

What did the research involve?

Researchers recruited 200 adults to the trial, although only 166 completed it. Participants had to be between the ages of 30 and 65, with a body mass index (BMI) of 27 to 38. A BMI of 25 or above is considered overweight, while a BMI of 30 or above is considered obese.

Participants also had to have at least two other features of metabolic syndrome, a condition characterised by symptoms such as high blood pressure, high blood sugar and abnormal blood fat levels, and is often associated with diabetes.

For a period of 18 to 24 weeks, 104 people were put on the Nordic diet, comprising wholegrain products, berries, fruits and vegetables, rapeseed oil, three fish meals a week, and low-fat dairy products. They also avoided sugar-sweetened products.

96 people were put on the control diet, comprising low-fibre cereal products and dairy fat-based spreads, with a limited amount of fish.

A clinical nutritionist or a dietitian gave instructions about the diets. The participants' dietary intake was monitored throughout using regular food records.

To reduce any confounding factors, the study participants were advised to keep their body weight and physical activity unchanged, and to continue their current smoking habits, alcohol consumption and drug treatment during the study.

Researchers took biopsy samples of the participants' adipose tissue at the beginning and end of the study, and extracted RNA, which is used to carry out DNA's genetic instructions.

A test called a transcription analysis was performed to study the expression of genes in the tissue.

Researchers also took various other clinical and biochemical measurements, including levels of blood sugar, cholesterol and triglycerides.

 

What were the basic results?

56 participants were included in the final analysis – 31 from the Nordic diet group and 25 from the control group.

People were excluded if there was a change in their body weight of more than 4kg, and if they started to use statins, had a BMI over 38, or poor adipose tissue samples.

The researchers report differences between the two groups in the activity of 128 genes.

Many of these genes were associated with pathways relating to the immune response, with a slightly reduced activity among people in the Nordic diet group and increased activity among people in the control diet group.

There were no differences between the groups in terms of clinical or biochemical measurements.

 

How did the researchers interpret the results?

The researchers say their study indicates that the Nordic diet reduced the activity of genes associated with inflammation in adipose tissue when compared with the control diet group.

The quality of diet may be an important factor for regulating adipose tissue inflammation independent of weight change, they say.

 

Conclusion

This study found that the activity of certain genes, some of which are associated with inflammation, was different in obese people who ate a Nordic diet compared to those on a control diet.

Yet there was little correlation between these findings and any changes in measurements of risk factors such as participants' cholesterol or blood pressure. The authors concede that the clinical relevance of their findings is unclear.

As the authors say, one limitation is that volunteers in the study may have had healthy eating habits before the study began.

If these volunteers had been randomised to the control diet group, they may have modified their diet to become more unhealthy, and therefore changes in gene expression would seem to be more evident in this group.

Being overweight or obese increases the risk of chronic illness such as diabetes, heart disease and some cancers, so it's important to maintain a healthy weight.

The Nordic diet is being touted as one of the latest trends in healthy eating. Whether it is a proven method to prevent chronic diseases is uncertain, but it does appear to be based on sensible nutritional principles, such as eating lots of wholegrains, fruit and vegetables, while cutting down on saturated fats.

Analysis by Bazian. Edited by NHS Choices. Follow Behind the Headlines on Twitter. Join the Healthy Evidence forum.

Links To The Headlines

High blood pressure? Eat like a Viking. The Daily Telegraph, January 7 2015

High blood pressure? Go Nordic: Eating like a Viking can reduce the damaging effects of being overweight - and stave off diabetes. Mail Online, January 7 2015

Links To Science

Kolehmainen M, Ulven SM, Paananen J, et al. Healthy Nordic diet downregulates the expression of genes involved in inflammation in subcutaneous adipose tissue in individuals with features of the metabolic syndrome. The American Journal of Clinical Nutrition. Published online November 19 2014

Categories: NHS Choices

New 'game-changing' antibiotic discovered

NHS Choices - Behind the Headlines - Thu, 08/01/2015 - 11:30

“New class of antibiotic could turn the tables,” on antibiotic resistance, The Guardian reports and is just one of many headlines proclaiming the discovery of a “super-antibiotic”. For once, such enthusiastic headlines might be largely justified.

The study in the spotlight shows the discovery of a new antibiotic, teixobactin, and is exciting for two main reasons.

Firstly, teixobactin proved effective against certain types of drug-resistant bacteria such as MRSA and tuberculosis (TB) in mice models. The way it works, by attacking cell walls rather than proteins, also suggested that bacteria would have a hard time evolving around its effects to develop resistance. This is the first potentially new antibiotic in over 20 years.

Secondly, the mechanism of discovery is potentially revolutionary. The research team used a device known as an iChip to make bacteria in soil “lab-ready” for use. Previously, only 1% of the organisms in soil could be grown and studied in the laboratory. This leaves 99% of bacteria as an untapped source of new antibiotics useful to people. Unlocking this natural reservoir of antibiotic production could potentially lead to the discovery of many more antibiotics in the future.

We now need to wait for tests on humans to make sure that teixobactin works and is safe. Also, teixobactin only appears to be effective against a subset of bacteria (Gram-positive bacteria), so is not a cure-all for Gram-negative bacterial infections, which include E.coli.

This is genuinely exciting news, but only time will tell whether this is a historical moment of similar magnitude to that of Alexander Fleming’s original discovery of penicillin in 1928.

 

Where did the story come from?

The study was carried out by researchers from the US, Germany and the UK, and was funded by the US National Institutes of Health, the Charles A King Trust, German Research Foundation and the German Centre for Infection Research.

