NHS Choices

Does moderate drinking reduce heart failure risk?

NHS Choices - Behind the Headlines - Tue, 20/10/2015 - 12:10

"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: NHS Choices

Gene testing could find those who would benefit most from statins

NHS Choices - Behind the Headlines - Wed, 04/03/2015 - 13:00

"Patients with the highest genetic risk of suffering a heart attack benefit the most from cholesterol-lowering statin drugs," The Guardian reports.

Statins are drugs that lower cholesterol and can help reduce the risk of coronary heart disease (CHD) developing – the leading cause of death both in the UK and worldwide.

Researchers studied genetic risk factors previously discovered for CHD in 48,421 adults, and used them to group people into low, intermediate and high risk categories. They next looked at the effect of statins on reducing new and recurring CHD "events" such as heart attacks. Compared with not taking them, statins reduced CHD events by 13% in the low-risk group, 29% in the intermediate group and 48% in the high-risk group.

Current UK recommendations are that people should be offered statins if there is at least a one in 10 chance of them developing CHD at some point in the next 10 years.

Critics of these recommendations argue that this means they are given to people who don’t really need them, which could waste money and subject people unnecessarily to the possible side effects of statins.

The work carried out in this study could improve the ability to assess who is at high risk.

The findings need to be confirmed by other research, but suggest that genetic risk factor categories could be used, alongside other risk factors, to identify groups who may benefit most from statins.

 

Where did the story come from?

The study was carried out by academic and medical research institutions in the US and Sweden, and was funded by the National Institutes of Health and a large number of public and private sources. The study used data from existing trials that were supported by drugs companies, as well as public research councils. 

Many of the authors have received funding, such as research grants, from drugs companies. Due to the nature of the research, this is not surprising. A study of this size and scale, involving so many researchers, would be near-impossible to carry out without any industry involvement. 

A detailed list of these declarations of interest was given in the publication. The publication stated: "For this analysis, the funders of the individual clinical trials had no role in the analysis or interpretation of the data, or writing of the report."

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

Generally, The Guardian reported the story accurately, but linked the risk reduction figures solely to heart attacks. The figures actually referred to a mixed group of CHD events. Most of them were fatal or non-fatal heart attacks, but it also included some cases of unstable angina, heart bypasses, or other heart interventions. This isn’t a big issue, but something to be aware of.

What kind of research was this?

This was a mixed method study looking at whether genetic risk factors can predict CHD, and if these might be used to identify people who would get the most benefit from using statins.

CHD is the leading cause of death both in the UK and worldwide.

It's responsible for around 73,000 deaths in the UK each year. About one in six men and one in 10 women die from CHD.

In the UK, there are an estimated 2.3 million people living with the condition and around 2 million people affected by angina – the most common symptom of CHD. Read more about the symptoms of CHD.

Genetic variations in DNA have been linked to higher risk of CHD in previous research. In this new study, they tested whether or not a combination of these variants could predict the risk of new or recurrent CHD events, and whether this could identify people who get the most benefit from statin therapy.

 

What did the research involve?

The researchers analysed data from four randomised controlled trials (RCTs) and one cohort study, to look at the link between genetic risk factors and CHD events. They then looked at the relative risk and absolute risk reductions in CHD through using statins, stratified across the different genetic risk groups.

The studies included were a Swedish community-based cohort study (the Malmo Diet and Cancer Study) and four RCTs. Two of the RCTs looked at the ability of statins or anti-hypertension medication to prevent cardiovascular disease (CVD) compared with placebo (JUPITER and ASCOT). The other two recruited people with a history of CVD and assessed statin therapy to prevent recurrences (CARE and PROVE IT-TIMI 22).

The researchers studied the association of a genetic risk score based on 27 genetic variants with new or recurrent CHD, which had been identified in previous studies. Risk scores were used to group people into low, intermediate and high-risk categories.

This provided results for 48,421 individuals, with 3,477 CHD events for the final analyses.

Results were pooled in a meta-analysis, which adjusted for traditional CHD risk factors:

  • age
  • sex
  • diabetes status
  • smoking
  • race (if applicable)
  • family history of coronary heart disease
  • HDL cholesterol
  • LDL cholesterol
  • hypertension

Definitions of CHD differed across the studies, so they used CHD events as the main outcome.

This covered:

 

What were the basic results?

Higher genetic risk scores were associated with a higher risk of CHD, independent of the known risk factors.

The main findings combined all four studies and outcomes for new and recurring CHD events. Compared with the lowest-risk group, those in the intermediate-risk category were 34% more likely to have a CHD event (hazard ratio [HR] 1.34, 95% confidence interval [CI] 1.22 to 1.47). Those in the high-risk group were 73% more likely (HR 1.72, 95% CI 1.55 to 1.92) to have a CHD event.

This was confirmation that the genetic grouping was potentially useful in signalling the risk of a CHD event.

The next results were on how effective statins were across the genetic risk groups. Compared with not taking them, statins reduced CHD events by 13% in the low-risk group, 29% in the intermediate group and 48% in the high-risk group.

Focussing on the JUPITER primary prevention trial, the number of people needed to take statins to prevent one CHD event in 10 years was 66 in the low-risk group, 42 for intermediate risk and 25 for the highest-risk.

