NHS Choices

Study links shift work to increased risk of diabetes

NHS Choices - Behind the Headlines - Fri, 25/07/2014 - 12:40

“Type 2 diabetes is more common in people who work shifts, a large international study suggests,” BBC News reports.

The BBC reports on a review that searched the literature and found 12 studies including more than 225,000 people which looked at the link between shift work and diabetes.

When pooling the results the researchers found that overall, shift work was associated with a 9% increased risk of diabetes. The association was found to be stronger in men (37%) and for those working rotating shifts – such as two weeks on nights, two weeks on days (42%).

However, there are problems with concluding from these studies that there really is a link between shift work and developing diabetes. For example, it is difficult to establish cause and effect, because it’s not completely clear that people hadn’t already got diabetes at the time their shift work pattern was being assessed. It’s further unclear whether the apparent relationship may not just be caused because of other factors that are associated with both shift work and diabetes (such as diet and activity).

Also, none of the 12 studies were conducted in the UK, and half were from Japan. While the results may be applicable here, different cultures may have different a work ethic, environmental and health differences, meaning that they cannot so easily be generalised to all populations.

The identified relationship is undoubtedly worthy of further study, to see whether shift work could have direct biological effects on the body that lead to the development of diabetes.

 

Where did the story come from?

The study was carried out by researchers from Huazhong University of Science and Technology, Wuhan, Hubei, and Jiangxi Science and Technology Normal University, Nanchang, Jiangxi, both in China.

No sources of financial support are reported and the authors declare no conflicts of interest.

The study was published in the peer-reviewed journal of Occupational and Environmental Medicine. 

The UK media accurately reports the results of this study, and discusses the possible causes and hazards of shift working, such as disruption to the “body clock”, which seem plausible, if unproven. However, they do not highlight the study's limitations.

 

What kind of research was this?

This was a systematic review and meta-analysis.

Researchers searched the literature from across the world to find observational studies that have examined whether shift work may be associated with the risk of type 2 diabetes. The researchers then pooled the results of these studies.

Type 2 diabetes is a global health problem, and it is estimated that in just over 10 years time the number of cases could have increased by 65% to reach 380 million cases worldwide.

Diabetes is associated with considerable ill health and mortality. So identifying modifiable risk factors that may reduce risk of the disease developing is highly important. Being overweight or obese is the most well established modifiable risk factor for type 2 diabetes.

The researchers say that shift work, with its irregular working hours and rotating schedule has been demonstrated to have some effect on sleep patterns, tiredness, cognitive capacity, and digestion.

Some studies have even linked it with breast cancer and vascular disease. Therefore, this review aimed to look at the possible association with diabetes.

 

What did the research involve?

The researchers searched several literature bases for studies published up to April 2014 that have examined an association between shift work and diabetes, using relevant search terms, including impaired glucose tolerance and insulin resistance. Any study design or study population was eligible, but only studies in the English language were included. The researchers pooled observational studies that had directly examined the link between shift work as an exposure and diabetes as an outcome.

Shift work schedules were categorised as rotating, irregular and unspecified, night, mixed and evening.

Studies examining non-work-related nighttime activities/light exposure were excluded. Two researchers extracted data and assessed the quality of the studies.

 

What were the basic results?

Twelve studies met inclusion criteria: eight cohort studies (seven prospective, one retrospective), and four cross sectional studies, published between 1983 and 2013. The 12 studies included a total 226,652 people, with sample size in individual studies ranging between 475 and 107,915. There were a total 14,595 people with diabetes (6% of the total sample). Six studies came from Japan, two from the US, two from Sweden, one from Belgium and one from China. Eight of the studies included only men, two both sexes, and two women only.

The pooled results of all studies found that shift work was associated with a 9% increased risk of diabetes (odds ratio (OR) 1.09, 95% confidence interval (CI) 1.05 to 1.12).

The odds ratios when pooling only cohort studies and only cross sectional studies were fairly similar (slightly higher odds for cohort studies of 12% versus 6% for cross sectional).

They then carried out further sub-analyses to examine whether specific factors were associated. The odds of diabetes were much higher for men (37% increased risk) than for women (9%).

There was a significant association with diabetes for rotating shifts, irregular or unspecific shifts and night shifts; but no link for mixed or evening shifts. The largest association with diabetes was for rotating shifts (42% risk).

Sub-analyses of studies that had controlled for body mass index (BMI) in their models, and of studies that had controlled for physical activity in their models still found similar, significant links (7% increased odds of diabetes).

 

How did the researchers interpret the results?

The researchers conclude that “shift work is associated with an increased risk of diabetes. The increase was significantly higher among men and the rotating shift group, which warrants further studies”.

 

Conclusion

This systematic review finds an association between shift work and diabetes, overall the pooled results found that shift work was associated with a 9% risk of diabetes. The review has strengths in that it has reviewed the global literature and identified a reasonable sample of 12 observational studies including more than 225,000 people.

However, there are various important limitations that need to be taken into account before concluding that shift work directly increases the risk of diabetes.

Type 1 or type 2?

The main point under investigation was whether shift work could be a modifiable risk factor for the development of type 2 diabetes – the condition where people either produce less insulin, or their body is less sensitive to the effect of insulin – rather than the autoimmune condition of type 1 diabetes, which is not caused by lifestyle. However, all of the review’s results and reports of the individual studies just discuss “diabetes”. It is likely that most of these studies would have been looking at how shift work was associated with type 2 diabetes, but this is not clear.

Lack of clarity on diagnosis

It is not clear from the review whether these studies had definitely included a population of people who were all free from type 2 diabetes at the start, assessed their shift working pattern, and then looked at whether they developed type 2 diabetes during follow-up.

All we know is that the studies have looked at the association between shift work and diabetes. We don’t know whether all studies excluded diabetes at the start, and then used valid criteria to diagnose diabetes during follow-up.

If people already had diabetes (diagnosed or undiagnosed) at the time their shift working pattern was being assessed, then this doesn’t tell us anything about cause and effect. Given that four of the studies were cross sectional anyway, meaning that they are just snapshots in time, the fact that people have diabetes and are currently shift working doesn’t necessarily mean that shift working has caused the diabetes. 

Confounders

Because all the studies were observational (some cross-sectional), we cannot exclude the possibility that any association between diabetes and shift work is being influenced by confounding.

The review conducted sub-analyses only of studies that controlled for BMI in their models, and those that controlled for physical activity (though none seem to have controlled for both).

But aside from family history, no other mention of confounding factors is given, and it is unclear how well studies may have controlled for other factors.

Various sociodemographic, health and lifestyle factors may be associated with both doing shift work, and with risk of diabetes. This could therefore mean that it is not shift work that directly causes diabetes, but the various factors that are associated with shift work that cause diabetes.

Limited study population

No included studies came from the UK, with half coming from Japan. Though it may well be the case that the results from all of these studies can be applied to the UK, different cultures may have different work ethic, environmental and health differences meaning that they cannot so easily be generalised to all populations.

Also, the majority of studies, eight of the 12, included male only populations, therefore the results may have more applicability to men doing shift work than women.

No information given on occupations

Finally, we do not know whether any association between shift work and diabetes may be influenced by the type of work that people are actually doing (routine or professional). 

The identified relationship is undoubtedly worthy of further study to see whether shift work could have direct biological effects on the body that lead to the development of diabetes. As we are increasingly a 24/7 economy, many people are expected to work unsociable shifts, and the health effects of shift work may become more noticeable.

If there is a link between shift work and diabetes (or other chronic diseases), it is equally possible at this stage that it could still be due to confounding from various sociodemographic, health and lifestyle factors that are associated with both shift work and risk of diabetes.

Overall, it cannot be firmly concluded at this stage whether and how shift work may be associated with diabetes.

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

Links To The Headlines

Shift workers 'face type 2 diabetes risk'. BBC News, July 25 2014

Shift workers at higher risk of diabetes, study finds. The Guardian, July 25 2014

Shift workers more likely to develop diabetes, claims new research. The Independent, July 25 2014

Shift workers at higher risks of Type 2 diabetes: Chance of developing condition are biggest for men on rotating patterns. Daily Mail, July 25 2014

Shift workers run 'higher diabetes risk'. ITV News, July 25 2014

Links To Science

Gan Y, Yang C, Tong X, et al. Shift work and diabetes mellitus: a meta-analysis of observational studies. Occupational and Environmental Medicine. Published online July 16 2014

Categories: NHS Choices

TV and gaming after work 'leads to feelings of guilt'

NHS Choices - Behind the Headlines - Fri, 25/07/2014 - 12:30

“Watching TV after work makes you feel ‘guilty and like a failure’,” says The Independent, citing a study looking at the concept of “ego depletion”.

Ego depletion is the idea that after a gruelling task your levels of self-control become drained. So after a hard day’s work, instead of going to the gym as you promised yourself, you spend the evening playing “Plants Vs Zombies” or watching repeats of “Mrs Brown’s Boys”.

Researchers felt that these procrastinations would cause feelings of guilt and shame. To test this hypothesis, they recruited 471 participants to take part in an online survey, either via a popular German gaming website, or directly through universities.

The survey involved asking people to say how strongly they agreed with 64 different heavily biased statements such as: “When I [watched TV/played video games] yesterday after work/school, I felt remorse.”

Unsurprisingly, the study reported that people used TV or video games to avoid doing other activities felt guilty about it. However, it is highly likely that this was due to the nature of these leading questions.

The study was also self-selecting, so results are not applicable to other populations who may use TV or games to relax.

A moderate amount of TV and gaming is unlikely to cause any serious problems as long as you balance it out with other real-world activities. Read more about how staying active can improve mental wellbeing.

 

Where did the story come from?

The study was carried out by researchers from Johannes Gutenberg University of Mainz in Germany and VU University Amsterdam. Sources of funding were not reported.

The study was published in the peer-reviewed Journal of Communication. It was published on an open-access basis so is free to read online.

The UK media have not discussed any of the limitations of this study but have simply focused on repeating the results without any critical analysis. They have also falsely implied that this study was able to confirm that watching TV or using video games causes feelings of guilt, when this type of study is not able to prove cause and effect.

It could have actually been the suggestive nature of the questions in the survey that made people report feeling guilty about their use of the media. The fact that the survey was self-selecting was also not discussed. University students and German-speaking fans of a video game website unlikely to be representative of the wider population.

 

What kind of research was this?

This was a cross-sectional study looking at TV and video game use, feelings of guilt, enjoyment and relaxation after working or studying during the day. This was performed using an online survey.

As this was a cross-sectional study, it takes place at one moment in time and thus cannot prove cause and effect, it can only show associations.

The researchers wanted to investigate the theory that people do not benefit from watching TV if they are “ego depleted”. This describes the emotional state a person is in after they have exhausted their willpower.

The researchers say this can occur after work from excessive self-regulation “found in making decisions, adjusting to social norms, avoiding mistakes”, and other tasks. 

Previous research has found that the likelihood of giving in to fleeting desires increased with the number of acts of self-control that had been done during the day. One example given was from a study that found that people were more likely to choose chocolate than a fruit salad as a snack if they had previously been given a series of puzzles to do.

The researchers proposed that use of media is one such desire used as a pleasurable task to put off doing more meaningful activities that demand more input and effort.

However, this could be interpreted by individuals as a sign of failed self-control and induce feelings of guilt and shame; lessening the experience of media use being a pleasurable experience.

The researchers aimed to assess the potential association between feeling “ego depleted” and negatively viewing their use of the media, and then the effects of this media use and perception of it on ego recovery (from the stress and strain of the day) and ability to enjoy the experience. They chose two different types of media – interactive (video games) and non-interactive (TV) to test their theories.

For TV, they also looked at whether the choice of programme made any difference.

 

What did the research involve?

The researchers recruited 293 people from an online gaming site and 342 students of psychology and communication (279 from a university in Germany and 63 from a university in Switzerland).

People were then excluded from the analyses who had not worked or studied the day before the survey and who had not played video games or watched TV.

The researchers say that in order to keep the questionnaire short, people who had used both types of media were assigned to only ask questions about their use of video games or TV use:

  • people who had been recruited from the gaming site and had used both media types were automatically assigned to questions about video game use
  • students who used both were assigned to answering questions about their TV use

The participants were asked to fill out the following online questionnaires:

  • State Self-Control Capacity Scale – 16 items to assess “ego depletion”, with responses from 1 (does not apply) to 7 (fully applies) for statements like “yesterday after work/school, I felt like my willpower was gone”
  • Procrastination Scale – 5 items to assess the level of stalling or putting off other activities
  • State Shame and Guilt Scale – 5 items, responding to statements such as “When I [watched TV/played video games] yesterday after work/school, I felt remorse”
  • Recovery Experience Questionnaire – 16 items on recovery such as becoming relaxed
  • Activation Deactivation Adjective Checklist – 10 items to assess levels of vitality, such as feeling energetic or sleepy after media use
  • Enjoyment – 3 items
  • Preference for challenging versus easy to watch TV – assessed using 9 items

They analysed the results to see if there was any evidence for their theory of an association between ego depletion, guilt about TV or video game use and lack of ego recovery in the form of relaxation.

 

What were the basic results?

Of the 653 respondents, 471 were eligible for the study and 61.8% of which were male. On average they had worked or studied for 6.5 hours the previous day, but this varied from half an hour to 16 hours.

Video game use was reported on by 262 people, who used it for an average of 2.6 hours (standard deviation (SD) 1.73). TV use was reported on by 209 people, and this was watched for on average 1.99 hours (SD 1.09).

The main results were:

  • video game and TV use were associated with putting off other activities
  • putting off other activities by using video games or TV was associated with feelings of guilt
  • guilt was associated with a negative effect on the ability of the media to induce ego recovery
  • guilt was associated with a negative effect on vitality
  • guilt was associated with a negative effect on the ability to enjoy the media
  • there was no difference in the results comparing use of video games or TV
  • people who were ego depleted were less likely to watch challenging TV content compared to easy TV content

 

How did the researchers interpret the results?

They conclude that their “results suggest that ego depletion is associated with similar patterns of negative appraisal and reduced positive outcomes in terms of wellbeing and enjoyment both in the context of interactive as well as non-interactive media use”.

 

Conclusion

This cross-sectional study reported an association between use of video games or TV after working and feelings of guilt about doing so, which hampered the ability to enjoy it or recover vitality.

However, there were numerous limitations in the study design, which casts doubt on the validity of the associations reported.

The results may not be applicable to the general population, as this was a selective group of participants who were:

  • active users of gaming websites
  • students of human psychology
  • able and happy to spend time filling out six questionnaires totalling 64 questions (which one could argue is another perfect way to avoid doing other activities)

There was a wide variation in the number of hours the participants had worked during the previous day, from half an hour to 16 hours.

It does not appear that potential confounding factors such as this were taken into account during the analyses.

The average age of the participants was not provided, nor were any other socioeconomic or demographic data.

There was no control group, as anyone who had not used either form of media was excluded from the study. People were only able to respond to either their use of TV or video games. We therefore can’t say whether use of one preceded another, how much time was actually spent on both or what the level of enjoyment or guilt was during that time.

The questionnaires were heavily loaded, suggesting that people should feel guilty for their TV and video game use and this would create a source of bias. Good surveys should address this issue with other questions to balance out their suggestive nature but it is not clear if this occurred.

There is also the possibility that the participants may have not answered truthfully, or skewed their answers in a way that was helpful, or even unhelpful, to the study organisers.

The questionnaires were self-reported and filled out online about the preceding day. This leaves room for inaccuracies in recall.

Overall, the results of this study are not reliable due to the extent of the limitations

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

Links To The Headlines

Watching TV after work makes you feel 'guilty and like a failure'. The Independent, July 25 2014

Tired? Then don't slump in front of TV: People who are stressed and exhausted end up being consumed with guilt after putting their feet up, study reveals. Daily Mail, July 25 2014

Why TV at the end of the day leaves workers feeling depressed. The Daily Telegraph, July 25 2014

Watching telly makes us feel like failures. Daily Express, July 25 2014

Links To Science

Reinecke L, Hartmann T, Eden A. The Guilty Couch Potato: The Role of Ego Depletion in Reducing Recovery Through Media Use. Journal of Communication. Published online June 24 2014

Categories: NHS Choices

Deadly MERS 'camel flu' may now be airborne

NHS Choices - Behind the Headlines - Thu, 24/07/2014 - 12:45

“Deadly Mers virus 'could now be airborne',” The Independent reports. The Middle East Respiratory Syndrome (MERS) virus, which has an estimated case fatality rate of 30%, has been detected in an air sample in a camel barn in Saudi Arabia. This raises the possibility the virus could be spread through the air in the same way as flu.

MERS emerged in 2012 and can be extremely serious, leading to severe breathing difficulties, kidney failure and death (though it appears some people may become unaffected carriers of the virus).

The World Health Organization (WHO) states that 837 laboratory-confirmed cases of infection have been reported since 2012, including at least 291 related deaths.

In 2013, evidence emerged that camels could be the main source of the virus (hence the nickname). 

The research behind the story highlights the case of a man and his camels living in Saudi Arabia. The man and some of his camels were infected with MERS, and the man sadly died as a result. 