Many of the authors declare financial conflicts of interest, as they are employees and consultants of NovoBiotic Pharmaceuticals, a biotech firm with an interest in creating new drugs.

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

The study attracted widespread attention from both the UK and international media. Generally, the media reported the story accurately, with many highlighting that while the study was promising, no human tests had yet taken place.

 

What kind of research was this?

This was a laboratory and mice study looking for new antibiotics.

Antibiotics – chemicals that kill bacteria – were first found in the early 20th century. This led to an explosion of antibiotic discovery that revolutionised medicine, and provided cures for previously incurable diseases. It also led to a marked decrease in complications arising from infection during surgical procedures we now regard as routine and safe, such as caesarean sections.

However, there have been no new antibiotic discoveries for decades. Existing antibiotics are becoming less effective because some bacteria are not killed by them and these bacteria can spread over time; these are so-called "drug-resistant bacteria".

Most people are aware of the "superbugs", such as MRSA and C-difficile, which are a leading cause of hospital-based infections. There are other candidates out there, such as extensively drug-resistant TB, which can take up to two years to treat. Therefore, the problem of drug-resistant bacteria is serious and growing, and could pose one of the greatest threats to public health in the 21st century.

This research sought to identify new bacteria from soil, which is heaving with micro-organisms harbouring naturally occurring antibiotics. Amazingly, the researchers tells us, only 1% of the organisms in soil can be grown and studied in the laboratory. This means the remaining 99% are potentially an untapped source of new antibiotics.

The team sought to devise a new way of growing and studying some of the soil micro-organisms, to screen them for any that display antibiotic properties and could be turned into new drugs.

 

What did the research involve?

The team designed and tested a number of methods to grow (culture) previously un-growable (unculturable) micro-organisms from soil.

This including making a device (iChip) that could be immersed in soil to “trick” the organisms into growing, but still allowed the team to isolate the micro-organisms for further study. This was used alongside a range of chemical growth factors to encourage and maintain growth.

When successful, they screened the newly cultured organisms for any signs that they were producing antibiotics. A number of new chemicals that looked promising were found and then tested in mice, including mice infected with methicillin-resistant Staphylococcus aureus (MRSA).

 

What were the basic results?

The results revealed a number of striking new discoveries:

  • Researchers could successfully grow a range of new organisms from the soil, which had never been done before.
  • Some of these newly grown organisms naturally produced antibiotics.
  • One such antibiotic, named teixobactin, was particularly promising and was subsequently studied intensely in the laboratory and in mice.
  • Tests in mice revealed teixobactin was effective against Gram-positive bacteria including MRSA and the bacteria that cause TB. However, it was not effective against Gram-negative bacteria such as E.coli, which have an extra layer of cell wall protection.
  • Teixobactin inhibited cell wall synthesis via a mechanism that bacteria are unlikely to develop resistance to, as it is so fundamental to their normal survival.
  • Backing this up, when teixobactin was used against bacteria Staphylococcus aureus or Mycobacterium tuberculosis no drug-resistant bacteria were found or developed. This is unusual, as most tests reveal some naturally occurring resistance over time.

 

How did the researchers interpret the results?

The research team simply concluded that: “The properties of this compound [teixobactin] suggest a path towards developing antibiotics that are likely to avoid development of resistance.”

 

Conclusion

This study shows the discovery mechanism of teixobactin and is exciting for two reasons. Teixobactin by itself shows effectiveness against MRSA and TB in mice models and has properties indicating that drug resistance may be unlikely to develop. This is encouraging for the potential future development of it for human diseases caused by Gram-positive bacteria.

Also, the mechanism of discovery shows great promise. The research team devised a completely new way of growing micro-organisms from soil that could not previously be grown. These micro-organisms, 99% of which are unknown to science, have the potential to produce natural antibiotics. Therefore, this discovery opens up the possibility that many more antibiotics can be found in the future. This is encouraging as there has been a lack of new antibiotic discoveries since the 1980s, while at the same time, the problem of drug-resistant bacteria has been growing.

While this discovery is undoubtedly good news, there are a number of moderating factors to bear in mind:

  • We don’t know what proportion of the 99% of currently ungrowable bacteria this new method will help to unleash, and what proportion of them might yield useful antibiotics.
  • Teixobactin has so far only been trialled in the lab and in mice. We need to await tests in humans before we can be sure it works and is safe.
  • Teixobactin looks effective against a subset of bacteria only (Gram-positive bacteria) so is not a cure-all for bacterial diseases.

With these limitations in mind, for once a study matches up to the media hype, as it discovered a promising new antibiotic candidate (teixobactin) and shows us a method that has the potential to lead to many more.

It is early days, but we could potentially be heading into a future where antibiotic-resistance is a thing of the past.

Analysis by Bazian. Edited by NHS Choices. Follow Behind the Headlines on Twitter. Join the Healthy Evidence forum.

Links To The Headlines

New class of antibiotic could turn the tables in battle against superbugs. The Guardian, January 8 2015

Antibiotics: US discovery labelled 'game-changer' for medicine. BBC News, January 7 2015

Teixobactin discovery: Scientists create first new antibiotic in 30 years - and say it could be the key to beating superbug resistance. The Independent, January 8 2015

First new antibiotic in 30 years discovered in major breakthrough. The Daily Telegraph, January 8 2015

Is this the answer to doctors' prayers? Super-antibiotic that could wipe out diseases from MRSA to TB is hailed as a 'game-changer' by scientists. Mail Online, January 8 2015

Scientists may have found first new antibiotic in 25 years. The Times, January 8 2015

New antibiotic could work for 30 years – if used right. New Scientist, January 7 2015

Links To Science

Ling LL, Schneider T, People AJ, et al. A new antibiotic kills pathogens without detectable resistance. Nature. Published online January 7 2015

Categories: NHS Choices

Could meal-in-a-pill 'trick' body into losing weight?