The corresponding figures in the ASCOT cohort were 57 low, 47 intermediate and 20 high.

Across all four studies, there were statistically significant reductions in relative and absolute risk reduction using statins, with higher-risk groups benefiting more.

 

How did the researchers interpret the results?

The authors said: "When combined into a 27-variant risk score, our multivariable-adjusted analyses showed that these variants could identify people at increased risk of CHD events, including incident CHD in primary prevention populations and recurrent CHD events in secondary prevention populations.

"Furthermore, when compared with people at low genetic risk, those with the highest genetic risk scores derived greater relative risk reduction and absolute risk reduction with statin therapy. Notably, in the primary prevention trials, we found a roughly threefold difference between the low and high genetic risk score groups in the number needed to treat to prevent one CHD event.

Dr Nathan Stitziel, from Washington University, in the US, who co-led the research, was quoted in the Guardian as saying: "We need more research to confirm these results. Regardless, we can say that patients with a high genetic risk score appear to benefit more from statin therapy, because they’re starting at a higher baseline risk, even controlling for all the clinical measures we routinely examine."

 

Conclusion

This study showed how a genetic risk factor score can categorise people into groups at low, intermediate and high risk of having a CHD event, like a heart attack. They found that statins helped all the groups reduce their risk of a CHD event, but helped those with the higher risks more.

The genetic risk categories were tested in over 48,000 people, but the authors themselves acknowledge that more research is needed to confirm the findings.

That withstanding, this type of research has potentially interesting implications. It may, for example, help us to understand how different groups may or may not benefit from statins, and attempt to quantify this benefit. This has the potential to help optimise statin prescriptions, taking into account genetic factors, as well as other risk factors used now, like age, diabetes status, smoking, cholesterol levels and high blood pressure.

Knowing about genetic risk factors may not be necessary in all decisions regarding statins, but might help in some.

A final factor not discussed in the study is the issue of cost. Genetic sequencing is a lot cheaper than it was a decade ago, and costs are expected to continue to fall, but it may not be cost-effective to run gene tests on large sections of the population.

You can always reduce your need to take statins and reduce your risk of a CHD event by stopping smoking, eating healthily, being physically active, and keeping your blood pressure and cholesterol within normal limits.

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

Links To The Headlines

Statins work for those at highest risk of heart attack – study. The Guardian, February March 4 2015

Links To Science

Mega JL, Stitzel NO, Smith JG, et al. Genetic risk, coronary heart disease events, and the clinical benefit of statin therapy: an analysis of primary and secondary prevention trials. The Lancet. Published online March 4 2015

Categories: NHS Choices

Adults may only get 'real flu' every five years

NHS Choices - Behind the Headlines - Wed, 04/03/2015 - 11:30

"Average adult catches virus just once every five years," the Daily Mail reports.

A study has estimated that influenza infections become less frequent with age and occur every five years from the age of 30.

The study analysed blood samples from volunteers in southern China, looking at antibody levels against nine different strains of influenza that circulated from 1968 to 2009. Using complex mathematical models, researchers estimated the frequency of influenza infections and how immunity changes over a lifetime as people encounter different strains of the virus.

The "twice in a decade" figure may sound surprisingly low, but it is only an estimated average for influenza A. It does not include infections with strains of influenza B or C. Also, the estimate is based on a small sample of just 150 people with an age range from seven to 64. Results may well differ in other countries.

It is important not to be complacent as flu can be dangerous. Precise figures are hard to come by, as flu is often a factor in increasing the risk of fatal complications, rather than a cause of death. A 2013 study estimated that flu was implicated in around 13,000 elderly deaths in England and Wales during the flu season from 2008 to 2009.

Despite the doubts raised about the most recent flu jab, it is important to get vaccinated if you are vulnerable to the flu. Read more about who should get the flu jab.

 

Where did the story come from?

The study was carried out by researchers from the London School of Hygiene and Tropical Medicine, Imperial College London and University of Liverpool in the UK; Johns Hopkins Bloomberg School of Public Health in the US; the University of Hong Kong; and Shantou University and Guangzhou No 12 Hospital, in China.

It was funded by the Medical Research Council, the National Institute for Health Research and the Wellcome Trust in the UK; and Fogarty International Centre, the Department of Homeland Security and the National Institute for General Medical Sciences in the US. 

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

This was a highly complex scientific paper (a sample quote – "Hence the titre μ was scaled by a factor s1(X, j) = (1 + τ1)|X"), so unsurprisingly, the media focused on the simple message that according to this study, flu is far less common than many people think. The Daily Mail also reported that "man flu" may be a myth, with no evidence that men are more likely than women to be "struck down" by the bug. The study itself does not look at rates of infection for each sex.

 

What kind of research was this?

In this study, scientists aimed to look at how our immunity to flu – specifically to influenza A strain (H3N2) – changes over a lifetime as we encounter different strains of the virus. It is important to understand this they say, because how the immune response develops influences the emergence of new strains of the virus, the size and severity of flu epidemics and the effectiveness of vaccination programmes. They say that factors that shape the human immune response are poorly understood, since individual infections and the development of immunity over a lifetime are rarely observed directly.

