NHS Choices

'Supercooling' may extend life of transplant organs

NHS Choices - Behind the Headlines - Mon, 30/06/2014 - 14:30

BBC News reports on a new method to keep donated organs fresher for longer: “supercooling”.

US researchers are developing a new technique for the longer term preservation of human organs before transplantation.

Current methods of organ preservation can keep an organ viable for transplant up to around 12 hours once it has been removed from the body. This new technique has potentially extended this time up to three days.

The researchers tested the technique using rat livers. They froze the livers to subzero temperatures of 0C to -6C, while at the same time, passing nutritional preserving fluids to help keep the organ viable.

When rats were transplanted with a liver that had been preserved in this way for 72 hours, they all survived to three months, showing no signs of liver failure.

The number of people needing organ transplant always outnumbers the number of suitable donors available. So a technique that could preserve organs for longer could potentially allow them to be transported across greater distances to suitable recipients.

Hopefully this technique could work in humans, though due to the size and complexity of human organs, this may turn out not to be the case.

 

Where did the story come from?

The study was carried out by researchers from Harvard Medical School, Boston; Rutgers University, Piscataway, New Jersey; and University Medical Center, Utrecht, the Netherlands. Funding was provided by the US National Institutes of Health, and the Shriners Hospitals for Children.

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

The BBC's reporting on the study is of a good quality and includes useful discussion from the researchers as well as independent experts about the new development.

Dr Rosemarie Hunziker, from the US National Institute of Biomedical Imaging and Bioengineering, is quoted as saying “It is exciting to see such an achievement in small animals by recombining and optimising existing technology. The longer we are able to store donated organs, the better the chance the patient will find the best match possible, and doctors and patients can be fully prepared for surgery. This is a critically important step in advancing the practice of organ storage for transplantation.”

 

What kind of research was this?

This was laboratory research which tested a new “supercooling” technique to preserve the life of donated organs. The current study tested the technique using rat livers.

The researchers explain the increasing number of people waiting for organ transplants, but the serious shortage of donor organs. When organs are removed from a living body their cells immediately begin to die, meaning they need to be transplanted into the donor as soon as possible to give the best chances of a successful transplant.

The researchers report how current preservation solutions and cooling methods for humans allow organs to remain viable for up to 12 hours.

Methods that could increase the preservation time to days could potentially allow for sharing of donor organs across much greater geographical distances to reach suitably matched recipients.

This could greatly help the problem of the shortage of donor organs. For example, it could be possible to transport an organ with a rare tissue type from Australia to the UK.

So far the researchers say that cryopreservation has been successful for various cell types and some sample tissues. However, its success for the long-term storage of vascularized solid organs (organs, like the liver, with a complex vascular blood system) has been difficult up to now due to freezing and the subsequent rewarming having damaging effects on the intricate anatomy of the organs.

The “supercooling” technique tested here involves freezing to subzero temperatures of 0C to -6C. So far, though previous studies have demonstrated freezing organs to subzero temperatures, they have yet to demonstrate that this can result in the long-term survival of the organ following transplantation. The current research expanded on this by supercooling to subzero temperatures, but additionally using a machine to perfuse the organ with a nutritional preserving solution to support the organ while frozen.

 

What did the research involve?

The researchers used livers from male rats. The organs were surgically removed and then perfusion and supercooling was carried out using a technique called subnormothermic machine perfusion (SNMP).

This makes use of a machine that carefully cools the tissue to below body temperature, and at the same time circulates a preserving solution through the tissue.

The machine first perfused the organ at room temperature (21C) with a nutritional preserving solution containing various substances (such as antibiotics, steroids, proteins and anti-clotting chemicals). There were various stages of recirculation and oxygenation. After one hour of perfusion, the temperature of the perfusing solution was gradually lowered by 1C every minute until the temperature of 4C was reached. At this point the liver was again briefly flushed through with preserving solution and then transferred to a sterile bag filled with the same solution and moved to a freezer, which gradually cooled at a controlled rate until the temperature of −6C was reached.

The liver was kept at this temperature for up to 96 hours (four days). The organ was then gradually rewarmed. The temperature was raised to 4C, and then the organ was again perfused using the SNMP machine for a further three hours. During this time they took various organ measurements, including analysing the organ’s weight, liver enzymes, dissolved oxygen and carbon dioxide, and bile flow.