NHS Choices - Behind the Headlines - Wed, 07/01/2015 - 12:00

“Weight loss drug fools body into reacting as if it has just eaten,” The Guardian reports. The drug, fexaramine (or Fex), stimulates a protein involved in metabolism that is usually activated when the body begins eating, though it has only been tested in mice.

Researchers found that obese mice given Fex stayed the same weight despite continuing to eat the same amount of a high-fat diet. However, unlike some media claims, they did not actually lose any weight. It had no effect on mice of normal weight.

The protein that is stimulated, FXR (farnesoid X receptor), is present in many organs of the body and plays a complex role in metabolism that is not fully understood. 

Previous drugs developed to activate this protein have shown conflicting results, possibly because they entered the bloodstream and so acted on all of the organs. Fex has been developed so that it appears to be barely absorbed into the blood stream, and so only acts on the FXR in the intestines. This provided better results for obese mice and also reduces the risk of side effects.

Further animal and primate studies will need to be conducted before the drug would be allowed to progress to human trials, but these are promising results. However, even if these trials passed with flying colours, we would estimate that it would take at least 5-10 years before any drug based on this research came to market.

 

Where did the story come from?

The study was carried out by researchers from the Salk Institute for Biological Studies in California and several other institutes in the US, Australia and Switzerland. It was funded by the US National Institutes of Health, the Glen Foundation for Medical Research, the Leona M. and Harry B. Helmsley Charitable Trust, Ipsen/Biomeasure, the California Institute for Regenerative Medicine, the Ellison Medical Foundation, the National Health and Medical Research Council of Australia, and the Eunice Kennedy Shriver National Institute of Child Health and Human Development.

A financial conflict of interest was reported. Many of the contributing authors “are co-inventors of FXR molecules and methods of use, and may be entitled to royalties from their use”.

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

In general, the media have reported the story accurately, pointing out that it is in the early stages of development and that it has only been tested on mice. However, as mentioned, headlines such as the Daily Mirror’s “'Imaginary meal' diet pill tricks body into losing weight”, or The Daily Telegraph’s assertion that the “pill makes you feel full” are inaccurate. None of the mice lost weight and none of their appetites were suppressed.

 

What kind of research was this?

This was an animal study to test whether a new drug could improve the metabolism of mice. The researchers conducted a variety of experiments of the drug, comparing their response with mice receiving a placebo.

The drug was created to mimic an effect of eating food. Food causes bile acids to be secreted and this activates a protein called FXR (farnesoid X receptor).

FXR plays a complex role in metabolism that is not fully understood. It is present in many organs of the body, including the kidney, stomach, intestines, gall bladder, liver and both white and brown fat cells.

Previously, drugs have been developed to activate FXR, but they have encountered problems because of activating FXR in all of the organs. This gave conflicting outcomes. For example, mice of normal weight given these drugs had improved glucose tolerance, whereas obese mice put on more weight and had even poorer glucose tolerance. It was not clear why this happened, so the researchers wanted to investigate whether just activating FXR in the intestines improved metabolism.

They developed Fex to activate the intestinal FXR drug instead of food, without it being absorbed into the general circulation, to see if this made a difference. They also say that limiting absorption means there would be less potential for side effects.

 

What did the research involve?

The researchers developed a drug called Fex and performed a number of tests using mice.

They first tested the absorption of Fex into the general circulation. They gave mice either a Fex pill by mouth or an injection of Fex into the fluid that surrounds the abdominal organs. The researchers then measured the level of FXR activation in each organ.

The researchers then gave normal weight mice either a Fex pill or a placebo for 35 days. They then compared their weight, metabolic rate and sensitivity to insulin.

Lastly, mice were fed a high-fat diet (60% fat) for 14 weeks to make them obese. The researchers then gave them different doses of the Fex pill or a placebo for five weeks. They compared their weight, metabolic rate, extent of unhealthy white fat and healthy brown fat, and markers of tissue inflammation.

 

What were the basic results?

The oral Fex pill activated FXR in the intestine and did not activate it in the liver or kidneys. The researchers say this shows that it was only minimally absorbed into the general circulation. This was in comparison to the injection of Fex into the abdominal cavity, which stimulated FXR in the intestine as well as the liver and kidneys.

There was no difference between normal weight mice given oral Fex for five weeks in terms of weight gain (small amount) and other metabolic measurements, compared to normal weight mice given placebo.

In obese mice, the Fex pill caused an improvement in metabolism compared to placebo, including:

  • reduced weight gain
  • increased sensitivity to insulin
  • more unhealthy white fat turning into healthy brown fat
  • reduced inflammation

These obese mice were 34 grams at the start of the experiment (normal weight mice would be around 28 grams). They continued on the high-fat diet (60% fat) for five weeks. Those given placebo increased in weight to 44 grams, but those given the highest dose of Fex did not gain any more weight. None of these mice lost weight. The researchers report that there was no change in appetite or food consumption between the mice given Fex and those given placebo.

 

How did the researchers interpret the results?

The researchers concluded that Fex might be a “promising” approach to stimulating FXR, in order to improve metabolism. The say that the “absence of a change in food intake is notable, as failure of appetite control is a major reason for weight gain”. They say that, as this drug appears to improve metabolism without any change in food intake, it “may offer a viable alternative for obesity treatments”. They also point out that as Fex is only minimally absorbed and only stimulates the intestinal FXR, it offers “improved safety profiles” by not circulating around the whole of the body.