The immune system responds to flu viruses by producing antibodies that specifically target proteins on the virus surface. These proteins can change as the virus evolves, but we keep antibodies in the blood that have a memory for strains we have encountered before.

 

What did the research involve?

There were two parts to this study.

Scientists used data from a survey in southern China that examined people’s antibody levels against nine different strains of influenza A (H3N2) from 1968 to 2009. Participants were selected from five different locations, with 20 households randomly selected from each location. Samples of blood were taken and tested for the presence of antibodies against different strains of flu.

To determine the effect of a lifetime of influenza infections on immunity, scientists developed a mathematical model capturing the specific strains with which an individual has been infected and the corresponding antibody response. They examined whether this was affected by factors such as:

  • "cross-reactivity", increased immune response to a new strain due to previous antibody response to a different strain
  • "antigenic seniority" – whether strains encountered earlier in life provoked a stronger immune response

 

What were the basic results?

Their model found that "antigenic seniority" and the reduction in cross-reactivity over time were important components of the immune response. 

They estimate that while children on average get flu every other year, infections become less frequent as people get older. From the age of 30 onwards, they estimate that flu infections tend to occur at the rate of about two every 10 years.

 

How did the researchers interpret the results?

The researchers say that the strains encountered early in life and the order in which individuals were infected with the flu virus influence their immune response, which in turn could shape the evolution of the flu virus. These findings, they argue, could also help us better understand future susceptibility to new strains and develop future vaccination programmes.

 

Conclusion

This complex scientific study looked at which factors might influence the immune response to flu over someone’s lifetime and also produced an estimate of how frequently people in different age groups are affected by flu. The details are of interest mainly to other scientists involved in studying the flu virus, how it may evolve and the best way to protect ourselves against it.

When considering the results, it is important to note that these are estimates. They are based on blood samples from 150 people. This means there would have been a limited number of people in each age group, which spanned age seven to 64. In addition, the participants were selected from 20 households in each of five study locations in southern China. People living together are more likely to infect each other with the virus, and so the results may be different among other population groups.

The estimates are also based on nine strains that were originally recorded in 1968, 1975, 1979, 1989, 1995, 2002, 2003, 2005 and 2008. It does not cover other strains, influenza B or C, or whether the immune response was due to previous vaccination or infection.

Additionally, the researchers had to make a number of assumptions, which need to be taken into account when considering the results:

  • They estimated the number of times people had been infected by each strain by assuming each subsequent infection with the same strain of virus would boost the immune response.
  • They considered that the immune response to a new strain would not be as high as to previous strains, with the first-ever infection creating the biggest immune response.

It’s important to protect yourself from flu as much as possible and to get vaccinated if you are elderly or particularly vulnerable to complications.

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

Links To The Headlines

Why your flu is probably just a cold: Average adult catches virus just once every five YEARS. Daily Mail, March 4 2015

Flu is much less common in adults than you might think. The Independent, March 3 2015

Adults get flu 'about once every five years'. BBC News, March 4 2015

Adults only get flu twice a decade, say scientists. The Daily Telegraph, March 3 2015

Links To Science

Kucharski AJ, Lessler J, Read JM, et al. Estimating the Life Course of Influenza A(H3N2) Antibody Responses from Cross-Sectional Data. PLOS Biology. Published online March 3 2015

Categories: NHS Choices

Coffee can 'cut risks of heart attack' claims

NHS Choices - Behind the Headlines - Tue, 03/03/2015 - 12:00

"Three coffees a day cuts the risk of heart disease and strokes," the Daily Mirror reports.

A large study of 25,000 adults from South Korea has found that people who drink between three and five cups of coffee per day were less likely to have the first signs of coronary heart disease.

This is a condition where atherosclerosis (hardening of the arteries) restricts the supply of blood to the heart. In some cases atherosclerosis can cause a blood clot to develop, which can trigger a heart attack.

The participants had a CT scan in which the level of calcium deposits in the coronary arteries was measured. Calcium deposits are one of the first signs of atherosclerosis.

They also completed a food frequency questionnaire to estimate their average food and drink consumption over the previous year.

People who drank between three and five cups of coffee were 19% less likely to have calcium deposits than people who did not drink coffee.

Despite media reports, as the study only looked at data from one point in time, it does not prove that drinking this amount of coffee each day is good for the heart.

 

Where did the story come from?

The study was carried out by researchers from Kangbuk Samsung Hospital in South Korea and there was no external funding.

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

In general, the UK media reported on the study accurately, but they did not explain that the only statistically significant result was for people drinking between three and five cups of coffee per day compared to those who do not drink coffee.

Also, the claim that the reduction in calcium deposits would help prevent heart attacks in later life, while arguably plausible, is unproven.

 

What kind of research was this?

This was a cross-sectional study that aimed to see if there was an association between coffee consumption and the early signs of heart disease. As it was a cross-sectional study it looked at data from one point in time. This means that it can only show an association, it cannot prove that coffee causes reduced levels of calcium to be deposited in the coronary arteries.

randomised controlled trial would ideally be required, though studies randomising people to food or drink items over a long period of time to look at cardiovascular outcomes would have serious feasibility issues; especially regarding compliance. For example, asking a seasoned "coffee addict" not to drink any coffee for the next 10 years probably won’t meet with much success.