The liver was then transplanted into a recipient rat, and the rat’s blood samples were analysed for one month. They then continued to observe the clinical condition of the rat for up to three months, particularly looking at clinical signs of liver cirrhosis and overall survival.

They compared the results with those when rats were transplanted with livers that were kept for the same duration using current preservation techniques.

 

What were the basic results?

All the rats transplanted with supercooled livers that had been preserved for 72 hours survived to three months, and showed no signs of liver failure. Comparatively when rats were transplanted with livers that were kept for three days under standard preservation techniques, all of those rats died from liver failure within the first two days.

Using standard preservation techniques the same survival results were only seen if the rat livers were preserved for no more than 24 hours – therefore the supercooling technique tripled the storage time.

Increasing supercooling duration to 96 hours however, resulted in only 58% rat survival, which the researchers say is comparable to the 50% survival following 48 hours of standard preservation.

Control rats transplanted with livers that had been frozen to the same subzero temperatures but which were not subjected to the full sequence and duration of perfusion with the nutritional solution also did not survive.

 

How did the researchers interpret the results?

The researchers say that as far as they are aware “supercooling is the first preservation technique capable of rendering livers transplantable after four days of storage”.

 

Conclusion

When organs are removed from a living body their cells immediately begin to die, meaning they need to be transplanted into the donor as soon as possible to give the best chances of a successful transplant. The number of people needing organ transplant always outnumbers the number of suitable matched donors available. So having a technique that could preserve organs for longer and potentially allow them to be transported across greater distances to suitable recipients could, as the researchers say, be a great breakthrough.

This is especially important as it can often be difficult to find a suitably matched donor (to prevent the body from rejecting the donation, the tissue type has to be as similar as possible), but if the geographical availability of donors were increased, then this could increase the likelihood of finding a matched donor. 

This research demonstrated the technique of preserving with a nutritional solution and then supercooling to subzero temperatures of 0C to -6C. When rats were transplanted with a liver that had been preserved in this way for 72 hours, all of them survived to three months, showing no signs of liver failure. This triples the preservation time from 24 hours, which is the maximum that can be successfully achieved using standard techniques in rats.

The 100% rat survival was limited to 72 hours of storage. When the storage time was extended by one day, rat survival almost halved to 58%. However, as the researchers say, with continued study of different additives for the preserving solution, or variations in protocol, additional improvements could be achieved from future experiments.

The researchers also importantly highlight that this is only a proof-of-concept study in small animals. As they say, the robustness and preservation properties of human liver cells differ from those of rodents.

Though their research with the rat livers was successful, with no signs of liver failure when stored for three days, they need to see whether the same results can be achieved with larger animals, before they can test with human livers.

They also need to perform longer follow up to see if survival and liver function are maintained for longer than three months

The current study also used healthy livers surgically removed from living, healthy rats.

The researchers also need to consider removing organs from dead bodies, so the organ has already been subjected to being starved of oxygen.

They also need to see if the technique can be extended to other organs, besides the liver.

Overall, this is promising early research, which paves the way for much further study.

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

Links To The Headlines

Organ transplants: 'Supercooling' keeps organs fresh. BBC News, June 29 2014

Links To Science

Berendsen TA, Bruinsma BG, Puts CF, et al. Supercooling enables long-term transplantation survival following 4 days of liver preservation. Nature Medicine. Published online June 29 2014

Categories: NHS Choices

Part of the brain for 'hangover guilt' identified

NHS Choices - Behind the Headlines - Mon, 30/06/2014 - 12:26

"Scientists pinpoint the part of the brain that tells us 'never again'," the Mail Online reports. New research in rats suggests part of the brain called the lateral habenula (LHb) helps us learn lessons from bad experiences after consuming too much alcohol.

The LHb is believed to play some role in preventing us repeating something that previously resulted in a negative outcome, such as getting extremely drunk and waking up with a dreadful hangover. But some people may lack activity in this part of the brain.

This study found causing surgical damage to the LHb stopped it having inhibitory effects on alcohol consumption. When given free access to alcohol, rats that did not have damage to this part of the brain had a high alcohol intake initially, but this then tailed off. Rats with LHb damage showed a continuously increasing rate of ethanol consumption.