 

Conclusion

This animal study has shown that a new drug called Fex prevents obese mice from further weight gain, despite remaining on a high-fat diet. There were also other metabolic improvements, including improved sensitivity to insulin and a reduction of unhealthy white fat cells. There were no differences in measures of metabolism between mice of normal weight given Fex or placebo, although both groups gained a small amount of weight.

This preliminary study appears to show that, unlike previous drugs that have stimulated FXR from the general circulation and shown conflicting results, by targeting intestinal FXR, obese mice benefit. As it has only been tested in mice for five weeks, there is limited information on what these side effects might be in humans.

Further animal and primate studies will need to be conducted before the drug would progress to human trials, but these are promising results.

As the drug appears to improve metabolic function rather than promote weight loss, it could be a candidate to treat diseases of the metabolism, such as type 2 diabetes or metabolic syndrome (where a person has a combination of diabetes, high blood pressure and obesity).

Due to the length of time it takes to bring a drug to market, as well as the chance of a drug proving to be ineffective or unsafe in humans, we can’t envisage Fex (or a variant) appearing in your local pharmacy anytime soon.

In the meantime, tips to help you lose weight can be found here and you can get online support here.

Analysis by Bazian. Edited by NHS Choices. Follow Behind the Headlines on Twitter. Join the Healthy Evidence forum.

Links To The Headlines

Weight loss drug fools body into reacting as if it has just eaten. The Guardian, January 5 2015

Could an 'imaginary meal' pill solve the obesity crisis? Drug tricks the body into feeling full - AND lowers cholesterol and blood sugar. Mail Online, January 5 2015

Diet pill that makes you feel full proven to keep weight off in mice, scientists say. The Independent, January 5 2015

'Imaginary meal' diet pill tricks body into losing weight. Daily Mirror, January 5 2015

'Imaginary meal' pill makes you feel full and burns fat. The Daily Telegraph, January 5 2015

An 'imaginary meal' pill to lose weight? Scientists reveal latest weapon to battle obesity. Daily Express, January 5 2015

Links To Science

Fang S, Suh JM, Reilly SM, et al. Intestinal FXR agonism promotes adipose tissue browning and reduces obesity and insulin resistance. Nature Medicine. Published online January 5 2015

Categories: NHS Choices

Out-of-character criminal actions linked to dementia

NHS Choices - Behind the Headlines - Wed, 07/01/2015 - 11:00

“Could criminal behaviour be the first sign of dementia?” the Mail Online asks. A US study found an association between sudden, unusual criminal behaviour, such as shoplifting or urinating in public, and various types of dementia.

The study looked at crimes committed by patients suffering from a number of diseases that damage the brain and cause dementia. It found more than 8% of patients had a history of criminal behaviour that first emerged during their illness.

Patients with Alzheimer’s disease, a common form of dementia – were the least likely to commit crimes, while those with a type of uncommon dementia called frontotemporal dementia (FTD) were the most likely to commit crimes including theft, traffic violations, sexual advances and urinating in public. This has long been recognised as an effect of the disorder, as it typically causes a change in personality and can lead to disinhibition.

This study suggests – but cannot prove – that, in older adults, new criminal behaviour could be a sign of brain damage caused by a dementing disorder.

If you are worried about a relative’s behaviour or changes in personality, it is sensible to seek medical advice.

 

Where did the story come from?

The study was carried out by researchers from Lund University in Sweden, the University of California, and the University of Notre Dame in Australia.

It was funded by the Hennerlöfska Foundation for Medical Research, The Swedish Society of Medicine and the Trolle-Wachtmeister Foundation for Medical Research in Sweden, and the National Institutes of Health (NIH), the Consortium for Frontotemporal Dementia Research, the Tau Consortium and the Hillblom Aging Network in the US.

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

The Mail’s coverage was accurate but uncritical. Its photos of someone handcuffed and an angry-looking older person were unnecessary.

 

What kind of research was this?

This was a retrospective study of patients seen at a memory and ageing centre in the US. It was designed to look at the frequency and type of criminal behaviour that occurred among those diagnosed with a dementing disorder.

Such neurodegenerative diseases can cause brain dysfunction in areas such as judgement, executive function, emotional processing, sexual behaviour, violence and self-awareness, and this can result in antisocial and criminal behaviour.

The crimes committed by people with dementia range from theft, traffic violations and violence to hypersexuality and homicide (but the latter is thought to be rare). The researchers wanted to quantify how often this happens and the extent to which this was the event that led the person to being diagnosed with a form of dementia.

 

What did the research involve?

Researchers reviewed the medical records of 2,397 patients seen at a US memory and ageing centre between 1999 and 2012. These patients had been diagnosed with a variety of neurodegenerative disorders that can cause dementia.

The researchers screened the patients’ medical notes for specific key words to identify criminal behaviour. Keywords were chosen to represent all the criminal behaviours that have been observed in people with dementia. These included court, arrest, criminal, detain, steal, speeding, violation and violence.

The types of criminal behaviour were then stratified according to the following categories:

  • driving under the influence (aka drink driving)
  • hit and run
  • traffic violations
  • speeding
  • insubordination towards legal authorities
  • sexual advances
  • loitering
  • public urination
  • theft
  • trespassing
  • violence (including physical and verbal threats)

Only criminal behaviours that occurred during the patient’s illness were included. The criminal behaviour was considered to be the presenting symptom if the doctor specifically indicated this in the medical record.