On investigation, genetic fragments from the MERS virus were detected in an air sample from the barn housing the infected camels.

There is no concrete evidence that the man was infected through the air, and it should also be noted that he had direct contact with the camels. However, the possibility of airborne transmission has raised concerns. 

It is important to keep researching this new virus and tracking its spread, to gain a better understanding of how it is transmitted to people.

 

Where did the story come from?

The study was carried out by researchers from King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia, and was funded by the same institution.

The study was published in the American Society for Microbiology, a peer-reviewed science journal.

This whole journal is open-access, meaning that anyone can read the publications for free online, including this latest research.

The study highlights new research into the origins and possible transmission of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) – a new human virus that causes severe respiratory symptoms and kidney failure.

Since it was recognised, the WHO reports there have been 837 laboratory confirmed cases in humans, and at least 291 deaths.

The authors report that these have been in at least 17 countries in Asia, Africa, Europe and North America – most originated from countries in the Arabian Peninsula, including Saudi Arabia.

They say the virus has the ability to infect close contacts such as family members and healthcare workers, and that it causes the death of many of those affected. This means the virus is a potential global public health threat. A case death rate of just under 30% is unusually high for a respiratory virus, a statistic that has sparked concern.

The authors say the origin and transmission of MERS is not fully understood, but it seems humans could contract it through direct contact with infected camels. However, intermediate steps in this process have been suggested, as well as airborne transmission.

This latest research aimed to investigate whether MERS-CoV might be transmitted from camels to humans via the air.

 

What kind of research was this?

This was a laboratory analysis of air samples collected from a camel barn in Saudi Arabia.

The researchers knew of a man and some of his nine camels that had contracted exactly the same MERS virus (100% identical when tested in the lab), suggesting that the camels had infected the man. 

However, it was not clear whether the man contracted the virus from touching the camels or from breathing in air containing the virus originating from the camels.

 

What did the research involve?

The researchers tested the air from the barn where the infected camels were housed for traces of the MERS virus to see if, at least in theory, it was possible for the virus to be transmitted through the air.

The man became unwell on October 26 2013 and reported that four of his camels had suffered respiratory illness since October 19. He was admitted to an intensive care unit (ICU) on November 3 2013. Three air samples were collected from the camel barn on three consecutive days from November 7. All three samples were screened for the presence of the MERS virus genetic material, and the camels were tested for the MERS-CoV infection.

The man died on November 18 2013; his camels appear to have survived.

 

What were the basic results?

Only the first air sample tested positive for airborne MERS genetic material. The other two samples, collected in the next two days, were negative. The authors note that the first sample was collected on the same day as one of the nine camels also tested positive for the MERS infection, although four of the nine camels had been showing signs of respiratory illness for many weeks.

They confirmed that the genetic fragments from the air were 100% identical to fragments found in the infected man and the infected camel. This, they said, suggested that the genetic material in the air had originated from the infected camel.

The virus material from the air samples was not able to infect cells in the laboratory, indicating there may have been loss of viral infectivity from the air sample.

 

How did the researchers interpret the results?

The authors say the data suggests that, “camels may be a source of infectious MERS-CoV, which can be transmitted to humans within confined spaces” and that, “these results also suggest that air sampling might be a useful approach to investigate the role of the airborne transmission of MERS-CoV spread and shedding.”

They added that, “further studies are urgently needed to fully understand the role of camels in the transmission of MERS-CoV and whether airborne transmission plays a role in MERS-CoV spread, in order to implement control and prevention measures to prevent the transmission of this deadly virus.”

 

Conclusion

This genetic research found genetic fragments from the MERS virus in an air sample of a barn housing MERS-infected camels. This raises the possibility that the owner contracted the MERS virus from airborne transmission, rather than through direct contact, as had previously been assumed.

However, it is important to realise that, based on this research alone, there is no concrete evidence to suggest the transmission was airborne, only that it is a possibility to investigate further.

It was also unusual that the virus was only detected in one of the three air samples, taken 12 days after the onset of illness and four days after the man had been admitted to an ICU. There could be many explanations for this – such as ventilation in the barn. 

Either way, it highlights that more investigation is needed to establish whether the MERS virus, or at least some strains of it, is regularly airborne and how long it may stay airborne.

Research needs to establish how MERS infection is spread between camels and humans, and whether this can happen through the air. If it can, this makes the virus more likely to spread quicker and more widely, like other airborne diseases, such as flu. Research also needs to establish whether the MERS virus can remain infectious when on surfaces, which may be touched by people, providing further indirect infection routes.

This study is important because the MERS virus is new, so is not yet fully understood. It will be important to keep researching this virus and tracking its spread to better understand how it is transmitted to humans. This will, ultimately, help inform better prevention or control measures, thereby protecting people from this potentially fatal infection.

In the meantime, the WHO recommends strict control measures such as gloves, mask and eye protection for healthcare workers when caring for affected individuals. There are as yet no travel or trade restrictions, and no screening recommendations for entry into other countries.

Read the latest WHO Disease outbreak news here.

Analysis by Bazian. Edited by NHS ChoicesFollow Behind the Headlines on TwitterJoin the Healthy Evidence forum.

Links To The Headlines

Deadly Mers virus 'could now be airborne', warn scientists in study on Saudi Arabian barn. The Independent, July 22 2014

Deadly MERS virus 'may be airborne', sparking fears it may spread quicker. Mail Online, July 23 2014

Links To Science

Azhar EI, Hashem AM, El-Kafraw SA, et al. Detection of the Middle East Respiratory Syndrome Coronavirus Genome in an Air Sample Originating from a Camel Barn Owned by an Infected Patient. mBio. Published online July 22 2014

Categories: NHS Choices

Paracetamol 'doesn't work' for lower back pain

NHS Choices - Behind the Headlines - Thu, 24/07/2014 - 12:30

“Paracetamol used to treat acute lower back pain is no better than a dummy pill,” BBC News reports. A well-conducted trial casts doubts on the widespread recommendation that paracetamol is an effective treatment for lower back pain.

It reports on a randomised double-blind controlled trial of people with acute low back pain. All participants were told to remain active and avoid bed rest. They were split into three groups and asked to take regular medication and “as required” medication, if needed. This was either paracetamol or a placebo.

The average number of days to recovery for each group was between 16 and 17 days. Sustained recovery by 12 weeks was achieved by between 83% and 85% in all groups.

The severity of acute low back pain in this group was not sufficient to cause anyone to have time off work. This means the results of this study may not be applicable to people with more severe acute low back pain.

This was a well conducted study that would appear to suggest that the advice regarding paracetamol as a first-line treatment may need re-examining. However, as the authors themselves argue, it is too soon to start rewriting clinical guidelines for lower back pain based on this evidence alone.

 

Where did the story come from?

The study was carried out by researchers from the University of Sydney, University of New South Wales and University of Newcastle, all in Australia. It was funded by the National Health and Medical Research Council of Australia and GlaxoSmithKline Australia. 

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

It was widely covered in the UK media, and most of the coverage was fair and of a good quality, with several sources reporting comments from independent experts.

 

What kind of research was this?

This was a double-blind randomised controlled trial (RCT) looking at the effectiveness of paracetamol in improving recovery time from acute low back pain, compared to placebo.

An RCT is the best type of study design to find out whether healthcare treatments are effective.

The authors say that low back pain is a leading cause of disability worldwide and that guidelines on the topic universally recommend paracetamol as a first-line treatment.

This is despite the surprising fact that there is no high-quality evidence to support this recommendation.

The only other RCT the authors could find on the use of paracetamol compared with no active treatment in treating low back pain involved just 46 people.

 

What did the research involve?

The researchers recruited people with acute low back pain from 235 primary care centres across Australia. Patients had to be suffering a new episode of acute lower back pain (defined as shorter than six weeks duration and preceded by one month of no pain), with or without leg pain. The pain had to be of at least moderate intensity as measured by a validated scale.

People suspected of having serious spinal diseases such as cancer or fracture, or who were already regularly using painkillers, or who had had spinal surgery in the previous six months were excluded from the trial.

The trial had a “double dummy” design, which is a method of keeping participants and researchers “blind” to the treatment allocated, when two treatments cannot be made identical; in this case, there is a clear difference between taking paracetamol regularly and taking it as needed.

Participants were asked to take two tablets three times per day from a sealed “regular” box of pre-prepared medication, and had access to a sealed “as required” box for additional pain relief.

From this box, they could take one or two tablets up to four times per day. They were randomised by computer to one of three treatment groups:

  • a “regular” box of paracetamol – (the equivalent of 3,990 mg daily) and a placebo “as required” box
  • a “regular” placebo box and “as required” paracetamol box  (maximum of 4,000 mg daily)
  • placebo pills in both boxes

Neither patients, researchers, doctors nor other staff knew to which group patients were allocated.

All patients received advice about keeping active, avoiding bed rest and reassurance about their back pain and were followed up at one, two, four and 12 weeks. They were asked to continue the medicine until they recovered, or for four weeks, whichever occurred first. “Rescue” medication – two day's supply of a painkiller called naproxen – was available for those with continuing severe pain assessed after one week.

Participants recorded pain scores into a daily pain and drug diary until they recovered or for four weeks, whichever was sooner. This was transcribed into a case report either by telephone interview or directly into an online database.

Researchers looked at the time until the participants recovered from pain, measured in days. Recovery was defined as the first day of 0 or 1 pain intensity as measured on a 0-10 pain scale, for seven consecutive days.

Using various validated scales, they also looked at

  • pain intensity
  • disability (assessed using a validated scale from 0 to 24)
  • function
  • global rating of symptom change
  • sleep quality 
  • quality of life
  • feelings of depression

They also monitored participants’ adherence to treatment, satisfaction with treatment, use of other drugs and absence from work.

They analysed the results using standard statistical methods.

 

What were the basic results?

There were 1,652 people in the trial and the mean level of pain intensity at the start of the trial was 6.3 out of 10.

The researchers found that there was no significant difference in the number of days to recovery between the three groups.

The average time to recovery from back pain was

  • 17 days (95% Confidence interval [CI] 14 to 19) in people taking paracetamol regularly
  • 17 days (95% CI 15 to 20) in those taking paracetamol as needed
  • 16 days (95% CI 14 to 20) in the placebo group

By 12 weeks, sustained recovery had occurred in 85% of participants in the regular group, 83% in the as required group and 84% in the placebo group.

Adherence to the regular tablets was initially high in all three groups, with median tablets consumed 5.4 out of the maximum of 6. This reduced in all three groups over the first four weeks to 1.6 in the regular group, 0.6 in the as required group and 1.2 in the placebo group. As required medication was only taken by any participant during the first week, with a mean average of 1.9 tablets per day in each group.

Rescue use of the non-steroidal medication, naproxen was only taken by up to 1% of participants during the first two weeks.

The number of participants reporting adverse events was similar between the groups (18.5% in the regular group, 18.7% in the as-needed group and 18.5% in the placebo group)

None of the participants were absent from work during the study period.

Between 72% and 76% of participants were satisfied with the treatment received, and around 30% of participants used other health services, such as physiotherapy.

Paracetamol had no statistically significant effect on short-term pain levels, disability, function, sleep quality or quality of life.

 

How did the researchers interpret the results?

The researchers say their findings suggest that paracetamol taken regularly or as needed does not affect recovery time compared with placebo in patients with acute low back pain.

“Simple analgesics such as paracetamol might not be of primary importance in the management of acute lower back pain”, said lead author Dr Christopher Williams from the University of Sydney in Australia, in an accompanying press release. “The results suggest we need to reconsider the universal recommendation to provide paracetamol as a first-line treatment for low-back pain, although understanding why paracetamol works for other pain states but not low-back pain would help direct future treatments.”

The researchers also say that recovery time in the trial was faster on average than in similar trials and say this could be because the advice and reassurance provided is more effective than drugs for acute low back pain.

 

Conclusion

This was a well-designed double-blind RCT to assess the effectiveness of paracetamol for acute low back pain.

Attempts were made to account for any confounding factors and there was good follow-up, with analysis provided for 97% of participants.

However, as the authors point out, this study had some limitations – for example, those taking part did not typically take the full recommended dose of paracetamol; and also, some used other treatments during the study period. It is also interesting to note that the severity of acute low back pain people were experiencing was not sufficient to cause anyone to have time off work. And very few required additional “as required” medication and only up to 1% took any of the non-steroidal anti-inflammatory medication, naproxen.

This suggests the results of this study might not be applicable to people with more severe acute low back pain, who may not respond to a placebo treatment in the same way.

Overall, however, this was a well-designed trial and the results are likely to be reliable. Why paracetamol may help with other types of moderate or severe pain – such as tooth extraction – but possibly not with low back pain, is uncertain.

As the authors say, further research is required on the effectiveness of paracetamol for low back pain before any changes are considered to existing guidelines.

Back pain is common and can be distressing, but in most cases it is not serious and usually gets better within 12 weeks. Encouragingly, sustained recovery was achieved by between 83% and 85% of the study participants which supports current advice to keep active and carry on with daily activities if you have acute back pain. Other treatments include hot and cold compression packs, manual therapy and exercise.

Paracetamol is safe when taken at the correct dose, but you should always check whether other medicines you are taking contain paracetamol. This way you can make sure that you do not accidentally exceed the maximum daily dose.

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

Links To The Headlines

Paracetamol for low back pain 'no better than placebo'. BBC News, July 24 2014

Paracetamol does not help lower back pain, study finds. The Guardian, July 24 2014

Paracetamol 'fails to ease low back pain’. The Daily Telegraph, July 24 2014

Paracetamol 'has no effect on back pain': Research casts doubt on most popular GP remedy. Daily Mail, July 24 2014

Paracetamol 'no better than a placebo' for lower back pain scientists claim. Daily Mirror, July 24 2014

Paracetamol cannot help back pain, say scientists. The Times, July 24 2014

Paracetamol is useless for easing back pain, say experts. Daily Express, July 24 2014

Links To Science

Williams CM, Maher CG, Latimer J, et al. Efficacy of paracetamol for acute low-back pain: a double-blind, randomised controlled trial. The Lancet. Published online July 24 2014

Categories: NHS Choices

Sleep deprivation may affect memory

NHS Choices - Behind the Headlines - Wed, 23/07/2014 - 16:19

The Mail Online states that “just one bad night’s sleep can have a dramatic effect on your memory – even leading to false memories”.

Though the results of this small experimental study involving US students are interesting, they're far from dramatic.

Researchers were interested in investigating whether sleep deprivation has an effect on a person’s susceptibility to false memories, which are surprisingly common.

In one famous study, many people claimed to have seen Bugs Bunny when visiting Disneyland as a child. This is plainly untrue, as Bugs Bunny is a Warner Brothers character.

In the first part of the experiment, people who self-reported having less than five hours sleep the night before the test were more likely to report seeing non-existent footage of the 9/11 plane crash in Pennsylvania.

People were then shown photos of two staged thefts, then given false written descriptions of it and questioned about what they had seen in the photos. In this test, there was no difference between people self-reporting sleep deprivation or not on recall.

In the second experiment, they took a separate group of students and then either let them sleep for a night or kept them awake, then saw how they performed on the same “misinformation” task. In this test, there was a mixed pattern of results, which does not give a clear picture of how, or if, sleep deprivation may be associated with false memories.

 

Where did the story come from?

The study was carried out by researchers from the University of California and Michigan State University, in the US. No sources of financial support are reported, and the authors declare no conflicts of interest.

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

The Mail Online and The Daily Telegraph’s reporting on the study overstates its findings. The Mail makes claims of a “dramatic effect on your memory”, while the Telegraph argues that the false memories related to sleep deprivation could cause relationship problems.

Neither news site noted the limitations of this experimental scenario and the fact that only a few of the results were statistically significant. This makes the relationship far from convincing.

 

What kind of research was this?

This was an experimental study designed to investigate whether sleep deprivation has an effect on a person’s susceptibility to false memories.

The researchers say that memories are not “recorded” in the brain, but are reconstructed from multiple sources, meaning they can be changed following exposure to altered information after the event or other suggestive influences.

People can sometimes have completely false memories, recalling clear and vivid experiences that never happened – imagined events are sometimes confused with actual memories.

The researchers say that many studies have explored what factors could be behind false memories, but sleep deprivation has not yet been explored. This is what they aimed to investigate.

The study was conducted in two parts. The first experiment tested whether self-reported sleep deprivation the night before was associated with false memories of a news event and false memories in a task giving misleading information (a “misinformation task”).

In the second experiment, people were deprived of sleep to see what effect this had on their performance in the misinformation task.

 

What did the research involve? Experiment 1

A total of 193 university students were recruited (average age 20, 76% women). They were asked to keep a sleep diary every morning for a week, detailing the time they went to bed, how long it took them to fall asleep, when they woke, when they got out of bed and how many times they woke up during the night.

They then took part in the first experiment, where they completed a questionnaire on the plane crash in Shanksville, Pennsylvania, during the September 11 2001 tragedy.