A similar mechanism may play a role in people with alcohol misuse problems. As a result of decreased LHb activity, they may fail to "learn" from alcohol-associated adverse events and continue to misuse the drug. This may explain why many people who experience the negative effects of alcohol continue to drink.

But intriguing as this hypothesis is, it remains unproven. The research also has no direct implications for humans at this stage, such as new ways to prevent and treat alcohol dependence.

 

Where did the story come from?

The study was carried out by researchers from the University of Utah School of Medicine in the US, and was funded by the US National Institutes of Health, the March of Dimes Foundation and the University of Utah.

It was published in the peer-reviewed scientific journal PLOS One. PLOS One is an open access journal, so the article is free to read online.

The Mail Online's reporting of the study is accurate.

 

What kind of research was this?

This was animal research that aimed to investigate the role of a particular region of the brain – the lateral habenula (LHb) – in conditioning our response to alcohol.

The LHb has been implicated as a brain region key in learning from adverse outcomes. It is believed to play a role in stopping us doing things if we had a negative experience when we did this previously.

As the researchers say, the positive effects of drugs are known to motivate further drug-seeking behaviours. But it is also known that the adverse effects of drugs can limit further intake.

Previous studies pointed towards the LHb being involved in reducing motivation to consume nicotine and cocaine.

Ethanol (alcohol) is well known to have downsides, including impairment of motion and hangovers.

Studies have shown that rats with sensitivity to these adverse effects decrease their voluntary intake of alcohol.

To further examine the role of the LHb in learning driven by adverse outcomes, the researchers studied voluntary ethanol consumption in rats with and without lesions (damage) in the LHb. 

 

What did the research involve?

The research involved 136 male rats. The rats were anaesthetised and half were given surgical damage to the LHb by passing an electrical current through it. The remainder of the rats received a similar surgery, but no electrical current was passed (a "sham" procedure).

The rats were given one week to recover before being included in various experiments. The researchers conducted various experiments looking at the role of the LHb in alcohol consumption.

In one experiment, sham and lesion rats (17 in each group) were given intermittent 24-hour access to two bottles over eight weeks. One bottle contained water and one contained a solution of water with ethanol (alcohol) at a concentration of 20%. On some days, they were given only water and no ethanol.

The researchers weighed the water and ethanol bottles to measure intake and preference. After eight weeks, they looked at various effects in subsets of rats, including looking at the effect of subjecting the rats to a long period of alcohol abstinence before restoring their alcohol intake.

Another group of sham and lesion rats (10 in each group) were given intermittent 24-hour ethanol access for eight weeks. The researchers then examined the effects of allowing the rats access to self-administer ethanol by pressing a lever. After a period of free self-delivery, the researchers tested what happened when pressing the lever no longer gave the rats alcohol.   

As a final test in a large group of 37 sham and 42 lesion rats, the researchers tested the theory of conditioned taste aversion, where an effect of one fluid conditions them to dislike fluids with a similar taste, even if they don't have the same effect.

These rats were housed with free access to food and water and a sugar solution. They were then given ethanol, and the subsequent effect on their consumption of sugar solution was measured.

 

What were the basic results?

The researchers found that intermittent 24-hour ethanol access resulted in a steady increase in ethanol consumption in both sham and LHb lesion rats.

However, after one week of ethanol, consumption in the lesion rats increased more than the sham rats and reached higher intake levels, reaching 6g per kg per 24 hours, compared with 4g per kg per 24 hours in the sham rats.

The rats with the LHb lesions continued to show higher intake than the sham rats when they were not given alcohol for a period before access was then reinstated.

After the eight weeks of intermittent ethanol access, the researchers found the LHb lesion rats pressed the lever to get alcohol significantly more than the sham rats.

When the lever presses no longer rewarded them with ethanol, the lesion rats still pressed the lever more than the sham rats on the first day, but not after that.

In the final test of conditioned taste aversion, after giving rats ethanol, those with no LHb damage also showed an aversion to drinking the sugary solution, while those with LHb damage did not show aversion.

 

How did the researchers interpret the results?

The researchers concluded that their results show that the lateral habenula (LHb) plays an important role in controlling ethanol-directed behaviours.

 

Conclusion

This was animal research that aimed to investigate the role of the lateral habenula (LHb) in conditioning responses to alcohol.

The LHb is a brain region key in learning driven by adverse outcomes. It is believed to play a role in stopping us repeating actions that have previously resulted in negative outcomes.