 

What did the research involve?

The researchers used information from a large cohort of 30,485 adults who were taking part in the Kangbuk Samsung Health study, which is an ongoing cohort study organised out of a Korean hospital.

All participants had a full health screen and a CT scan of the heart between March 2011 and April 2013 to measure the level of calcium in the coronary arteries. This was taken as an early indicator of atherosclerosis, hardening of the arteries, which leads to heart disease.

A self-administered 103-item food frequency questionnaire was also completed. The participants were asked to estimate how often, on average, they consumed each type of food or drink in the previous year. This included coffee, but did not discriminate between caffeinated and decaffeinated. The researchers say that decaffeinated coffee is not widespread in South Korea.

The researchers then compared the level of coffee consumption with the amount of calcium in the coronary arteries. They adjusted their results to take into account the following confounders:

  • age
  • sex
  • educational level
  • physical activity level (inactive, minimally active or "health enhancing physically active")
  • smoking status
  • body mass index (BMI)
  • parental history of heart disease
  • alcohol consumption
  • total energy consumption
  • consumption of fruit and vegetables
  • consumption of red and processed meats
  • systolic blood pressure
  • fasting blood sugar
  • cholesterol and triglycerides (levels of fat in the blood)

People were excluded from the study if they already had a history of cardiovascular disease or incomplete information.

 

What were the basic results?

The final sample consisted of 25,138 adults. The average age was 41 years and 83.7% were male.

After adjusting the results for all the potential confounding factors listed above, compared to people who did not drink coffee:

  • people who drank between three and five cups of coffee were 19% less likely to have calcium in the coronary arteries (odds ratio (OR) 0.81, 95% confidence interval (CI) 0.66 to 0.98)
  • there were no statistically significant changes in risk for people who drank less than one cup, between one and three cups or five or more cups of coffee

 

How did the researchers interpret the results?

The researchers concluded that "moderate daily coffee consumption was associated with decreased prevalence of CAC [coronary artery calcium] in a large sample of [symptom-free] adults free of CVD".  They say that "further research is warranted to confirm our findings and establish the biological basis of coffee’s potential preventive effects on coronary artery disease".

 

Conclusion

This large cross-sectional study found that people who reported drinking between three to five cups of coffee per day in the previous year were less likely to have calcium deposits in the coronary arteries than people who did not drink coffee. There was no statistically significant difference for people consuming any other level of coffee compared to those who don’t drink coffee.

This type of study cannot prove that drinking this level of coffee stopped calcium being deposited in the arteries, an early sign of atherosclerosis (hardening of the arteries). It shows there is an association, but does not explain why.

Strengths of the study include the large sample size and extent to which potential confounding factors were taken into account. However, there are some limitations:

  • As with many attempts to collect data on dietary consumption, there is the potential for inaccurate estimates and recall bias.
  • Most of the participants were male, so the results may not be as robust for women.
  • It is not clear how applicable the results would be to the UK population as there may be many unmeasured features of the South Korean diet that could have affected the results. Indeed, South Korea has a lower cardiovascular disease death rate than the UK, though reasons for this are likely to be multifactorial.
  • None of the participants had any symptoms of cardiovascular disease. The study provides a snapshot of the level of calcium in their coronary arteries. It does not show how drinking coffee might affect these levels over time.

Though the results of this study are interesting and warrant further investigation, they do not prove that drinking three to five cups of coffee a day is good for the heart.

You can reduce your risk of heart disease by stopping smoking, eating healthily, being physically active, and keeping your blood pressure and cholesterol within normal limits, through lifestyle choices and use of medication, where required.

Read more about reducing your heart disease risk.

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

Links To The Headlines

Three to five cups of coffee a day may prevent heart attacks, says study. The Guardian, March 3 2015

Regular coffee drinkers have 'cleaner' arteries. BBC News, March 3 2015

Drinking three to five cups of a coffee a day could reduce risk of heart attacks, study finds. The Independent, March 3 2015

Coffee Prevents Heart Attacks, Study Says. Sky News, March 3 2015

Three to five cups of coffee a day could reduce the risk of heart attack. The Daily Telegraph, March 3 2015

Links To Science

Choi Y, Chang Y, Ryu S, et al. Coffee consumption and coronary artery calcium in young and middle-aged asymptomatic adults. Heart. Published online March 2 2015

Categories: NHS Choices

Is long-term paracetamol use not as safe as we thought?

NHS Choices - Behind the Headlines - Tue, 03/03/2015 - 12:00

"Daily paracetamol could raise the risk of heart attacks, stroke and early death," the Mail Online reports.

A new review of previous observational studies found that long-term use of paracetamol was linked with a small increased risk of adverse events such as heart attacks, gastrointestinal bleeds (bleeding inside the digestive system) and impaired kidney function.

It is important to be aware that, as these are observational studies, there is the potential for various sources of bias. The studies were highly variable in their study populations. For example, four studies included female nurses, one male doctor, one person with kidney disease, and other adults prescribed paracetamol (i.e. they weren’t taking it over the counter). They also examined highly variable paracetamol exposures (e.g. days of use per month, grams intake in a lifetime, or number of prescriptions). Overall, this gives quite a mixed group of study designs and results, which may be influenced by many things, including inaccurate estimations of intake and significant health differences between users and non-users of paracetamol.