This crash was never captured on video, but the participants were asked to answer “yes” or “no” to the question of whether they had seen “video footage of the plane crashing, taken by one of the witnesses on the ground”. Following this questionnaire, they were then interviewed about it, where the interviewers again repeatedly suggested that footage of this crash was widely available.

In the misinformation task, they were shown two sets of 50 photographs – one set showing a man breaking into a parked car, and the other showing a woman encountering a thief who steals her wallet. Around 40 minutes later they then read two textural descriptions of each photo set. Each description contained three false statements of the event shown, embedded within the correct information. A further 20 minutes later they were then asked multiple choice questions relating to what they had seen in the photos.  

Experiment 2

In the second experiment, they experimentally manipulated the amount of sleep in a separate group of 104 university students (average 19 years, 54% women) who took part in the misinformation test. All were reported to regularly sleep at least six hours a night. 

The study used a two-by-two design so that the influence of two different things could be examined – sleep deprivation or normal sleep – and the timing that certain parts of the test were completed, morning or evening.

In the evening, all participants completed validated mood and sleep questionnaires. 

Participants were then split into two.

One group was assigned to sleep deprivation or normal sleep and then completed all parts of the misinformation task at 9am.

This means that those participants assigned to the sleep deprivation arm of this experiment would perform all parts of the task while sleep deprived.

The other group was assigned to sleep deprivation or normal sleep and then shown the two series of photographs in the evening before sleep (or not). This means that the photos were seen by all participants when they were not sleep deprived. Then at 9am they completed the remaining two parts of the misinformation task – being shown the misleading text descriptions about the photos and then completing the multiple choice questions.

Those who were assigned to sleep were allowed to sleep for eight hours, from midnight to 8am. Those assigned to stay awake were not allowed to sleep and were kept awake by watching films, playing games, using computers, eating snacks and again completing the sleep and mood questionnaires every two hours.

 

What were the basic results? Experiment 1

Participants reported an average of 6.8 hours of sleep, and 28 participants (15%) reported five hours or less of sleep the night before the study. They coded these 28 participants as having restricted sleep, and compared their results with the remaining 165 participants (85%).

When completing questionnaires about the plane crash, the restricted sleep group was more likely to answer "yes" when asked if they had seen footage of the plane crash.

However, in the follow-up interviews, they were no more likely than the normal sleep group to falsely say they had seen the crash.

On the misinformation task, there was no significant difference between the restricted sleep and normal sleep groups.

Experiment 2

The researchers found no main effect of the timing of the misinformation task alone, when comparing all people who completed all three parts of the task (photos, text descriptions and questions) in the morning, with those who had been shown the photos the night before instead. The researchers found they had no difference in their recall.

Similarly, there was no main effect of sleep deprivation alone. There was a trend for memory scores to be lower in the sleep deprived group compared to the sleep group, but the differences fell short of statistical significance.

There was some interaction between sleep and time of test, however. When people did all parts of the test in the morning, those who were sleep deprived were more likely to have falsely reported on the multiple choices questions something that didn’t happen in the photos.

However, when people were shown the photos the night before sleep/no sleep, there was no difference in false memories between the sleep deprived and sleep groups.

As expected, when given the mood and sleep questions in the morning, people who were sleep deprived were more sleepy and had poorer mood than those who had slept.

 

How did the researchers interpret the results?

On the first experiment, the researchers say the findings “tentatively suggest” that restricted sleep is related to memory suggestibility. On the second, they say that the sleep-deprived group was more likely to have false memories compared to the rested group, but only when participants were sleep deprived for all three stages of the misinformation task (i.e. all parts completed in the morning).

 

Conclusion

This experimental study is thought to be one of the first that has investigated how sleep deprivation may be associated with false memories.

In the first part of the experiment, self-reported restricted sleep the night before the test was associated with false questionnaire reports of seeing footage of the 9/11 plane crash in Pennsylvania (which doesn’t exist). However, people with restricted sleep weren’t more likely to give false reports when subsequently directly interviewed about it.

In these people, self-reported restricted sleep was not associated with poorer performance on the misinformation task.

In the second experiment, where they took a separate group of people and manipulated their sleep, there was some evidence that people who were not allowed to sleep were more likely to have false recall of the photos, but only if all parts of the test were performed in the morning (i.e. when people were sleep deprived). If they were shown the photos the night before instead (when not sleep deprived), on completing the task in the morning, there was no difference between sleep deprived and sleep groups.

Therefore, overall, the mixed pattern of significant and non-significant results does not give a very clear picture. There are also further important limitations, including:

  • The small, specific groups tested – there were only two separate groups of 193 and 104 young, US university students. Other groups could give very different results.
  • In the first test, the definition of sleep deprivation was self-reporting five hours or less of sleep the night before the test. This is likely to include many inaccuracies, including that people may not be able to give a very reliable indication of their sleep quality and quantity in the sleep diary questions used. Previous research has found that people often under-estimate the amount of sleep they get.
  • There were also only 28 people in this “sleep deprived” group, making them a small group to compare against.
  • Similarly, preventing a group of people from sleeping at all during one night does not give a very reliable proxy for sleep deprivation in the real life situation, e.g. a pattern of poor sleep quality and quantity persisting over a much longer time period.
  • The tests used – asking people whether they have seen footage of the 9/11 plane crash in Pennsylvania, and giving them a test where they are shown photos of two incidents, then given incorrect descriptions of them – is also only a very restricted experimental test. They cannot reliably test how sleep deprivation may be associated with the recall of the wealth of our daily and lifetime experiences.
  • Also, if there is an association between sleep deprivation and false memories, the study is not able to take into account the various confounding factors (e.g. psychological, health-related and lifestyle) that may be associated with this.

Overall, any association between false memories and sleep is likely to be complex and influenced by many factors. This single experimental study does not provide very clear evidence of a definite link.

Analysis by Bazian. Edited by NHS ChoicesFollow Behind the Headlines on TwitterJoin the Healthy Evidence forum.

Links To The Headlines

Lack of sleep implants 'false' memories in brain. The Daily Telegraph, July 22 2014

Feeling forgetful? Just ONE bad night's sleep can have a dramatic effect on your memory - and even lead to false memories, researchers warn. Mail Online, July 22 2014

Links To Science

Frenda SK, Patihis L, Loftus E, et al. Sleep Deprivation and False Memories. Psychological Medicine. Published online July 16 2014

Categories: NHS Choices

Umami flavouring 'may help you feel fuller faster'

NHS Choices - Behind the Headlines - Wed, 23/07/2014 - 12:30

"Always hungry? You need more umami in your life: study finds so-called 'fifth taste' in sauces and meat helps us feel satisfied," reports the Mail Online.

Umami is a Japanese term that roughly translates as "pleasant savoury taste" and has been described as the fifth taste, the other four being sweet, sour, bitter and salty.

The sensation of eating umami-rich food, such as soy sauce and shellfish, is caused by glutamate. Glutamate is an amino acid, a building block of proteins. The salt form, monosodium glutamate (MSG), is a flavour enhancer.

In this study, researchers proposed that another chemical, inosine-5'-monophosphate (IMP), which is also derived from an amino acid, may act synergistically with MSG to improve flavour and increase feelings of fullness.

To test the effect of MSG and IMP, researchers gave 27 participants one of four types of carrot soup 45 minutes before giving them lunch.

Participants were either given a plain carrot soup, carrot soup with added MSG and IMP, carrot soup with added protein and carbohydrate, or carrot soup with added protein, carbohydrate, MSG and IMP.

The researchers then looked at how the soups influenced how much food the participants ate at lunch, as well as how the soups affected the participants' mood and appetite. 

They found adding MSG and IMP caused an immediate increase in appetite, but people then ate less at lunch. It is possible eating a healthy umami-rich breakfast, such as tomatoes and mushrooms, could reduce cravings later in the day.

 

Where did the story come from?

The study was carried out by researchers from the University of Sussex and was funded by Ajinomoto North America, Inc.

Ajinomoto is a Japanese food and chemical corporation that produces a number of products, including the chemicals used in this study: monosodium glutamate (MSG) and inosine-5'-monophoshate (IMP).

In fact, the founder of the company discovered the "umami" taste and invented MSG as a seasoning that captures this taste.

The researchers state Ajinomoto had no role in the study design, data collection or analysis.

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

The research was reported in the Mail Online, who seemed to have got most of their coverage from another website, Medical Daily.

Although the conclusions from the study are basically correct, many of the details of how the study was performed are wrong. 

For example, the Mail says only two types of soup were used by the researchers, when in fact four types were used.

 

What kind of research was this?

This was a crossover trial. In this trial, each participant ate one of four different soups on four non-consecutive days to see if the addition of the following substances influenced how much pasta they ate 45 minutes later:

  • protein and carbohydrate
  • MSG and IMP
  • protein, carbohydrate, MSG and IMP

 

What did the research involve?

The researchers recruited 27 people into the study. Participants were studied on four non-consecutive days and told to fast from 11pm the night prior to one of the study days.

On the study day, they were given breakfast (a fixed portion of milk and cereal with juice) and told to only drink water until they returned three hours later.

When they returned, they were asked to rate how alert, clear-headed, energetic, full, hungry, nauseous and thirsty they felt.

They were then given a sample of spiced carrot soup. The soup was either:

  • spiced carrot soup (low-energy control)
  • spiced carrot soup with added maltodextrin (a carbohydrate) and whey protein (high-energy, high-carbohydrate, high-protein soup)
  • spiced carrot soup with MSG and IMP (low-energy soup plus MSG and IMP)
  • spiced carrot soup with added maltodextrin and whey protein plus MSG and IMP (high-energy, high-carbohydrate, high-protein soup plus MSG and IMP)

Participants were asked to rate how filling, pleasant, salty, savoury, strong and sweet the sample was, and also rated their appetite.

They were then given a 450g bowl of soup and were asked to rate their appetite every time they ate 50g.

Forty-five minutes later, the participants were again asked to rate how alert, clear-headed, energetic, full, hungry, nauseous and thirsty they felt.

They were then provided with lunch, which was a 450g plate of pasta with sauce, and instructed to eat as much as they liked until they felt comfortably full. A refill was provided when only 50g of pasta remained.

Appetite and mood ratings were assessed again after lunch. The researchers looked at how the different soups influenced how much pasta was eaten at lunch and participants' ratings of appetite and mood.

 

What were the basic results?

The researchers found:

  • people ate less pasta at lunch if MSG and IMP were added to the soups
  • people ate less pasta at lunch if they had previously been given the high-energy, high-carbohydrate, high-protein soup

The researchers looked at whether the addition of MSG and IMP to the high-energy, high-carbohydrate, high-protein soup influenced the amount of pasta people ate.

They found people were able to compensate better for the calories they had eaten in the soup by eating less pasta after eating the soup with MSG and IMP.

The researchers also found the addition of MSG and IMP to soup increased ratings of the soup's pleasantness and caused an immediate increase in appetite when the soup was first tasted. However, this increase in hunger was not maintained.

 

How did the researchers interpret the results?

The researchers concluded this study has shown MSG and IMP had two effects on appetite:

  • it acts to stimulate hunger when it is first tasted as a result of increased palatability
  • it then acts to enhance feelings of being full

 

Conclusion

In this study, researchers have found adding MSG and IMP to soup increased the soup's pleasantness and caused an immediate increase in appetite when it was first tasted, but people ate less food 45 minutes later if they had been given a soup containing MSG and IMP.

This study involved a small number of participants, which limits the reliability of any of the results. It may be the case similar results would have been obtained had hundreds of people been studied, but this cannot be assumed. Similarly, the study only tested a specific scenario of eating enhanced soup followed by pasta.

It remains to be determined whether adding these chemicals to food on a long-term basis would result in any health benefits or, most importantly, any harms.

It should also not be assumed from this study that, if the combination of MSG and IMP acts to enhance satiety, these chemicals should necessarily be used in the battle against obesity – for example, by adding them to soups or drinks to stop people snacking or eating more at mealtimes.

The best way of staying healthy is to eat a balanced diet high in fruit and vegetables and low in saturated fats, salt and sugars.

The eatwell plate highlights the different types of food that make up our diet, and shows the proportions we should eat them in to have a well-balanced and healthy diet.

It is also important to take regular exercise in line with recommendations.

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

Links To The Headlines

Always hungry? You need more UMAMI in your life: Study finds so-called 'fifth taste' in sauces and meat helps us feel satisfied. Mail Online, July 22 2014

Links To Science

Masic U, Yeomans MR. Umami flavor enhances appetite but also increases satiety. The American Journal of Clinical Nutrition. Published online June 18 2014

Categories: NHS Choices

Study offers insight into genetics of schizophrenia

NHS Choices - Behind the Headlines - Tue, 22/07/2014 - 12:30

"More than 100 schizophrenia genes have been pinpointed," reports the Daily Mail. In one of the largest studies of its kind, researchers have gained further insights into the genetics of the condition, which it is hoped could lead to new treatments.

Researchers have identified genetic differences at 108 positions in the genome (the complete set of DNA that "defines" an individual organism) that are more likely to be present in people with schizophrenia.

The study compared the genetic make-up of more than 36,000 people with schizophrenia with that of more than 110,000 controls. They found differences in 108 positions in the genome, 83 of which had not previously been reported.

A particularly interesting finding was evidence of genetic differences in genes active in the immune system. Whether or not the immune system plays a role in the development of schizophrenia is a possibility not previously considered by most experts.

This study provides further evidence of a genetic element to the condition, but it does not prove that the genetic differences actually cause schizophrenia.

However, it is hoped these results will lead to new avenues of research that can be explored, and may eventually lead to better treatments for the condition.

 

Where did the story come from?

The study was led by researchers from Cardiff University and involved hundreds of researchers from around the world as part of the Schizophrenia Working Group of the Psychiatric Genomics Consortium.

It was funded by the US National Institute of Mental Health and grants from governmental bodies and charities.

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

The UK media reported the study accurately. The Independent's coverage was particularly informative, providing independent expert opinions on the findings.

It also included a balanced viewpoint from charities highlighting the need for holistic care regardless of whether new drug treatments are developed.

People living with schizophrenia usually require a combination of medication and talking treatments, such as cognitive behavioural therapy (CBT), to better control their symptoms.

 

What kind of research was this?

This was a genome-wide association study that aimed to combine all of the data from published and unpublished studies that had analysed the genetic make-up of people with schizophrenia, comparing this data with the genetics of people who do not have the condition.

This type of study is able to identify small variations in genes present more frequently in people with a particular disease, compared with people without the disease.

But it is only able to show an association and cannot prove that the genetic variations found cause the disease.

This type of study is useful, however, as it can point to new areas that may be involved in the disease process. These can then be investigated further in other types of studies and could eventually lead to new treatments.

 

What did the research involve?

The researchers obtained data from all the available genome-wide association studies of people with schizophrenia from around the world. This included 46 European case-control samples, three east Asian case-control samples, three European family-based studies, and results from Icelandic population studies.

Overall, the genetic make-up of 36,989 people with schizophrenia was compared with that of 113,075 healthy controls. This involved sophisticated analysis looking at 9.5 million genetic variants.

 

What were the basic results?

The researchers found variations in 108 loci (positions in the genome) that met genome-wide significance, 83 of which had not been previously implicated in schizophrenia. Genome-wide significance means there is a statistically significant possibility a variation is associated with a condition.

Of these 108 loci, 75% coded for proteins. Several of the proteins are thought to have a role in schizophrenia. Variations were found in a gene that codes for the dopamine receptor, the main target of medication to treat schizophrenia, and other genes involved in neurotransmission and synaptic plasticity.

The researchers also found variations occurred in genes expressed in the brain, as well as in genes expressed in the immune system.

 

How did the researchers interpret the results?

The researchers concluded that they have identified variations in genes expressed in the brain. More specifically, they found variations in the gene that encodes a protein that has been a target for drug therapies for schizophrenia for years, as well as in other genes involved in neurotransmission.

They have also found variations in genes expressed in the immune system, which they say provides "support for the speculated link between the immune system and schizophrenia".

However, they are also excited about the fact there are variations in a number of other genes and how this creates "the potential to provide entirely new insights into aetiology [the cause of the disease]".

 

Conclusion

This large genome-wide association study has found genetic variations in 108 loci more likely to be found in people with schizophrenia than in healthy controls.

While some of these variations fell in genes that code for proteins that are already targets for drug treatments for schizophrenia, variations at 83 of the loci had not previously been implicated as being involved in schizophrenia. This provides new insights for further research.

The study's strengths include the large number of cases and controls involved.

But this study cannot prove that these genetic variants cause schizophrenia. It remains likely that a combination of environmental factors and genetic susceptibility increases the risk of the condition.

A further consideration is the huge variability in the level of severity and the type of symptoms that can be present within the "umbrella" diagnosis of schizophrenia.

It is hoped the identification of these genes will pave the way towards a greater understanding of this complex condition.

Read more about schizophrenia, the current treatments for the condition and the available support.