In this study in rats, surgical damage to the LHb stopped the rats learning to moderate their alcohol consumption.

When given free and open access to ethanol, rats with LHb damage showed continuously increasing rates of ethanol consumption and reached higher blood alcohol levels.

Comparatively, rats without damage to this brain region had a high intake initially, but their liking then tailed off.

The researchers also found damage to the LHb reduced conditioned taste aversion – after being given ethanol, rats without damage to this region had an aversion to drinking a sugar solution, but the rats with LHb damage did not.

Overall, this rat study supports the belief that the LHb may be involved in learning driven by adverse outcomes. But it isn't clear what negative effects the rats could have been having – for example, whether this was linked to them having anything like a hangover after drinking alcohol.

The direct implications for humans are currently very limited. It is plausible that some people have an underperforming LHb. This could lead to self-destructive patterns of behaviour, despite a previous history of adverse events such as hangovers.

Even if this highly speculative hypothesis turns out to be true, it is currently unclear what treatments this could lead to.

Current treatments for alcohol misuse include medications that can help relieve cravings, as well as counselling – both one-to-one and in groups.

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

Links To The Headlines

Scientists pinpoint the part of the brain that tells us 'never again' while suffering a hangover. Mail Online, June 27 2014

Links To Science

Haack AK, Sheth C, Schwager AL, et al. Lesions of the Lateral Habenula Increase Voluntary Ethanol Consumption and Operant Self-Administration, Block Yohimbine-Induced Reinstatement of Ethanol Seeking, and Attenuate Ethanol-Induced Conditioned Taste Aversion. PLOS One. Published online April 2 2014

Categories: NHS Choices

Blood test for breast cancer 'has potential'

NHS Choices - Behind the Headlines - Fri, 27/06/2014 - 16:19

"Blood test could give early warning of breast cancer," The Guardian reports. Researchers have identified a genetic signature that may be useful in predicting whether a woman is likely to develop non-inherited breast cancer.

Reliable blood tests for inherited (genetic) cases of breast cancer already exist. These tests look for mutations in the BRCA gene and may be used in women with a strong family history of breast cancer.

They can predict whether a woman is at risk of developing breast cancer with a high degree of accuracy. Such tests provide women with the opportunity to take preventative treatment, as was the case recently with the actress Angelina Jolie.

But only a very small proportion of all breast cancers are in people with BRCA mutations, described as being fewer than 1 in 10.

New research has focused on looking at DNA methylation of the BRCA1 gene. Methylation is when chemical groups attach to a gene. This does not amount to a mutation as the DNA sequence remains unchanged, but it can nevertheless alter gene activity.

In this study the researchers identified a set of DNA methylations that could provide a unique "signature" and potentially predict breast cancer risk in people without BRCA mutations.

This is interesting and promising research, but a reliable blood test for non-inherited breast cancer does not seem to be on the cards any time soon. The test showed potential, but it currently isn't very accurate – it is only marginally better than a guess at predicting risk.

 

Where did the story come from?

The study was carried out by researchers from University College London and the University of Manchester in the UK, the First Faculty of Medicine and General University Hospital, Charles University in the Czech Republic, and the Shanghai Institute for Biological Sciences in China.

The research received various sources of funding, including the European Union's Seventh Framework Programme.

It was published in the peer-reviewed medical journal Genome Medicine, an open access publication available free online. This is a provisional publication and there may be some revisions before its final version.

The quality of the UK media's reporting of the study is mixed. Most sources included useful discussion from experts, who on the whole are encouraged by the findings and discuss the need to build on the results.

However, the media does not make it clear that no such screening or diagnostic test is imminent. Much more work is needed before developing such a test can be considered or before it could be brought into widespread use.

Such considerations would need to include the possibility of false negative and false positive test results. A false negative result is where a woman is told she isn't at risk of breast cancer when she is, and a false positive tells her she is at risk of breast cancer when she isn't.

Even if a test correctly identified a woman as being at risk of breast cancer, the psychological consequences of this risk and what to do about it are great.

The Daily Mail also suggests the research has developed a test that can tell whether a woman's lifestyle puts her at risk of breast cancer. This is a misleading and incorrect interpretation of the study.

While it is plausible such a test could become part of a more detailed risk stratification process also taking lifestyle factors into account, no actual research was carried out looking at this.

