Medical News

Female lung cancer deaths 'may outstrip breast cancer' in 2015

Medical News - Tue, 01/27/2015 - 15:12

The Mail Online states: “Lung cancer death rates among European women set to overtake breast cancer for first time this year,” adding that “researchers blame high levels of smoking, especially in Britain and Poland”.

The study used historical information on deaths from cancer (1970 to 2009) for the EU, to predict the number of deaths in 2015. It also did this for some individual countries, including the UK.

The overall results from the study were arguably positive. Cancer death rates for the EU have been declining in most cancers and are likely to continue declining in 2015. However, this masked less positive trends in specific cancer types, specific countries, and differences between men and women.

What hit the headlines was the prediction that lung cancer deaths in women will rise. The lung cancer death rate would be the highest of all cancer types for women, exceeding that of breast cancer for the first time.

The study didn’t investigate the reasons for the lung cancer mortality trend, but said that smoking was the likely culprit. Women who took up the habit in the past are likely to be now reaching the age where the cumulative effects of tobacco smoke will mean that approximately half of them will be killed by their habit.

Quitting smoking is likely to be the single biggest thing you can do to improve your health and many people don’t find it that difficult. Read our stop smoking advice.

 

Where did the story come from?

The study was carried out by researchers from universities based in Italy and Switzerland, and was funded by the Swiss League against Cancer, the Swiss Foundation for Research against Cancer, the Italian Association for Cancer Research and COST Action EU-Pancreas.

The study was published in the peer-reviewed medical journal Annals of Oncology. The study is free to view and download online.

The media coverage was generally balanced and included useful information on the potential explanations for the high rates of smoking in UK women.

The Mail Online quoted lead researcher Professor Carlo La Vecchia as saying, “This is due to the fact that British women started smoking during the Second World War, while in most other EU countries women started to smoke after 1968. It is worrying that female lung cancer rates are not decreasing in the UK, but this probably reflects the fact that there was an additional rise in smoking prevalence in the UK as well in the post-1968 generation – those born after 1950”.

 

What kind of research was this?

The research was an ecological study estimating the number of cancer cases across Europe for 2015, based on past trends.

The report’s authors wanted to update previous predictions for the EU made in 2012 and to explore prostate cancer, the third largest cause of male cancer deaths in the EU, in more depth.

An ecological study is good at estimating what happens at a wide geographic level to large groups of people. The drawback is that it cannot tell us what will happen to any one person. We could say that more women in the UK will probably die from lung cancer in 2015 than 2009, but we can’t say, based on this type of study, who will.

 

What did the research involve?

The researchers fed a statistical model with sets of historical data on stomach, colorectal, pancreas, lung, breast, uterus, prostate, cancers of the white blood cells, and total cancers from across the EU. The model estimated what cancer rates would be like in 2015, based on the previous trends.

Estimates of death rates by age group and gender were calculated for the EU as a whole, and individually for its most populous countries of France, Germany, Italy, Poland, Spain and the UK.

The data for the EU as a whole covered a period from 1970 to 2009. The UK-specific data was up-to-date as of 2010.

Data were obtained from the World Health Organization and Eurostat – both publically available sources of European statistics. These sources rely on official death certificate data, as well as population level estimates.

 

What were the basic results?

The overall picture was that cancer rates have been falling in the EU and in the UK since the 1970s, and that this trend is likely to continue overall. However, this masks a number of increasing trends for specific types of cancer, and differences between men and women.

Predicted overall cancer deaths in the EU for 2015

More than a million cancer deaths were predicted in the EU in 2015 (766,200 men and 592,900 women), corresponding to standardised death rates of 138.4 per 100,000 men and 83.9 per 100,000 women. Comparing 2009 data to 2015, total cancers are predicted to fall by 7.5% in men and 6% for women.

Pancreatic cancer had a negative outlook in both sexes, rising by 4% in men and 5% in women between 2009 and 2015.

Predicted female cancer deaths in the EU for 2015

In women, breast and colorectal cancers had favourable downward trends (-10% and -8%), but predicted lung cancer rates are set to rise 9% to 14.24 deaths per 100,000 women, becoming the cancer with the highest rate, reaching, and possibly overtaking, the breast cancer rate.

The total number of deaths predicted for 2015 remain higher for breast (90,800) than lung (87,500).

Predicted male cancer deaths in the EU for 2015

In men, predicted rates for the three major cancers in 2015 were lower than in 2009, with prostate falling by 12%, lung cancer by 9% and colorectal by 5%.

Prostate cancer showed estimated falls of 14%, 17% and 9% in the 35-64, 65-74 and over-75 age groups.

 

How did the researchers interpret the results?

The overall conclusions of the researchers were that: “Cancer mortality predictions for 2015 confirm the overall favourable cancer mortality trend in the EU, translating to an overall 26% fall in men since its peak in 1988, and 21% in women, and the avoidance of over 325,000 deaths in 2015, compared with the peak rate”.

 

Conclusion

This ecological study used historical information on deaths from cancer for the EU region (1970 to 2009) to predict the numbers of deaths in 2015.

The overall news was positive: cancer death rates for the EU have been declining in most cancers and are likely to continue declining in 2015. However, this masked other less positive trends in specific cancer types, specific countries, and differences between men and women.

The predictions that hit the headlines were that lung cancer deaths in women are going to rise. Moreover, that the rates (number of deaths per 100,000 women) would be the highest of all cancer types for women, knocking breast cancer off the top spot for the first time.

The study did not investigate the potential causes for the lung cancer death increases directly, but the likely culprit is smoking, which is one of the biggest risk factors for developing lung cancer. Women who took up the habit in the past are now reaching the age where the cumulative effects ensure that approximately half of them will be killed by their habit.

As with all ecological studies, these results cannot predict local variations in cancer rates or whether any specific individuals will get cancer. For example, there may be some areas in the UK where women’s lung cancer rates are actually declining, contrary to the EU or overall UK trend, whereas in others they may be increasing more rapidly than predicted. More focused data will help us when targeting public health resources to areas most in need.

Quitting smoking is likely to be the single biggest thing you can do to improve your health, and many people don’t find it that difficult. There are a number of proven aids to increase the chance of you beating the habit.

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

Links To The Headlines

Lung cancer death rates among European women set to overtake breast cancer for first time this year. Mail Online, 27 January 2015

Lung cancer fatalities to overtake breast cancer deaths among European women. The Guardian, 27 January 2015

More British women now die from lung cancer than breast cancer. Daily Miror, 26 January 2015

Links To Science

Malvezzi M, et al. European cancer mortality predictions for the year 2015: does lung cancer have the highest death rate in EU women? Annals of Oncology. Published 26 January 2015

Categories: Medical News

Media dementia scare over hay fever and sleep drugs

Medical News - Tue, 01/27/2015 - 12:54

"Hay fever tablets raise risk of Alzheimer's," is the main front page news in the Daily Mirror. The Guardian mentions popular brand names such as Nytol, Benadryl, Ditropan and Piriton among the pills studied.

But before you clear out your bathroom medicine cabinet, you might want to consider the facts behind the (somewhat misleading) headlines.

The first thing to realise is although some of these drugs can be bought over the counter, the study only included prescribed medicines.

These were medicines that have an "anticholinergic" effect, including some antihistamines, antidepressants and drugs for an overactive bladder.

If you have been prescribed these medicines, do not stop taking them without speaking to a doctor first. The harms of stopping might outweigh any potential benefits.

That said, this large, well-designed US study suggested those taking the highest levels of anticholinergic prescribed medicines were at a higher risk of developing dementia compared with those not taking any.

Importantly, the increased risk was only found in people who took these medicines at the equivalent of once every day for more than three years. No link was found at lower levels.

However, this shouldn't make us complacent. These are not unrealistic doses of medicines, so the results may be applicable to a significant proportion of older adults.

Furthermore, we can't say if reducing the amount of anticholinergic medicines will reduce the risk of dementia to normal.

The bottom line? Do not stop taking prescribed medications without a full consultation with a doctor. It may do more harm than good.

 

Where did the story come from?

The study was carried out by researchers from the University of Washington.

It was funded by the National Institute on Aging, the National Institutes of Health, and the Branta Foundation.

The study was published in the peer-reviewed medical journal, JAMA Internal Medicine.

A number of the study's authors reported receiving research funding from pharmaceutical companies, including Merck, Pfizer and Amgen.

The story made almost all the newspapers and many online and broadcast services, with front page "splash" stories in the Mirror and The Times.

This coverage lacked the necessary caution and has all the hallmarks of a media scare story.

The media reporting of the study generally took the findings at face value and did not highlight the potential risks associated with stopping medications suddenly.

On Radio 4 this morning, one of the study authors advised people to stop taking these types of medicines.

This is potentially dangerous, and we do not support this advice. Any changes to prescribed medicines should be made after full consultation with a medical professional and should factor in your individual circumstances.

Poor media reporting also included:

  • Failing to mention the study was based on prescribed drugs, rather than those bought over the counter – an error made by the Mirror and The Daily Telegraph.
  • Failing to make it clear the antihistamines involved were only one, older class known to cause drowsiness (and avoided by many people because of this) – a mistake made by The Times, The Independent and the Mail.
  • Naming a brand (Benadryl) focused on by researchers that has a completely different drug in it in the UK – a mistake made by The Times, the Mail, The Independent and The Telegraph.
  • Having headlines that didn't make it clear the association was only seen in people over the age of 65 – a mistake made by most papers, except The Times.
  • Playing fast and loose with statistics – the Mail said up to 50% of elderly people could be taking an anticholinergic, a statement so vague it could mean half of them take them, or none take them.

Today, the Mirror, with its front page "Shocking new report" headline, was perhaps the most overblown coverage, although it was among one of the most factually correct.

The Telegraph also did well to include suggestions for alternative antihistamines and antidepressants that could be used by over-65s.

 

What kind of research was this?

This was a prospective cohort study looking at whether the use of medicines that have anticholinergic effects are linked to dementia or Alzheimer's disease.

Medications with anticholinergic effects are commonly used for a wide variety of conditions affecting older adults, such as an overactive bladder. 

Some of these medications can be bought over the counter, such as antihistamines like chlorphenamine – which is mainly sold under the brand name Piriton and is not to be confused with other antihistamine products, such as Piriteze – and sleeping pills, such as diphenhydramine, sold under the Nytol brand.

The study authors stated the prevalence of anticholinergic use in older adults ranges from 8% to 37%.

A prospective cohort study cannot definitively prove this drug class causes Alzheimer's disease or dementia, but it can show they are linked in some way. Further research is needed to properly investigate and explain any links identified.

 

What did the research involve?

The research team analysed data on 3,434 US people aged over 65. These people had no dementia at the start of the study.

The study's participants were tracked for an average of 7.3 years to see who developed dementia or Alzheimer's disease.

The researchers also gathered information on what anticholinergic medications they were prescribed in the past.

The researchers' main analysis looked for statistically significant links between these prescribed medications taken in the past 10 years and the likelihood of developing dementia or Alzheimer's disease.

Cases of dementia and Alzheimer's were first picked up using a test called the Cognitive Abilities Screening Instrument, which was given every two years.

This was followed up with investigations by a range of specialist doctors, and laboratory tests, to arrive at a consensus diagnosis.

Medication use was ascertained from a computerised pharmacy dispensing database that included the name, strength, route of administration (such as in tablets or in syrup), date dispensed, and amount dispensed for each drug. This was linked to each individual's US health insurance plan so it was personalised.

Prescriptions in the most recent one-year period were excluded because of concerns about bias. This bias could occur when a medication is inadvertently prescribed for early signs of a disease that has not yet been diagnostically detected. For instance, medications may be prescribed for insomnia or depression, which can be early symptoms of dementia.

Drugs with a strong anticholinergic effect were defined as per an American Geriatrics Society consensus panel report. Data for the medicines was converted into an average daily dose, and this was added up over the number of years people were taking them to estimate their total cumulative exposure.

This cumulative exposure was defined as cumulative total standardised daily doses (TSDDs).

The statistical analysis adjusted for a range of potential confounders identified from past research, including:

  • demographic factors such as age, sex, and years of education
  • body mass index
  • whether or not they smoked
  • their exercise levels
  • self-rated health status
  • other medical problems, including hypertension, diabetes, stroke, and heart disease
  • whether they had a variant of the apolipoprotein E (APOE) gene
  • Parkinson's disease
  • high levels of depressive symptoms
  • cumulative use of benzodiazepine medicines – this could indicate a sleep or anxiety disorder

 

What were the basic results?

The most common anticholinergic classes used over the long term were antidepressants, antihistamines, and bladder control medicines.

During an average (mean) follow-up of 7.3 years, 797 participants (23.2%) developed dementia. Most people diagnosed with dementia (637 of the 797, 79.9%) had Alzheimer's disease.

Overall, as cumulative anticholinergic exposure over 10 years increased, so did the likelihood of developing dementia, including Alzheimer's disease. Results were reported to stand up to secondary analyses.

For dementia, cumulative anticholinergic use (compared with no use), was associated with:

  • for TSDDs of 1 to 90 days, a confounder adjusted hazard ratio (HR) of 0.92 (95% confidence interval [CI], 0.74-1.16) 
  • for TSDDs of 91 to 365 days 1.19 (95%CI, 0.94-1.51)
  • for TSDDs of 366 to 1,095 days 1.23 (95%CI, 0.94-1.62)
  • for TSDDs of more than 1,095 days 1.54 (95% CI, 1.21-1.96)

It is important to note the only statistically significant result was in the group with the highest long-term exposure level.

At standardised cumulative doses of between 1 and 1,095 days (three years), there was no statistically significant increase in incidence of dementia compared with those with no exposure.