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

Links To The Headlines

New DNA hope on schizophrenia: Discovery of 100 genes could help to transform treatment for the condition. Daily Mail, July 22 2014

DNA hope on schizophrenia: Research breakthrough points at over 100 genes. The Independent, July 22 2014

'Eighty new genes linked to schizophrenia'. BBC News, July 22 2014

Schizophrenia gene study: what we've learned is how little we know. The Daily Telegraph, July 22 2014

Links To Science

Schizophrenia Working Group of the Psychiatric Genomics Consortium. Biological insights from 108 schizophrenia-associated genetic loci. Nature. Published online July 22 2014

Categories: NHS Choices

Probiotics 'may improve blood pressure'

NHS Choices - Behind the Headlines - Tue, 22/07/2014 - 12:00

“Eating probiotics may lower blood pressure,” The Daily Telegraph reports.

Probiotics, so-called “friendly bacteria”, have been found to moderately reduce blood pressure in a new study.

The study is what is known as a systematic review, which is essentially a study of studies. Researchers combined the results of nine randomised controlled trials (regarded as the “gold standard” in evidence-based medicine).

The results suggest that probiotics led to a modest but significant reduction in blood pressure.

The reliability of any systematic review depends on the included studies, and the researchers point out that there were some weaknesses in the studies they included. For example, six of the trials were only conducted on 20 to 40 people. With such a small sample size, any effect on blood pressure could have been the result of chance.

As the lead researcher is quoted as saying in the media, more research is required before doctors can confidently recommend probiotics for high blood pressure control and prevention.

Proven methods to improve blood pressure levels include quitting smoking, sticking to the recommended levels of alcohol consumption, eating a healthy diet (in particular, reducing salt consumption) and taking regular exercise.

 

Where did the story come from?

The study was carried out by researchers from Griffith University and Gold Coast Health, Australia. No source of funding was reported.

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

The story was accurately reported in the media, though the Daily Express’s claims that eating “a pot a day [could] … help save your life” is probably overstating the findings of the study.

 

What kind of research was this?

This was a systematic review and meta-analysis that aimed to determine the effect of probiotic consumption on blood pressure. Systematic reviews aim to identify all the evidence related to a specific research question and synthesise the findings from individual studies or reports in an unbiased way. Meta-analysis is a mathematical technique for combining the results of individual studies to arrive at one overall measure of the effect of a treatment.

The researchers also aimed to use their results to provide information on the most effective probiotic and dose, and how long probiotics need to be taken.

A systematic review, when performed well, should give the best possible estimate of the true effect of probiotics on blood pressure.

 

What did the research involve?

The researchers searched databases of published literature and trials to identify randomised controlled trials (RCTs) that had given people probiotics and had assessed the effect on blood pressure.

Once they had identified relevant trials, the researchers assessed them to see if they were well-performed and extracted data.

The results of all the trials were then combined to produce a "bottom line" on the effectiveness of probiotics on blood pressure.

 

What were the basic results?

The researchers included nine RCTs with 543 participants in total. Six of the trials had between 20 and 40 participants.

Some trials involved healthy people, others included patients with hypertension (high blood pressure), hypercholesterolemia (high levels of cholesterol in the blood), metabolic syndrome (a combination of diabetes, high blood pressure and obesity) or who were overweight or obese. The species and dose of probiotics used, and how they were given, also varied across the trials.

Trials used either yoghurt, fermented and sour milk, probiotic cheese, encapsulated supplements or rose-hip drinks.

The trials gave people between a single species and three species of probiotic at the same time, and the daily dose of probiotics varied between 109 colony-forming units and 1012 colony-forming units. A colony-forming unit is an estimate of the amount of micro-organisms, usually bacteria or fungi, in a given sample.

The duration of the trials varied from three weeks to nine weeks.  

After combining the results of the trials the researchers found that:

  • Probiotic consumption significantly reduced systolic blood pressure by 3.56 mm Hg compared to control (systolic blood pressure is the "top" number and is the blood pressure in the arteries when the heart beats).
  • Probiotic consumption significantly reduced diastolic blood pressure by 2.38 mm Hg compared to control (diastolic blood pressure is the "bottom" number and is the blood pressure in the arteries between heart beats).

By combining the results of different sub-groups of studies they found that:

  • Using dairy products as the source of probiotics resulted in significant reductions in systolic and diastolic blood pressure, whereas using other sources of probiotics did not.
  • Using multiple species of probiotics resulted in significant reductions in systolic and diastolic blood pressure, whereas using a single species did not.
  • Using a dose of at least 1011 colony-forming units per day resulted in significant reductions in systolic and diastolic blood pressure, whereas using lower doses did not.
  • Taking probiotics for at least eight weeks resulted in significant reductions in systolic and diastolic blood pressure, whereas taking probiotics for shorter periods did not.
  • People who had blood pressure of 130/85 mm Hg (higher than ideal but still normal) or higher had significant improvements in diastolic blood pressure but people with blood pressure less than 130/85 mm Hg did not.

 

How did the researchers interpret the results?

The researchers concluded that their results suggest consuming probiotics may improve blood pressure by a modest degree, and that this effect may be greater if blood pressure is high to begin with, multiple species of probiotics are consumed, probiotics are taken for eight weeks or longer, and if each dose contains at least 1011 colony-forming units.

They go on to say that “the reduction [in blood pressure] reported in this meta-analysis is modest; however, even a small reduction of [blood pressure] may have important public health benefits and cardiovascular consequences.”

 

Conclusion

This systematic review and meta-analysis has found that probiotic consumption results in moderate reductions in blood pressure.

The results of a systematic review depend on the included studies, and the researchers point out that there were some weaknesses in the studies they included. They say that “more randomised, controlled studies with larger sample groups, longer durations and adequate blinding of conditions trials are needed to confirm the effect of different probiotic species and products on BP [blood pressure] and hypertension.”

Analysis of subgroups of studies led the researchers to conclude that blood pressure improvements may be greater among those with elevated blood pressure, when the daily dose of probiotics is at least 1011 colony-forming units, when more than one species of probiotic is taken and when probiotics are taken for at least eight weeks.

However, they also point out that these conclusions are based on the results of only a few studies, and the majority of them were very small – six of the trials were only conducted on between 20 and 40 people.

As the lead researcher is quoted as saying in the media, more research is required before doctors can confidently recommend probiotics for high blood pressure control and prevention.

Proven methods to improve blood pressure levels include quitting smoking, sticking to the recommended levels of alcohol consumption, eating a healthy diet (in particular, eating a low salt diet) and taking regular exercise.

Read more about how to improve your blood pressure.

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

Links To The Headlines

Eating probiotics may lower blood pressure. The Daily Telegraph, July 22 2014

Eating probiotic yoghurt could lower blood pressure and protect against heart disease. Mail Online, July 21 2014

Yoghurt can beat high blood pressure, claims new study. Daily Express, July 22 2014

Links To Science

Khalesi S, Sun J, Buys N, Jayasinghe R. Effect of Probiotics on Blood Pressure - A Systematic Review and Meta-Analysis of Randomized, Controlled Trials. Hypertension. Published online July 21 2014

Categories: NHS Choices

HIV 'reservoirs' may form earlier than expected

NHS Choices - Behind the Headlines - Mon, 21/07/2014 - 12:26

"Early HIV drugs 'may not stop virus'," BBC News reports. The report is based on a study of HIV treatments in monkeys, and has been linked by the BBC to the emergence of HIV in a four-year-old girl thought to have been cured of the virus as the result of treatment from birth – the so-called "Mississippi girl".

HIV infection levels in the blood can be managed through antiretroviral therapy (ART), allowing most people to live a normal life. But if the therapy is stopped, the virus re-emerges from "viral reservoirs" in the body that are immune to ART.

It was thought these reservoirs are formed during the initial infection, when the virus spreads to the bloodstream. But this study has shown the monkey version of HIV can form reservoirs within three days of infection. This occurs before the virus is detectable in the bloodstream.

It is likely such rapid development of reservoirs also occurs in humans and gives very limited chances of success for current ART to prevent their formation.

This is likely to have happened to the "Mississippi girl", who is reported to have been given ART within hours of birth and for 18 months afterwards, until she stopped attending appointments. The virus was not detectable and she was believed to have been cured, but it has now resurfaced.

Read the latest BBC report on the "Mississippi girl" for more information.

Drug development for treating the HIV virus will therefore continue to focus on new techniques to target the cells in these reservoirs.

 

Where did the story come from?

The study was carried out by researchers from Harvard and universities and institutes in Massachusetts, Bioqual in Maryland, Gilead Sciences in California, and the US Military HIV Research Program in Maryland.

It was funded by the National Institutes of Health, the US Army Medical Research and Material Command, the US Military HIV Research Program, and the Ragon Institute of MGH, MIT and Harvard.

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

The BBC reported the story accurately and informatively.

 

What kind of research was this?

This was an animal study using rhesus monkeys to investigate simian immunodeficiency virus (SIV), a monkey virus similar to HIV. The researchers wanted to investigate the speed of infection – in particular, how quickly "viral reservoirs" are formed.

HIV infection is known to create what are known as viral reservoirs. These are pockets of infected memory CD4+ cells that are the source of reactivation of the virus when antiretroviral therapy (ART) is stopped.

It was believed these reservoirs are formed during the initial stages of infection, when the virus is present in the bloodstream (viraemia), but it was not known how quickly they form.

As ART is largely ineffective against the cells located in the reservoirs, the researchers wanted to know if there is a window of opportunity after infection to prevent the reservoirs forming in the first place.

 

What did the research involve?

Twenty rhesus monkeys were given an injection of SIV into the lining of the rectum. At this point, the virus was not detectable in the bloodstream.

Some of the monkeys then received antiretroviral therapy (ART), starting on either day 3, 7, 10 or 14 after infection and continued for 24 weeks. Control monkeys did not receive ART.

The monkeys were monitored during the six months to see if and when the virus was detectable in the bloodstream, lymph nodes and rectal lining. They were also monitored for 24 weeks after the ART was stopped to see if or how quickly the SIV came back.

 

What were the basic results?

After stopping treatment, SIV infection became detectable in the bloodstream of all of the monkeys. This took a little longer to occur in the monkeys that started treatment on day 3 (mean 21 days) compared with days 7, 10 or 14, (mean 7 days), but it still occurred.

This indicated the viral reservoirs, where cells are able to effectively hide from ART, are formed within the first three days of infection with SIV.

The virus was not detectable in the blood of monkeys given ART on day 3, either before the injections started or during the next 24 weeks. The researchers did find the virus in lymph nodes and the rectal lining, but both reduced during ART treatment.

All other monkeys had detectable, rapidly increasing levels of the virus in the blood, lymph nodes and rectal lining. The ART reduced the levels compared with the control monkeys.

The levels of the treated monkeys became undetectable within three to four weeks, and this continued for the treatment period. The control monkeys had sustained, high levels of virus in the bloodstream throughout the length of the study.

Monkeys given ART on days 10 and 14 had viral infection in the lymph nodes, which initially reduced a little but then remained constant from week 12.

 

How did the researchers interpret the results?

The researchers conclude that: "These data demonstrate that the viral reservoir is seeded rapidly after intrarectal SIV infection of rhesus monkeys, during the 'eclipse' phase, and before detectable viraemia. This strikingly early seeding of the refractory viral reservoir raises important new challenges for HIV-1 eradication strategies."

 

Conclusion

This study has shown SIV infection spreads to locations in the bodies of monkeys, forming "viral reservoirs" during the first three days of infection, before the virus is detectable in the bloodstream.

Cells in the reservoirs are resistant to treatment with ART and are the source of rebound infection when treatment is stopped. Because of the similarities between SIV and HIV, it is likely an equivalent chain of events occurs when humans are infected with the HIV virus.

This appears to have been the case for the "Mississippi girl", a four-year-old girl who was treated with ART for the first 18 months of her life and was presumed to be cured, but has now shown evidence of the infection.

This research indicates drug-resistant HIV reservoirs are likely to occur rapidly during infection in humans, and remain a challenging target for drug development.

Although it is not yet possible to eradicate HIV infection, long-term treatment with ART can help most people live full and normal lives. 

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

Links To The Headlines

Early HIV drugs 'may not stop virus'. BBC News, July 21 2014

A proof of concept for an HIV cure exists. Now even our setbacks are useful. The Guardian, July 21 2014

Links To Science

Whitney JB, et al. Rapid seeding of the viral reservoir prior to SIV viraemia in rhesus monkeys. Nature. Published online July 20 2014

Categories: NHS Choices

Could new potential treatment mean safer IVF?

NHS Choices - Behind the Headlines - Mon, 21/07/2014 - 08:46

“Dozen babies born using 'safer' IVF treatment,” reads today’s headline in The Independent.

This headline was based on a new study providing proof of concept that the natural hormone kisspeptin-54 could be used to stimulate egg maturation in women requiring in vitro fertilisation (IVF).

The modified IVF treatment on trial, which is hoped to be safer than standard IVF, led to 12 healthy babies being born from 53 women undergoing a single IVF treatment.

One of the main hopes is that using kisspeptin-54 could lead to a safer version of IVF by reducing the need to use human chorionic gonadotropin (hCG), which has a small risk of causing ovarian hyperstimulation syndrome (OHSS). This can be potentially fatal. However, this study was much too small to prove kisspeptin-54 was safer. Much larger trials are required to prove this, and are the logical next step for this early stage research.

The study looked mainly at different doses of kisspeptin-54, but did not compare it with current IVF treatment. It will be vital for future clinical trials to include a control group, so that the effectiveness and safety of the new IVF treatment can be directly compared to the existing treatment, to see which is better overall.

 

Where did the story come from?

The study was carried out by researchers from Imperial College London and Hammersmith Hospital, and was funded by the Medical Research Council, Wellcome Trust and National Institute for Health Research.

The study was published in The Journal of Clinical Investigation, a peer-reviewed medical journal.

The media’s reporting of this story has been generally accurate, with the BBC including important quotes at the end of their piece, illustrating some of the research's key limitations. The Independent’s coverage did not highlight the limitations inherent in the study, and instead focused on the potential positives of the finding, leaving readers with a less balanced account.

 

What kind of research was this?

This was a randomised clinical trial (RCT) investigating whether a new hormone could be used in the early stages of IVF to potentially improve its safety.

IVF is one of several techniques available to help couples with fertility problems have a baby. During IVF, eggs are surgically removed from the woman's ovaries and fertilised with sperm in a laboratory. The fertilised egg is grown for a few days in the lab, and the best one or two embryos are then returned to the woman's womb to implant, grow and develop.

IVF starts with women being given hormones to suppress their natural monthly cycle. They are then given fertility-stimulating hormones to increase the number of immature eggs produced in the ovaries. These are too immature to be collected, so a second hormone is injected, typically human chorionic gonadotropin (hCG), to stimulate these eggs to mature. These matured eggs can then be collected for fertilisation in the laboratory.

However, hCG tends to linger in the body and is associated with a small risk of the ovaries being stimulated too much, causing the condition OHSS. The researchers wanted to see if there was a safer way of stimulating women’s ovaries to produce mature eggs for the IVF process, but without the increased risk of OHSS.

In previous research, the group had come across a naturally occurring hormone called kisspeptin-54, which when faulty makes a person infertile, as they cannot go through puberty. They thought there was a chance it might stimulate egg maturation over a shorter period of time, lessening the chance of the ovaries being overstimulated, theoretically reducing the risk of OHSS. They designed a clinical trial to investigate whether it was possible to use kisspeptin-54 instead of hCG in the IVF process, specifically to stimulate egg maturation.

 

What did the research involve?

The researchers randomly allocated 53 women who had opted for IVF to different doses of kisspeptin-54 treatment. They wanted to see whether it could partially replace the hormone normally used to stimulate the maturation of eggs during IVF.

All of the women were given follicle-stimulating hormone (FSH) to stimulate the ovaries to produce lots of immature eggs. They were also given gonadotropin releasing hormone (GnRH) antagonist injections to prevent the eggs from leaving the ovaries too early. They were then given different doses of kisspeptin-54 to trigger egg maturation. When at least three ovarian follicles (immature eggs) of 18 mm or greater diameter were visible on an ultrasound scan, the women were given an injection of kisspeptin-54 to trigger egg maturation.

The women were recruited from a list of women requiring IVF treatment at Hammersmith Hospital, London. The inclusion criteria were specific and included:

  • age 18-34 years
  • early follicular phase level of serum FSH ≤12 mIU/ml
  • serum anti-Mullerian hormone of 10-40 pmol/l (1.4-5.6 ng/ml)
  • both ovaries intact, regular menstrual cycles of 24-35 days duration
  • body mass index (BMI)18-29 kg/m2 (this includes women of a healthy weight and overweight, but not those who are obese or underweight)

Women were excluded if they:

  • had moderate or severe endometriosis
  • had poor response to, or more than one previous cycle of, IVF treatment
  • had clinical or biochemical hyperandrogenemia (an excess of androgens)
  • had polycystic ovarian syndrome

The researchers primarily wanted to know whether a single treatment of kisspeptin produced egg maturation. They assessed this by looking at the number of mature eggs, and the percentage of all eggs collected that were mature. Secondary outcomes included the later stages of IVF, such as fertilisation rates, successful implantation rates, pregnancy rates and healthy births.