 

What kind of research was this?

This was a case control study that aimed to see whether it was possible to develop a blood test that could predict whether a person was at risk of developing non-hereditary breast cancer.

The BRCA1 gene has long been associated with the risk of breast cancer. People who have inherited mutations of this gene are reported to have an 85% risk of developing breast cancer.

However, most people who develop breast cancer have not got a mutation of the BRCA1 gene (or the BRCA2 gene, which is similarly associated with risk). This makes it difficult to predict the risk of breast cancer among the majority of people, who have not inherited mutations of the BRCA genes.

The research centred on trying to identify people who have DNA methylation of the BRCA1 gene. This means they have not inherited a mutation of the BRCA1 gene, but the gene has a methyl chemical group attached to it.

Although the DNA sequence of the BRCA1 gene is "normal", this methyl group addition still alters the activity of this gene. 

The case control study design involved analysing and comparing the blood samples of "cases", who carry a BRCA1 gene mutation, and "controls", who have normal BRCA1 and 2 genes.

 

What did the research involve?

The DNA from the blood samples of 72 people with a BRCA1 gene mutation and 72 people without BRCA gene mutations was extracted in the laboratory (specifically, their white blood cells were examined).

DNA methylation at specific CpG sites was examined (C and G being two of the four base molecules in the DNA sequence) in a model that took age and presence of cancer into account.

The researchers then verified the predictive accuracy of the methylation profiles using blood and tissue samples collected in two additional studies:  

  • the Medical Research Council National Survey of Health and Development (NSHD) – taking a birth cohort of men and women born in 1946, the researchers analysed the blood and buccal cell (inside of the cheeks) samples of 75 people who developed cancer (19 cases of breast cancer) and 77 who did not develop cancer
  • the United Kingdom Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) – the researchers analysed the blood samples from 119 postmenopausal women who went on to develop breast cancer (on average two years later) and 122 who remained cancer free during the average 12-year follow-up

 

What were the basic results?

The researchers observed a vast number of different methylations at the CpG sites in people who had BRCA1 gene mutation. From this they identified a "DNA methylation signature" that included 1,829 CpGs, which are different in people with and without BRCA1 gene mutations.

When they validated this in the NSHD study, they found the DNA methylation signature was a possible predictor of breast cancer. In statistical terms, the area under the curve for this signature was 0.65 (95% confidence interval [CI] 0.51 to 0.78).

The area under the curve – related to a curved line on a graph – is a measurement of predictive accuracy. When interpreting area under the curve, a value of 1.0 would be perfect accuracy, while a value of 0.5 would be considered random chance (the test would be little better than guessing).

Values of less than 0.5 would be a very poor diagnostic test, worse than guessing. Therefore, 0.65 may be indicated as a bit better than guessing. The DNA methylation signature also similarly predicted the risk of other types of cancer (area under the curve 0.62).

This predictive ability only worked when using the blood samples taken from this cohort – analyses using the buccal tissue sample didn't work.

When the researchers then looked at the UKCTOCS samples, they found the signature predicted the development of oestrogen receptor-positive breast cancer, with an area under the curve of 0.57 (suggesting this was a bit better than guessing).

In this cohort, they carried out further sub-analyses using data on breast cancer risk factors they had information on for this cohort. They found the DNA methylation signature predicted breast cancer (and breast cancer deaths) only in the group of women without a family history of breast cancer, but not in the women with a family history.

However, as the researchers acknowledge, the number of women who developed breast cancer and had a family history of the disease was very small. 

 

How did the researchers interpret the results?

The researchers conclude that the DNA methylation signature derived from BRCA1 carriers "is able to predict breast cancer risk and death years in advance of diagnosis".

Importantly, they say that future studies may need to focus on DNA methylation profiles in body cells (rather than the white blood cells used here) to reach the area under the curve thresholds required of preventative measures or early detection strategies.

 

Conclusion

This is early-stage research into the development of an indicator that could predict the risk of breast cancer in people who are not carrying the hereditary BRCA gene.

This accounts for the vast majority of people who develop breast cancer. Only a very small proportion of all breast cancers are in people with BRCA mutations.

Although there are many different health and lifestyle factors associated with the risk of breast cancer, predicting breast cancer risk in people without hereditary gene mutations is not currently possible.