Nevertheless, the findings that paracetamol could potentially have adverse longer-term effects, particularly when used at higher doses, is important, especially as the drug is used by millions. Therefore, further investigation is needed.

 

Where did the story come from?

The study was carried out by researchers from the Maudsley Hospital, London; University of Leeds; Newcastle University; Keele University; and other UK institutions. The review was undertaken by the National Clinical Guidelines Centre, UK, and the authors report no conflict of interest.

The study was published in the peer-reviewed Annals of the Rheumatic Diseases, a British Medical Journal, on an open-access basis, so it is free to read online or download as a PDF.

Some of the UK’s media reporting is likely to cause needless alarm, particularly with figures such as the Mail’s "63% more likely to die suddenly" and claims that "risk of heart attack or stroke 68% higher". Such reporting takes a rather simplistic view of research that has included a highly variable mix of studies.

Ideally, the studies that have contributed different risk figures would benefit from being considered on an individual basis (i.e. taking into account their specific study designs and methods, and potential biases) rather than it simply being applied to the general population.

For example, the 63% figure for mortality accounted for adults prescribed paracetamol or ibuprofen in one particular study participant who had been receiving the highest number of repeat prescriptions for paracetamol, with the shortest gaps between prescriptions. The 68% risk figure for heart attacks was for US female nurses taking more than 15 paracetamol tablets a week.

 

What kind of research was this?

This was a systematic review of observational studies that aimed to look at the adverse effects of paracetamol.

As the researchers say, paracetamol is the most widely used over-the-counter and prescription painkiller worldwide, and is often the first painkiller taken for a wide variety of conditions. It is generally considered to be safer than other painkillers that may be considered in later steps on the "pain ladder", such as non-steroidal anti-inflammatory drugs (NSAIDs) or opiates. However, both health professionals and patients need to have up-to-date evidence on the possible harms of a drug, and recent estimates of the possible risks of paracetamol are not currently available. Therefore, this review aimed to address this gap.

A systematic review is the best way of gathering all the available studies that have addressed the effects of a particular treatment. However, the findings of the review are always going to be inherently limited by the underlying studies. The best way of looking at the benefits and harms of a treatment is a randomised controlled trial. However, it is not ethical to randomise a person to take, for example, a daily dose of paracetamol for a long period of time purely to look at its adverse effects.

When looking at adverse effects of a treatment in observational studies, there is always the possibility that results are being influenced by other factors, such as health differences between people who choose to take the treatment or not. This is known as channelling bias – people who are in poor health are more likely to be "channelled" on to a specific drug regime than people who are healthy.

 

What did the research involve?

The researchers searched two literature databases up to May 2013 to identify observational studies in adults (aged >18 years) that had examined the adverse effects of taking standard dose oral paracetamol (0.5 to 1g, 4 to 6 hourly to a maximum of 4g per day) compared with non-use.

The main outcomes examined were all-cause mortality, cardiovascular effects (specifically heart attacks, strokes and high blood pressure), gastrointestinal (gut) effects (specifically bleeding), and kidney effects (poorer kidney function as indicated by kidney filtration rate, blood chemistry or need for replacement therapy, such as dialysis).

 

What were the basic results?

Eight studies met the inclusion criteria, all were cohort studies. Five were conducted in the US, one in the UK, one in Sweden and one in Denmark. Included sample size ranged from 801 to 382,404 participants, and duration of follow-up ranged between two and 20 years. The studies included specific populations:

  • four of the US studies included female registered nurses aged 30-55 years
  • the other US study included male doctors
  • the UK study involved people over 18 years prescribed paracetamol or ibuprofen
  • the Swedish study included people diagnosed with chronic kidney disease
  • the Danish study comprised of people over 16 years (though the systematic review inclusion criteria did specify 18 years) that were prescribed paracetamol

The studies each looked at some of the outcomes being studied, and examined various levels of exposure compared with non-use. For example, some looked at number of days use per month (e.g. one to four days, ranging to more than 22 days); others looked at number of grams (g) of lifetime intake (e.g. ranging from 100g lifetime intake to >3000g); the gaps between prescriptions; another looked at the number of pills taken over a set 14-year time period.

Looking at outcomes:

  • One of two studies looking at mortality reported an increased mortality ratio for paracetamol users compared with non-users (overall 28% increased risk). This was in a study of adults prescribed paracetamol or ibuprofen. Sub-analyses found the highest risk with the greatest number of prescriptions (63% increased risk).
  • Four studies found paracetamol use was associated with cardiovascular effects, with increased risk linked to increased exposure. One study found a 68% risk of cardiovascular events for people (one of the nurses’ studies) who took more than 15 tablets per week. Another study also found higher doses was associated with heart attack and stroke, and two others found associations with high blood pressure.
  • One study reported gastrointestinal effects and found overall (36%) increased risk of gastrointestinal bleeds. This was in the study of adults prescribed paracetamol or ibuprofen, with the highest associated with first prescription (74%) and greatest number of prescriptions (49%).
  • Four studies reported kidney effects, and three found a poorer kidney function with increasing dose.