Importantly, there was no control group of women who received normal IVF with gonadotropins to act as a comparison, so only the relative effects of the different doses of kisspeptin were under investigation. The study did not compare the effect of the experimental kisspeptin IVF treatment with regular IVF treatment.

 

What were the basic results?

Egg maturation was observed in response to each tested dose of kisspeptin-54, and the average (mean) number of mature eggs per woman broadly increased in a dose-dependent manner.

Fertilisation of eggs and transfer of embryos to the uterus occurred in 92% (49/53) of patients treated with kisspeptin-54.

Clinical pregnancy rates using the technique were 23% (12/53) overall. 10 of the 53 women gave birth to healthy babies (12 babies in total, as two women had twins) following the kisspeptin IVF. Two women who initially became pregnant had a miscarriage.

In terms of safety and side effects, kisspeptin was reported to be well tolerated by all of the women. Five negative events were recorded in the group, but these were related to established complications of IVF, rather than the new hormone treatment. Two patients experienced an ectopic pregnancy, one had a heterotopic pregnancy (where an ectopic pregnancy and a viable intrauterine pregnancy occur at the same time) and two had miscarriages.

 

How did the researchers interpret the results?

They said the study "demonstrates that a single injection of kisspeptin-54 can induce egg maturation in women with subfertility undergoing IVF therapy. Subsequent fertilisation of eggs matured following kisspeptin-54 administration and transfer of resulting embryos can lead to successful human pregnancy.”

 

Conclusion

This study provided a “proof of concept” that the naturally occurring hormone kisspeptin-54 can be used to stimulate egg maturation in women requiring IVF. The modified IVF – which is hoped to be safer than standard IVF – led to 12 healthy babies being born from 10 mums. Out of the 53 women undergoing a single IVF treatment, this gave a 19% success rate.

Researchers hoped that using kisspeptin-54 could lead to a safer version of IVF by reducing the risk of OHSS. Although theoretically plausible, this study was much too small to prove that the new technique was safer; much larger trials will be required to prove this. What this study does prove is that it is possible to achieve IVF success to stimulate egg maturation by using kisspeptin-54.

Another factor limiting the interpretation of the results is the fact that there was no control group. The study did not compare the effect of the experimental kisspeptin-54 treatment with regular IVF treatment. Therefore, the study told us about the relative effects of the different doses of kisspeptin, rather than how they stacked up against the current IVF treatment. This is something fully acknowledged by the research authors, but much less clear in the media's reporting.

Future studies will need to examine not only whether the new treatment is safe, but also whether it leads to the similar success rates in terms of fertilisation and healthy births as the current technique.

The BBC carries a quote indicating that the next clinical trials will take place in women with polycystic ovary syndrome (PCOS), who are more vulnerable to overstimulation. This will be a useful way to investigate the potential safety benefits of this technique in this higher risk group.

 

Analysis by Bazian. Edited by NHS ChoicesFollow Behind the Headlines on TwitterJoin the Healthy Evidence forum.

Links To The Headlines

Dozen babies born using 'safer' IVF treatment. The Independent, July 20 2014

'Safer IVF' with kisspeptin hormone shows promise. BBC News, July 19 2014

Natural 'chocolate hormone' that makes IVF safer: Women desperate to become mothers could soon benefit from treatment named after Hershey's sweet. Daily Mail, July 19 2014

First babies born from safe new IVF technique. The Daily Telegraph, July 19 2014

Links To Science

Jayasena CN, et al. Kisspeptin-54 triggers egg maturation in women undergoing in vitro fertilization. The Journal of Clinical Investigation. Published online July 18 2014

Categories: NHS Choices

Obese women may have 'food learning impairment'

NHS Choices - Behind the Headlines - Fri, 18/07/2014 - 12:30

"Obese women show signs of food learning impairment," is the headline on the BBC News website.

It reports on a behavioural study involving 67 individuals of normal weight and 68 obese individuals.

Each participant was shown a series of either blue or purple squares, and then asked to predict whether the square would yield a reward. Depending on the phase of the experiment, this would be a picture of either food or money, followed by actual food or money at the end of the experiment.

The pattern of rewards was not random – one colour square was more weighted to provide a reward than another. Crucially, halfway through the experiment the reward pattern was reversed.

Researchers were interested in seeing how long it took for participants to recognise and adapt to the shift.

They found obese women were less able to recognise and adapt to the shift compared with other groups (non-obese women and men of any weight) when the rewards were food based. However, their performance was the same as other groups when the rewards involved money.

According to the researchers, the implication is that an image of food somehow skews the rational predictive and decision making part of the brain in obese women (but, strangely, not obese men).

Overall, this study will add to research in the field of behavioural learning related to food, but on its own it provides a very limited explanation or new therapeutic angles for tackling the obesity epidemic.

 

Where did the story come from?

The study was carried out by researchers from Yale University and School of Medicine, and Icahn School of Medicine at Mount Sinai, New York. No sources of financial support are reported.

The study was published in the peer-reviewed scientific journal Current Biology.

BBC News' reporting of the research is broadly accurate. However, the limitations of this piece of experimental research were not acknowledged – deficits in learning were seen in a very specific test scenario in a small group of people. 

The LA Times provides a more informative summary of how the experiment was carried out and the alleged implications of the results.

 

What kind of research was this?

This was an experimental study that aimed to see if there is a difference in learning when responding to food cues, comparing obese people with those of a normal weight.

One of the main drivers of the global obesity epidemic is known to be the consumption of foods high in fat and sugar. The "rewarding" properties of these types of foods are thought to be what causes us to keep on eating them.

However, it is thought these reward circuits in the brain may differ between people, causing some to have a propensity for overeating and obesity. This is what this study aimed to investigate.

 

What did the research involve?

The study included 67 individuals of a normal weight (35 of these were women) and 68 obese individuals (of which 34 were women) who were recruited from the community.

They took part in a behavioural learning test assessing their reward association. The participants had to try to work out the relationship between two different coloured squares (blue and purple), and images of either food or monetary rewards. 

Half the participants took part in a money task where the reward was either $5 or $10, and half took part in a food task where the reward was either 10 or 15 peanut M&Ms, or 6 or 12 pretzels (depending on the person's preference).

In the first part of the test, a picture of a reward appeared after the colour A one-third of the time, and never after colour B (total: 14 presentations of each colour, intermixed with 7 presentations where colour A was associated with the reward).

The colours were reversed in the second part of the test, so a picture of a reward appeared after the colour B one-third of the time, and never after colour A was paired with the reward in one-third of the trials, and the colour B was never paired with the rewards (total: 18 presentations of each colour, intermixed with 9 presentations, where colour B was associated with the reward).

When the participants were shown a colour, they had to indicate on a scale of one to nine the degree to which they expected to get a reward.

The researchers asked all participants to fast for four hours before taking part in the trials to try to increase the salience (importance) of the food rewards.

The participants were told at the end of the tasks that they would received the accumulated amount of all the money or food they saw during the experiment. This resulted in $100 in the money condition and a bag of peanut M&Ms or pretzels in the food condition. 

The researchers examined the differences between obese people and people with normal body mass indexes (BMIs), and looked to see if there were differences between men and women.

 

What were the basic results?

The researchers found a significant association between test performance and BMI. The magnitude of the difference between obese and normal-weight participants was further influenced by the test modality (food or money) and whether the participant was male or female. 

When looking at all participants who took part in the food tests, they found that compared to normal weight people, obese people had a food-specific learning deficit. However, when they split the group by gender, they found the association was significant only in obese women, but not in obese men.

Obese women were less able to tell which of the two colours was associated with the food on the first part of the test, or then able to switch this association on the second part of the test.

Meanwhile, on the monetary test, there was no significant learning deficit between obese and normal-weight men or women.

 

How did the researchers interpret the results?

The researchers say their analyses demonstrated a "robust negative association between BMI and learning performance in the food domain in female participants" – that is, as BMI goes up, learning performance goes down when food is part of the equation. The same impairment was not observed in obese men.

They say: "These findings suggest that obesity may be linked to impaired reward-based associative learning and that this impairment may be specific to the food domain."

 

Conclusion

This experimental study included fairly small groups of obese and normal-weight men and women.

It found that, overall, obese women demonstrated a learning deficit when food was used as a reward compared with normal-weight women.

On the food tasks, obese women were generally less able to discriminate between which of the two colours was associated with the food, and then to respond when the association was switched.

The difference was not significant between obese men and normal-weight men. There was also no difference among participants when money was used as a reward.

While this may possibly demonstrate some difference in food-related learning and reward associations between obese and normal-weight people – and specifically obese and normal-weight women – the applications of this single small piece of research seem to be quite limited.

The study only included a small number of people in the US: 67 normal-weight individuals and 68 obese individuals. These people where then divided between the two monetary and food tasks.

This meant all of the results related to the "food-related learning deficit in obese women" were obtained from tests in only 18 obese and 18 normal-weight women.

This is a very small group, and it is possible the results could be down to chance. Other groups of people, including those of different countries and cultures, could have given different results.

This was also only a single very specific test, seeing if people could spot which of two colours was associated with the food reward of either some M&Ms or pretzels. Interpreting the meaning from this single test is very difficult. It tells us very little about how people become obese.

For example, someone being unable to link which particular colour is associated with a food item doesn't tell us about the various drivers that have led to that individual becoming obese.

Even if we do take the findings of the study at face value, it leaves several important questions unanswered.

For example, does "food-related learning deficit" lead to obesity, or does being obese make it more likely you will go on to develop a food-related learning deficit?

And why were these deficits only seen in obese women and not obese men?

One possible answer to the second question is this could be because of the very small samples of men and women tested. The findings of no difference in men but a difference in women could be purely down to chance, and there may not be a difference between the genders at all. 

While the psychology of obesity is certainly an avenue worth investigating further, it is difficult to see what insights or opportunities for new treatments this study could offer.

Analysis by Bazian. Edited by NHS ChoicesFollow Behind the Headlines on TwitterJoin the Healthy Evidence forum.

Links To The Headlines

Obese women 'show signs of food learning impairment'. BBC News, July 18 2014

When food's the reward, obese women's judgment fails them. LA Times, July 17 2014

Links To Science

Zhang Z, Manson KF, Schiller D, Levy I. Impaired Associative Learning with Food Rewards in Obese Women. Current Biology. Published online July 17 2014

Categories: NHS Choices

'More adults should be taking statins,' says NICE

NHS Choices - Behind the Headlines - Fri, 18/07/2014 - 11:40

"Doctors have been told to offer cholesterol-lowering statins to millions more people," BBC News reports.

New guidelines from the National Institute for Health and Care Excellence (NICE) recommend lowering the bar for statin use in adults at risk of heart disease. 

NICE suggests up to 8,000 lives could be saved every three years if everyone with a 10% risk of developing cardiovascular disease within the next 10 years is offered one of the widely used cholesterol-lowering medications.

Cardiovascular diseases are diseases affecting the heart and blood vessels, such as heart disease and stroke.

NICE says the evidence clearly shows statins are safe and effective and would be a good use of healthcare resources if given to these people.

The announcement has been met with a variable response, with the Daily Mail saying up to half of all adults could now be eligible for the drugs, and that, "GPs warn of chaos" at being "told to trawl medical records to find at-risk patients".

On the other side of the argument, Professor Baker, director of the Centre for Clinical Practice at NICE, says the new recommendations would not create an additional workload for GPs.

On the NICE website, he said: "Most patients will already be under surveillance by their GPs, so this won't add any additional workload. But you can do the QRISK2 risk assessment yourself. It can be done online or via an app, so it doesn't need to be done by the GP."

You can assess your own risk online using a risk assessment tool based on factors such as smoking history, body mass index (BMI) and family history of heart disease.

The NICE guidelines have now been published, which means they will come into effect in the NHS in England. However, NICE still recommends preventable lifestyle measures, such as losing weight or stopping smoking, are addressed first before starting statin treatment.

Ultimately, the decision to take a statin – even if it is recommended – will always remain a choice that sits with the patient.

 

What are statins?

Statins are usually the first medication of choice to reduce the levels of low-density lipoprotein (LDL, or "bad") cholesterol in the blood.

Cholesterol and other fatty substances can build up and clog the arteries in the heart and elsewhere in the body, leading to cardiovascular diseases. Reducing cholesterol levels helps reduce the risk of cardiovascular events such as heart attack or stroke.

Examples of statin drugs are simvastatin and atorvastatin, which come as tablets. The recommended treatment course is to usually take a tablet once a day for life.

 

What is NICE recommending?

NICE has published an update to its previous clinical guideline on the cardiovascular risk assessment and management of lipids (fats in the blood, which includes cholesterol and triglycerides) in people who either already have cardiovascular disease (such as those who've had a heart attack or stroke), or people who are at risk of developing cardiovascular disease.

The main new recommendations are that:

  • A systematic strategy should be used in general practice to identify people who are likely to be at high risk for developing cardiovascular disease (CVD).
  • People should be prioritised for a full risk assessment if their estimated 10-year risk of CVD is 10% or more (using the QRISK2 assessment tool).
  • Before starting lipid-lowering medications for the prevention of CVD, at least one blood sample should be taken to measure total cholesterol, high-density lipoprotein (HDL, or "good") cholesterol, non-HDL cholesterol, and triglyceride concentrations.
  • In people who have a 10% or greater risk of developing CVD within the next 10 years, the recommended statin to start treatment with is atorvastatin, given at a dose of 20mg daily.
  • In people who already have established CVD (people who have heart disease or have had a stroke), the recommended starting dose of atorvastatin is 80mg daily (unless there are side effects or other contraindications).

For people at risk of developing CVD within the next 10 years, the recommendations to start 20mg atorvastatin applies to adults of all ages, including people over the age of 85 years (in very elderly people, statins may reduce the risk of a non-fatal heart attack). This advice stands unless there are other health-related factors that make statin treatment inappropriate.

NICE does make several important provisions around decisions to start treatment for the prevention of CVD in people considered to be at risk.

These are outlined below.

Patient-doctor discussion

The decision whether to start a statin should be made after an informed discussion between the doctor and patient about the risks and benefits of treatment, taking into account factors such as:

  • possible benefits from lifestyle modifications (measures that could be tried first before starting a statin, such as exercising more, eating a healthier diet and stopping smoking)
  • patient preference
  • other medical illnesses
  • the problems of adding another tablet if the person is already taking a lot of daily medications
  • general frailty and life expectancy
Lifestyle changes

Before starting statin treatment, assessment should be made into other health and lifestyle factors that may need management, including:

  • smoking and alcohol consumption
  • blood pressure
  • BMI
  • diabetes
  • kidney or liver disease

The benefits of optimising all other modifiable lifestyle risk factors (for example, overweight/obesity or smoking) should be discussed, and people offered support for this if needed, such as exercise referral programmes.

Statin treatment may then be considered if lifestyle modifications don't work.

 

What is the rationale for lowering the threshold for the drugs?

Currently, one-third of deaths in the UK are caused by cardiovascular disease, accounting for around 180,000 deaths each year.

Cardiovascular disease is well known to have a significant burden of disability. It is believed £8 billion of healthcare resources are tied up in the disease.

Professor Mark Baker, director of the Centre for Clinical Practice at NICE, says: "Doctors have been giving statins to 'well people' since NICE first produced guidance on this in 2006. We are now recommending the threshold is reduced further.

"The overwhelming body of evidence supports their use, even in people at low risk of CVD. The effectiveness of these medicines is now well proven and their cost has fallen. The weight of evidence clearly shows statins are safe and cost effective for use in people with a 10% risk of CVD over 10 years."

Dr Anthony Wierzbicki, from Guy's and St Thomas' Hospitals, London, and chair of the Guideline Development Group, also commented on the new guidance: "We've been able to simplify the guideline so it's now much easier for patients to be assessed and for GPs and nurses to make sense of the results. There is greater clarity, a simpler framework, and a systematic way of identifying people who could benefit from treatment.

"We've got the best evidence base, huge numbers, and the biggest set of clinical trials ever done. Other areas of medicine would give their teeth for this evidence, it's that good. Statins work, they are very cheap, and are becoming considerably cheaper as they come off-patent, which, in a cost-limited health service, is a big consideration.

"That enables us to actually say that we should treat people with heart disease a lot more intensively because we know that will prevent further events. In people with diabetes or kidney disease, giving a statin will reduce heart attacks and strokes. For people at risk of heart disease, if lifestyle measures fail, we have a second option of giving them a statin if they want and require it."

 

Are there any risks or side effects with statins?

Statins are fairly safe drugs, though there are a range of possible side effects and groups of people who should use them with caution. This includes people with an underactive thyroid, kidney disease and liver disease. Women should also not take statins while pregnant or breastfeeding.

Possible side effects include headaches and dizziness, sleep disturbances, fatigue, tummy disturbances, altered sensation, and sensitivity reactions such as rash or itching.

Very rarely, statins have been associated with the risk of having a toxic effect on the muscles, causing muscle pain and weakness, and even a serious condition called rhabdomyolysis, where the muscle fibres start to break down.