This laboratory research focused on examining white blood cells for DNA methylation of the BRCA1 gene, which does not alter its DNA sequence but nevertheless alters its activity. The research found a vast number of different methylations combined into a "DNA methylation signature" that could possibly predict risk of breast cancer.

However, in the current study, the predictive power of this test was not very good – it was better than guessing, but not much more. Such a poor predictive accuracy could never be used as the basis of decisions about treatment. It has also only been tested in fairly small cohort samples.

As it currently stands, a test that could predict breast cancer development in people without hereditary BRCA gene mutations does not seem to be on the cards any time soon. As the researchers acknowledge, given the low predictive accuracy when using the blood samples, they next need to test this using other body cells.

Much work is needed to improve the accuracy of this test. And even then, if researchers can one day develop an accurate test using methylation profiles, there are great considerations to make in weighing up the risks and benefits before a screening test could be introduced for widespread use.

For now, the most well-established lifestyle factors that reduce the risk of non-hereditary breast cancer are a healthy balanced diet, regular physical activity to avoid becoming overweight or obese, avoiding smoking, and limiting your alcohol intake. 

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

Links To The Headlines

Blood test could give early warning of breast cancer. The Guardian, June 27 2014

Breast cancer blood test gives women hope for early warning. The Times, June 27 2014

Women offered hope of breast cancer-predicting blood tests. The Daily Telegraph, June 27 2014

New blood test warns 10 years in advance if lifestyle may put women at risk of breast cancer. Mail Online, June 27 2014

Breast cancer breakthrough: New test could predict risk the of the disease 10 years ahead. Daily Express, June 27 2014

Expert: Breast cancer blood test data 'encouraging'. ITV News, June 27 2014

Links To Science

Anjum S, Fourjaka E, Zikan M, et al. A BRCA1-mutation associated DNA methylation signature in blood cells predicts sporadic breast cancer incidence and survival. Genome Medicine. Published online June 27 2014

Categories: NHS Choices

Moderate TV viewing linked to premature death

NHS Choices - Behind the Headlines - Fri, 27/06/2014 - 12:30

“Watching TV for three hours a day can be deadly – doubling your risk of dying early,” the Mail Online reports.

The website reports on a study involving a relatively large group of Spanish university graduates. The participants were asked to self-report time spent on three types of sedentary behaviour: TV viewing, computer use and time spent driving.

They were then followed for between 2 and 10 years to see if any of the participants died prematurely, and if so, if there was a significant association between premature death and types of sedentary behaviour.

In their analysis, the researchers took into consideration potential confounding factors, such as the age, smoking status and total energy intake of participants.

The main finding from this study was that the risk of death was doubled for participants reporting three or more hours of TV viewing a day, compared to those reporting less than one hour a day. Time spent using a computer or driving was not significantly associated with risk of early death.

This unexpected association with TV watching, but not other forms of sedentary behaviour, could be due to the very small sub-group of people who died during the follow-up period – just 0.7% of the cohort. In such a small sample size, there is a significant possibility that any association is simply down to chance.

 

Where did the story come from?

The study was carried out by researchers from the University of Navarra, in Pamplona, Spain. It was funded by various Spanish government grants, the Navarra Regional Government and the University of Navarra. The study was published in the peer-reviewedopen-access Journal of the American Heart Association, so it is freely available to read online.

The study was picked up by The Mail Online, which appropriately reported the methods and findings, but failed to adequately discuss the study's limitations. It also failed to put the risks of increased premature death into a useful context for readers. During the length of the study, only 0.7% of participants died prematurely – equivalent to around 1 in 142 people.

 

What kind of research was this?

This was a dynamic prospective cohort study looking at the associations between three types of sedentary behaviour (TV viewing, computer use and time spent driving) and all-cause death in a group of Spanish university graduates. It is called a dynamic study because recruitment to the study is permanently open.

cohort study examines how particular exposures affect outcomes in groups of people over time. A prospective study looks at these exposures and measures outcomes of interest in these people over the following months or years. Results from prospective studies are usually considered as more robust then retrospective studies, which either use data that was collected in the past for another purpose, or ask participants to remember what has happened to them in the past.

 

What did the research involve?

This study used data from the wider “Sun Cohort” research. The Sun Cohort is a multi-purpose prospective cohort study, using Spanish university graduates as participants, that was designed to assess the association of diet or lifestyle with the rate of several diseases and death. Recruitment of participants began in 1999.