Researchers then calculated the frequency of criminal behaviour for the following categories of dementia or dementia-like conditions:

  • Alzheimer’s disease
  • frontotemporal dementia
  • semantic variant of primary progressive aphasia – a type of dementia that effects language and communication, such as speaking, reading and understanding
  • Huntington’s disease – a genetic condition that can cause dementia-like symptoms
  • vascular dementia – dementia caused by reduced blood flow to the brain

 

What were the basic results?

Of the 2,397 patients studied, 204 (8.5%) had a history of criminal behaviour that emerged during their illness.

Of the major diagnostic groups, the following proportions exhibited criminal behaviour:

  • 42 of 545 people (7.7%) with Alzheimer’s disease
  • 64 of 171 people (37.4%) with FTD
  • 24 of 89 people (27.0%) with the semantic variant of primary progressive aphasia
  • six of 30 people (20%) with Huntington’s disease 
  • nine of 61 people (14.8%) with vascular dementia

Criminal behaviour was one of the symptoms that caused 14% of people to be diagnosed with FTD, compared with 2% of patients with Alzheimer’s disease. Of those diagnosed with FTD, 6.4% were more likely to have exhibited violence in this criminal behaviour compared with 2% of people with Alzheimer’s.

Common types of criminal behaviour in the FTD group included theft, traffic violations, sexual advances, trespassing and public urination. In the Alzheimer’s group, the most common crime was traffic violations, often related to memory loss.

 

How did the researchers interpret the results?

The researchers point out that new criminal behaviours are associated with specific dementing disorders such as FTD, but not with others.

"The findings from this study suggest that individuals who care for middle-aged and elderly patients need to be vigilant in the diagnosis of degenerative conditions when behaviour begins to deviate from the patient's norm, and work hard to protect these individuals when they end up in legal settings," they concluded.

 

Conclusion

This study looks at an important issue, but it had several limitations that make the results less reliable:

  • It used data on criminal behaviour taken from patients’ medical notes rather than relying on official criminal records.
  • Patients referred to the centre may have had more behavioural problems than those with dementia in the general population.
  • The study cannot show the criminal behaviour was caused by dementia.
  • The study had no control group, so cannot compare crime rates among healthy adults with those with dementia.

Dementia can lead to changes in behaviour and, in some people, loss of inhibition and aggression.

However, it’s important that people with dementia are not labelled as potential criminals and it should be noted that most are more of a danger to themselves then others.

If you are worried about a relative’s behaviour or changes in personality, it is sensible to seek medical advice.

Analysis by Bazian. Edited by NHS Choices. Follow Behind the Headlines on Twitter. Join the Healthy Evidence forum.

Links To The Headlines

Could criminal behaviour be the first sign of DEMENTIA? Offending for the first time in old age may be due to brain damage. Mail Online, December 6 2015

Links To Science

Lijegren M, Naasan G, Temlett J, et al. Criminal Behavior in Frontotemporal Dementia and Alzheimer Disease. JAMA Neurology. Published online January 5 2015

Categories: NHS Choices

Wholegrains, not just porridge, may increase life

NHS Choices - Behind the Headlines - Tue, 06/01/2015 - 09:54

"The key to a long and healthy life? A bowl of porridge every day," is the somewhat inaccurate headline in the Daily Mail.

The study it reports on was looking at the health benefits of wholegrains in general, not just porridge.

These headlines are based on a study of more than 110,000 men and women in the US, who were followed up from the 1980s to 2010.

Their diets were assessed every two to four years, and the researchers looked at whether the quantity of wholegrains people ate was related to their likelihood of dying during follow-up.

Fans of wholegrains, which include brown rice and oats, claim they can improve digestion, reduce cholesterol levels and make people feel fuller so they are less likely to snack.

The researchers found people who ate the most wholegrains were about 9% less likely to die during follow-up, and about 15% less likely to die from heart disease specifically, compared with people who ate the least.

We know that people who eat wholegrains also tend to have healthier lifestyles, so researchers tried to take this into account. But, as the authors acknowledge, it is impossible to be certain that other factors aren't contributing.

With that limitation in mind, this is a good-quality study, which supports the benefits of eating more wholegrain foods.

 

Where did the story come from?

This research was carried out by researchers at the Harvard School of Public Health and other research centres in the US and Singapore.

It was funded by the US National Institutes of Health and the National Heart, Lung, and Blood Institute.

It was published in the peer-reviewed Journal of the American Medical Association (JAMA) Internal Medicine. 

While the general content of the stories that appeared in the Daily Mail and The Daily Telegraph was accurate, the headline writers developed a strange obsession with porridge.

While porridge can be a good source of wholegrains, the foodstuff was never actually mentioned in the study. All dietary sources of wholegrains were added together for the analyses, so the study did not show whether one source was better than another.

 

What kind of research was this?

This was an analysis of data from two prospective cohort studies looking at whether eating more wholegrains is associated with living longer.

The researchers note wholegrains have been found to be associated with a reduced risk of diseases such as type 2 diabetes and heart disease.

But while some studies have suggested they are associated with living longer, others have not. The researchers wanted to use a large, good-quality study to assess this question.

This type of study is the best way to assess this question, as it would not be feasible to do a randomised controlled trial where people's diets were controlled over a long period of time.

Collecting data prospectively gives the best chance of getting complete and correct information about people's exposures (such as what they ate) and their outcomes during follow-up (such as whether they died).

As with all studies of this type, people who eat more wholegrains may also have other healthier behaviours or characteristics, such as taking regular exercise, which could affect their risk of death during follow-up.