However, the risks and benefits would be discussed and taken into account for any individual before a statin is prescribed, including their personal and family medical history.

 

How has the announcement been received by the media?

As the BBC News headline indicates, NICE's decision has been met with controversy. 

Professor Mark Baker, the director of the Centre for Clinical Practice at NICE is quoted as saying: "Prevention is better than cure. One of the mainstays of modern medicine is to use treatments to prevent bad things happening in the future. It's why we use vaccines and immunisation to prevent infectious disease, it's why we use drugs to lower blood pressure to prevent heart attacks, strokes, and kidney disease, and it's why we're using statins now."

Meanwhile, in opposing camps there is debate about "medicalising" a nation and encouraging people to just pop a pill rather than following a healthy lifestyle.

The British Medical Association's General Practitioner Committee is quoted as saying: "There is insufficient evidence of significant overall benefit to low-risk individuals to allow GPs to have confidence in the recommendation. The measure would distort health spending priorities and disadvantage other patients."

However, as quoted in the Daily Mail, Professor Baker responded: "It is ludicrous to suggest that we are overmedicalising the population when the whole point of using modern, safe and effective drugs in an economic way is to prevent bad things happening in the future."

Dr Chaand Nagpaul, chair of the British Medical Association's GP committee, feels NICE has not taken into account the additional pressures they'll be placing on GPs. "In making their decision, NICE has failed to take the current pressures on general practice into account, and the further impact this will have on already overstretched GPs and those patients requiring treatment for other illnesses."

Despite the extensive debate and opposition, as BBC News also highlights, the 10% threshold for statin treatment is comparable to that already used in other European countries.

As the president of the Academy of Medical Sciences, Professor Sir John Tooke, points out on the BBC News website: "Whether or not someone takes drugs to diminish their risk is a matter of personal choice, but it must be informed by accurate information on the balance of risk and benefit in their particular case. The weight of evidence suggests statins are effective, affordable and have an acceptable risk-benefit profile."

 

Conclusion

Despite somewhat hysterical media coverage to the contrary ("millions more to be given statins," according to the Daily Express), nobody will be forced to take statins.

If your GP does recommend statins, you should ask them to explain the benefits and risks for you personally of starting statin treatment. You may want to find out more about statins before making up your mind – the NHS Choices Health A-Z information on statins is a good place to start.

If you do experience troublesome side effects while taking statins, contact your GP or the doctor in charge of your care. It could be the case that adjusting your dosage or switching to a different type of statin could help relieve any side effects.

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

Links To The Headlines

Statins: Millions more to get drugs in controversial plans. BBC News, July 18 2014

Prescribing statins more widely 'could avert tragedy', new medical guidelines suggest. The Independent, July 18 2014

NHS medicines watchdog lowers bar for statins prescriptions. The Guardian, July 18 2014

Forty per cent of adults advised to take statins under new NHS guidance. The Daily Telegraph, July 18 2014

GPs warn of chaos over bid to offer statins to 17m to prevent heart disease: Doctors being told to trawl medical records to find at-risk patients. Daily Mail, July 18 2014

Statins to be offered to '40% of adult population'. ITV News, July 18 2014

Give statins to 17m says NHS watchdog. Daily Express, July 18 2014

Links To Science

National Institute for Health and Care Excellence. Lipid modification: cardiovascular risk assessment and the modification of blood lipids for the primary and secondary prevention of cardiovascular disease. July 2014

Categories: NHS Choices

Steroid asthma inhalers restrict children’s growth

NHS Choices - Behind the Headlines - Thu, 17/07/2014 - 12:50

“Children who use inhalable steroids for asthma grow slower than their peers in the first year of taking the medication,” The Guardian reports. While this is an accurate report of the science, the effect found by researchers was small. On average, a reduction of around half a centimetre per year was seen, compared to children taking a placebo or other asthma medication.

The researchers were studying the effects of inhaled corticosteroids. These are known as “preventers” – the brown inhalers that deliver a dose of steroids to the airways reducing inflammation, to prevent symptoms.

After pooling the results of 25 trials, they found a small but significant link between the use of preventer inhalers and restricted childhood growth, which was estimated to be an average reduction of 0.48cm (or 0.19in).

The authors recommend that these drugs should be prescribed at the “lowest effective dose” and that the growth rate of children treated with inhaled corticosteroids should be monitored, as they will affect each child differently.

However, as the authors point out, the small effect on growth is a minor risk compared to the proven benefits of these drugs in controlling asthma, and ensuring children’s lungs grow to their full capacity.

Untreated childhood asthma is much more likely to have a harmful effect on a child’s development than a small reduction in growth.

It is therefore important that parents ensure their children use their inhalers as advised by their doctor.

 

Where did the story come from?

The study was carried out by researchers from the Federal University of Rio Grande, Brazil, and the University of Montreal, in Canada. There was no external funding.

The study was published by the Cochrane Collaboration – an independent research body looking at the effects of healthcare treatments.

As with all Cochrane Collaboration publications, the research was peer-reviewed. It is available on an open-access basis, so is free to read online.

Not surprisingly, it was widely covered by the media, with most news sources responsibly including warnings from independent researchers and doctors that uncontrolled asthma can be dangerous.

The Independent rightly report that the effect of inhalers on growth was “a small price to pay” to protect against potentially lethal asthma attacks.

 

What kind of research was this?

This was a systematic review and meta-analysis of the evidence on whether drugs called “inhaled corticosteroids” (steroids) can affect the growth of children with persistent asthma.

Children with persistent asthma often require regular use of this medication to prevent symptoms, such as wheezing, from reoccurring.

The researchers also investigated whether factors such as the type of medication, dose, the length of time taken and the type of inhalation device used had any role in modifying the potential effect on growth.

Systematic reviews of randomised controlled trials (RCTs) are the best way of assessing the benefits and risks of healthcare interventions. A meta-analysis is a statistical technique that combines the results of several studies.

Inhaled steroids are recommended as a first line treatment for children with persistent, mild to moderate asthma. These drugs are the most effective method of treating asthma and are generally considered safe. However, parents and doctors remain concerned about the potential negative effect on growth, which has been suggested by previous research. Their aim was to evaluate the adverse effects on growth in children of all the currently available inhaled steroids.

 

What did the research involve?

The researchers searched for trials that addressed this question on a Cochrane specialist register of trials, which is derived from systematic searches of various electronic databases. They also hand-searched respiratory journals and meeting abstracts. All databases were searched from their inception to January 2014.

They looked for RCTs involving children up to 18 years of age, with persistent asthma, who had used ICS daily for at least three months, and who had been compared with children using a placebo or non-steroid drug.

They then assessed children’s rate of linear growth by measuring height at a number of points in the study.

Differences between growth rate and predicted normal growth rates for children of the same age, sex and ethnicity, and changes from baseline in height over time were also considered.

The authors of the Cochrane research assessed the abstracts of all studies identified as potentially relevant, and where they met the study criteria, extracted the relevant data. They also independently assessed the quality of the trials and the risk of bias. The quality of RCTs may vary, depending on how well they are designed, conducted and reported.

They used validated statistical methods to analyse the results.

 

What were the basic results?

The review included 25 trials, involving 8,471 children with mild to moderate persistent asthma.

The trials tested six medications (beclomethasone dipropionate, budesonide, ciclesonide, flunisolide, fluticasone propionate and mometasone fumarate), given at low or medium daily doses during a period of three months to four to six years.

They found that:

  • compared with placebo or non-steroidal drugs, inhaled steroids produced a statistically significant reduction in a person’s growth rate (mean difference -0.48cm/y, 95% Confidence Interval [CI] 0.65 to 0.30, moderate quality evidence)
  • this represented an overall decrease from the expected baseline in height (mean difference 0.61cm/y, 95% CI 0.83 to 0.38, moderate quality evidence) during a one-year treatment period (that is, on average, children were 0.61cm shorter than would have been expected)
  • the scale of growth reduction in children treated with inhaled steroids varied according to the type of drugs used, with the smallest reduction found for ciclesonide, but this was based on just one study of 202 children
  • results for further years varied between trials, but overall, growth reduction was less pronounced in subsequent years of treatment
  • one trial that followed children into adulthood showed that prepubertal children treated with the drug budesonide for an average of 4.3 years had an average reduction of 1.20cm (95% CI 1.90 to 0.50) in adult height, compared to those treated with a placebo

second Cochrane review of 22 trials found that the effects on growth were minimised when lower doses of inhaled steroids were used.

 

How did the researchers interpret the results?

The researchers say the evidence suggests that children treated daily with inhaled steroids may grow about half a centimetre less during their first year of treatment, with the effect on growth less pronounced in subsequent years.

Further research is now needed, they say, comparing different inhaled doses of corticosteroids, especially in children with more severe asthma, who require higher doses.

They conclude that while the benefits of inhaled steroids outweigh the potential risk of a relatively small suppression in growth rates, these drugs should be prescribed at the “lowest effective dose”, and the growth rate of children treated with inhaled steroids drugs should be monitored, since individual susceptibility may vary.

 

Conclusion

This systematic review has found that inhaled corticosteroid drugs suppress growth in children with persistent asthma who take them regularly, during the first year of treatment.

This was high quality, well-conducted research, and its conclusions are likely to be reliable. 

While the results are likely to worry parents, uncontrolled asthma can restrict a child’s activities and lower their quality of life. In severe cases, it can lead to life-threatening asthma attacks.

Even low-grade, persistent symptoms can lead to fatigue, underperformance or absence from school as well as psychological problems, including stress, anxiety and depression.

It's important that children continue to take their asthma medication as prescribed. Parents should discuss any concerns about their child’s prescription with their doctor.

Analysis by Bazian. Edited by NHS ChoicesFollow Behind the Headlines on TwitterJoin the Healthy Evidence forum.

Links To The Headlines

Asthma inhaler use in children slows growth, research finds. The Guardian, July 17 2014

Asthma inhalers make children half a centimetre shorter. The Daily Telegraph, July 17 2014

Asthma inhalers 'can stunt growth of kids'. Daily Mirror, July 17 2014

Asthma inhalers 'stunt growth': Most widely-used device found to reduce height in first year of use. Mail Online, July 17 2014

Asthma inhalers can stunt growth in children, new research finds. The Independent, July 17 2014

Links To Science

Zhang L, Prietsch SOM, Ducharme FM. Inhaled corticosteroids in children with persistent asthma: effects on growth. Cochrane Database of Systematic Reviews. Published online July 17 2014

Categories: NHS Choices

Protein may help control diabetes symptoms

NHS Choices - Behind the Headlines - Thu, 17/07/2014 - 12:25

"Diabetes could be cured 'in single jab'," is the misleading headline in the Daily Express. The news comes from an exciting new mouse study which found promising results for a treatment for type 2 diabetes.

However, the study did not show that it would cure diabetes, and certainly not after a single injection.

Researchers performed experiments in mice using a protein called fibroblast growth factor 1 (FGF1). FGF1 works in a similar way to an existing class of diabetes drugs called thiazolidinediones by making the body's cells more sensitive to insulin-reducing blood sugar levels.

Unfortunately, using thiazolidinediones in humans causes side effects such as weight gain, which can be problematic in patients who are often already overweight.

Researchers found repeated injections of FGF1 every other day for 35 days in mice improved their insulin sensitivity and lowered blood sugar levels without any noticeable side effects. However it is unlikely there would be no side effects in humans.

It is too early to say this would be a "cure" for diabetes, and further research is required before human trials are conducted. This is a promising new avenue of study, however.

 

Where did the story come from?

The study was carried out by researchers from the Salk Institute for Biological Studies, New York University School of Medicine, and the University of California, San Diego, in the US, the University of Groningen in the Netherlands, and the Westmead Millennium Institute and the University of Sydney in Australia.

It was funded by the US National Institutes of Health, the Glenn Foundation for Medical Research, the Australian National Health and Medical Research Council, the European Research Council, and several US and Dutch foundations and research organisations.

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

The Daily Express' headline claiming this study could lead to a diabetes cure was inappropriate and not supported by the study's findings.

The Daily Mail and Daily Mirror's coverage was more restrained, and the Mirror print edition included a useful diagram explaining how the treatment could work in humans.

There are, however, some inaccurate reports the treatment reverses insulin resistance. This was not shown in the study – the treatment improved insulin sensitivity by about 50%. This is not the same thing as reversing insulin resistance.

 

What kind of research was this?

This was a series of laboratory and animal experiments that aimed to see if a protein normally present in mammals called fibroblast growth factor 1 (FGF1) could reduce high blood glucose (sugar) levels.

The FGF1 protein is known to have a role in new blood vessel formation (angiogenesis) and cell division, and is also thought to be involved in organ development. It has been used in human studies as a treatment for peripheral vascular disease.

Scientists have suspected FGF1 is also involved in the regulation of blood glucose levels, as genetically modified mice that do not have this protein develop insulin resistance when they are given a high-fat diet.

The hormone insulin is required for cells to take in glucose for energy. When insulin resistance occurs, there is a reduction in the ability of cells to take in glucose. This can lead to type 2 diabetes. The researchers wanted to see if the insulin resistance could be reversed by giving mice FGF1.

 

What did the research involve?

The researchers conducted a variety of experiments to investigate the effects of FGF1 on blood glucose levels in mice.

They gave a single injection of recombinant FGF1 (rFGF1) from rodents into diabetic mice and normal mice, and then measured their blood glucose levels.

The researchers also injected recombinant human FGF1 to see if it had the same effect. They injected other types of fibroblast growth factors, such as FGF2, FGF9 and FGF10, into diabetic mice and then measured blood glucose levels.

The researchers performed repeated injections of rFGF1, one every other day for 35 days, assessed the effects on blood glucose and insulin sensitivity, and monitored the mice for side effects.

They investigated whether the effects were related to rFGF1 increasing the levels of insulin being released, or whether it was using a different mechanism. This also involved injecting mice that could not produce insulin (similar to type 1 diabetes).

Another aspect of the study investigated whether the researchers could modify the rFGF1 to stop it causing unwanted cell division, but still be able to reduce blood glucose levels. They did this by removing some of the amino acids in the protein and testing it in the laboratory and then in mice.

 

What were the basic results?

A single injection of rFGF1 into diabetic mice reduced their high blood sugar levels to normal levels with a maximum effect between 18 and 24 hours. The effect lasted for more than 48 hours. Blood sugar levels did not go dangerously low (hypoglycaemia).

Similar results were found if the injection was into the bloodstream or the peritoneal cavity (the space around abdominal organs).

When normal mice were injected, there was no change in blood sugar level. Other types of FGF proteins did not reduce blood sugar levels. Human rFGF1 injections were also found to work in the mice.

Repeated injections of rFGF1 improved the ability of skeletal muscle to take in glucose, indicating it improved the cells' sensitivity to insulin.

The fasting blood glucose level of the mice was 50% lower than mice given a control injection with saline. Insulin tolerance test (ITT) results also improved, showing the mice had become more sensitive to insulin again.

The mice did not gain weight, their livers did not become fatty, and there was no bone loss with the treatment, all side effects of current therapies that aim to improve insulin sensitivity, such as thiazolidinediones.

The mice appeared to have normal activity levels and breathing rates. FGF1 did not make the pancreas release more insulin in laboratory or mouse experiments.

In mice without the ability to produce insulin (similar to type 1 diabetes), rFGF1 did not reduce their blood sugar levels. However, it did improve the level of blood sugar reduction when insulin was then injected.

These results suggest that rFGF1 may cause cells to become more sensitive to insulin.

Removing some of the amino acids from rFGF1 stopped it inducing cell division in laboratory experiments, but it was still able to reduce blood sugar levels in the mice.

 

How did the researchers interpret the results?

The researchers concluded they have uncovered an unexpected action of human FGF1, which they say has "therapeutic potential for the treatment of insulin resistance and type 2 diabetes".

 

Conclusion

This exciting study has shown potential for rFGF1 to become a treatment for both type 1 and type 2 diabetes. The mouse studies have shown that for type 2 diabetes, rFGF1 reduces blood glucose levels in a sustained manner, and its prolonged use improves insulin sensitivity.

There is also potential for rFGF1 to improve blood glucose control for type 1 diabetes, though it would not replace the requirement for insulin injections.

The researchers have also shown they can modify rFGF1 so it doesn't cause unwanted cell division in laboratory experiments.

But further investigations are needed to see whether this version only has an effect on blood glucose levels or whether it retains its other known functions, such as new blood vessel formation, which may potentially cause side effects.

Encouragingly, the researchers did not find any side effects with the treatment, but it was only given over a maximum of 35 days.

Further research will be required before human trials are conducted, but this is a promising new avenue of study.

Even if any drug that stems from this research did prove to be effective and safe in humans, it is unlikely it would lead to a permanent cure for diabetes. It is more likely it would become a maintenance treatment a person would need to take long term on a regular basis.