 

How did the researchers interpret the results?

The researchers conclude that, "the dose-response seen for most endpoints suggests a considerable degree of paracetamol toxicity, especially at the upper end of standard analgesic doses". However, they give due caution that, "given the observational nature of the data, bias may have had an important impact".

 

Conclusion

This is a valuable review that has searched the literature and identified eight observational studies in adults that have looked at the adverse effects that may be associated with paracetamol use. As the researchers say, it will add to information on the potential harms of paracetamol – an area where up-to-date information has been lacking.

The studies included very large population sizes, and collectively provide some evidence suggesting potential effects upon the cardiovascular system, kidney and gastrointestinal system. There was also a suggestion of increased risk of all-cause mortality.

However, it is very important that these findings are interpreted in the right context. The eight studies were a very variable mix, with very different populations, study duration, measurement of paracetamol exposure and outcomes examined. Most of the individual risk figures identified and reported in the media (e.g. 63% increased risk of mortality or 68% increased risk of heart attack) actually came from individual studies, and would ideally benefit from being interpreted in the specific context of that study. For example, the 68% risk figure for heart attacks was for US female nurses taking more than 15 paracetamol tablets a week.

A possibility for all of these studies is that their results could be influenced by confounding factors (confounders); that is, other differences between the non-users and users of paracetamol that are accounting for the differences. When looking at people using the greatest amounts of paracetamol in these studies – those with, generally, the highest risk figures – their health differences compared to non-users may be even more considerable. For example, increased paracetamol use was associated with increased risk of gastrointestinal bleeds, but this was in a study where people were prescribed paracetamol or ibuprofen.

Ibuprofen, like other NSAIDs, is known to be associated with gastrointestinal bleeds, and it could be that people needing to take more paracetamol were also needing to take more ibuprofen, which could have been influencing the risk. Similarly, other studies included people who may have been suffering from various chronic diseases, which could have increased their risk of cardiovascular events, poorer kidney function and mortality, and also cause them to need more painkilling medication.

It is not known whether, or how well, these studies took into account all the potential health and lifestyle differences that may be associated with increased paracetamol use, as well as increased risk of adverse health outcomes.

Another potential source of inaccuracy is in estimations of paracetamol intake. For example, it is difficult to know how someone could reliably estimate the number of grams of paracetamol they had taken in a lifetime, or how many pills they had taken over a 14-year period.

Overall, the findings that paracetamol could potentially have adverse longer-term effects, particularly higher doses, are undoubtedly important and will need further investigation. 

Paracetamol is an effective treatment for mild to moderate pain and fever in adults and children, when used as directed in product information. The maximum dose within a 24-hour period must not be exceeded. However, if you find you need to use paracetamol on a regular basis, it is worth consulting your GP to look at the cause, and possible treatments. You may find your symptoms respond better to an alternative painkiller or possibly a non-drug type of treatment, such as physiotherapy.

There are also a number of self-help techniques that can help people cope better with chronic pain.

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

Links To The Headlines

Paracetamol linked to heart attack risk: Fears over high doses taken for a long time. Mail Online, March 3 2015

Paracetamol should come with warnings about possible long-term health risks, say scientists. The Independent, March 3 2015

Long-term use of paracetamol can lead to high blood pressure and stroke. The Daily Telegraph, March 3 2015

Paracetamol in new health ALERT: Doctors warned over prescribing daily painkiller. Daily Express, March 3 2015

Links To Science

Roberts E, Nunes VD, Buckner S, et al. Paracetamol: not as safe as we thought? A systematic literature review of observational studies. Annals of the Rheumatic Diseases. Published online March 2 2015

Categories: NHS Choices

Immune changes found in people with CFS/ME

NHS Choices - Behind the Headlines - Mon, 02/03/2015 - 11:39

"Distinct stages to chronic fatigue syndrome identified," reports BBC News online.

People with chronic fatigue syndrome (CFS), sometimes called myalgic encephalopathy (ME), can have debilitating exhaustion affecting their everyday life that does not go away with sleep or rest.

The authors of this study say there are no laboratory tests to diagnose or manage the condition, despite efforts to find biological markers of the disease.

They aimed to address this by looking for differences in immune system signalling chemicals (cytokines) between people with CFS/ME and healthy controls.

Comparing all CFS/ME participants with controls found few differences. However, differences were found when the CFS/ME group was divided into those with short- (three years or less) and long-term (more than three years) disease.

These results suggest that people with CFS/ME may have higher levels of some cytokines until around the three-year mark, at which point the differences disappear. 

The study is not reliable enough on its own to prove that the disease has distinct stages, and it doesn't give us any more clues as to how or why these particular cytokines might be involved in the condition.

Other studies, and study types, are needed to build on these initial findings.

Find out more about CFS/ME.

 

Where did the story come from?

The study was led by researchers from Columbia University Mailman School of Public Health in New York, and was funded by the CFI/Hutchins Family Foundation and the US National Institutes of Health.

It was published in the peer-reviewed journal Science Advances.

The BBC reported the story accurately, and included useful quotes from independent experts who commented on this research.