However, those in the highest cumulative anticholinergic exposure group were 54% more likely to develop dementia compared with those with no anticholinergic exposure over the previous 10-year period.

 

How did the researchers interpret the results?

The researchers' conclusions were grounded, and warned of a potential risk if the results were true. They said that, "Higher cumulative anticholinergic use is associated with an increased risk for dementia.

"Efforts to increase awareness among healthcare professionals and older adults about this potential medication-related risk are important to minimise anticholinergic use over time."

 

Conclusion

This large US prospective cohort study suggests a link between those taking high levels of anticholinergic medicines for more than three years and developing dementia in adults over 65.

The main statistically significant finding was in a group taking the equivalent of any of the following medications daily for more than three years:

  • xybutynin chloride, 5mg
  • chlorpheniramine maleate, 4mg
  • olanzapine, 2.5mg
  • meclizine hydrochloride, 25mg
  • doxepin hydrochloride, 10mg

These are not unrealistic doses of medicine, so the results may be applicable to a significant proportion of older adults.

The main limitations of the research were recognised and openly discussed by the study authors. Although we don't expect them to have significantly biased the results, we cannot rule out the possibility.

These limitations include the potential misclassification of "exposure". This is possible because some anticholinergic medicines are available without a prescription – called "over-the-counter" medicines. These would have been missed in this study, which relied on a database of prescribed medicines only.

It is therefore possible people who were reported to have no exposure may actually take, for example, regular doses of Piriton for hay fever without needing a prescription.

A related point is there is no guarantee the prescribed medications were actually taken – although it is likely they were, especially in the groups in the higher exposure categories.

Finally, we don't know whether these results can be generalised to other groups of people. The study sample was overwhelmingly white (91.5%) and university educated (66.4%). The findings will need replication in studies that recruit larger and more diverse participants to reflect wider society.

Studies are needed to better understand whether any increase in dementia risk is counteracted after people stop using anticholinergic medicines.

While there are biologically plausible theories, the mechanism by which anticholinergics might contribute to dementia risk is not well understood.

It is important to realise this study was about prescribed medicines. If you have been prescribed anticholinergic medicines, do not stop taking them without speaking to your GP first as everyone's circumstances are different. The harms of stopping might outweigh any potential benefits.

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

Links To The Headlines

Study suggests sleeping drugs can increase risk of Alzheimer’s. The Guardian, 27 January 2015

Popular sleep remedies and hay fever pills 'increase risk of Alzheimer's by more than 50%'. Daily Mail, 26 January 2015

Hay fever and sleeping tablets 'can increase risk of Alzheimer's and dementia'. Daily Mirror, 26 January 2015

Routine drugs for elderly ‘raise risk of dementia’. The Times, 26 January 2015

Hayfever pills and sleeping aids can 'significantly increase' risk of Alzheimer’s, says US study. The Independent, 26 January 2015

Hayfever drugs raise risk of Alzheimer's disease, say scientists. The Daily Telegraph, 26 January 2015

Dementia 'linked' to common over-the-counter drugs. BBC News, 27 January 2015

Links To Science

Gray SL, et al. Cumulative Use of Strong Anticholinergics and Incident Dementia. A Prospective Cohort Study. JAMA Internal Medicine. Published 26 January 2015

Categories: Medical News

People with autism have 'unique' brain patterns

Medical News - Mon, 01/26/2015 - 14:40

"The brains of people diagnosed with autism are 'uniquely synchronised'," the Mail Online reports.

Researchers used brain scans to study the brain activity of people with high-functioning autism spectrum disorders (ASD), and found distinct and differing patterns of connectivity in adults with high-functioning ASD compared with adults who do not have the condition.

This headline is based on a study comparing resting functional magnetic resonance imaging (fMRI) scans in 141 people with or without high-functioning ASD.

High-functioning ASD tends to be the term used when people have the characteristic features of autism, such as difficulties with social interaction, but without the intellectual impairment that is classically seen.

The study found communication between different areas of the brain at rest in people with high-functioning ASD differs from that of adults without ASD. In some areas, there is more communication going on, and in other areas there is less.

The exact patterns of communication differed between different people with high-functioning ASD, and people with more differences seemed to have higher levels of ASD symptoms.

We cannot say whether these differences are the cause or a result of ASD, as all of the individuals already had the condition at the time of the brain scan.

It is not yet clear whether this finding will help with diagnosing ASD earlier, as the study did not test this.

 

Where did the story come from?

The study was carried out by researchers from the Weizmann Institute of Science in Israel and Carnegie Mellon University in the US.

It was funded by an Israeli Presidential Bursary, the Simons Foundation, the Pennsylvania Department of Health, the European Union, the Israel Science Foundation, Israeli Centers of Research Excellence, and the Helen and Martin Kimmel award.

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

It isn't possible to say whether the Mail Online's suggestion that the findings "may help earlier diagnosis" will be the case.

 

What kind of research was this?

This was a cross-sectional study comparing the brains of adults with high-functioning ASD and adults without ASD.

ASD is the term used for developmental conditions characterised by difficulties with social interaction (such as difficulties in picking up on the emotions of others), communication (such as problems holding a conversation), and having a restricted or repetitive collection of interests or set routines and rituals.

Individuals with typical autism tend to have these features in addition to some degree of intellectual impairment.

Individuals with high-functioning autism or Asperger's syndrome tend to have normal or enhanced intellectual ability.

When we are at rest, our brains still send signals (messages) within each half (hemisphere) of the brain, and between the hemispheres.

In the past, there have been suggestions people with ASD have less signalling (communication) going on between different parts of the brain at rest than people without ASD.

However, recent studies suggest the opposite might be true. The researchers in this study wanted to resolve this by looking at more information on brain activity in people with high-functioning ASD, and those without ASD.

The design of this study is appropriate for comparing brain signalling in people with high-functioning ASD and without ASD. However, it cannot say whether these differences are the cause or a result of the ASD.

 

What did the research involve?

The researchers used a database of resting brain scans from adults with high-functioning ASD and adults without ASD. They compared the level of communication going on between and within the hemispheres, and in more specific regions of the brain, to see if there were any differences.

The resting brain scans were obtained using fMRI. The scans were from the Autism Brain Imaging Data Exchange (ABIDE) database, which stores resting fMRI brain scans of people with ASD and controls (people without ASD) for research purposes.

The data used in the current study was collected at a range of US universities. For some individuals, the data available also included measures of IQ and the individuals' behavioural symptoms, using the Autism Diagnostic Observation Schedule (ADOS) for symptoms in adulthood, and the Autism Diagnostic Interview (ADI) for childhood history of ASD.

The study only included people classified as having high-functioning ASD according to these scales.

The individuals whose data was analysed had an average age of around 26 years, and were mostly male (91% of those with ASD and 81% of those without).

There were 141 people in the main brain connection analyses (68 with ASD and 73 without), but not all had all of the information available on symptoms, for example. 

 

What were the basic results?

The researchers found there was greater communication between some regions of the brain in adults with high-functioning ASD than those without ASD, but less communication between others.

This essentially meant those with high-functioning ASD showed a different pattern of resting communication in their brain from the typical pattern seen in people without ASD.

This pattern also showed differences between different individuals with high-functioning ASD – so not all people with this diagnosis had the same pattern of brain signalling at rest.

The researchers found the more the communication between the reciprocal areas in the two halves of the brain differed from the "typical" pattern, the more severe behavioural symptoms the person with ASD tended to have as an adult, using the ADOS scale (total scores).

The brain differences did not appear to be related to measures of childhood history of ASD (ADI scores) or IQ scores.

 

How did the researchers interpret the results?

The researchers say their findings suggest there are different spatial patterns in the connection patterns seen in the brains of people with high-functioning ASD at rest, in comparison with people who do not have the condition.

They say these connection differences could be used to measure brain differences and symptom severity in people with ASD. They also explain why previous studies have conflicting findings about the amount of signalling in the brains of people with ASD.

 

Conclusion

This study suggests resting brain communication in people with high-functioning ASD differs from that of adults without ASD. In some areas, there is more communication going on, and in other areas there is less.

In addition, the exact pattern of communication differs between different people with high-functioning ASD.

This may explain why different studies of brain activity in people with ASD have had different findings in the past. The level of differences also seems to be related to the level of symptoms a person has.

The researchers say more research is needed to see whether the resting brain connection differences seen in people with high-functioning ASD represent the extreme end of a range of differences seen in the general population.

This is particularly important, as only a relatively small number of controls were assessed, and this may not capture the full range of brain communication across people without ASD.

The researchers note they could not control for differences across the sites where data was collected – for example, how the data was compiled.

However, they say the robustness of their findings is supported by how the potential differences distorted the patterns of connections across the different sites in the brain scans of people with high-functioning ASD.

They also only used data from adults with high-functioning ASD and processed the data using the same techniques to try to reduce variability.

It's important to note we cannot say whether these differences are the cause or a result of the ASD. The results are also only applicable to adults with high-functioning ASD, and may not apply to children or people with ASD who are not in the "high-functioning" category.

At the moment, we don't know whether this information could help make a diagnosis of ASD earlier, as this study did not look at this. More studies would be needed to determine whether this is the case.

Despite being a relatively common condition, affecting around 1 in 100 people, the cause(s) of ASD remain unclear. It is thought several complex genetic and environmental factors are involved.

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

Links To The Headlines

People with autism show 'unique brain patterns', say scientists who believe discovery may help earlier diagnosis. Mail Online, January 23 2015

Links To Science

Hahamy A, Behrmann M, Malach R. The idiosyncratic brain: distortion of spontaneous connectivity patterns in autism spectrum disorder. Nature Neuroscience. Published online January 19 2015

Categories: Medical News

Brown fat may protect against diabetes and obesity

Medical News - Mon, 01/26/2015 - 13:30

"Fat can protect you against obesity and diabetes," the Mail Online reports. However, the small study it reports on was looking at brown fat, which is only found in small amounts in adults.

In humans, brown fat is mostly found in newborns, who are more prone to heat loss and are unable to shiver to help keep themselves warm. Brown fat compensates by burning calories to create heat. As we grow older, we have less need for brown fat and it is mostly replaced by white fat ("bad fat").

The current study involved just 12 men. It looked at whether men with detectable levels of brown fat differed from men who didn't in terms of how their bodies dealt with sugar, particularly in cold conditions.

The researchers wanted to see what happened when the men were exposed to cold over five to eight hours.

The researchers found that, when exposed to the cold over five to eight hours, only the men with brown fat showed an increase in the energy they were burning and how fast they used up the sugar circulating in their blood.

This has led to the idea the effect could in some way be harnessed to help protect against type 2 diabetes or obesity.

However, any such advances are a long way off. This study was very small, only in men and, crucially, we cannot currently control the amount of brown fat we have.

Eating fatty foods will result in more white fat if you consume more calories than you burn off, and being overweight or obese increases your type 2 diabetes risk.

 

Where did the story come from?

The study was carried out by researchers from the Shriners Hospital for Children in Texas and other research centres in the US, Greece, Sweden, and Canada.

It was funded by the University of Texas Medical Branch, the National Center for Advancing Translational Sciences, the National Institutes of Health, the American Diabetes Association, Shriners Hospital for Children, the John Sealy Memorial Endowment Fund, the Claude D Pepper Older Americans Independence Center, and the Sealy Center on Aging.

One study author is a shareholder and consultant to Ember Therapeutics, a company that seems to work on treatments for type 2 diabetes and obesity by targeting brown fat. This represents a potential conflict of interest.

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

The Mail Online covers this study reasonably well, pointing out early on that brown fat is not the type of fat you get from eating too many calories. However, it did not mention the small number of men in the study.

The suggestion from the study authors that, "This is good news for overweight and obese people" or those with diabetes probably overestimates the practical implications of these findings.

 

What kind of research was this?

This was an experimental study carried out in men with and without detectable brown fat. It aimed to see whether brown fat might influence how the body deals with sugar.

Brown fat generates heat to help keep the body's temperature constant. In humans, it is mostly found in newborns, who are unable to shiver and keep themselves warm.

As we grow we have less of a need for brown fat, so most is replaced by white fat. White fat differs from brown in that it stores energy for the body when we consume more calories than we burn off.

 

What did the research involve?

The researchers enrolled 12 healthy men for their study: seven with detectable brown fat and five without.

They then tested them at normal room temperatures (about 19C or 66.2F) and after five to eight hours of exposure to cold.

They looked at how much energy the men's bodies were burning at rest, and how their bodies were dealing with sugar and fat.

Participants were cooled by wearing a temperature-controlled vest and blanket, which gradually dropped in temperature until the participant was shivering and then raised in temperature by one degree. The participant was then kept at this temperature for five to eight hours.

At the start of the study, to check whether the man had detectable brown fat, their bodies were cooled and injected with a radioactively labelled glucose (a type of sugar).

Their bodies were then scanned using a positron emission tomography (PET) scan, which could identify where in the body the glucose was located.

As brown fat generates heat to help keep the body temperature stable, the idea was that as the men were cold, if they had brown fat, it would take up more glucose to make more heat.

This meant the researchers could see where the brown fat was in the body. They looked for brown fat specifically in the area just between the collar bone (clavicle) and the base of neck. They also took samples of tissue from this area to look for brown fat.

Men with and without brown fat were similar in their characteristics. Men without brown fat were slightly older (average 49.8 years versus 41.2 years).

Once the researchers knew which men had detectable brown fat and which did not, they then carried out a range of tests at normal temperature and at cold temperatures.

This included testing how much energy the men were burning at rest and how their bodies dealt with sugar and fat (fatty acids) infused into their bloodstreams. The normal temperature and cold temperature experiments were carried out two weeks apart.