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

Links To The Headlines

Diabetes could be cured 'in single jab'. Daily Express, July 17 2014

Protein discovery that could reverse the damage of diabetes: Breakthrough could lead to cheap drug that would halt disease. Daily Mail, July 17 2014

Diabetes breakthrough drug can work for two days from a single jab. Daily Mirror, July 16 2014

Links To Science

Suh JM, Jonker JW, Ahmadian M, et al. Endocrinization of FGF1 produces a neomorphic and potent insulin sensitizer. Nature. Published online July 16 2014

Categories: NHS Choices

Owning a dog may make older adults fitter

NHS Choices - Behind the Headlines - Wed, 16/07/2014 - 13:00

“Want to appear 10 years younger? Just buy a dog,” is the dubious claim on the Mail Online.

A study has found a link between dog ownership and increased physical activity in older adults, but how this is linked to looking younger is unclear.

Contrary to the headline, the study did not measure or mention physical appearance.

The study actually measured physical activity levels of 547 older adults in Tayside, Scotland. After taking factors such as weather, environment, medical illnesses and socioeconomic status into account, dog owners were 12% more physically active than people who did not own a dog.

The authors say that this difference was equivalent to the activity level of someone 10 years younger.

Although the study also revealed that dog owners had better general health and physical functioning, it cannot prove that this was due to owning a dog.

It should also be noted that these results are based on just 50 dog owners and so may not be generalisable to the whole population.

However, it is clear that exercise and walking are beneficial to physical and mental health and should be encouraged across all age groups.

So it is recommended that you go for regular “walkies”, whether or not you are accompanied by a canine companion.

 

Where did the story come from?

The study was carried out by researchers from the University of St Andrews, the University of Dundee and the University of Newcastle and was funded by a Chief Scientist Office Scottish government grant.

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

Like many Mail Online health stories, while the story itself was broadly accurate (though it didn’t make clear that the study cannot prove causality) the headline bore little resemblance to reality.

Regular exercise can improve flexibility and bone strength and make you feel younger, but this is not the same as “appear[ing] 10 years younger”.

It could be the case that the headline was shoehorned in due to the Mail Online’s obsession with physical appearance. The most notorious example being the so-called “Sidebar of Shame” – the list of photo captions on the right of the website, which are mainly about how celebrities look.

 

What kind of research was this?

This was a cross-sectional study of older adults in Scotland. It aimed to see if there was a link between owning a dog and increased activity levels. As it is a cross-sectional study, it is only able to look at one point in time therefore it cannot prove cause and effect, it can only show associations.

 

What did the research involve?

The researchers used data from a study called the Physical Activity Cohort Scotland (PACS). Adults over the age of 65 were recruited from 17 GP practices across Tayside in Scotland. They were randomly selected from these practices to have a sample that included people from rural, urban, deprived and less deprived areas.

People were excluded from the study if they were in residential care, wheelchair or bedbound, had cognitive impairment, or were in another study.

Of the 3,343 people invited to take part, 584 people agreed and this study used the details from 547 of them.

The study was conducted between October 2009 and February 2011. Each participant was asked to wear an accelerometer (a device, usually electrical, that measures physical movement) for seven days to record their level of physical activity. They were requested not to change their usual pattern of activity during that week. They also filled out the following questionnaires:

  • Older People and Active Living (OPAL) questionnaire which included information on their housing, marital status, education level, pet ownership and chronic medical illnesses
  • Hospital Anxiety and Depression Score (HADS)
  • SF-36, which measures general health status
  • Social Capital Questionnaire, which captures relationship networks – such as how many friends and family an individual is in regular contact with
  • London Health and Fitness Questionnaire, which covers attitudes towards physical activity and past experiences of physical activity
  • an item from the Extended Theory of Planned Behaviour Questionnaire, which asked them to rate how strongly they agreed or disagreed with the sentence “I intend to do 30 min of moderate-intensity physical activity on five or more days in the forthcoming week”

The researchers also collected data on weather conditions during the accelerometer use from the UK Meteorological Office as they say that “dog walking behaviour is fairly robust to inclement weather especially in a temperate climate, whereas other types of walking are not”. That is dog walkers are more likely to brave the rain than people who walk for pleasure or exercise.

They performed statistical analyses to look for associations between level of physical activity and pet ownership. They then accounted for various potential confounding factors such as their environment, medical illnesses and socioeconomic status.

 

What were the basic results?

The average age of the participants was 79. Fifty people (9%) owned a dog, and their average age was 77.

When no other factors were taken into account, according to the accelerometer readings, dog owners were 27% more physically active than non-dog owners. When the analysis took into account all of the environmental and medical factors, dog owners still had 12% higher levels of physical activity.

Dog owners were significantly more likely to:

  • be married
  • live in rural areas
  • have been physically active between leaving school and being 25 years old
  • have the intention to be physically active
  • have perceived behavioural control
  • have better general health and physical functioning

Dog owners were also less likely to have symptoms of depression.

How did the researchers interpret the results?

The researchers say that this study shows that “on average, older dog owners were 12% more active than their counterparts who did not own a dog. This difference is equivalent to the levels of PA [physical activity] between people who differ by 10 years in age”.

They suggest that “interventions to increase activity amongst older people might usefully attempt to replicate elements of the dog ownership experience”.

In an interview with the Mail, the lead researcher Dr Zhiqiang Feng, mentions the possibility of developing an app that replicates the experience of owning a dog by prompting its “owner” to take it for “walkies” at regular intervals.

 

Conclusion

Despite media claims, this study has not shown that dog owners have bodies that appear 10 years younger than people who do not own dogs.

However, it has shown a difference in physical activity between dog owners and non-dog owners of around 12%. This was reported by the authors as being the same as the difference between people who are 10 years apart in age.

It should be noted that this figure comes from the same sample of people, reported in a previous paper. It found that the accelerometry counts were highest in affluent adults aged 65 to 80, followed by deprived adults aged 65 to 80, with lowest levels in deprived adults over 80 years old.

Strengths of the study include the attempt to recruit a diverse section of the population. However there is potential bias in the population sample as only 19% of people invited to take part in the study agreed.

Therefore it may be that this sample is not representative of the whole population, but is perhaps a group of people who are more motivated or interested in physical activity. The results are also based on a sample of just 50 dog owners. It also excluded people who were in residential care, wheelchair or bedbound or had cognitive impairment, some of whom are likely to be dog owners.

The researchers attempted to account for differences in physical activity levels according to the weather at the time the accelerometer readings were taken.

However, it is not clear whether each participant wore the accelerometer at the same time of the year, which could have an effect on activity levels and ability to be outside.

Overall this study shows that being a dog owner is associated with higher levels of physical activity and general health, presumably because of the requirement to take them for walks each day, but this study cannot prove that this is the cause of the results seen.

However, it is clear that exercise and walking are beneficial to physical and mental health and should be encouraged across all age groups.

Walking just 30 minutes, five times a week, can bring considerable health benefits over time.

And, as a story we covered earlier this week suggested, it may even help lower your dementia risk.

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

Links To The Headlines

Want to appear 10 years younger? Just buy a dog. Mail Online, July 15 2014

Links To Science

Feng Z, Dibben C, Witham MD, et al. Dog ownership and physical activity in later life: A cross-sectional observational study. Preventive Medicine. Published online June 12 2014

Categories: NHS Choices

Prediabetes label unhelpful, experts argue

NHS Choices - Behind the Headlines - Wed, 16/07/2014 - 12:17

“Pre-diabetes label ‘worthless’, researchers claim,” reports the BBC.

The headline is based on an opinion piece published in the British Medical Journal (BMJ) by John Yudkin and Victor Montori, both of whom are professors of medicine.

They argue that diagnosing people with “prediabetes” puts people at risk of unnecessary medicalisation and creates an unsustainable burden on healthcare systems.

The piece is part of an ongoing BMJ series called “Too much medicine”, which is examining what is known as over-medicalising – treating “problems” that don’t actually require treatment.

They argue that money would be better spent changing food, education, health and economic policies.

This is an opinion piece. Although the authors support their opinions with studies, other evidence available could contradict their views.

 

What is meant by ‘prediabetes’?

Prediabetes is used to describe people at risk of diabetes because they have impaired glucose metabolism, but who do not meet the criteria for diabetes and often have no noticeable symptoms.

It is a term that was introduced by the American Diabetes Association (ADA), but has not been accepted by other health organisations, such as the World Health Organization (WHO).

It may be defined as:

  • impaired glucose tolerance
  • above normal glucose blood concentration after fasting
  • above normal glycated haemoglobin (a marker of average blood glucose concentration)

Supporters of the term’s usage argue that it allows doctors to identify high-risk patients, so they can be treated in order to prevent diabetes from occurring.

 

What objections do the authors have about the use of the term?

The authors point out that there has been little support for the ADA’s prediabetes label from other expert groups, including WHO, the International Diabetes Federation and the UK’s National Institute for Health and Care Excellence (NICE).

The authors say this is because the ADA has lowered the thresholds for impaired fasting glucose and glycated haemoglobin. Because it encompasses all three aspects of impaired glucose metabolism (impaired glucose tolerance, above normal fasting blood glucose, above normal glycated haemoglobin), the lowered thresholds have created a large, poorly characterised and heterogeneous (mixed) category of glucose intolerance.

In other words, the diagnostic criteria are now so broad (in the opinion of the authors) that it is, essentially, useless.

The authors say that using the ADA’s definition of prediabetes would result in two to three times as many people being diagnosed with impaired glucose metabolism. This would lead to 50% of Chinese adults being diagnosed with prediabetes – over half a billion people.

The authors also question the value of diagnosing people with prediabetes.

They point out that the drugs used to treat people with prediabetes in order to stop them developing diabetes are often the same as the drugs they would take if they actually developed diabetes.

The side effects of these drugs must be measured against the fact that many people with prediabetes, who remain untreated, will not go on to develop the condition.

They also discuss the merits of lifestyle interventions, such as regular exercise and improved diet.

They point out that these types of interventions are of use for all adults, so they question the wisdom of only promoting these interventions to specific groups. A better use of campaigning would be to target all adults, they say.

 

What dangers or risks do they claim could occur by using the term?

The authors suggest that a label of prediabetes, while not causing any physical symptoms, could still cause:

  • problems with self-image
  • anxiety about future complications
  • challenges with insurance and employment
  • a need for medical care and treatment
  • increased healthcare costs
  • medication side effects, if prediabetes is treated with drugs

In their opinion, the diagnosis would cause more problems than it solves.

 

What do the researchers suggest instead?

The researchers say that the risk factors for developing a whole host of chronic diseases overlap, and that money would be better spent changing food, education, health and economic policies.

 

What should I do if I have been told I have prediabetes or that I am at high risk of developing diabetes?

If you have been told you have prediabetes, or that you have a high risk of developing diabetes, you can reduce your risk of developing the illness by:

Read more advice about lowering your diabetes risk.

Analysis by Bazian. Edited by NHS ChoicesFollow Behind the Headlines on TwitterJoin the Healthy Evidence forum.

Links To The Headlines

Pre-diabetes label 'worthless', researchers claim. BBC News, July 16 2014

Millions unnecessarily labelled pre-diabetic, health experts say. The Guardian, July 15 2014

Links To Science

Yudkin JS, Montori VM. The epidemic of pre-diabetes: the medicine and the politics. BMJ. Published online July 15 2014

Categories: NHS Choices

Study explores effect of plain cigarette packs

NHS Choices - Behind the Headlines - Tue, 15/07/2014 - 13:00

"Long-term smokers find the taste of plain-packaged cigarettes worse than that of branded cigarettes," The Guardian reports.

The news comes from Australian research into the impact of plain packaging and health risk warnings on packets of cigarettes and anti-smoking TV adverts.

The researchers found highly emotive warnings were more likely to capture the attention of the study's participants. However, these warning messages did not actually prompt the smokers to try to quit.

Interestingly, some smokers reported they felt the quality and taste of cigarettes had worsened or different brands now all tasted the same after plain packs were introduced.

While this may well be a minority view, it does suggest the effects of branding could have a psychological influence on some smokers, changing how they perceive the quality of the product.

This may explain why tobacco companies have been lobbying against similar laws being introduced in the UK.

Further research is needed to determine the best ways of engaging with vulnerable smokers.

 

Where did the story come from?

The study was carried out by researchers from the University of Newcastle and the Hunter Medical Research Institute in Newcastle, Australia.

It was funded by an Australian Postgraduate Award PhD Scholarship, the Cancer Institute New South Wales, and Newcastle Cancer Control Collaboration.

The study was published in the peer-reviewed journal Health Education Research.

The Guardian's headline, "Long-term smokers find plain-packaged cigarettes taste worse", gives a false impression of the findings of this study. The researchers did not compare the taste of branded and plain-packaged cigarettes.

Following the implementation of plain packaging, perceptions of the quality and taste of cigarettes did change for some participants.

However, it is unclear from the research article whether this was a majority view, and the research itself was not designed to address the question of whether plain-packaged cigarettes taste different.

 

Links To The Headlines

Long-term smokers find plain-packaged cigarettes taste worse. The Guardian, July 15 2014

Links To Science

Guillaumier A, Bonevski B, Paul C. Tobacco health warning messages on plain cigarette packs and in television campaigns: a qualitative study with Australian socioeconomically disadvantaged smokers. Health Education Research. Published online June 25 2014

Categories: NHS Choices

Spoons lead to inaccurate medicine doses for kids

NHS Choices - Behind the Headlines - Tue, 15/07/2014 - 12:15

“Using a spoon to measure medicine for children can lead to potentially dangerous dosing mistakes,” the Daily Mail reports.

Parents have long been instructed to provide liquid medication to their children in dosages measured using teaspoons and tablespoons. The rationale behind the advice is that this provides a quick and easy way for parents to calculate the correct dose.

However, a new study suggests that many parents misinterpret this advice, leading to either under or overdosing, which could be potentially harmful for a child.

The study involved 287 parents of children aged under nine years who were prescribed a daily oral liquid medication for two weeks or less.

After the end of the medication course, parents were asked about the dose of medication they were supposed to be giving their child and how they measured it. 

The researchers found that dosing errors of medications are common, with nearly a third of parents making an error in knowledge of the prescribed dose. Around one in six parents used a kitchen spoon rather than a teaspoon or tablespoon to measure out liquid medicines.

The researchers found that errors were less common when the unit of measurement used to describe the dose was millilitre rather than teaspoon/tablespoon.

The researchers conclude that this suggests moving to a millilitre-only standard – which can be delivered using a dropper, oral syringe or dosing spoon – as this could reduce confusion and decrease medication errors.

Where did the story come from?

The study was carried out by researchers from New York University School of Medicine, Bellevue Hospital Center and Woodhull Medical Center in New York, and Pennsylvania State University College of Medicine.

It was funded by the US National Institutes of Health, the National Institute of Child Health and Human Development and Nation Center for Research Resources.

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

The research was well reported by the Daily Mail.

 

What kind of research was this?

This was a cross-sectional study, with information gathered at one point in time.

The researchers were concerned about the lack of standard units of measurement for oral liquid medications for children.

Instead, parents may be told to measure doses in:

  • millilitres (ml)
  • teaspoons
  • tablespoons
  • milligrams
  • dropperfuls
  • cubic centimetres

Understandably, this can lead to confusion.

In addition, the researchers were also concerned about expressing doses in teaspoons and tablespoons, because if parents mix-up these units it can lead to children being given either a third or three times the intended dose. One teaspoon is equivalent to 5ml and one tablespoon is equivalent to 15ml. 

Furthermore, expressing doses in this way may lead to kitchen spoons being used to measure doses, and these vary widely in size and shape.

 

What did the research involve?

The researchers studied 287 parents of children aged under nine years who were prescribed a daily oral liquid medication for two weeks or less at one of two hospital paediatric emergency departments in New York.

Between four days and eight weeks after the end of the prescribed medication course, parents were asked to report the dose they gave their child, and the researchers performed a dosing assessment.

In the dosing assessment, researchers watched parents after they were asked to dose the medication as they would at home.

They were given a standard medication bottle and asked to use the dosing instrument they used or to select a comparable one from a range provided. The range consisted of a kitchen teaspoon, kitchen tablespoon, dosing spoon, measuring spoon, dosing cup, 5ml dropper, acetaminophen (the US term for paracetamol) infant dropper, ibuprofen-specific dropper and 1-, 3-, 5-, 10- and 12-ml oral syringes.

The researchers compared the results with the prescribed dose to see if there was an error:

  • in knowledge of the child’s prescribed dose
  • in measurement compared to the parent’s intended dose (dose the parent reported giving)
  • in measurement compared to the child’s prescribed dose

To be classified as an error the difference had to be more than 20%.

The researchers looked at if the likelihood of an error depended on:

  • whether parents used a nonstandard dosing instrument (kitchen teaspoon or tablespoon)
  • the unit of measurement used

The researchers adjusted their analyses for child and parent age and gender, parent-preferred language, ethnicity, level of education, socioeconomic status, parent health literacy and child’s chronic disease status.

 

What were the basic results?