 

What kind of research was this?

This case-control study used data from two cohort studies to investigate biological makers of CFS/ME.
 
This type of study is an effective way of finding out the ways in which people with a disease – in this case, CFS/ME – differ from those without.

However, the links established usually mean that the two things are found together, not that one causes the other.

 

What did the research involve?

The study used disease diagnostic information and blood samples taken from two recent large multicentre US cohort studies of people with CFS/ME.

The researchers analysed the relationship of 51 immune system chemical messengers called cytokines with diagnosis of CFS/ME and other clinical variables, such as the duration and severity of the disease.

People without CFS/ME (the controls) were matched with people with CFS/ME based on key variables known to affect immune status, including the season of sampling, geographic site, age and sex.

The main analysis looked for statistically significant differences in the 51 immune system markers in people with and without CFS/ME.

 

What were the basic results? All CFS/ME versus all controls

Comparing all 298 people with CFS/ME with all 348 controls led to few statistically significant results. In rare instances where there were differences, levels of cytokines were lower in people with CFS/ME.

Short- and long-duration CFS/ME versus controls

In a sub-analysis, the researchers looked at the effect of grouping CFS/ME into short-duration (having the condition for three years or less) and long-duration (more than three years) disease.

They found significant differences in more than half the 51 immune system markers tested in the group of 52 people early on in the course of the disease, relative to the healthy controls. These differences were not present in the 246 people with longer-duration illness.

Cytokine levels, which differed between short- and long-duration groups, were correlated with duration of illness.

The two most prominent cytokines associated with short-duration CFS/ME were interferon-gamma and interleukin-12p40, both known to be important for an effective immune system.

 

How did the researchers interpret the results?

On the BBC website, lead author Dr Mady Hornig said: "It appears that ME/CFS patients are flush with cytokines until around the three-year mark, at which point the immune system shows evidence of exhaustion and cytokine levels drop … this shows there are distinct stages to the disease."

In their research paper, the researchers suggested that their findings "have critical implications for the discovery of interventional strategies and early diagnosis of ME/CFS".

 

Conclusion

This case-control study found cytokine differences in people diagnosed with CFS/ME for three years or less, compared with healthy controls. The same was not found for people with CFS/ME of more than three years' duration.

The study authors interpreted this as a sign that CFS/ME might have two stages. The implications are that this may one day help researchers better understand the disease, and potentially develop new ways of testing and diagnosing the condition.

Optimism notwithstanding, there are significant limitations to this study design, meaning it cannot say anything reliable or solid on its own. Further research needs to repeat, confirm and build on its findings.

Professor Michael Sharpe, professor of psychological medicine at the University of Oxford, said: "Whilst this finding that some patients with CFS/ME have an immune abnormality is potentially interesting, we should treat it with great caution … This type of study [a case-control study] is notorious for producing findings that other researchers subsequently fail to replicate."

He added: "Everyone who has worked clinically with patients with CFS/ME knows this is a real illness; this study neither proves nor disproves that observation."

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

Links To The Headlines

First biological proof that ME is real found by scientists. The Daily Telegraph, February 27 2015

Chronic fatigue syndrome: Scientists now have 'robust' evidence that points to biological cause. The Independent, February 27 2015

Distinct stages to chronic fatigue syndrome identified. BBC News, February 28 2015

Links To Science

Hornig M, et al. Distinct plasma immune signatures in ME/CFS are present early in the course of illness. Science Advances, Published February 27 2015

Categories: NHS Choices

MS stem cell treatment only a 'miracle' for some

NHS Choices - Behind the Headlines - Mon, 02/03/2015 - 10:28

The Daily Telegraph reports a “miracle” stem cell therapy that reverses multiple sclerosis and which, according to The Sunday Times, gets “wheelchair-bound” people dancing.

Multiple sclerosis (MS) affects nerves in the brain and spinal cord, causing problems with muscle movement, balance and vision. It’s an autoimmune disease, where the body’s immune system attacks its own nerve cells. There is currently no cure, but many different treatments are available to help with symptoms.

This study was mainly about relapsing remitting MS, the most common type, where people have distinct attacks of symptoms, which then fade away either partially or completely.

The new treatment was very aggressive. It used high doses of chemotherapy to “knock out” the existing faulty cells of the immune system, before rebuilding it using stem cells taken from the patient’s own blood. This, in effect, gave the immune system a chance to reboot from scratch.

The therapy was tested in 145 patients and led to significant reductions in their levels of disability in almost 64% of people up to four years after treatment. Improvements were seen in quality of life and other ratings of symptoms and disability. Because of the difficulty in treating MS effectively, any improvements are good news.

The downside is that there was no control group. We don’t know if some people would have improved on their own, or whether the improvements are any better than best available care. It’s also worth noting that not everyone will be able to tolerate the aggressive chemotherapy used, and that the technique did not work for people with more severe or longstanding MS (over 10 years).

Find out more about multiple sclerosis.

 

Where did the story come from?

The study was led by researchers from Northwestern University Feinberg School of Medicine, Chicago, US, and was funded by the Danhakl family, the Cumming Foundation, the Zakat Foundation, the McNamara Purcell Foundation, and Morgan Stanley and Company.