During the study, the volunteers followed a controlled diet and wore standardised clothing to make them as comparable as possible.

 

What were the basic results?

The researchers found exposure to cold increased the amount of energy the men with brown fat were burning at rest. This was not the case for men without brown fat.

The extra energy being used up by the brown fat was coming from glucose and fatty acids being taken up from the blood.

Cold exposure increased the total amount of glucose being taken up by the cells of the body in men with brown fat, but not those without brown fat.

The researchers estimated brown fat could take up a considerable amount of glucose from the circulation and therefore could help control blood glucose levels.

This was also the case if the men were given insulin to reproduce what would happen after a meal. Insulin increased glucose uptake in both groups, but uptake was still higher in men with brown fat.

 

How did the researchers interpret the results?

The researchers concluded they found brown fat has a significant impact on the ability of the whole body to dispose of glucose.

They say this supports a role for brown fat in controlling glucose levels and sensitivity to insulin in humans.

They suggest brown fat could be a target for combating obesity and diabetes if we can develop ways to activate brown fat in the body, or get white fat to behave more like brown fat.

 

Conclusion

This small experimental study has suggested that in healthy men, brown fat can increase the uptake of blood glucose by cells in response to cold, and increase the amount of energy being used up at rest.

Because of the small size of this study and the fact it only included healthy men, it is not possible to say whether the results are representative of the general population.

With such small numbers, there could have been other unmeasured differences between the groups (such as biological and lifestyle differences) that influenced the results, rather than just brown fat.

Other groups of people or other tests, rather than just this single experiment, could have given different results. Larger studies will be needed to confirm its findings.

The study also only looked for an indication of brown fat in one area of the body, and this may not be representative of the rest of the body.

These results do not have implications for the general public, as we currently cannot control the amount of brown fat we have. The excess calories we eat are stored as white fat rather than brown fat, and being overweight or obese increases the risk of diabetes rather than reducing it.

Even for those who happen to have brown fat, standing in the cold for prolonged periods is unlikely to be a practical long-term way to improve your glucose metabolism or energy consumption.

As the researchers say, investigations will undoubtedly continue into finding ways to capitalise on brown fat in the fight against obesity and diabetes, but we will need to wait to see whether this brings results.

Until then, the most effective method to reduce your diabetes risk is to try to achieve or maintain a healthy weight.

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

Links To The Headlines

Fat can PROTECT you against obesity and diabetes, improving blood sugar control and metabolism, study finds. Mail Online, January 23 2015

Links To Science

Chondronikola M, Volpi E, Børsheim E, et al. Brown Adipose Tissue Improves Whole-Body Glucose Homeostasis and Insulin Sensitivity in Humans. Diabetes. Published online July 23 2014

Categories: Medical News

Statin use may be widening health inequalities in England

Medical News - Fri, 01/23/2015 - 15:30

“Mass prescription of statins ‘will widen social inequalities’," The Independent reports. 

The headline is based on a new study looking at deaths from coronary heart disease in England from the years 2000 to 2007.

The good news is that overall deaths from heart disease were estimated to be down by a third (34.2%) during the time period.

The bad news, at least for those concerned about health inequalities, is that the use of statins (a cholesterol-lowering drug), benefitted the richest 20% more than the poorest 20% of society.

This is unlikely to be due to any biological factor and may instead arise due to a combination of socioeconomic and cultural reasons, such as people with chaotic lifestyles associated with poverty being less likely to stick to a treatment plan.

The study also found that population-based approaches – such as encouraging people to stop smokingeat a healthy diet and take regular exercise – have had a much bigger impact than medical approaches, like statins.

This led the study authors to suggest that there needs to be a greater emphasis on population-based approaches in the future, if we are not to see health inequalities widen further.

This study usefully informs debate in the public health sector about the best and fairest way of continuing this reduction in the future. 

 

Where did the story come from?

The study was carried out by researchers from the University of Liverpool, University of Chester, University College London, Public Health Wales and the University of British Columbia (Canada). It was funded by the National Institutes for Health Research School of Public Health Research and Liverpool PCT FSF scheme.

The study was published in the peer-reviewed medical journal BMJ Open. As the name suggests, this journal is open-access, meaning anyone can read that full article online for free.

Different UK newspapers emphasised different angles of the story (which seemed to be linked to their political editorial line), but they all covered the facts of the study accurately. 

 

What kind of research was this?

This was a modelling study trying to work out what proportion of a fall in coronary heart disease deaths in England was due to preventative medications, like statins, and what proportion was due to population-wide changes like diet and exercise. They were also interested in exploring the relative effects on different socioeconomic groups.

The UK, the study authors inform us, has experienced a remarkable 60% reduction in coronary heart disease mortality since the 1970s, largely due to reductions in things like smoking. However, coronary heart disease remains the leading cause of premature death.

This study wanted to find out whether the decline was mainly due to medicines, like statins, or population-wide approaches like stopping smoking, good diet and exercise. They also knew that many of the risk factors of coronary heart disease show a social gradient, with the poorest worst affected. The team were interested in whether medicines or lifestyle changes made these social inequality differences bigger or smaller.

Modelling studies like this use existing data to estimate the relative impact of different variables (e.g. statin use) on an outcome (e.g. death). The advantage of models are that you can play around with the parameters to see what the most important influences are, and this can help target resources to give the most value for money in the future. However, all models rely on a range of assumptions and are only as good as the quality of their inputs and their design.

As the old software engineer saying goes “GIGO”: garbage in, garbage out.

It’s important to assess whether the model has realistic assumptions and if its data is relevant and of good quality.

 

What did the research involve?

The study team pulled together data from randomised controlled trials, meta-analyses, national surveys and official statistics to input into a statistical model. They then ran a series of statistical tests to estimate whether the relative contribution preventative medicines, reduction in blood pressure and cholesterol levels had contributed to the decrease in coronary heart disease deaths. The data came from adults over 25 living in England, gathered between 2000 and 2007. 

The main outcome of interest was number of deaths prevented or postponed (DPPs) in 2007, stratified by socioeconomic status.

For the number crunching, they used a model called the “IMPACTSEC model”.

This is a statistical technique that takes results from previous studies to make an estimate about the relative contributions, specific treatment and risk factors make to reductions in death rates. 

Or, in laypersons’ terms: it takes results from previous studies to make an estimate about how likely a particular intervention is in preventing or postponing deaths.

The first part of the IMPACTSEC model calculates the net benefit of statins and antihypertensive treatment in 2007. The second part of the IMPACTSEC model estimates the number of DPPs related to changes in systolic blood pressure and cholesterol levels in the population. They realised that there was overlap between pharmacological and non-pharmacological contributions to risk factors, and adjusted for this in their model.

 

What were the basic results? Populations approach vs. medications

In 2007, the model estimated that there were approximately 38,000 fewer coronary heart disease deaths than if death rates had continued at 2000 levels. A large proportion of these, approximately 20,400 DPPs, were attributable to reductions in blood pressure and cholesterol in the English population (population-based approached). A much smaller number, approximately 1,800 DPPs, came from medications such as statins.

The remaining DPPs were attributed to other factors.

Impact by socioeconomic group

Reductions in population blood pressure prevented almost twice as many deaths in the most deprived fifth of society compared with the most affluent.

Reductions in cholesterol resulted in approximately 7,400 DPPs, of which 5,300 DPPs were attributable to statin use and approximately 2,100 DPPs to population-wide changes.

Statins prevented almost 50% more deaths in the most affluent fifth of society compared with the most deprived. Conversely, population-wide changes in cholesterol prevented threefold more deaths in the most deprived fifth of society compared with the most affluent.

 

How did the researchers interpret the results?

The study team welcomed the reductions in death rates from coronary heart disease over the last 30 years, but raised concerns that the improvements were not spread equally amongst society. They questioned whether health inequalities might get worse if future efforts focussed on policies to increase the use of statins, rather than on population-based approaches.

They concluded: “Our results strengthen the case for greater emphasis on preventive approaches, particularly population-based policies to reduce SBP [systolic blood pressure] and cholesterol”.

 

Conclusion

This modelling study estimated that population-based approaches to reduce heart disease death rates in England have helped the poorest in society the most, while the effect of statins has benefited the most affluent. This led the study authors to suggest that there needs to be a greater emphasis on population-based approaches in the future, if we are not to see health inequalities widen.

Report author Martin O'Flaherty said in the Telegraph that: “The success of clinical cardiology in providing cost-effective treatments that are based on scientific evidence needs to be celebrated. However, population-wide measures might offer substantially bigger health gains, relieve pressure on an already stressed health system and reduce health inequalities. Measures like controlling tobacco, increasing physical activity, improving the contents of processed food products, restricting the marketing of junk food, taxation of sugary drinks, and subsidies to make healthier foods more affordable require renewed attention not just from academics, but crucially from people and policymakers”.

It is not totally clear how reliable and robust the model used in the study was, or the conclusions that stemmed from it. It is possible that different results and conclusions could have been reached if the inputs had been from different data sources, or the model configured differently.

That said, the researchers took all reasonable measures to mitigate this, and their conclusions remained stable throughout, so we can consider it relatively reliable. The reliability of the conclusions would be increased if they were supported by other studies using a variety of data sources.

The study is useful in informing debate in the public health world about the best and fairest way of reducing heart disease deaths in England, which is always a question of targeting and prioritising finite resources. 

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

Links To The Headlines

Mass prescription of statins ‘will widen social inequalities’. The Independent, January 23 2015

Fall in heart deaths is due to healthy living - NOT statins, study claims. Mail Online, January 23 2015

Statins save fewer lives than exercising and eating sensibly, say scientists. The Daily Telegraph, January 23 2015

Links To Science

Guzman M, Ahmed R, Hawkins N, et al. The contribution of primary prevention medication and dietary change in coronary mortality reduction in England between 2000 and 2007: a modelling study. BMJ Open. Published online January 22 2015

Categories: Medical News

Angry Twitter communities linked to heart deaths

Medical News - Fri, 01/23/2015 - 14:10

"Angry tweeting 'could increase your risk of heart disease','' is the poorly reported headline in The Daily Telegraph. The study it reports on found there is a link between angry tweets and levels of heart disease deaths.

Researchers were interested in investigating how various forms of negative psychological stress are linked to heart disease. They looked at how angry tweets, at a community level, may be a reflection of this stress.

For example, people living in an area with a high crime rate and high unemployment may be more likely to vent their anger on Twitter than people living in luxury flats in Mayfair.

And stress and other negative psychological emotions could increase the risk of heart disease.

The study looked at 148 million tweets across US counties and linked them to information on heart disease deaths, as well as demographic risk factors such as age and ethnicity.

Inputting this information into a mathematical model allowed the researchers to broadly predict death rates from heart disease using only the language analysis of Twitter posts, such as looking for swear words.

From a research point of view, this is exciting as it is a new avenue for gathering health insights, which in turn could ultimately help us target health resources at areas that need them most. It would be interesting to see if a UK-based study yielded similar results.

 

Where did the story come from?

The study was carried out by researchers from the University of Pennsylvania.

It was funded by The Robert Wood Johnson Foundation's Pioneer Portfolio through an Exploring Concepts of Positive Health Grant, and a grant from the Templeton Religion Trust.

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

The Daily Telegraph's headline that, "Angry tweeting could increase your risk of heart disease" is not correct. The study was about how existing psychological stress is linked to heart disease, and angry tweets may be a reflection of this stress.

A more accurate (if a little lengthy) headline would be: "Stress and other negative psychological emotions increase risk of heart disease, and these people are more likely to send angry tweets".

Despite the misleading headline, the rest of the article was accurate. It ran useful quotes from experts explaining how language patterns can reflect negative emotions such as stress, and this in turn is linked to poorer health, particularly heart health.

"Psychological states have long been thought to have an effect on coronary heart disease. For example, hostility and depression have been linked with heart disease at the individual level through biological effects […].

"But negative emotions can also trigger behavioural and social responses; you are also more likely to drink, eat poorly and be isolated from other people, which can indirectly lead to heart disease."

 

What kind of research was this?

This was a cross-sectional study looking at whether the language used on Twitter across a range of US counties was a good predictor of underlying psychological characteristics and death rates from heart disease.

Heart disease is the leading cause of death worldwide. Identifying and addressing key risk factors for heart disease, such as smoking, hypertension, obesity and physical inactivity, has significantly reduced this risk, the researchers state.

Psychological characteristics, such as depression and chronic stress, have also been shown to increase risk through physiological effects.

Like individuals, communities have characteristics, such as cultural norms (beliefs about how members of a community should behave), social connectedness, perceived safety and environmental stress, that contribute to health and disease.

One challenge of addressing community-level psychological characteristics is the difficulty of assessment. Traditional approaches using phone surveys and household visits are costly and have limited precision.

The study team thought Twitter might provide a more cost-effective assessment of community-level psychology, which is linked to death and disease.

Previous studies based on user-generated content, such as using Google searches to predict the likely spread of flu, have proved successful.

 

What did the research involve?

The researchers gathered 148 million tweets geographically linked to 1,347 counties in the US. It was reported more than 88% of the US population lives in the counties included.

The team then gathered country-level information on heart disease (coronary heart disease) and death, as well as a range of demographic and health risk factor information, such as average income and proportion of married residents.

In 2009 and 2010, Twitter made a 10% random sample of tweets (a data-mining initiative titled the "Garden Hose") available for researchers through direct access to its servers. This was how the researchers accessed the tweets.

The language analysis automatically calculated how often words and phrases were used on Twitter for each county, such as "hate" or "jealous", and categorised them according to theme.

They also searched for swear words we couldn't possibly repeat to a PG audience. Themes included anger, anxiety, positive and negative emotions, engagement, and disengagement.