The researchers collected information on participants through self-administered questionnaires sent by mail at baseline and every two years. The baseline questionnaire included items to assess TV viewing, computer use and time spent driving. Each of these items had 12 possible categories for responding, ranging from “never” to “more than nine hours a day”.

Information on weekday and weekend use was measured separately, calculated to provide data over a week (five weekdays, two weekend days) and divided by seven, to give each participant’s total time spent per day.

Additional information was captured on the participants':

  • medical history
  • lifestyle
  • sociodemographic factors
  • body measurements
  • physical inactivity
  • smoking status
  • dietary habits
  • adherence to the Mediterranean dietary pattern

In December 2012, there were 20,572 participants who had completed the baseline questionnaire and had been followed up for at least 2 years, up to 10 years. Participants who reported diabetes, cardiovascular disease or cancer at the baseline assessment were excluded from the analyses. Also excluded were those with missing data on TV viewing and those people who were not followed up (who dropped out). Accounting for these exclusions, the researchers carried out their analyses on a total of 13,284 participants.

The main outcome of interest was death from any cause. Most deaths were reported to be identified from next of kin, work associates and postal authorities. The Spanish National Death Index was also checked every six months. 

The researchers then used statistical techniques to analyse the data. They considered participants with the lowest exposure time at baseline (the lowest time spent viewing TV, or the lowest amount of time spent driving) as a comparison group to higher levels of exposure. In their analysis, the researchers provided results with varying types of adjustments.

The most adjusted results took into account the following confounders:

  • age
  • sex
  • smoking status
  • total energy intake (kcal/day)
  • Mediterranean diet adherence
  • baseline body mass index (BMI in kg/m2)
  • leisure time physical activity (metabolic equivalent tasks (METs) per week)

 

What were the basic results?

There were 13,284 participants (61.6% female) included in the analysis, who had an average age of 37 years and were followed for a median of 8.2 years. There were a total of 97 deaths registered from all causes among these participants (0.7%). The researchers say the expected number of deaths from this population was estimated at 128 for this sample size.

At baseline, participants spent on average:

  • 1.6 hours watching TV a day (standard deviation [SD] 1.3)
  • 2.1 hours using computers a day (SD 2.1)
  • 0.9 hours driving a day (SD 1.2)

The main findings from this study were that in the most adjusted analyses:

  • TV viewing was positively associated with all-cause death. The risk of death was doubled for participants reporting three or more hours of TV viewing per day compared to those reporting less than one hour a day (Incidence rate ratio (IRR) 2.04, 95% confidence interval (CI) 1.16 to 3.57). When analysed in a different way, each additional two hours of TV viewing had an incidence rate ratio of 1.40 (95% CI 1.06 to 1.84)
  • time spent using a computer or driving was not significantly associated with death

 

How did the researchers interpret the results?

The researchers conclude that, in this study, TV viewing was directly associated with all-cause mortality. They said, however, that computer use and time spent driving were not significantly associated with higher mortality.

When discussing the findings of this study, lead researcher Professor Miguel Martinez-Gonzalez from The University of Navarra  is reported as saying the findings "are consistent with a range of previous studies where time spent watching TV was linked to mortality”.

 

Conclusion

This prospective cohort study provides some limited evidence of an association between TV viewing and death from all causes among a group of relatively young Spanish university graduates. It found that the risk of death was higher for people who watched three or more hours of TV a day compared to people who watched less than an hour a day. Computer use and time spent driving was not found to increase the risk of death.

This study included a relatively large number of people followed prospectively, and it attempted to adjust results for several potential confounders, such as energy intake, age and smoking status.

However, the main limitation of this study is that only the baseline information on participants' total daily time spent on TV viewing, computer use and driving was analysed in its association with risk of early death. Therefore, this study is based on data collected at one point in time and does not reflect changes to the participants' time spent in these activities over the years they were included in the study. A more appropriate analysis would have also considered time spent in these activities at each of the two-year follow-ups.

An additional limitation worth noting, is that time spent in these three activities was collected via self-reporting, so there is a possibility that participants inaccurately reported time spent in these activities.

There is always the possibility that other factors may be influencing the results. As the researchers note, there is a possibility that eating and drinking is more likely to occur with TV viewing than with computer use and driving. However, the researchers say that the associations hardly changed after adjustment for energy intake and of these two factors.