To try to remove the effect of these other factors (called confounders), researchers need to measure them and take them into account in their analyses.

 

What did the researchers do?

The researchers collected detailed information on the diets and other characteristics of 118,085 adults. They followed them for up to 26 years to find out who died.

They then looked at whether people who ate more wholegrains were less likely to die in this period than those who ate fewer wholegrains.

The researchers analysed data collected in two US studies called the Nurses' Health Study (all-female participants) and the Health Professionals Follow-Up Study (all-male participants) between the 1980s and 2010.

They only included people who did not have heart disease or cancer at the start of the study, and those who had completed full questionnaires on their diets.

The studies collected information on participants' diets using accepted food frequency questionnaires every two to four years.

These questionnaires asked about how often the individual had eaten specified portions of a wide range of foods in the past year.

The researchers used the information collected to estimate each person's wholegrain intake from grain-containing foods such as pasta, rice, bread and breakfast cereal.

The following foods were considered wholegrains:

  • whole wheat and whole wheat flour
  • whole oats and whole oat flour
  • whole cornmeal and whole corn flour
  • whole rye and whole rye flour
  • whole barley
  • bulgur wheat
  • buckwheat
  • brown rice and brown rice flour
  • popcorn
  • amaranth and psyllium (two other types of grains)

This included wholegrains that were intact (such as brown rice) and those where the grain had been broken down, but the food still retained all of the contents of the wholegrain (such as whole wheat flour). The questionnaire also asked how much added bran or wheat germ a person ate.

The researchers identified people who had died through the US National Death Index, the postal service, or through relatives of the participants. They used death certificates to identify the cause of death in each case.

The researchers then analysed whether those people who ate more wholegrains on average were less likely to die during follow-up.

This involved dividing people into five groups according to how many wholegrains they ate, and then comparing the proportion of people who died in each group.

In their analyses, they took into account a wide range of factors that could influence results, such as:

  • total calorie intake
  • age
  • gender
  • ethnicity
  • smoking
  • alcohol
  • body mass index (BMI)
  • physical activity
  • taking multivitamins
  • taking aspirin
  • family history of heart disease, cancer or diabetes
  • medical conditions such as high blood pressure, diabetes or high cholesterol
  • overall healthiness of the diet (using a score based on intake of 10 foods and nutrients linked with a higher or lower risk of chronic diseases, such as red or processed meat and fruit and vegetables)

They also discounted any dietary information collected after a person developed diabetes or heart disease, or had a stroke, as this led to these people changing their diets as a result. They looked at total deaths overall, as well as deaths specifically from heart disease and cancer.

 

What were the results of the study?

Women with the lowest intake of wholegrains ate about four grams of wholegrains per day on average, and this figure was about six grams per day for men.

Women with the highest intake of wholegrains ate about 36 grams per day on average, and this figure was about 53 grams per day for men.

Men and women with higher wholegrain intake also tended to be more physically active, less likely to be current smokers, have lower alcohol intake, and eat healthier diets overall. They were also more likely to have had a high cholesterol level at the beginning of the study.

On average, participants were in their 50s when the study started. In total, the researchers collected more than 2.7 million years of follow-up (the sum of the number of years each person was followed up for). During this time, 26,920 of 118,085 participants (about a quarter) died.

After taking into account potential confounders, the researchers found a significant trend for reduced risk of death during follow-up with increasing wholegrain consumption.

People who had the highest wholegrain consumption were 9% less likely to die during follow-up than those with the lowest wholegrain consumption (hazard ratio [HR] 0.91, 95% confidence interval [CI] 0.88 to 0.95).

When looking at death from specific causes, people who had the highest wholegrain consumption were 15% less likely to die from heart disease during follow-up than those with the lowest consumption (HR 0.85, 95% [CI] 0.78 to 0.92). Wholegrain consumption was not linked to risk of death from cancer.

The researchers estimated each additional 28 gram serving of wholegrains per day was associated with a 5% reduction in overall risk of death during follow-up (HR 0.95, 95% CI 0.93 to 0.98) and a 9% reduction in the risk of death from heart disease (HR 0.91, 95% CI 0.87 to 0.96).

 

How did the researchers interpret the results?

The researchers concluded that eating more wholegrains is associated with a reduced risk of death during follow-up, and of death from heart disease specifically, in women and men in the US.

This link remained even after taking other lifestyle factors into account. They say their findings support recommendations to increase wholegrain intake to reduce the risk of chronic diseases.

 

Conclusion

This analysis of two large prospective cohort studies from the US has found an association between higher wholegrain intake and a reduced risk of death during follow-up, particularly from heart disease.

The study benefits from its large size (more than 100,000 participants) and long duration, as well as the thorough collection of information on the participants as the study progressed (prospective data collection).

Our diets and lifestyles are very complex, and it is very difficult to entirely isolate the effect of one dietary component and remove the effect of all other factors.

However, the researchers have assessed and taken into account a wide range of factors in their analyses that could affect the risk of death. This means the results are more likely to reflect the effect of wholegrain foods specifically, rather than other factors.

But the authors themselves acknowledge some factors may still be having an effect. In addition, the study relies on self-reported estimates of dietary intake from the participants, which may not be entirely accurate.

All of the participants in the study were health professionals from the US. The results may not be representative of what would be seen in other groups – for example, those of lower socioeconomic status.

Also, while the study found no reduction in deaths from cancer overall, it did not look at deaths from individual types of cancer, such as bowel cancer.

With these limitations in mind, the researchers have produced a large, useful and good-quality study. The findings reinforce the benefits of including more wholegrains in our diet.