Because words can have multiple senses, act as multiple parts of speech, and be used ironically, the researchers manually checked a sample of the automatically generated themes to ensure they were accurate.

All the information was fed into a statistical model to see if it was possible to predict heart disease death rates from the language used on Twitter alone.

 

What were the basic results?

Greater use of anger, negative relationship, negative emotion, and disengagement words on Twitter was significantly correlated with greater age-adjusted heart disease mortality. Protective factors included positive emotions and psychological engagement.

Most correlations remained significant after controlling for income and education.

The statistical model – based only on Twitter language – predicted heart disease deaths significantly better than a model that combined 10 common demographic, socioeconomic, and health risk factors, including smoking, diabetes, hypertension, and obesity.

 

How did the researchers interpret the results?

The researchers reached a simple conclusion: "Capturing community psychological characteristics through social media is feasible, and these characteristics are strong markers of cardiovascular mortality at the community level."

 

Conclusion

This study shows it is possible to broadly predict death rates from heart disease at a US county level using language analysis of Twitter posts from those US counties.

From a research point of view, this study is exciting as it gives an extra way of gathering information that could ultimately help target health resources in areas that need it most.

The cost effectiveness of this type of psychological insight would be interesting to weigh against existing methods such as telephone interviews.

But this was just a single study, so we cannot be sure this technology is practical or useful in a wide range of applications. This would depend on how speech is related to other health risk factors.

Nonetheless, this is an interesting avenue for further investigation. The research community is always looking for new cost-effective methods of gathering data to improve people's health.

This study suggests language analysis of Twitter, in some circumstances, might be a useful activity. This could potentially be used to assess a wide range of issues, such as depression rates, the prevalence of eating disorders, and levels of alcohol or drug misuse in a given community.

It will be interesting to see where this avenue of research, based on user-generated content, takes us.

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

Links To The Headlines

Angry tweeting 'could increase your risk of heart disease'. The Daily Telegraph, January 22 2015

Links To Science

Eichstaedt JC, Schwartz HA, Kern ML, et al. Psychological Language on Twitter Predicts County-Level Heart Disease Mortality. Psychological Science. Published online January 20 2015

Categories: Medical News

New heart attack test shows promise for women

Medical News - Thu, 01/22/2015 - 15:00

"Doctors could spot twice as many heart attacks in women by using a newer, more sensitive blood test," BBC News reports.

In women, for reasons that are unclear, a heart attack often doesn't trigger the symptom most people associate with the condition: severe chest pain, memorably described as like having an elephant sitting on your chest. This can lead to delays in diagnosis, which may impact on clinical outcomes.

A more sensitive blood test has been developed that can help determine if a person with the symptoms of a heart attack has actually had one.

The new test is more sensitive to levels of a protein called troponin, which is released into the bloodstream when there is damage to heart muscle.

The test was used on more than 1,000 people investigated for a suspected heart attack, in addition to the standard diagnostic protocols, such as an electrocardiogram (ECG).

The researchers found if the new test was used alongside standard protocols, the rate of accurate heart attack diagnoses in women would have doubled. The test had less impact on the diagnosis for men.

If the larger studies now underway confirm these results, more women may be identified who have had a heart attack and are therefore in need of preventative strategies, which, as the BBC rightly concluded, could save thousands of lives.

 

Where did the story come from?

The study was carried out by researchers from the University of Edinburgh, the Royal Infirmary of Edinburgh, Southern General Hospital, St George's Hospital and Medical School, and the University of Minnesota.

It was funded by the British Heart Foundation with support from the legacy of Violet Kemlo. The tests were provided by the US pharmaceutical company Abbott Laboratories, but it is reported they had no role in the study design or analysis.

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

The UK media covered the story accurately, and BBC News also provided expert opinion from Professor Peter Weissberg of the British Heart Foundation (BHF).

He reported the BHF are now funding a larger study to confirm the results, and from this it is hoped more women will be identified who could benefit from preventative measures.

However, the media did not discuss the important finding that even after a diagnosis of heart attack has been made, women were not referred for further investigations or treatment as often as men.

This could suggest potential gender inequality in terms of diagnostic and treatment protocols that may need to be investigated further.

 

What kind of research was this?

This was a cohort study that aimed to see if a more sensitive blood test could improve the diagnosis of a heart attack and help predict who is at risk of having a further heart attack.

The blood test was used in addition to standard investigations for people who presented to hospital with a suspected heart attack.

The results of the test were not given to the doctors, so did not influence their decisions on treatment, prevention or management.

The researchers recorded which people went on to have a heart attack or die in the next 12 months to see if the new blood test was more accurate.

When there is damage to heart muscle, the cells that die release a protein called troponin into the bloodstream. Higher levels of troponin indicate greater damage.

Troponin levels are routinely checked when someone has symptoms of acute coronary syndrome, a medical emergency where the supply of blood suddenly becomes restricted, resulting in damage to the heart.

Acute coronary syndrome includes:

  • myocardial infarction (heart attack)
  • unstable angina (symptoms and ECG changes, but no increase in troponin levels)
  • non-ST-elevation myocardial infarction – a "milder" type of heart attack (though still extremely serious) where there is a partial blockage of the blood supply to the heart (symptoms and increased troponin levels, but no ECG changes)

People with acute coronary syndrome are at risk of having a heart attack or another heart attack, depending on the diagnosis. For example, if unstable angina is left undiagnosed and untreated, the condition can escalate into a heart attack.

 

What did the research involve?

All adults presenting to Edinburgh Royal Infirmary with suspected acute coronary syndrome were enrolled in the study between August 1 and October 31 2012.

Troponin levels were measured using the standard test as well as the new, more sensitive test. The tests were performed on admission and again six to 12 hours later.

The doctors were not given the results of the new test, so they based their diagnosis and management on the standard troponin test, symptoms, ECG results and other imaging.

The researchers looked at the clinical records from admission to 30 days. They analysed whether the level of troponin in the new test could predict outcomes such as a heart attack or death.

They used a single cut-off level of troponin 26ng/L, and then a higher level for men of 34ng/L and a lower threshold of 16ng/L for women.

They then calculated whether these levels could predict outcomes at 12 months, and adjusted the results to take into account age, kidney function and other medical conditions.

 

What were the basic results?

In total, 1,126 people attended the hospital with suspected acute coronary syndrome (mean age 66, 55% men).

Test results

A heart attack was diagnosed in:

  • 55 women (11%)
  • 117 men (19%)

If the new troponin test had been used with the sex-specific cut-offs, twice as many women would have been diagnosed with a heart attack:

  • 111 women (22%)
  • 131 men (21%)

These additional women had a similar risk of having a heart attack or dying within the next 12 months as women who were diagnosed.

After adjusting the results to take account of age, renal function and diabetes, compared with people with no ECG changes and negative troponin tests, the likelihood of having a heart attack or dying within the next 12 months was:

  • six times more likely in women diagnosed with the new test and ECG changes (odds ratio [OR] 6.0, 95% confidence interval [CI] 2.5 to 14.4)
  • nearly six times more likely in women diagnosed with the standard test and ECG changes (OR 5.8, 95% CI 2.3 to 14.2)
  • just over five times more likely in men diagnosed with the new test and ECG changes (OR 1.5 to 19.9)
  • three times more likely in men diagnosed with the standard test and ECG changes (OR 1.1 to 3.8)

The new test would not have missed anyone currently diagnosed with a heart attack.

Management

Women with a diagnosis of heart attack using the standard tests were less likely than men to:

  • be referred to a cardiologist (80% women versus 95% men)
  • be given statin treatment (60% versus 85%)
  • have coronary angiography – imaging of the heart (47% versus 74%)
  • have coronary angioplasty – a surgical intervention to reopen the vessels of the heart (29% versus 64%)

Women who would have been diagnosed with a heart attack using the new test and the ECG changes were the least likely to have any further investigations.

 

How did the researchers interpret the results?

The researchers concluded that, "Although having little effect in men, a high-sensitivity troponin assay with sex-specific diagnostic thresholds may double the diagnosis of myocardial infarction in women, and identify those at high risk of reinfarction [further heart attack] and death."

They go on to say that, "Whether use of sex-specific diagnostic thresholds will improve outcomes and tackle inequalities in the treatment of women with suspected acute coronary syndrome requires urgent attention."

 

Conclusion

This new study showed how a more sensitive test of troponin levels would have led to a diagnosis of heart attack in double the number of women studied.

The test made less of a difference to the diagnosis for men. This could be because the troponin levels in the standard test were much higher in men than women.

The research also indicates that even with a diagnosis of heart attack, women were less likely to be referred to cardiologists or have any further investigations or treatment, such as a coronary angiography or coronary angioplasty.

The researchers found women who would have been diagnosed with a heart attack with the new test were even less likely to be referred, prescribed a statin, or have vessel surgery, despite having ECG changes.

In both cases, the reasons for this are unclear. It is also not known what other preventative strategies were actually implemented, such as:

  • thinning the blood with aspirin
  • treating high blood pressure
  • optimising the treatment of any comorbid conditions, such as diabetes
  • supporting lifestyle changes, including stopping smoking, reducing obesity and inactivity

The reasons for this are not clear. So it is also unclear what difference an increase in diagnosis would make to outcomes if these underlying gender inequalities in heart attack management are not also addressed. Arguably, this issue warrants further investigation.

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

Links To The Headlines

Newer heart attack test 'could save women's lives'. BBC News, January 21 2015

New test could detect twice as many heart attacks in women. The Daily Telegraph, January 21 2015

£20 heart attack test will save thousands of women: Doctors believe new check will double chance of identifying damaged cells. Mail Online, January 21 2015

Links To Science

Shah ASV, Griffiths M, Lee KK, et al. High sensitivity cardiac troponin and the under-diagnosis of myocardial infarction in women: prospective cohort study. BMJ. Published online January 21 2015

Categories: Medical News

Claims that 'men worsen labour pains' are unproven

Medical News - Thu, 01/22/2015 - 14:00

"It’s official: men really shouldn’t be at the birth,” is the bizarre headline in The Times, as it reports on a pain study on women who were not even pregnant, let alone giving birth.

Researchers wanted to explore whether a woman’s “attachment style” (whether they sought or avoided emotional intimacy) had any influence on whether it was beneficial to have their partners present while having painful medical procedures.

They administered a series of painful laser pulses to 39 female volunteers in both the presence and absence of their romantic partners, while recording the women’s pain ratings.

The study found that the more women reported wanting to avoid closeness and intimacy, the more pain they experienced when their romantic partner was present.

However, describing the partner as “present” is misleading. The partner was in the same room, but hidden behind a curtain, so they could not see each other or have basic physical contact, such as holding hands. They were also told not to communicate. This does not mimic real-life situations, where a partner might be able to offer support. Therefore, media attempts to extrapolate these findings to childbirth are misguided.

The study makes the interesting point that health professionals should not assume a romantic partner is the best choice to accompany a patient undergoing a painful medical procedure. A relative or friend may be a better option.

 

Where did the story come from?

The study was carried out by researchers from King’s College London, the University of Hertfordshire and University College London. It was funded by the Volkswagen Foundation, the European Research Council and the Economic and Social Research Council.

The study was published in the peer-reviewed journal Social, Cognitive and Affective Neuroscience on an open-access basis, so it is free to read online or download as a PDF.

The Times’ reporting of this study was poor. Its headline of “It’s official: men really shouldn’t be at the birth” fails to communicate the fact that this study did not actually involve pregnant women.

The term “It’s official” is also deeply unhelpful. It implies that there is some official guideline dictating who should be a woman’s birth partner. Even if there were such a guideline, a small study involving 39 non-pregnant women wouldn’t be a reason to change it.

Other UK media sources ran similar reports to The Times, with the honourable exception being BBC News, which reported the study accurately, though they did not explain that the partner was silent and behind a curtain.

 

What kind of research was this?

This study was a comparative case series. It looked at whether the degree of pain women experience during medical procedures is affected by the presence or absence of their romantic partner. It also looked at whether this is influenced by the woman’s “attachment style” in terms of whether they sought or avoided emotional intimacy in their relationships.

Previous research on the subject has been mixed, with some studies indicating that the presence of someone close is beneficial in reducing pain, and others suggesting that the opposite is true. The researchers decided to look at how personality factors, specifically “adult attachment style”, might influence the effects of the presence of someone close, when a woman is experiencing pain.

 

What did the research involve?

The researchers recruited 39 heterosexual couples in a romantic relationship, using university circular emails. The female participants had to fulfil the specific criteria to be included. They had to:

  • be right-handed
  • have been in their current relationship at least a year
  • have no history of mental illness
  • have no history of medical or neurological conditions
  • have no history of substance abuse
  • had not taken any medication, including painkillers, on the day of testing

The average age of participants was about 25 for women and 27 for men, and they were predominantly white British. They were paid £30 per couple for participating.

The couples all underwent three experiments, in which the woman was given moderately painful laser pulses on one of their fingers, lasting for around 10 minutes. They were told that the experiments were aimed to test empathy in the partner, rather than the actual intention of rating the level of pain experienced by the woman. These experiments were performed in different orders across the couples.

In one experiment, the male partner was asked to rate his empathy for his partner while she was receiving the painful stimuli. Each partner was given visual information on the intensity of the laser, but they could not see each other as they were divided by a curtain.

In the second experiment, the partner was asked to rate his empathy for another participant who had previously taken part in the experiment, by viewing information on the laser intensities they had received, while their own partner received laser stimuli. In this experiment, the male partner was therefore unable to pay attention to his own partner and they were still separated by a curtain.