Another important potential confounder could be the health and disability of the people taking part. For example, people with poor health and a disability may be more likely to spend more time viewing the TV, and also more likely to die early. However, as the researchers say, the cohort was fairly young, and they also excluded people with diabetes, cardiovascular disease, and cancer and baseline. This may reduce the possibility of ill health and disability confounding the results.

Another possibility is that they may only be chance observations.

Despite the large sample of over 13,000 people, because of the relatively young age of the population, there were only 97 deaths during follow-up – just 0.7% of the cohort. Examining lifestyle factors associated with such a small number of deaths increases the possibility of chance observations.

However, despite its limitations, the study supports established health recommendations to limit sedentary time and take regular physical activity. Current recommendations are that healthy adults should take at least 150 minutes of exercise a week.

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

Links To The Headlines

Three hours of TV a day 'doubles early death risk' as scientists say sedentary behaviour leads to illnesses such as diabetes and heart disease. Mail Online, June 26 2014

Links To Science

Basterra‐Gortari FJ, Bes-Rastrollo M, Gea A, et al. Television Viewing, Computer Use, Time Driving and All‐Cause Mortality: The SUN Cohort. Journal of the American Heart Association. Published online June 25 2014

Categories: NHS Choices

'Strength & Flex made me a better runner'

NHS Choices - Live Well - Thu, 26/06/2014 - 17:15
'Strength & Flex made me a better runner'

Father-of-two Cliff Hobby started Strength & Flex and Couch to 5K as a way to get back into regular exercise.

He did Strength & Flex every other day and found that the five-week programme really improved his running.

Below, the IT manager from Alton in Hampshire, talks about his experience of progressing through the Strength & Flex podcasts.

"Strength & Flex has helped keep me free from injury since starting running."

Cliff Hobby

Where did you find out about Strength & Flex?

I found Strength & Flex on the NHS Choices website when I was looking for a way back in to regular exercise midway through 2013. It seemed quite straightforward and I liked the podcast approach, with coach Laura guiding you through each week.

 

How active were you before starting the plan?

Before Strength & Flex, my exercise had been mostly bike rides, walking and swimming at weekends, plus some weight training – but it was patchy, and I wanted something that I could follow more regularly and that would improve my overall fitness.

 

Why did you decide to get more active?

I realised that I ought to be much more active than I was, and that it was up to me to do something about it. I spend a lot of time working and found that I didn't have as much time or energy for other things, and wanted to change that. I enjoy sport and wanted to improve my fitness, as well as lose a little weight.

 

Where do you do Strength & Flex?

I'm lucky enough to have the space to complete Strength & Flex indoors, and although the pull-ups took a bit of lateral thinking, most of the exercises are simple enough to do inside.

 

Do you ever feel self-conscious exercising in public?

I haven't completed Strength & Flex outside yet, but I've never felt self-conscious about exercising outdoors. It's something I enjoy and it’s improving my health, plus there are plenty of other runners and cyclists around.

 

Has your health improved since starting Strength & Flex?

I've noticed a real improvement in my overall health since starting Strength & Flex, and also Couch to 5K. I have much better stamina, more energy, have lost weight and generally feel more alert. I've also developed more of an interest in my own health and wellbeing.

 

Has Strength & Flex helped your running?

I have gone from not running at all to now regularly running distances that I used to find challenging to complete on a bike. I find cycling much easier too, and have the confidence to tackle longer distances for both, with a marathon on the horizon for 2015. I know from experience that if I have completed Strength & Flex regularly, running will be a little easier, and the Strength & Flex stretches have helped keep me free from injury since starting.

 

What do you like most about Strength & Flex?

Strength & Flex was a great way to get back into regular exercise and is something that I can complete in my own time. The exercises are really straightforward, yet you still feel like you have achieved something at the end of a session.

 

Did you find the Strength & Flex exercises challenging?

I think it was more about the challenge of completing the five weeks, as I had tried other programmes before and not really stayed the course. One or two of the exercises make you realise how unfit you really are to start with, but it's good as you can see yourself progressing over the five weeks.

 

Do you still do Strength & Flex?

I still use the week five podcast from Strength & Flex on non-running days, and it seems like a good warm up now, which I guess shows my fitness has improved since starting it! 

Categories: NHS Choices

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