Analysis by Bazian. Edited by NHS Choices. Follow Behind the Headlines on Twitter. Join the Healthy Evidence forum.

Links To The Headlines

The key to a long and healthy life? A bowl of porridge every day, say scientists. Daily Mail, January 5 2015

Porridge could be key to a long and healthy life, says Harvard University. The Daily Telegraph, January 5 2015

Links To Science

Wu H, Flint AJ, Qi Q, et al. Association Between Dietary Whole Grain Intake and Risk of Mortality. JAMA Internal Medicine. Published online January 5 2015

Categories: NHS Choices

Why common cold may thrive at low temperatures

NHS Choices - Behind the Headlines - Tue, 06/01/2015 - 09:50

The “common cold 'prefers cold noses',” reports BBC News today, while The Independent recommends that you “heed your mother’s warning: cover up or you’ll catch a cold”.

While these headlines might make you think this study is proof of a link between colder temperatures outside and catching a cold, this isn’t quite what the researchers looked at.

Our nasal passages are naturally a few degrees colder than the core of our body. It has long been known that rhinovirus – the most common cause of the human cold – grows much better at these lower temperatures.

The current study has looked at why this might be. It found that mouse airway cells were less able to mount immune defences against the cold virus at the lower temperature seen in the human nose than at the higher temperature seen at the core of the body.

While this study may suggest a possible explanation for the known effect of temperature on cold viruses, it is very early stage research, testing just one strain of rhinovirus in mouse cells. The experiments will need to be repeated with different strains and ideally with human airway cells.

Also, while the authors speculate about whether this could explain beliefs around the impact of cold environmental temperatures on catching a cold, and wrapping up warm to prevent a cold, this study didn’t actually assess this.

 

Where did the story come from?

This study was carried out by researchers at Yale University. It was funded by the US National Institutes of Health, National Institute of Allergy and Infectious Diseases, and National Science Foundation.

It was published in the peer-reviewed journal Proceedings of the National Academy of Sciences of the United States of America (PNAS).

The media has focused on the potential impact of cold outdoor temperatures on our risk of catching a cold, when this is not what the study assessed. The common cold-causing rhinovirus was already known to grow better at the naturally cooler temperatures in the nose than at higher temperatures found in the centre of the body. This study looked at why this might be the case.

 

What kind of research was this?

This was a laboratory study looking at whether temperature affects how the cells in the airways are able to respond to the cold virus.

The insides of our noses are naturally a few degrees cooler than our core body temperature: 33C – 35C, compared to 37C. The cold virus is already known to be able to reproduce itself better in cells at these cooler temperatures. However, it is not known why this is. Researchers wanted to test whether it could be because the cells in the airways are less able to mount defences against the cold virus at cooler temperatures.

Laboratory research is often the first step to understanding what happens in our bodies. As cells in isolation in the lab may behave differently to when they are in the body, these early experiments usually need to be followed up by studies in animals or humans to confirm their findings.

 

What did the research involve?

The researchers took samples of the cells lining mouse airways and grew them in the lab at either 33C or 37C. They exposed these cells to the rhinovirus – the most common cause of the cold in humans. The virus was selected and grown in a way that allowed it to better infect the mouse cells. They then compared what responses the cells were having to the virus at the different temperatures. In particular, they looked at how well the cells were switching on the production of proteins to help them fight the virus.

 

What were the basic results?

The researchers found that the mouse airway cells were better at switching on the production of proteins to help them fight the cold virus at the warmer (core body) temperature than the cooler (nasal cavity) temperature. The researchers went on to identify some of the proteins involved in prompting this response. They found that if these proteins were not present, then the virus was better able to replicate itself in cells at the warmer temperature. 

 

How did the researchers interpret the results?

The researchers concluded that airway cells are less able to mount defences against the cold virus at the cooler temperatures of the nasal passages than in warmer temperatures at the core of the body. This at least partly explains why the cold virus is able to grow better in the cooler nasal passages than in the warmer lungs. They say that this could be a possible explanation for the “popular but controversial idea that exposure to cool weather conditions can increase susceptibility to common colds”.

 

Conclusion

This laboratory study looked into why the cold virus is able to grow better in the cooler temperatures found in the nasal passages, than in the warmer core body temperature found, for example, in the lungs. The authors note that while this difference has been known since the 1960s, the reasons are still not clear.

Their findings, using cells from mouse airways grown in the laboratory, suggest that at the cooler temperatures these cells are less able to switch on the production of proteins that fight the virus. However, it is important to bear in mind some of the limitations of this early stage research. One limitation was that it tested just one strain of the most common human cold virus (rhinovirus) in mouse cells. The experiments will need to be repeated with different strains of rhinovirus and other cold-causing viruses, and with human airway cells. The authors also note that this might not be the only reason why cold viruses grow better in the nose.

Also, while the authors speculate that this could explain the impact of cold environmental temperatures on colds, this study only really looked at cells at the normal temperature of the human nose, and didn’t assess the impact on nose temperature of it being colder outside.

Regardless of this, it is important to protect your body against the potentially harmful effects of very cold weather. Older people, those who cannot afford heating, and those with long-term health conditions or who are disabled are particularly vulnerable to cold-related illnesses. 

Read more about keeping well in winter

Analysis by Bazian. Edited by NHS Choices. Follow Behind the Headlines on Twitter. Join the Healthy Evidence forum.