In the third experiment, the researchers led couples to believe that due to a technical fault, the file for the previous participant would not load onto the lab computer. The partner was therefore going to rate his empathy on a computer next door, and would be absent from the testing room.

Couples were instructed not to communicate during the procedures, to avoid biasing participants’ pain ratings.

In each experiment, the women were asked to rate the intensity of the pain on an 11-point scale, ranging from 0 (no pinprick sensation) to 10 (the worst pinprick sensation imaginable). The level of laser stimulation was set individually for each woman before the experiments, during “familiarisation with the equipment” so that it delivered a pain rating of 8. During each experiment, the women entered their ratings on a computer screen, using a numeric keypad. 

The researchers also positioned 11 electrodes on each woman’s scalp to measure the brain’s electrical activity while she was having the laser stimulation. Using the EEG recording, researchers measured whether this electrical activity “spiked” in response to the laser pulses.

Each woman also completed a validated 36-item questionnaire on close relationships, to measure the extent to which she either sought closeness or emotional intimacy in relationships. The questionnaire included 18 questions about “attachment style”.

 

What were the basic results?

The study found that the more women reported wanting to avoid closeness, the more pain they experienced when their romantic partner was present, and the stronger their “peaks” in brain activity.

Whether the partner was focusing on them or on another woman’s pain made no difference to the pain experienced.

 

How did the researchers interpret the results?

The researchers say that the effects of a partner’s presence on women’s pain ratings depended on their “attachment style” and that a partner’s presence may not have beneficial effects on the experience of pain when the individual in pain has “higher attachment avoidance”.

Partner support during painful procedures may need to be tailored to individual personality traits, they conclude. Senior author Dr Katerina Fotopoulou, from UCL Psychology & Language Sciences, says: “Individuals who avoid closeness may find that the presence of others disrupts their preferred method of coping with threats on their own. This may actually maintain the threat value of pain and ultimately heighten individual’s pain experience.”

 

Conclusion

This small study found that during painful stimuli, how much pain women reported experiencing depended on their attachment style – with more pain being experienced by women who have a "higher attachment avoidance", when their romantic partner was present.

The study was interesting, but had several limitations. The major one was that it did not allow the partners to communicate, have visual contact or basic physical contact, such as holding their hand during the painful procedures. This does not reflect the support that would be expected from a partner in a real life situation and may have influenced the results. In addition, the study's findings may not be generalisable to older couples or those from ethnic minorities.

Neither is it certain if these results would apply to real life painful procedures or experiences –including childbirth. As Dr Fotopoulou points out: “The physical and psychological nature of labour pain may simply be different than other types of pain. Future studies could test how having a partner present during labour affects the pain felt by women who tend to avoid closeness in relationships.”

It makes sense that some women – or people in general – may feel they can cope with pain better when alone than with a partner. Deciding who should be present during labour is entirely personal, although many women find the support of someone close, whether it is a partner, friend or relative, comforting.

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

Links To The Headlines

It’s official: men really shouldn’t be at the birth. The Times, January 21 2015

Fathers in delivery room could make pain of childbirth worse, study suggests. The Daily Telegraph, January 21 2015

Partners can worsen childbirth pains for the intimacy-averse, study finds. The Guardian, January 21 2015

Childbirth pain could be made WORSE by presence of partner, says study. Daily Mirror, January 21 2015

Women patients feel more pain when with partner, study suggests. BBC News, January 21 2015

Links To Science

Krahé C, Paloyelis Y, Condon H, et al. Attachment style moderates partner presence effects on pain: a laser-evoked potentials study. Social Cognitive and Affective Neuroscience. Published online January 1 2015

Categories: Medical News

Nordic IVF outcomes improving - is the same true for the UK?

Medical News - Wed, 01/21/2015 - 15:00

"The health of artificially conceived children has steadily improved in the last 20 years," The Guardian reports. Researchers who analysed data from Nordic countries described the decline in premature and stillbirths as "remarkable".

This was the main finding of a large cohort study comparing the health of babies born using assisted reproduction technology (ART), such as in vitro fertilisation (IVF), with those conceived naturally over the last 20 years.

They found big improvements over time in a number of areas, including reductions in the number of miscarriages and babies born prematurely or with a low birth weight. All of these can be complications of multiple births (twins, triplets, or sometimes more).

The study looked at ART in Norway, Sweden, Denmark and Finland, and it is unclear whether we could expect to see similar improvements in the UK.

While it is likely we share similar advances in technology and improved protocols with Nordic countries, there may be other important differences as a result of eligibility for treatment.

In some Nordic countries, eligibility for reproductive treatment has been extended to include couples with less severe fertility problems. This may have accounted for some of the improvements seen over the years.

The most recent UK data from 2013 (PDF, 2.54Mb) reports the ART multiple birth rate has fallen from 25% in 2008 to 16% in 2013. This would suggest a potentially similar improvement in UK outcomes for ART.

 

Where did the story come from?

The study was carried out by researchers from universities based in Denmark, Norway, Sweden and Finland.

It was funded by the European Society of Human Reproduction and Embryology, the University of Copenhagen, the Nordic Federation of Societies of Obstetrics and Gynecology, and the Danish Agency for Science, Technology and Innovation.
 
The study was published in the peer-reviewed medical journal Human Reproduction. The article was published on an open-access basis, meaning anyone can view it and download it for free.

Generally, The Guardian and the Mail Online reported the study accurately, though neither made it clear in their headlines this was actually research involving Nordic countries and not the UK.

 

What kind of research was this?

This was a population-based cohort study looking at the health outcomes of babies born through assisted reproductive technology over the last 20 years.

Assisted reproductive technology (ART) is a catch-all term for a number of techniques that can help parents to conceive and have a baby. Two of the most common are IVF and intra-cytoplasmic sperm injection (ICSI).

In IVF, a woman's eggs are removed from her ovaries by a doctor and cultured with many sperm in a laboratory. This allows fertilisation to take place "naturally", but outside the body.

If embryos develop, one, or sometimes two or three (depending on circumstances), are transferred to the woman's uterus to grow and develop into a baby.

Intra-cytoplasmic sperm injection (ICSI) differs from IVF in that a specialist selects a single sperm to be injected directly into an egg, instead of fertilisation taking place in a dish, where many sperm are placed near an egg.  

The study also included people who have had frozen embryo transfer. After IVF, a couple may have a number of unused (non-transferred) embryos. They can freeze them for use in later treatment cycles or for other purposes, such as donation.

 

What did the research involve?

The researchers analysed the health outcomes shortly after birth of 62,379 single babies and 29,758 twins born by ART between 1988 and 2007 in Sweden, Norway, Denmark and Finland.

They compared babies born through ART (IVF, ICSI or frozen embryo transfer) with a control group of 362,215 babies conceived naturally.

Twins conceived after ART were compared with all naturally conceived twins (n=122, 763) born in the Nordic countries during the study period.

The rates of several adverse health outcomes were stratified into the time periods 1988-92, 1993-97, 1998-2002 and 2003-07 to assess possible changes over time.

Babies born though ART were matched to naturally conceived babies according to parity (whether they were born as a single baby, twins, triplets or higher multiples) and year of birth.

Adverse outcomes they were looking at included:

  • low birth weight – defined as birth weight less than 2,500g
  • very low birth weight – less than 1,500g
  • preterm birth – defined as birth before 37 weeks of development
  • very preterm birth – birth before 32 weeks of development
  • small for gestational age – less than two standard deviations
  • large for gestational age – more than two standard deviations calculated using Marsal's formula
  • stillbirth – defined in this study as death of the infant after more than 28 weeks of development (in the UK it is above 24 weeks)
  • infant death – death of the infant in the first year of life

Statistical analysis adjusted for parity, year of birth, and country of birth.

 

What were the basic results?

For singletons conceived after ART, a decline in the risk of being born preterm and very preterm was observed.

The proportion of ART singletons born with a low and very low birth weight also decreased.

The stillbirth and infant death rates declined among both ART singletons and twins.

Throughout the 20-year period, fewer ART twins were stillborn or died during the first year of life compared with spontaneously conceived twins.

The researchers thought this was "presumably due to the lower proportion of monozygotic [identical] twins among the ART twins".

 

How did the researchers interpret the results?

Discussing the wider implications of their findings, the team says that, "It is assuring that data from four countries confirm an overall improvement over time in the perinatal [around the time of birth] outcomes of children conceived after ART.

"Furthermore, data show the beneficial effect of single embryo transfer, not only in regard to lowering the rate of multiples, but also concerning the health of singletons."

 

Conclusion

This study found an improvement in health outcomes around the time of birth for babies conceived using artificial reproductive technology (IVF, ICSI and frozen embryo transfer) over the last 20 years in four Nordic countries (Norway, Sweden, Denmark and Finland). 

The study sample was large and the methods robust. This means we can be relatively confident these results paint an accurate picture of what is going on in these countries.

But two questions remain: are similar results found in the UK, and what is behind the improvement?

On the first question, it is difficult to say without having direct UK data. The Nordic countries are famous for having highly developed and supportive healthcare systems, which may include differences in specific ART techniques and follow-up care.

Each country is also likely to have different eligibility criteria that must be met to receive ART. These differences could influence whether improvements in ART would be seen across other countries.

The bottom line is we can't be sure the same situation is happening in the UK based on this study. We need solid information from the UK system itself.

There are a number of possible explanations for what caused the improvements. The most important reason, the research team said, was the dramatic decline in multiple births due to elective single embryo transfer.

In IVF, there is the option of implanting a single embryo into the mother, or more than one. During the study, the rate of twin births was reduced by one-third. Twin births are much more likely when implanting more than one embryo. Some research has associated double embryo transfer with an increased risk of preterm birth and perinatal mortality in ART children.

The improvements may also reflect a change in the people who were undergoing ART. The study authors, for example, say previously only couples with severe fertility problems would be eligible to undergo ART treatment, whereas in recent years this has been extended to allow less severe cases.

ART may be less likely to be successful and may result in poorer birth outcomes in more severe cases (depending on the nature of the problem).

Refinement of clinical and laboratory skills also may have had a positive impact on the outcomes of the children.

But there has been a similar decline in multiple births through ART in the UK, dropping from one in four in 2008 to around one in six in 2012. This would suggest the quality of ART services in the UK are moving in the right direction.

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

Links To The Headlines

IVF babies see health improvement with fewer underweight or stillborn. The Guardian, January 21 2015

IVF babies are less likely to be born prematurely or die in infancy than 20 years ago, study reveals. Mail Online, January 21 2015

Links To Science

Henningsen AA, Gissler M, Skjaerven R, et al. Trends in perinatal health after assisted reproduction: a Nordic study from the CoNARTaS group. Human Reproduction. Published online January 20 2015

Categories: Medical News

'Social jet lag' linked to obesity and 'unhealthy' metabolism

Medical News - Wed, 01/21/2015 - 14:30

"Social jet lag is driving obesity" is the misleading headline in The Daily Telegraph. A new study only found a link between "social jet leg", obesity, and metabolic markers that may indicate a person has an increased risk of obesity-related diseases, such as type 2 diabetes. A cause and effect relationship was not found.

Social jet lag is the term used to describe the difference in someone's sleep patterns between work days and free days – also known as having a lie-in at the weekend.

The researchers' hypothesis was that regularly disrupting our sleep patterns could upset the body clock (circadian rhythms), which could then have a harmful effect on the metabolism.

The study of more than 800 non-shift workers found people with a greater difference in sleep patterns between free days and work days were more likely to be obese and "metabolically unhealthy" (have markers for obesity-related diseases) than those with little or no difference between these timings.

But the study does not prove regular lie-ins cause obesity or obesity-related diseases, as it assessed sleep patterns and health at the same time. It is possible with this type of study that the reverse is true – that obesity and any associated health conditions may cause people to lie in more.

Overall, this study provides no proof having a lie-in will affect your health, though the occasional early-morning Saturday stroll may improve both your fitness and wellbeing.

 

Where did the story come from?

The study was carried out by researchers from the Medical Research Council (MRC) and the University of London in the UK, Duke University and the University of North Carolina in the US, and the University of Otago, New Zealand.

It was funded by the US National Institute of Aging and the MRC.

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

The quality of the UK's media coverage of the study was mixed. The Independent correctly mentioned there was no proof social jet lag causes obesity, but none of the papers mentioned the possibility of reverse causation: that obesity makes people more likely to lie in, rather than lie-ins causing obesity.

The Daily Telegraph's choice of headline was particularly unhelpful, as it implied social jet lag was now a proven partial cause of the obesity epidemic and the related complications. This is not the case.

 

What kind of research was this?

This was a cross-sectional analysis of a cohort study that aimed to look at the association between obesity and metabolic markers that may indicate obesity-related disease, and social jet lag. Social jet lag is a measure of the discrepancy in sleep timing between our work and free days.

The researchers say travel-induced jet lag results in problems with circadian rhythms (the body's internal clock), which causes temporary problems with metabolic rate (the rate at which the body uses up energy).

However, they suggest social jet lag can become chronic throughout someone's life and therefore have longer term consequences for metabolism, possibly increasing the risk of metabolic syndrome. Metabolic syndrome is the medical term for a combination of diabetes, high blood pressure and obesity.

The researchers also say recent research found people with higher social jet lag and a greater discrepancy between internal and social clocks were found to have a higher self-reported body mass index (BMI).

They consider it possible that if our internal clocks are at odds with external schedules, this may partly underlie the increase in obesity seen in the last few decades.

Cross-sectional studies look at all data at the same time, so they cannot be used to see if one factor (in this case, social jet lag) has caused the others (in this case, obesity or metabolic markers).

 

What did the research involve?

This study included 815 non-shift workers who were participants of an ongoing health study in New Zealand (Dunedin Longitudinal Study), which is following more than 1,000 people born between 1972 and 1973 to investigate links between health and behaviour.