The researchers found that:

  • nearly a third (31.7%) of parents made an error in knowledge of the prescribed dose
  • about 40% (39.4%) made an error in measurement of dose compared to the parent’s intended dose
  • about 40% (41.1%) made an error in measurement of dose compared to the child’s prescribed dose
  • around one in six parents (16.7%) used a kitchen spoon rather than a standard measurement instrument (oral syringe, dropper, dosing cup or spoon, or measuring spoon)

The researchers found that units of measurement in the child’s prescription, on the medication bottle, and that the parent reported often did not correspond, with the bottle label not containing the same units as the prescription more than a third of the time (36.7%), and parents not using the unit listed in the prescription or label. The researchers thought that parents were likely to have been exposed to different units as part of verbal instructions from the clinician prescribing the medication.

Units of measurement on the prescription or the bottle were not associated with errors in knowledge or measurement; however, the unit reported by the parent was associated with both types of error:

  • Compared with parents who used ml only, parents who used teaspoons or tablespoons were more likely to make errors in measurement compared to their intended dose (adjusted odds ratio [AOR] 2.3; 95% confidence interval [CI], 1.2 to 4.4) and to the prescribed dose (AOR = 1.9; 95% CI, 1.03 to 3.5)
  • Parents who reported their dose using teaspoon or tablespoon units were more likely to use a nonstandard instrument than those who used ml.
  • Parents using a nonstandard instrument had more than twice the odds of making an error in measurement compared with both their intended (AOR = 2.4; 95% CI, 1.1 to 5.0) and prescribed (AOR = 2.6; 95% CI, 1.2 to 5.5) doses.

 

How did the researchers interpret the results?

The researchers conclude that their findings "support a millilitre-only standard to reduce medication errors”. 

 

Conclusion

This US cross-sectional study has found that parent dosing errors of medications for children are common. Around one in six parents use a kitchen spoon rather than a standard measurement instrument to measure out liquid medicines.

It also found that errors were less common when the unit of measurement was ml rather than teaspoon/tablespoon.

A limitation of this study was that parents were assessed between four days and eight weeks after the end of the child’s prescribed medication course, meaning that memory could have had an impact. There is also the possibility that the accuracy was actually even worse than they observed, as the parents are likely to have been paying full attention to measuring the medication during the supervised assessment, rather than having distracting children around. There would also be a likelihood that they would not have wanted to “fail” the test.

In addition, as this is a cross-sectional study, it cannot show that the unit of measurement caused the errors in measurement.

However, overall, the main findings of the study would certainly seem to support the researchers’ call for a standard unit of measurement to avoid potential confusion.

In the UK, many of the leading manufacturers of liquid medication for children provide oral syringes or droppers with the medication, so this may be less of a problem than in the US.

If in doubt about any aspect of the use of children’s medication, ask your pharmacist for advice.

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

Links To The Headlines

Why a spoon WON'T help the medicine go down: Risk of dosage mistakes is 50% higher, doctors warn. Daily Mail, July 15 2014

Links To Science

Yin HS, Dreyer BP, Ugboaja DC, et al. Unit of Measurement Used and Parent Medication Dosing Errors. Pediatrics. Published online July 14 2014

Categories: NHS Choices

Sex addiction affects brain in 'same way as drugs'

NHS Choices - Behind the Headlines - Mon, 14/07/2014 - 16:19

“Is compulsive sexual behaviour comparable to drug addiction?” asked The Guardian today.

This and other related headlines came from a UK study that looked at brain scans of 19 men with compulsive sexual behaviour (CSB) while they watched either sexually explicit, erotic or non-sexual videos.

CSB is a not a well-established diagnosis as it does not have a formal, universally accepted, definition. It has been described as the inability to control the sexual urges, behaviour or thoughts, often with negative consequences for the individual concerned.

Examples given in the study include spending large amounts of money on escort services and losing a job due to viewing pornography at work.

The study indicated that some areas of the brain were activated more when viewing sexually explicit content in men with CSB than in similarly aged men without the disorder.

Given the pattern of brain activity and other ratings of desire, the researchers indicated that the behaviour showed similarities with drug addiction. However, this comparison was theoretical and was not actually tested in this study.

The research did not involve many men, so the results cannot be taken as definitive. Research in larger groups will be needed to confirm these initial observations and to increase confidence that the observations are true in more general terms.

It is hoped that these initial investigations will give addiction researchers some focus for future research into the condition, which has been poorly studied.

 

Where did the story come from?

The study was carried out by researchers from the University of Cambridge and was funded by the Wellcome Trust, National Institutes for Health (US) and the National Centre for Responsible Gaming.

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

Generally, the media reported the facts of the study accurately. The Guardian provided especially useful background context on the issue of CSB and pornography.

 

What kind of research was this?

This was a human study investigating the brain activity of men who had compulsive sexual behaviour.

CSB was described in the paper as excessive or problematic engagement in sex, which has also been described as “sex addiction”. Like other compulsive disorders, this is far more than just enjoying sex a lot.

It is described as the inability to control sexual urges, behaviours or thoughts, which often has a detrimental effect on the person’s life, such as not being able to engage in stable relationships.

They may not actually want or enjoy what they are doing. The researchers suggest CSB may have common brain signals and networks as other natural and drug addictions. The researchers say little is known about how the brain reacts to sexually explicit material in individuals with CSB and those without – so the researchers decided to find out.

Studying brain activity is a common tool for indicating which areas of the brain are triggered and active during different stimuli. During the scans, researchers see areas of the brain light up corresponding to activity and, depending on the area, can infer whether this is in areas of reward, fear, excitement and other emotions and responses.

 

What did the research involve?

Researchers scanned the brains of 19 men with CSB while watching videos – some sexually explicit, some erotic and others non-sexual – to compare the brain activity in each scenario. They also asked the men to rate their sexual desire and whether they liked the videos. The same experiment was carried out with 19 age-matched healthy volunteers without CSB, to act as a comparison group.

Men with CSB were recruited via internet-based advertisements or referrals from therapists, and were interviewed by a psychiatrist to ensure that they met diagnostic criteria for the disorder. They were aged over 18 (with an average age of 25.6 years), heterosexual and free from any other compulsive disorders or serious mental health issues. The men filled in questionnaires assessing their impulsivity, depression, anxiety, alcohol dependence and intelligence. Age-matched heterosexual males without CSB were recruited by community advertisement.

Two of the 19 CSB subjects were taking antidepressants or had coexisting generalised anxiety disorder and social phobia (two of them), social phobia (one of them), or a childhood history of ADHD (one of them). One man with CSB and one healthy volunteer used cannabis intermittently.

The team used functional magnetic resonance imaging to observe changes in brain activity while the men watched the videos.

 

What were the basic results?

There were both similarities and differences in the brain responses of men with CSB and those without. Sexual desire or watching of the explicit sexual videos was linked to activation in a part of the brain called dACC ventral striatal-amygdala functional network across both groups. However, it was more strongly activated and linked to sexual desire in the CSB group.

Sexual desire ratings to explicit videos were greater in men with CSB compared to healthy volunteers, but not to erotic cues, whereas liking ratings to erotic cues were greater in CSB compared to healthy volunteers, but not to explicit cues. This showed that men’s rating of desire and liking were not always related.

The researchers said that the dissociation between desire and liking is consistent with theories of motivation underlying CSB seen in drug addictions.

 

How did the researchers interpret the results?

The researchers highlighted similarities between the brain activity they had observed in men with CSB and similar findings from other research in the brains of drug addicts.

 

Conclusion

This observational study used the brain scans of 19 men with CSB to point to some areas of the brain that were activated more when viewing sexually explicit content, compared with men without the compulsive behaviour.

There were many similarities between the brains and responses of men with and without CSB, indicating that the distinction was complex and overlapping. However, some areas were identified as being more active in men with CSB. This gives researchers in the field of addiction a better focus for future research.

The research did not compare the brains of men with CSB to those people with substance misuse, or those with other forms of addiction (such as gambling), to look for differences directly. These comparisons were theoretical and were not tested empirically in this study.

Given the research involved so few men, the results cannot be taken as definitive. More research in larger groups will be needed to confirm these initial observations and to increase confidence that the observations are true in more general terms.

It is important to note that there is no formal diagnostic criteria for CSB, and there is debate as to whether it should be labelled as a condition.

Similar debate has surrounded other addictive behaviour associated with excessive or compulsive use of the internet or computer games.

Research like this is important in understanding the brain biology and the psychological processes behind this behaviour – which often has a negative impact on a person’s life.

If you are concerned that a preoccupation with sex or sexual content online may be having a negative impact on your life, it is reassuring to know that there is help available.

It may be useful to discuss the issue with your GP. The Sex and Love Addicts Anonymous website also provides information on sexually compulsive behaviours. 

Analysis by Bazian. Edited by NHS ChoicesFollow Behind the Headlines on TwitterJoin the Healthy Evidence forum.

Links To The Headlines

Is compulsive sexual behaviour comparable to drug addiction? The Guardian, July 14 2014

Scientists probe 'sex addict' brains. BBC News, July 12 2014

Love is the drug, scientists find. The Daily Telegraph, July 11 2014

The brain on porn: Researchers find sex addicts get the same high as a drug addict getting a hit. Daily Mail, July 12 2014

Links To Science

Voon V, Mole TB, Banca P, et al. Neural Correlates of Sexual Cue Reactivity in Individuals with and without Compulsive Sexual Behaviours. PLOS One. Published online July 11 2014

Categories: NHS Choices

'Exercise may help prevent Alzheimer's disease'

NHS Choices - Behind the Headlines - Mon, 14/07/2014 - 12:17

"Cut Alzheimer's risk by walking," the Daily Mail recommends. This advice is prompted by a statistical modelling study looking at population attributable risks (PARS) – factors known to influence the prevalence of a disease, such as Alzheimer's, at a population level.

The seven risk factors researchers looked at included diabetes, smoking, high blood pressure, lack of exercise, obesity, depression and low educational level. In theory, some cases of Alzheimer's disease might be prevented by reducing these risk factors.

For example, the study estimated physical inactivity accounted for 21.8% of the risk of developing Alzheimer's in the UK. Another way of saying this is that if nobody was inactive, the risk of Alzheimer's in the UK population could reduce by 21.8%.

But this is only a theory that applies to an entire population, not individuals. We cannot say for sure that living a healthier life will definitely prevent Alzheimer's disease.

One of the biggest risk factors for Alzheimer's is age, and it is possible age will interact with the seven modifiable factors over different stages of a person's life. This could create a more complex risk profile than the current study was able to describe.

But a healthy lifestyle does have other benefits – regular exercise can reduce your risk of developing heart disease and some types of cancer.

 

Where did the story come from?

The study was led by researchers from the psychology department at the Institute of Psychiatry, King's College London, and was funded by an award from the National Institute for Health Research Collaboration for Leadership in Applied Health Research and Care for Cambridgeshire and Peterborough.

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

The UK media's reporting was generally accurate, with most focusing on the physical activity risk, which was the most important factor for the UK data.

 

What kind of research was this?

This modelling study used existing data on potential risk factors for developing Alzheimer's disease, including sociodemographic and lifestyle factors, and health-related factors such as diabetes and high blood pressure.

The researchers then predicted the amount of disease that might be prevented if these risk factors were reduced through changes in lifestyle.

While this type of research can provide useful predictions, they are just that – hypothetical predictions.

Similarly, the predictions apply to entire populations of people, such as everyone in UK. This means the study cannot say that living a healthier life will prevent Alzheimer's for any specific individual, only that it may prevent some cases across the group as a whole. 

 

What did the research involve?

The researchers used existing population-based research to identify the main modifiable risk factors that may be associated with Alzheimer's disease.

They then predicted how many cases of Alzheimer's disease might be prevented if the risks were reduced across the US, the UK and the rest of the world.

The main analysis was the calculation of the population attributable risk, or PAR. This is the proportion of cases of a disease in a population that is attributable to the risk factor.

A modifiable risk factor, such as smoking, is a risk you can potentially reduce – for example, by stopping smoking. The main modifiable risk factors linked to developing Alzheimer's disease were:

  • diabetes – adult prevalence of diagnosed diabetes between the ages of 20 and 79
  • midlife high blood pressure – adult midlife prevalence of hypertension between the ages of 35 and 64
  • midlife obesity – adult midlife prevalence of body mass index greater than 30 between the ages of 35 and 64
  • physical inactivity – proportion of adults who do not do either 20 minutes of vigorous activity on three or more days, or 30 minutes of moderate activity on five or more days per week
  • depression – lifetime prevalence of major depressive disorder using Diagnostic and Statistical Manual of Mental Disorders or International Classification of Diseases criteria
  • smoking – the proportion of adult smokers
  • low educational level – the proportion of adults with an International Standard Classification of Education level of two or less (pre-primary, primary and lower secondary education)

The researchers made projections for the number of cases of Alzheimer's disease up to the year 2050. They then modelled risk reductions of 10% and 20% for each decade from now until 2050 to see how many disease cases could be prevented.

They did this for each risk factor both individually (to see which ones had the biggest impact) and combined.

The predictions took account of associations between risk factors – for example, that a person who is obese is more likely to have high blood pressure.

 

What were the basic results?

The study calculated PAR for the world, the US and the UK. We focus on the UK results below.

The largest PAR for an individual risk factor in the UK was for physical inactivity (PAR 21.8% 95% confidence interval [CI], 6.1% to 37.7%).

This meant that 21.8% of the Alzheimer's cases were predicted to be attributable to physical inactivity, which could potentially be prevented if people were more active.

The next highest PAR was for low educational level (PAR 12.2% 95% CI, 7.6% to 16.9%), followed by smoking (10.6%, 95% CI, 2.9% to 19.4%).

Diabetes, midlife hypertension, midlife obesity and depression gave PARs in the range of 1.9% to 8.3%.

Combining the seven risk factors together gave a UK PAR of 30.0% (95% CI, 14.3% to 44.4%).

This means the researchers predicted around 30.0% of the risk of developing Alzheimer's disease in the UK was attributable to a combination of these seven modifiable risk factors.

This estimate adjusted for associations between risk factors, such as obesity and diabetes.

 

How did the researchers interpret the results?

The researchers concluded that, "After accounting for non-independence between risk factors, around a third of Alzheimer's diseases cases worldwide [and in the UK] might be attributable to potentially modifiable risk factors.

"Alzheimer's disease incidence might be reduced through improved access to education and use of effective methods targeted at reducing the prevalence of vascular risk factors [for example, physical inactivity, smoking, midlife hypertension, midlife obesity and diabetes] and depression."

 

Conclusion

This study suggests around a third of the risk of developing Alzheimer's disease might be caused by a combination of seven lifestyle-related risk factors, including low educational level, physical inactivity and smoking. In theory, by reducing these risk factors some cases of Alzheimer's disease might be prevented.

Predictive studies such as this one are only as good as the assumptions and data used in the calculations. As the researchers themselves acknowledge, despite their best efforts to the contrary, this still involves "substantial uncertainty". Consequently, there may be some variation in the estimates of the PARs presented because of potential inaccuracies or natural variations in prevalence data.

The strength of the association between the risk factor and the disease may also vary in different groups. This accuracy could be tested by repeating the research using a range of different data sources and assumptions. 

The predictions this study makes apply to entire populations of people, such as everyone in the UK. It therefore cannot say that living a healthier life will definitely prevent Alzheimer's for any specific individual, only that it may reduce the risk and prevent some cases across the group as a whole.

If everyone in the UK was physically active (defined in this study as 20 minutes of vigorous activity on three or more days a week, or 30 minutes of moderate activity on five or more days a week) the study predicts around 20% of the risk of developing Alzheimer's would be cut, which would reduce the number of people developing the disease overall.

But because we are modelling the effect in large groups, it is not possible to pinpoint which people would get Alzheimer's and which would not. Other types of test and analysis would need to be developed to be able to predict this.

These predictions assume that all the risk factors tested directly cause or contribute to Alzheimer's disease. The researchers acknowledge this is open to debate in some areas. This means the risk accounted for by these factors could potentially be lower than estimated in this study.

One of the biggest risk factors for Alzheimer's disease is age, and it is likely age will interact with the seven modifiable factors over different stages of a person's life, creating a more complex risk profile than this study was able to describe.

For example, it is unlikely that someone who decides to quit smoking and start exercising regularly at 20 would have the same risk reduction as someone deciding the same thing at 70.

Nonetheless, there are a host of other good reasons for leading a healthy lifestyle, no matter what your age. Keeping active once you reach retirement age can also help you stay more energetic, healthy and independent as you get older.

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

Links To The Headlines

Cut Alzheimer's risk by walking: It only takes 20 minutes, 3 times a week, say Cambridge scientists. Daily Mail, July 14 2014

One in three Alzheimer's cases preventable, says research. BBC News, July 14 2014

The key to reducing risk of Alzheimer's unlocked – and the answer is exercise. Metro, July 14 2014

One hour of exercise a week 'can halve dementia risk'. The Daily Telegraph, July 13 2014

Third of Alzheimer's cases could be 'preventable'. ITV News, July 14 2014

How to beat Alzheimer's: Exercise & better education can ward off dementia, experts claim. Daily Express, July 14 2014

Links To Science

Norton S, Matthews FE, Barnes DE, et al. Potential for primary prevention of Alzheimer's disease: an analysis of population-based data. The Lancet Neurology. Published online July 13 2014 

Categories: NHS Choices

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