Links To The Headlines

You are more likely to get a cold in winter - but keeping your nose warm may be the secret to avoiding it. Mail Online, January 6 2015

Common cold 'prefers cold noses'. BBC News, January 6 2015

Heed your mother’s warning: cover up or you’ll catch a cold. The Independent, January 6 2015

Common cold really is triggered by chilly weather, Yale scientists find. The Daily Telegraph, January 6 2015

Why chilly weather really can give you a cold. The Times, January 6 2015

Links To Science

Foxman EF, Storer JA, Fitzgerald ME, et al. Temperature-dependent innate defense against the common cold virus limits viral replication at warm temperature in mouse airway cells. PNAS. Published online January 5 2015

Categories: NHS Choices

New skin cancer drugs show promise in lab tests

NHS Choices - Behind the Headlines - Mon, 05/01/2015 - 10:29

"New skin cancer drug set for clinical trials," The Guardian reports. In fact, two new compounds designed to treat malignant melanoma are due for trials after promising results in laboratory research.

Both are signalling inhibitors, which work by disrupting the messages a cancer uses to co-ordinate its growth. These have proven effective in the short to medium term, but it is common for the cancer to develop resistance to their effects.

This new research involved two new compounds, both part of a family called panRAF inhibitors, which work using a slightly different mechanism from existing signalling inhibitors.

The findings, involving mice and lab studies, were certainly encouraging, but we should not get ahead of ourselves. The research is barely out of the laboratory, which is the very first phase in the drug discovery timeline.

This means we have no idea whether these new drugs will be safe or effective when used on people.

Clinical trials will provide the answers over the coming years, although there are no guarantees that the drugs will be successful.

Small-scale clinical trials are the next stage in research, and the authors say this is planned.

 

Where did the story come from?

The study was carried out by researchers from the Cancer Research UK Manchester Institute, and the Institute of Cancer Research London.

It was funded by the Cancer Research UK Manchester Institute, Cancer Research UK, the Wellcome Trust and the Division of Cancer Therapeutics at the Institute of Cancer Research.

The study was published in the peer-reviewed science journal Cancer Cell as an open access article. This means that anyone can read the full article online for free.

Generally, The Guardian and the Mail Online reported the story accurately, though it wasn't made clear that the researchers were actually looking at two compounds, not a single drug.

The Mail also claims the research will lead to a "new pill". The study did not use a pill in the mice experiments – rather, the compounds were given orally as a liquid and an injection into a vein. 

It is too early to say with any assurance what form the drug would take if used in people.

The drug was for a resistant form of skin cancer, and these findings are at an early stage of research. 

 

What kind of research was this?

This was a laboratory study investigating biological compounds that have the potential to treat malignant melanoma with specific mutation in the BRAF gene. This is said to account for up to half of people with melanoma.

Melanoma is the most serious type of skin cancer, which can spread rapidly to lymph nodes and other organs in the body if not treated as soon as possible.

The most common sign of melanoma is the appearance of a new mole or a change in an existing mole. This can happen anywhere on the body, but the back, legs, arms and face are most commonly affected.

The study group say existing drug classes called BRAF and MEK inhibitors are initially effective when treating melanoma with the specific BRAF gene mutation.

However, in most people, the cancer comes back as the drugs stop working. In others, the drugs do not work very well to start with.

The team wanted to find new ways of treating this specific drug-resistant form of melanoma and began their investigations in the laboratory.

 

What did the research involve?

The research group designed and synthesised a variety of compounds as part of a drug discovery programme.

They focused their efforts using their understanding of the biological pathways involved in melanoma and, specifically, mechanisms by which current drugs stop working against the BRAF mutation.

The discovery programme led to two promising compounds, which underwent more in-depth biological and chemical experiments to work out exactly how they were working.

None of the experiments involved giving the newly developed drugs to people, although many involved testing the chemical on human cells cultured in the laboratory.

 

What were the basic results?

The discovery programme found two promising compounds. They are called pan-RAF inhibitors, named CCT196969 and CCT241161 respectively.

They were found to inhibit melanoma development through a different biological mechanism from previous drugs.

Because of this, it was hoped there may be less chance that resistance to these drugs will develop, as has happened in the past.

 

How did the researchers interpret the results?

The research team suggested the new chemicals they found, if developed into effective drugs, "could provide first-line treatment for BRAF and NRAS mutant melanomas and second-line treatment for patients who develop resistance".

In other words, these chemicals could potentially be developed into drugs to treat some melanomas in the first instance, and used as a second line of attack for others that have become resistant to existing drugs.

 

Conclusion

This laboratory study discovered two new chemicals, which show anti-cancer properties for melanoma with a specific gene mutation that can make it resistant to existing treatments.

The next stage for research is small-scale, phase I clinical trials to see whether these chemicals could one day be developed into drugs that could be available to treat patients. The authors say this is planned.

These types of trials generally assess whether the drug in development can be safely tolerated in people, and in what doses.

Only after they are deemed safe can further, larger trials be conducted to see whether the drugs work, or are cost-effective, in comparison to other treatments. These trials usually take many years.

There are no guarantees that any new drugs coming out of this research will turn out to be a winner, but there is hope.

Analysis by Bazian. Edited by NHS Choices. Follow Behind the Headlines on Twitter. Join the Healthy Evidence forum.

Links To The Headlines

New skin cancer drug set for clinical trials. The Guardian, January 2 2015

Revolutionary new PILL could treat skin cancer: Scientists discover drug could help patients resistant to standard treatments. Mail Online, January 3 2014

Links To Science

Girotti MR, Lopes F, Preece N, et al. Paradox-Breaking RAF Inhibitors that Also Target SRC Are Effective in Drug-Resistant BRAF Mutant Melanoma. Cancer Cell. Published online December 11 2014

Categories: NHS Choices

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