At the age of 38, each participant was asked to fill in a standard questionnaire to assess social jet lag, as well as sleep duration and chronotype (their "natural" preference in sleep timing). 

Social jet lag was measured by subtracting each person's midpoint of sleep on work days from their midpoint of sleep on free days (assuming five work days and two free days a week as standard).

So, for example, if someone slept from 12am to 8am on workdays, the midpoint was 4am. If they then slept from 1am to 11am on free days, the midpoint was 6am, giving a social jet lag of two hours.

Researchers also measured participants' height and weight to calculate BMI, with obesity defined as a BMI of 30 or more. Waist circumference and fat mass were also measured.

The researchers also assessed whether participants had markers of metabolic syndrome, a disorder associated with diabetes and obesity.

They assessed five biomarkers, and people with "high-risk values on three or more" were defined as having metabolic syndrome. These were:

  • waist circumference (88cm or more for women, 102cm or more for men)
  • high blood pressure (130/85mm Hg or higher)
  • low levels of high-density lipoprotein (HDL, or "good") cholesterol
  • high triglycerides (another blood fat)
  • high blood levels of a glycated haemoglobin (an indicator of blood glucose control –  a marker for diabetes)

They also assessed blood levels of an inflammatory marker called C-reactive protein.

The authors say recent research has shown a subset of obese individuals who are "metabolically healthy". They therefore created a measure for obesity status with three levels:

  • non-obese (a BMI of below 30)
  • healthy obese (a BMI of 30 or above, but no metabolic syndrome)
  • unhealthy obese (a BMI of 30 or above and metabolic syndrome)

Researchers also asked people about their current smoking status (since smoking is positively associated with jet lag and may also keep weight low) and socioeconomic status, assessed by their current or most recent occupation.

They were then allocated to one of six categories (from 1 – unskilled labourer to 6 – professional). Those not working were rated according to their educational status.

Researchers analysed their results to determine if social jet lag was associated with "unhealthy" obesity. They created three models, with one adjusting the figures for potential confounders, including smoking, socioeconomic status, sleep duration, and sleep preferences.

 

What were the basic results?

The researchers report social jet lag was associated with numerous measures of metabolic dysfunction and obesity, with higher social jet lag levels in "metabolically unhealthy" obese individuals.

Among metabolically unhealthy obese individuals, social jet lag was additionally associated with high blood levels of glycated haemoglobin and CRP (an indicator of inflammation).

Individuals with higher social jet lag scores were more likely to be obese (odds ratio [OR] 1.2, 95% confidence interval [CI] 1.0 to 1.5) and to meet the researchers' criteria for metabolic syndrome (OR 1.3, 95% CI 1.0 to 1.6) – though both of these risk increases are only of borderline statistical significance.

 

How did the researchers interpret the results?

The researchers say the findings are consistent with the possibility that, "living against our internal clock may contribute to metabolic dysfunction and its consequences".

They suggest a two-hour difference in sleep patterns at the weekend is the "threshold" for a higher BMI and other biomarkers, although they also point out this association was weakened or non-significant once smoking and socioeconomic status were taken into account.

Further research is needed, they say, to determine the physiological mechanisms underlying these associations.

 

Conclusion

The study involved 815 non-shift workers. It found people with a greater difference in sleep patterns between free days and work days (so-called "social jet lag") were more likely to be obese and "metabolically unhealthy" (have markers for obesity-related diseases) than those with little or no difference between these timings.

This study adds to previous research in both animals and humans that has explored the possible effects altering the body clock may have upon our metabolism, being overweight or obese. A recent UK survey found a link between shift work and chronic diseases, which we discussed at the end of 2014.

However, this new study cannot prove regular lie-ins cause obesity or obesity-related diseases.

The study is cross-sectional, assessing sleep patterns and health at the same time. It is possible with this type of study that the reverse is true – that obesity and any associated health conditions may cause people to lie in more whenever possible.

There may be many underlying factors this study has not taken into account that are influencing the apparent relationship between obesity, metabolic markers, and higher levels of social jet lag.

For example, the study did not take account of people's diets or their exercise levels, which are two key factors that influence BMI and may also influence our sleep patterns.

The increased risks of obesity and metabolic syndrome with social jet lag were only of borderline statistical significance in any case, which further indicates the overall lack of strength in these associations.

Experts tend to agree it is best to keep to a regular sleep schedule on week days and weekends to prevent sleep problems. Whether following this advice can also keep the weight off is uncertain. Overall, this study provides no proof having a lie-in will affect your health.

Still, we can't help but agree with the recommendations of one of the authors of the study, as quoted on the Mail Online website: "I don't want to tell people not to have a lie-in because I enjoy one myself," lead study author Michael Parsons said. He then went on to recommend that employers could offer flexible hours, so staff could synchronise their week days with their weekends.

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

Links To The Headlines

Social jet lag is driving obesity and illness, say scientists. The Daily Telegraph, January 20 2015

Fancy a lie-in on weekends? New study finds it could lead obesity and diabetes. The Independent, January 20 2015

Looking forward to your Saturday lie-in? Careful, it may be a health hazard: Changes in sleep pattern between work days and weekend can raise chance of obesity and diabetes. Daily Mail, January 21 2015

Links To Science

Parsons MJ, Moffitt TE, Gregory AM, et al. Social jetlag, obesity and metabolic disorder: investigation in a cohort study. International Journal of Obesity. Published online December 22 2014

Categories: Medical News

Becoming healthier may motivate your partner to join in

Medical News - Tue, 01/20/2015 - 15:30

“Fitness 'rubs off on your partner’,'' BBC News reports.

This headline is based on a study of more than 3,000 married couples aged 50 and over in the UK, where at least one of the partners smoked, was inactive, or was overweight or obese at the start of the study. It followed them up and looked at their and their partner’s behaviours over time.

It found that a person was more likely to change their unhealthy behaviours if their partner did too, more so than if they had a partner who was always healthy, or one who remained unhealthy.

These behaviours included quitting smoking if they smoked, increasing physical activity levels and losing some weight.

There are some limitations to the study. For example, while the researchers took into account some factors that could affect the results, others – such as unmeasured health conditions – could still be having an impact.

Still, the findings seem plausible; working together as a team to improve health, whether it be just you or your partner, or in a larger exercise or weight loss group, may help in practical ways (such as eating the same foods), as well as boosting motivation and confidence levels.

 

Where did the story come from?

The study was carried out by researchers from University College London. Funding was provided by the US National Institute on Aging and a consortium of UK government departments co-ordinated by the Office for National Statistics. Additional support for the authors was provided by the British Heart Foundation and Cancer Research UK.

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

The coverage of this study in the news has been generally reasonable. The BBC’s headline “Fitness ‘rubs off on your partner’” may make it sound like you don’t have to do anything to get fitter – as long as your partner is – but unfortunately this is not the case.

 

What kind of research was this?

This was an analysis of data from an ongoing cohort study of older adults called the English Longitudinal Study of Ageing (ELSA). It aimed to look at the effect of a partner’s behaviour on a person making healthy behaviour changes.

If a person has unhealthy behaviours (such as eating unhealthily), their partner is also likely to, and if one of them changes this behaviour then the other often does too.

In this study the researchers specifically wanted to look at whether there was a difference in the effect of having a partner who is consistently healthy (e.g. had always eaten healthily) and one who had unhealthy behaviour but then makes a positive change (e.g. starts eating healthily).

While other studies have assessed the impact of partners changing behaviour, few have assessed this specific question.

This type of study is the best way of looking at the impact of behaviour that people choose themselves in real life. The main limitation to this type of study is that factors other than the one the researchers are looking at (called confounders) could also have an effect. The researchers can take steps in their analyses to reduce the effect of potential confounders, but they can never be entirely sure they have accounted for every confounder.

 

What did the research involve?

The ELSA study started prospectively collecting data on adults aged 50 and over in England in 1998.

For the current study researchers looked at information on 3,722 married couples who lived together, where at least one had an unhealthy behaviour or characteristic at the start of the study (smoking, physically inactive, or overweight or obese). They then looked at whether their partner’s behaviour over time had an influence on whether the person changed their unhealthy behaviours.

Participants in ELSA had taken part in the Health Survey for England in 1998, 1999 and 2001. All household members aged 50 and over, as well as partners were invited for interview. Those who enrolled were sent a computer-assisted interview and self-administered questionnaires every two years from 2002. Smoking and physical activity were assessed in every questionnaire. Every four years this assessment included a health assessment, where a nurse visited the participants in their homes. This assessment included measuring height and weight.

For the current study, the researchers analysed data for the first two consecutive assessments that the person and their partner completed. They looked at smoking, physical activity and weight in people and their partners, and whether individuals:

  • quit smoking (said they smoked at the first assessment but not at the second assessment)
  • became active after being inactive (said they took part in moderate to vigorous activity less than once a week at the first assessment, but took part more often than this at the second assessment)
  • lost weight (were overweight or obese at the first assessment and had lost at least 5% of their body weight by the second assessment)

A partner was considered “consistently” healthy if they did not have the unhealthy behaviour at either the first or the second assessment.

Couples where the partner moved from a healthy behaviour to a less healthy behaviour were excluded from the analyses, as there were so few of them.

The researchers took into account a number of potential confounders in their analyses, including:

  • age
  • gender
  • socioeconomic status (household non-pension wealth)
  • health conditions (cancer, diabetes, heart disease, stroke, heart attack, or other long-standing illness that limited their activities)
What were the basic results?

At the start of the study:

  • 13.9% of men and 14.8% of women smoked
  • 31.2% of men and 35.5% of women were physically inactive
  • 77.3% of men and 67.6% of women were overweight or obese

By the next assessment overall:

  • 17% of smokers had quit
  • 44% of inactive individuals had become active
  • 15% of overweight or obese individuals had lost at least 5% of their body weight

The researchers found that when one partner changed to a healthier behaviour, the other person was more likely to also change to a healthier behaviour than if their partner had remained unhealthy. This was the case across all three behaviours:

  • If their partner stopped smoking 50% of women and 48% of men stopped smoking also, compared to only 8% stopping smoking if their partner kept smoking.
  • If their partner became more physically active 66% of women and 67% of men also became more physically active, compared to 24% of women and 26% of men becoming more active if their partner remained inactive.
  • If their partner lost weight 36% of women and 26% of men also lost weight, compared to 15% of women and 10% of men if their partner did not lose weight.

Having a consistently healthy partner also increased the likelihood that a person would stop smoking or become more active, but not the likelihood of losing weight. For all three behaviours, having a partner who changed to a healthier behaviour was associated with a greater likelihood of a person themselves changing behaviour than having a partner with consistently healthy behaviour. The impact of a partner’s behaviour was limited to that specific behaviour (e.g. smoking, or activity, or weight loss) and was not associated with changes in other behaviours in the other partner.

 

How did the researchers interpret the results?

The researchers conclude that “men and women are more likely to make a positive health behavior (sic) change if their partner does too, and with a stronger effect than if the partner had been consistently healthy in that domain”. They suggest that involving partners in programmes aiming to get a person to change their behaviour might improve the outcomes of these programmes.

 

Conclusion

This cohort study has found that individuals with unhealthy behaviours such as smoking, being inactive or being overweight are most likely to change these behaviours if their unhealthy partner also changes these behaviours.

Having a partner who has consistently healthy behaviours was also associated with a greater likelihood of change in smoking and activity compared to a consistently unhealthy partner, but less so than having a partner who changed behaviour.

There were some limitations to the study, including that:

  • The study took into account some confounders, such as age and some health conditions, but other factors could also be having an effect – such as unmeasured health conditions or events. For example, there could have been a mutual life event experienced by both partners that motivated the change, such as the death of a friend or relative from lung cancer leading to quitting smoking.
  • As both partners were assessed at the same time it is not possible to say which person changed first, or whether they both changed together.
  • Smoking and physical activity were reported by the participants themselves and not verified, so may not be accurate.
  • Weight was measured by a nurse and was therefore more likely to be accurate.
  • Behaviours were assessed only twice, either two or four years apart. If a person changed between those assessments but then reverted to their original behaviour this would not have been picked up, and it is not possible to say how long the changes lasted.
  • Results may not apply to younger couples, as the study was restricted to couples with at least one partner aged 50 or over at the start of the study.

It is known that social support from family, friends or other groups can be an important component in people changing their behaviours.

This study supports this concept, and suggests that the impact may be greatest, for partners at least, if that partner is also changing their behaviour.

Our Find Services section can provide details of exercise, stop smoking and weight loss services, many of which are free, in your local area.

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

Links To The Headlines

Fitness 'rubs off on your partner'. BBC News, January 19 2015

Let’s quit together: health kicks are easier if your partner signs up too. The Guardian, January 19 2015

The best way to get in shape? Get your partner involved: Couples who ditch bad habits are more likely to succeed than those going it alone. Mail Online, January 19 2015

Couples who get fit together more likely to succeed. The Daily Telegraph, January 19 2015

Links To Science

Jackson SE, Steptoe A, Wardle J. The Influence of Partner’s Behavior on Health Behavior Change - The English Longitudinal Study of Ageing. JAMA Internal Medicine. Published online January 19 2015

Categories: Medical News

Does moderate drinking reduce heart failure risk?

Medical News - Tue, 01/20/2015 - 14:10

"Seven alcoholic drinks a week can help to prevent heart disease," the Daily Mirror reports. A US study suggests alcohol consumption up to this level may have a protective effect against heart failure.

This large US study followed more than 14,000 adults aged 45 and older for 24 years. It found those who drank up to 12 UK units (7 standard US "drinks") per week at the start of the study had a lower risk of developing heart failure than those who never drank alcohol.

The average alcohol consumption in this lower risk group was about 5 UK units a week (around 2.5 low-strength ABV 3.6% pints of lager a week).

At this level of consumption, men were 20% less likely to develop heart failure compared with people who never drank, while for women it was 16%.

The study benefits from its large size and the fact data was collected over a long period of time.

But studying the impact of alcohol on outcomes is fraught with difficulty. These difficulties include people not all having the same idea of what a "drink" or "unit" is.

People may also intentionally misreport their alcohol intake. We also cannot be certain alcohol intake alone is giving rise to the reduction in risk seen.

Steps you can take to help reduce your risk of heart failure – and other types of heart disease – include eating a healthy diet, achieving and maintaining a healthy weight, and quitting smoking (if you smoke).

 

Where did the story come from?

The study was carried out by researchers from Brigham and Women's Hospital in Boston, and other research centres in the US, the UK and Portugal.

It was published in the peer-reviewed European Heart Journal.

The UK media generally did not translate the measure of "drinks" used in this study into UK units, which people might have found easier to understand.

The standard US "drink" in this study contained 14g of alcohol, and a UK unit is 8g of alcohol. So the group with the reduced risk actually drank up to 12 units a week.

The reporting also makes it seem as though 12 units – what is referred to in the papers as "a glass a day" – is the optimal level, but the study cannot not tell us this.

While consumption in this lower risk group was "up to" 12 units per week, the average consumption was about 5 units per week. This is about 3.5 small glasses (125ml of 12% alcohol by volume) of wine a week, not a "glass a day".

And the poor old Daily Express got itself into a right muddle. At the time of writing, its website is actually running two versions of the story. 

One story claims moderate alcohol consumption was linked to reduced heart failure risk, which is accurate. 

The other story claims moderate alcohol consumption protects against heart attacks, which is not accurate, as a heart attack is an entirely different condition to heart failure.

 

What kind of research was this?

This was a large prospective cohort study looking at the relationship between alcohol consumption and the risk of heart failure.

Heavy alcohol consumption is known to increase the risk of heart failure, but the researchers say the effects of moderate alcohol consumption are not clear.

This type of study is the best way to look at the link between alcohol consumption and health outcomes, as it would not be feasible (or arguably ethical) to randomise people to consume different amounts of alcohol over a long period of time.

As with all observational studies, other factors (confounders) may be having an effect on the outcome, and it is difficult to be certain their impact has been entirely removed.

Studying the effects of alcohol intake is notoriously difficult for a range of reasons. Not least is what can be termed the "Del Boy effect": in one episode of the comedy Only Fools and Horses, the lead character tells his GP he is a teetotal fitness fanatic when in fact the opposite is true – people often misrepresent how healthy they are when talking to their doctor.

 

What did the research involve?

The researchers recruited adults (average age 54 years) who did not have heart failure in 1987 to 1989, and followed them up over about 24 years.

Researchers assessed the participants' alcohol consumption at the start of and during the study, and identified any participants who developed heart failure.

They then compared the likelihood of developing heart failure among people with different levels of alcohol intake.

Participants came from four communities in the US, and were aged 45 to 64 years old at the start of the study. The current analyses only included black or white participants. People with evidence of heart failure at the start of the study were excluded.

The participants had annual telephone calls with researchers, and in-person visits every three years.

At each interview, participants were asked if they currently drank alcohol and, if not, whether they had done so in the past. Those who drank were asked how often they usually drank wine, beer, or spirits (hard liquor).

It was not clear exactly how participants were asked to quantify their drinking, but the researchers used the information collected to determine how many standard drinks each person consumed a week.

A drink in this study was considered to be 14g of alcohol. In the UK, 1 unit is 8g of pure alcohol, so this drink would be 1.75 units in UK terms.

People developing heart failure were identified by looking at hospital records and national death records. This identified those recorded as being hospitalised for, or dying from, heart failure.

For their analyses, the researchers grouped people according to their alcohol consumption at the start of the study, and looked at whether their risk of heart failure differed across the groups.

They repeated their analyses using people's average alcohol consumption over the first nine years of the study.

The researchers took into account potential confounders at the start of the study, including:

  • age
  • health conditions, including high blood pressure, diabetes, coronary artery disease, stroke and heart attack
  • cholesterol levels
  • body mass index (BMI)
  • smoking
  • physical activity level
  • educational level (as an indication of socioeconomic status)

 

What were the basic results?

Among the participants:

  • 42% never drank alcohol
  • 19% were former alcohol drinkers who had stopped
  • 25% reported drinking up to 7 drinks (up to 12.25 UK units) per week (average consumption in this group was about 3 drinks per week, or 5.25 UK units)
  • 8% reported drinking 7 to 14 drinks (12.25 to 24.5 UK units) per week
  • 3% reported drinking 14 to 21 drinks (24.5 to 36.75 UK units) per week
  • 3% reported drinking 21 drinks or more (36.75 UK units or more) per week

People in the various alcohol consumption categories differed from each other in a variety of ways. For example, heavier drinkers tended to be younger and have lower BMIs, but be more likely to smoke.

Overall, about 17% of participants were hospitalised for, or died from, heart failure during the 24 years of the study.

Men who drank up to 7 drinks per week at the start of the study were 20% less likely to develop heart failure than those who never drank alcohol (hazard ratio [HR] 0.80, 95% confidence interval [CI] 0.68 to 0.94).

Women who drank up to 7 drinks per week at the start of the study were 16% less likely to develop heart failure than those who never drank alcohol (HR 0.84, 95% CI 0.71 to 1.00).

But at the upper level of the confidence interval (1.00), there would be no actual difference in risk reduction.

People who drank 7 drinks a week or more did not differ significantly in their risk of heart failure compared with those who never drank alcohol.

Those who drank the most (21 drinks per week or more for men, and those drinking 14 drinks per week or more for women) were more likely to die from any cause during the study.

 

How did the researchers interpret the results?

The researchers concluded that, "Alcohol consumption of up to 7 drinks [about 12 UK units] per week at early middle age is associated with lower risk for future HF [heart failure], with a similar but less definite association in women than in men."

 

Conclusion

This study suggests drinking up to about 12 UK units a week is associated with a lower risk of heart failure in men compared with never drinking alcohol.

There was a similar result for women, but the results were not as robust and did not rule out the possibility of there being no difference.

The study benefits from its large size (more than 14,000 people) and the fact it collected its data prospectively over a long period of time.

However, studying the impact of alcohol on outcomes is fraught with difficulty. These difficulties include people not being entirely sure what a "drink" or a "unit" is, and reporting their intakes incorrectly as a result.

In addition, people may intentionally misreport their alcohol intake – for example, if they are concerned about what the researchers will think about their intake.

Also, people who do not drink may do so for reasons linked to their health, so may have a greater risk of being unhealthy.

Other limitations are that while the researchers did try to take a number of confounders into account, unmeasured factors could still be having an effect, such as diet.

For example, these confounders were only assessed at the start of the study, and people may have changed over the study period (such as taking up smoking). 

The study only identified people who were hospitalised for, or died from, heart failure. This misses people who had not yet been hospitalised or died from the condition.

The results also may not apply to younger people, and the researchers could not look at specific patterns of drinking, such as binge drinking.

Although no level of alcohol intake was associated with an increased risk of heart failure in this study, the authors note few people drank very heavily in their sample. Excessive alcohol consumption is known to lead to heart damage.

The study also did not look at the incidence of other alcohol-related illnesses, such as liver disease. Deaths from liver disease in the UK have increased 400% since 1970, due in part to increased alcohol consumption, as we discussed in November 2014.

The NHS recommends that:

  • men should not regularly drink more than 3-4 units of alcohol a day
  • women should not regularly drink more than 2-3 units a day
  • if you've had a heavy drinking session, avoid alcohol for 48 hours

Here, "regularly" means drinking this amount every day or most days of the week.

The amount of alcohol consumed in the study group with the reduced risk was within the UK's recommended maximum consumption limits.

But it is generally not recommended that people take up drinking alcohol just for any potential heart benefits. If you do drink alcohol, you should stick within the recommended limits.

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

Links To The Headlines

Seven alcoholic drinks a week can help to prevent heart disease, new research reveals. Daily Mirror, January 20 2015

A drink a day 'cuts heart disease risk by a fifth' researchers claim...so don't worry about having a dry January. Mail Online, January 19 2015

A drink a night 'is better for your heart than none at all'. The Independent, January 19 2015

Glass of wine a day could protect the heart. The Daily Telegraph, January 20 2015

Daily drink 'cuts risk' of middle-age heart failure. The Times, January 20 2015

Drinking half a pint of beer a day could fight heart failure. Daily Express, January 20 2015

Links To Science

Gonçalves A, Claggett B, Jhund PS, et al. Alcohol consumption and risk of heart failure: the Atherosclerosis Risk in Communities Study. European Heart Journal. Published online January 20 2015

Categories: Medical News

Shell shock remains 'unsolved'

Medical News - Mon, 01/19/2015 - 13:30

The Mail Online tells us shell shock has been "solved" after scientists claimed they have pinpointed the brain injury that causes pain, anxiety and breakdowns in soldiers.

The Mail's claim is prompted by a study that carried out autopsies on five military veterans who had a history of blast exposure to see what type of brain damage this might have caused.

Four out of five of these people showed signs of what is called diffuse axonal injury, where there is damage to the long nerve fibres that carry electrical signals throughout the brain. This nerve fibre damage seemed to have accumulated in "honeycomb" patterns.

However, we cannot conclude with any degree of certainty that blast injury was the direct and only cause of this damage, as these results are clouded by several factors.

Three of the five veterans died from an opiate overdose. People without a military background who died from an overdose also showed this nerve fibre damage, as did people who had suffered other types of brain injury, such as from a traffic accident – albeit without the honeycomb pattern.

This means it is difficult to know how much other factors contributed to this nerve fibre damage. In short, shell shock has not been "solved", as the Mail Online would have us believe.

 

Where did the story come from?

The study was carried out by researchers from the Johns Hopkins University School of Medicine in the US.

Funding was provided by the Johns Hopkins Alzheimer's Disease Research Center, the Kate Sidran Family Foundation, and the Sam and Sheila Giller family.

The study was published in the peer-reviewed medical journal, Acta Neuropathologica Communications on an open-access basis, so it is free to read online or download as a PDF.

The Mail Online coverage does not acknowledge that we cannot draw any firm conclusions on cause and effect from the results of this small study.

Claims stating shell shock has been "solved" are simplistic and cannot be supported by the results of such a small study, where multiple confounding factors are involved.

 

What kind of research was this?

This was a laboratory study that aimed to look at the brain changes that may occur from exposure to blast injury during military deployment.

The researchers say there are thought to be 250,000 veterans of conflicts in Iraq and Afghanistan with traumatic brain injury, many resulting from a blast.

This a complex form of injury said to incorporate "the direct effects of overpressure wave (primary injury), the gunshot-like effects of debris and shrapnel showering the head (secondary injury), the fall impact from translocation of the body by the overpressure wave (tertiary injury), as well as flash burns from the intense heat and asphyxiation or inhalation injuries".

Though there is a 100-year history of blast injuries, starting with those resulting from artillery shelling during the First World War, there is still a lack of understanding of the actual physical damage and injury it causes the brain.

Recent animal studies suggest these blasts cause what is called diffuse axonal injury. Diffuse means the injury is spread throughout the brain, rather than being isolated to one specific area.

It usually results from acceleration or deceleration forces moving the brain within the skull, similar to what may occur through vigorous shaking, which causes tearing injuries to the long nerve fibres (axons) that transmit signals throughout the brain.

Diffuse axonal injury is one of the most common types of traumatic brain injury, and effects can range from concussion to coma and death. 

This study conducted autopsies of veterans who had a history of blast injury to see whether there was any evidence of diffuse axonal injury.

 

What did the research involve?

The study included five male veterans with a history of blast injury who died at an average age of 28. Three died from an opiate or alcohol overdose. Similarly aged control subjects used as a comparison included:

  • six people who died from an opiate overdose (four females, two males)
  • six people who died from a lack of oxygen to the brain (three males, three females)
  • five people who died from another type of traumatic brain injury, such as falls or road traffic accidents (all male)
  • seven people who died with no history of traumatic brain injury, overdose or oxygen starvation

The researchers carried out brain autopsies on these people, particularly looking for evidence of amyloid precursor protein (APP), which is said to accumulate when there is diffuse axonal injury.

 

What were the basic results?

The researchers found four out of five of the blast injury cases showed evidence of APP accumulation in the nerve fibres in various parts of the brain, most predominantly in the frontal area.

These areas of damage were described to have formed into irregularly shaped "honeycomb" patterns.

The one person who did not show these abnormalities was said to have died from a gunshot wound to the head, and had a history of exposure to several IED attacks.

Three out of four of these cases with APP accumulation in the nerve fibres died from an opiate overdose. When compared with six non-military people who also died from opiate overdose, five of these controls were also found to have a few APP abnormalities, but they were significantly fewer in number.

Also, compared to the war veterans, none of these controls displayed the same "honeycomb" distribution of nerve fibre damage. 

In the controls who also died from traumatic brain injury, but not military related, these people showed quite a different pattern of nerve fibre damage from both the veterans and those who had died from an opiate overdose.

Their nerve fibre abnormalities tended to be "thick with prominent undulations and bulbs", while the non-military controls who died from an opiate overdose tended to have thin, straight abnormalities.

The controls who died as a result of a lack of oxygen to the brain showed quite variable APP accumulation – two showed APP abnormalities, four did not.

The controls without any history of traumatic brain injury, oxygen starvation or overdose did not show any APP abnormalities at all.

 

How did the researchers interpret the results?

The researchers say that: "Our findings demonstrate that many cases with history of blast exposure are featured by APP [nerve fibre damage] that may be related to blast exposure, but an important role for opiate overdose, [lack of oxygen to the brain before death], and concurrent blunt traumatic brain injury events in war theatre or elsewhere cannot be discounted."

 

Conclusion

This research aimed to shed light on the type of brain damage that blast exposure during military conflict may cause.

Previous research suggested blast exposure can cause diffuse axonal injury, where the forces acting upon the brain cause tearing and damage of the long nerve fibres that connect different parts of the brain.

This study found some supportive evidence suggesting this might be the case. Four of the five veterans with a history of blast injury did show this type of nerve fibre damage.

Researchers also observed a distinctive "honeycomb" pattern of nerve fibre damage, which was not present in other controls.

However, it cannot be concluded with much certainty that blast injury was the direct and only cause of this damage, as these results are clouded by several factors. Three of these five veterans died from an opiate overdose.

Non-military people who also died from an overdose still showed this nerve fibre damage, albeit in a different pattern. Similarly, people who suffered other types of traumatic brain injury also had this type of nerve fibre damage, though again with a different pattern.

Therefore, as the researchers acknowledge, it is difficult to rule out the influence that opiate overdose, lack of oxygen to the brain around the time of death, and other non-blast trauma may have had upon these brain changes in this military sample.

It is also not known whether these nerve fibre injuries had any effect on the person's subsequent health and brain function, or whether the injury was related to their cause of death in any way.

This is likely to depend on the severity of the brain damage: as is already recognised, diffuse axonal injury can encompass a wide extent of brain damage, from mild concussion to death.

The reliability of this study's conclusions would be improved if the results were replicated in a larger number of people, or in studies that better accounted for the wide range of other confounders (such as associated injuries or causes of death) that could explain the difference observed.

Although this study is of interest, the small sample sizes examined here – both the military personnel and the various control groups – make it difficult to draw any firm conclusions about the type of damage and subsequent health effects that may result from blast injuries during military conflict.

If you serve, or have served, in the armed forces and think your experiences have taken a psychological toll, there is help and support available. Read more about accessing healthcare for military personnel and veterans.

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

Links To The Headlines

Shell shock solved: Scientists pinpoint brain injury that causes pain, anxiety and breakdowns in soldiers. Mail Online, January 16 2015

The mystery of shellshock solved: Scientists identify the unique brain injury caused by war. The Independent,  January 15 2015

Links To Science

Ryu K, Horkayne-Szakaly I, Xu L, et al. The problem of axonal injury in the brains of veterans with histories of blast exposure. Acta Neuropathological Communications. Published online November 25 2014

Categories: Medical News

Could 'DNA editing' lead to designer babies?

Medical News - Mon, 01/19/2015 - 12:54

"Rapid progress in genetics is making 'designer babies' more likely and society needs to be prepared," BBC News reports.

The headline is prompted by advances in “DNA editing”, which may eventually lead to genetically modified babies (though that is a very big “may”).

The research in question involved the technique of intacytoplasmic sperm injection (ICSI), where a mouse sperm cell was injected into a mouse egg cell. At the same time, they injected an enzyme (Cas9) capable of cutting bonds within DNA, alongside “guide” RNA to guide the enzyme to its target location in the genome. This system then “cut out” targeted genes.

So far, the techniques have only been tested in animals and for “cutting out” very specific genes (currently, under UK law, any attempt to modify human DNA is illegal).

Although this is very early stage research, the potential uses could be vast. They range from arguably more “worthy” uses, such as editing out genes linked to genetic conditions such as cystic fibrosis, to opening up the possibility for a whole manner of cosmetic or “designer” uses – such as choosing your baby’s eye colour.

Such a possibility is always going to be controversial and lead to much ethical debate. As the researchers say, the possibility that these findings could one day lead to similar tests using ICSI techniques in human cells suggests that it is time to start giving this careful consideration.

 

Where did the story come from?

The study was carried out by researchers from the University of Bath and was funded by the Medical Research Council UK and an EU Reintegration Grant.

The study was published in the peer-reviewed scientific journal Scientific Reports. The study is open access, so it is free to read online or download as a PDF.

The BBC accurately reports this study, including quotes from experts about the possible implications.

 

What kind of research was this?

This was laboratory and animal research, which aimed to explore whether the DNA of mammals can be “edited” around the time of conception.

The researchers explain how recent study has developed the use of an enzyme that cuts bonds within DNA (Cas9). This enzyme is guided to its target location in the genome by “guide” RNA (gRNA). To date, the Cas9 system has been used to introduce targeted DNA mutations into various species including yeast, plants, fruit flies, worms, mice and pigs.

In mice, Cas9 has been used successfully to introduce mutations in single-cell embryos, called pronuclear embryos. This is the stage where the egg has just been fertilised and the two pronuclei – one from the mother and one from the father – are seen in the cell. Such early targeting of the embryo’s genome directly leads to an offspring with the introduced genetic mutation.

However, it is unknown whether Cas9 and gRNA could be used to introduce genetic change immediately before the pronuclei are formed (that is, when the sperm cell is fusing with the egg cell, but before the genetic material from the sperm has formed the paternal pronucleus). Therefore, in this study, the researchers aimed to see whether it was possible to use Cas9 to edit the paternal mouse DNA immediately following ICSI. 

 

What did the research involve?

Briefly, the researchers collected egg cells and sperms cells from 8-12 week old mice. In the laboratory, the sperm were injected into the egg cells using the ICSI technique.

The Cas9 and gRNA system was used to introduce targeted gene mutations. This was tried in two ways: firstly, by a one-step injection, where the sperm cell was injected in a Cas9 and gRNA solution; and secondly, where the egg cell was first injected with Cas9 and then the sperm was subsequently injected in a gRNA solution.

The sperm cell that they used had been genetically engineered to carry a certain target gene (eGFP). They were using the Cas9 and gRNA system to see whether it could “edit out” this gene. Therefore, the researchers examined the subsequent stages of blastocyst development (a mass of cells that develops into an embryo) to see whether the system had introduced the required genetic change.

They followed the studies targeting eGFP with studies targeting naturally occurring genes.

Resulting embryos were transferred back to the female to grow and develop.

 

What were the basic results?

Following ICSI, around 90% of fertilisations developed to the blastocyst stage.

When the researchers first carried out a fertilisation using the male sperm that had been genetically engineered to carry the eGFP gene, about half of the resulting blastocysts had a functioning copy of this gene (i.e. they made the eGFP protein). When the sperm were simultaneously injected with the Cas9 and gRNA system to “edit” this gene, none of the resulting blastocysts showed a functioning copy of this gene. 

When they next tested the effect of pre-injecting the egg cell with Cas9, and then injecting the sperm cell with gRNA, they found that this was also effective at editing the gene. In fact, subsequent tests showed that this sequential method was more effective at “editing” than the one-step injection method.

When the eGFP gene was introduced into the egg cell rather than the sperm, and then the Cas9 and gRNA system introduced in the same way, only 4% of the resulting blastocysts demonstrated a functioning copy of this gene.

When next testing the naturally occurring genes, they chose to target a gene called Tyr because mutations to this gene in black mice resulted in a loss of pigment to the coat and eyes. When the Cas9 and gRNA system was similarly used to target this gene, loss of pigment was transmitted to the offspring.

 

How did the researchers interpret the results?

The researchers conclude that their experiments show that injecting egg cells with sperm, along with Cas9 and guide RNA, “efficiently produces embryos and offspring with edited genomes”.

 

Conclusion

This laboratory research using sperm and egg cells from mice demonstrates the use of a system to produce targeted alterations in the DNA – a process the media like to call “genetic editing”. The editing happened just before the genetic material of the egg and sperm cell fuse together.

The system makes use of an enzyme (Cas9) capable of cutting bonds within DNA, and a “guide” molecule targeting it to the correct genetic location. So far, the techniques have only been tested in animals, and for “editing out” a small number of genes.

However, though this is very early stage research, the results do unavoidably lead to questions about where such technology could lead. ICSI techniques are already widely used in the field of assisted human reproduction. ICSI is where a single sperm is injected into the egg cell, as in this study, as opposed to in vitro fertilisation (IVF), where an egg cell is cultured with many sperm to allow fertilisation to take place “naturally”.

Therefore, the use of ICSI makes it theoretically possible that this study may one day lead to similar techniques being possible to edit the human DNA around the time of fertilisation and so prevent inherited diseases, for example.

As the research importantly states: “this formal possibility will require exhaustive evaluation”.

Such a possibility is always going to be controversial and lead to much ethical and moral debate over whether such steps are “correct” and where they could possibly then lead to (such as altering other non-disease aspects of inheritance, like personal traits).

As one of the lead researchers reports to BBC News, extreme caution will be needed with any further developments. However, they consider that the time is right to think about this, as it is an issue that the UK’s Human Fertilisation and Embryology Authority (HFEA) – the body that monitors UK research involving human embryos – is likely to have to face at some point.

While the possibility of DNA editing in humans may seem like the stuff of science fiction, our Victorian ancestors would have felt the same way about organ transplants.

A spokesman for the HFEA is quoted in BBC News as saying: “We keep a watchful eye on scientific developments of this kind and welcome discussions about future possible developments…It should be remembered that germ-line modification of nuclear DNA remains illegal in the UK”. They say that new legislation would be needed from Parliament “with all the open and public debate that would entail” for there to be any change in the law.

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

Links To The Headlines

'Designer babies' debate should start, scientists say. BBC News, January 19 2015

Links To Science

Suzuki T, Asami M, Perry ACF. Asymmetric parental genome engineering by Cas9 during mouse meiotic exit. Scientific Reports. Published online December 23 2014

Categories: Medical News

Wearing killer high heels could lead to osteoarthritis, study warns

Medical News - Fri, 01/16/2015 - 14:30

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

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

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

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

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

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

 

Where did the story come from?

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

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

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

 

What kind of research was this?

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

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

The team were testing two theories.

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

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

 

What did the research involve?

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

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

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

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

 

What were the basic results?

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

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

 

How did the researchers interpret the results?

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

 

Conclusion

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

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

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

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

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

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

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

Links To The Headlines

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

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

Links To Science

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

Categories: Medical News

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

Medical News - Fri, 01/16/2015 - 14:30

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

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

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

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

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

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

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

 

Where did the story come from?

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

It was funded by a Wellcome Trust Investigator Award.

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

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

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

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

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

 

What kind of research was this?

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

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

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

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

 

What did the research involve?

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

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

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

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

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

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

 

What were the basic results?

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

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

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

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

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

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

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

 

How did the researchers interpret the results?

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

 

Conclusion

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

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

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

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

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

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

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

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

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

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

Links To The Headlines

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

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

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

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

Links To Science

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

Categories: Medical News

Inactivity 'twice as deadly' as obesity

Medical News - Thu, 01/15/2015 - 14:30

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

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

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

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

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

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

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

 

Where did the story come from?

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

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

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

 

What kind of research was this?

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

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

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

 

What did the research involve?

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

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

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

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

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

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

  • active
  • moderately active
  • moderately inactive
  • inactive

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

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

 

What were the basic results?

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

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

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

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

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

 

How did the researchers interpret the results?

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

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

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

 

Conclusion

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

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

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

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

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

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

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

Links To The Headlines

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

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

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

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

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

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

Links To Science

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

Categories: Medical News

'Hibernation protein' could help repair dementia damage

Medical News - Thu, 01/15/2015 - 14:00

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

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

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

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

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

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

 

Where did the story come from?

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

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

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

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

 

What kind of research was this?

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

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

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

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

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

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

 

What did the research involve?

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

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

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

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

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

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

 

What were the basic results?

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

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

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

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

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

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

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

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

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

 

How did the researchers interpret the results?

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

 

Conclusion

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

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

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

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

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

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

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

Read more about dementia prevention.

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

Links To The Headlines

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

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

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

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

Links To Science

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

Categories: Medical News

How therapy and exercise 'may help some with CFS'

Medical News - Wed, 01/14/2015 - 15:00

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

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

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

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

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

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

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

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

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

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

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

 

Where did the story come from?

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

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

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

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

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

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

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

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

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

 

What kind of research was this?

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

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

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

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

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

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

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

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

 

What did the research involve?

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

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

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

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

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

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

These factors included the level of participants':

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

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

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

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

 

What were the basic results?

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

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

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

 

How did the researchers interpret the results?

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

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

 

Conclusion

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

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

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

The advantages of the study include that this is a pre-planned analysis of an RCT, as well as the fact that after the treatments were started, mediators and outcome were measured in temporal order (i.e. “one after the other”). The latter means that it is possible that the treatments are influencing the mediators, which are then influencing outcomes.

The authors acknowledge that the outcomes were showing changes by 12 weeks when the mediators were measured, so it is possible that they were both affecting each other. However, without measurements of the mediators before 12 weeks they were not able to look at this more closely to see if they could be certain which change came first.

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

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

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

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

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


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

Links To The Headlines

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

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

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

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

Links To Science

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

Categories: Medical News

Under-80 cancer deaths 'eliminated by 2050' claim

Medical News - Wed, 01/14/2015 - 12:54

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

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

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

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

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

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

 

Where does the report come from?

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

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

 

What type of study is it?

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

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

 

What are the figures?

The basic UK figures provided are:

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

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

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

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

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

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

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

What changes are proposed to improve cancer prevention?

The authors suggest:

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

 

What measures do they say could improve cancer survival rates?

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

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

 

Conclusion

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

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

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

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

Links To The Headlines

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

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

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

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

Categories: Medical News