Two study authors declared financial conflicts of interest by serving as consultants to pharmaceutical companies including Biogen Idec, which makes treatments for patients with “neurological, autoimmune and hematological disorders”.

The study was published in the peer-reviewed Journal of the American Medical Association.

Generally, the papers reported the story accurately. It is always difficult to justify the use of a “miracle” cure, because it means different things to different people – and the improvements cited for some people do seem worthy of the tag. However, while the treatment looks promising, it’s at an early stage of development. The treatment is very aggressive, and also tested in specific types of MS, so may not be suitable for all people with MS. Similarly, the treatment has not yet been proven effective or safe in large enough groups for the results to be reliable.

We have not been able to independently assess if the truth of the claims that “wheelchair-bound” MS patients who were treated in this way are now able to dance.

 

What kind of research was this?

This was a case-series testing a new stem cell treatment in people with relapsing remitting MS or secondary progressive MS.

Most people in the study had relapsing-remitting MS, which tends to have distinct attacks of symptoms, which then fade away either partially or completely. This is the most common type of MS, affecting around 85% of people with the condition, according to the MS Society.

The research also included a smaller group of people with secondary progressive MS. Many people with relapsing remitting MS progress to this form, where there is a sustained build-up of disability that no longer fades away. There is no cure for MS, but many different treatments are available to help with symptoms.

Case series are useful to test new treatments, but they have several limitations, meaning they can’t prove the treatments are effective very accurately or reliably. The big downside is a lack of a comparison group, called a control group. This means that you never know how much better or worse the new treatment is compared with an existing treatment, or doing nothing. This limitation applies to this study.

 

What did the research involve?

The study gave 123 patients with relapsing remitting MS and 28 with secondary progressive MS a stem cell transplant. The transplants were carried out at a single US institution between 2003 and 2014, and researchers followed the patients for up to five years to see how they did.

The average age of participants was 36 (ranging from 18 to 60) and most were women (85%). The average follow-up after treatment was 2.5 years.

The new treatment used chemotherapy drugs cyclophosphamide and alemtuzumab or cyclophosphamide and thymoglobulin, followed by infusion of stem cells isolated from the patients’ blood.

Before treatment, participants were subjected to a range of questionnaires and assessments to rate their symptoms, level of disability and quality of life. These were repeated at regular intervals after to measure any changes.

The main measure of interest was an improvement in score of 1.0 or more on the Expanded Disability Status Scale (EDSS). The EDSS is a way of quantifying disability in MS and monitoring changes over time. It is widely used in clinical trials and in the assessment of people with MS.

The main analysis compared EDSS ratings before and after treatment, looking for statistically significant improvements. Similar comparisons were done for other measures of MS-related disability and quality of life.

 

What were the basic results? Change in disability scores

There was significant improvement in disability up to four years after treatment. Reductions in the EDSS (disability) score of 1.0 or more were seen in half of patients at two years (50%, 95% confidence interval (CI) 39% to 61%) and almost two out of every three people at four years (64%, 95% CI 46% to 79%).

Scores from the EDSS improved significantly. Before treatment, the average (median) EDSS score was 4.0, which improved to 3.0 at two years and to 2.5 at four years. Both were statistically significant reductions.

Taking the reduction of 4.0 to 2.5, this means the person went from having “Significant disability, but self-sufficient and up and about some 12 hours a day. Able to walk without aid or rest for 500m” to “Mild disability in one functional system or minimal disability in two functional systems”.

However, some people did not improve. The EDSS score did not improve in people with secondary progressive MS or in those with disease duration longer than 10 years.

Ratings of disability and quality of life

Many other measures also improved, including neurological function, walking function, hand function and self-reported quality of life. The tests also involved a brain scan assessing the size of inflammation at a specific part of the spinal cord in the upper back (the T2 vertebra), which is said to correlate with disease severity. After treatment, the size of the damage reduced, and stayed lower up to two years longer.

Improvements quoted in the news

Some of the more miraculous findings were reported in the news, but not in the study publication itself. The Telegraph, for example, reported: “Patients who have been wheelchair-bound for 10 years have regained the use of their legs … while others who were blind can now see again.”

We couldn’t confirm these biblical results, based on the publication alone. They may have come from interviews with the study team or case studies provided by the research institutions.

 

How did the researchers interpret the results?

The researchers summed up that, “Among patients with relapsing remitting MS, nonmyeloablative hematopoietic stem cell transplantation was associated with improvement in neurological disability and other clinical outcomes.”

To their knowledge: “this [was] the first report of significant and sustained improvement in the EDSS score following any treatment for MS”.

 

Conclusion

This case-series showed that a new stem cell treatment reduced the disability in people with relapsing remitting MS up to four years after treatment. It worked in more than half of those given treatment. The authors claim that this was the first time this had been achieved, and is important because there is currently no cure for MS.

Given the relative lack of alternative treatments for MS, these results are encouraging. However, there are issues to bear in mind.

The average EDSS score before treatment in the group was 4.0. The scale goes from 10 (death due to MS), to 1.0 (no disability). Ratings above 5.0 involve impairment with walking. An average of 4.0 suggests most people didn’t have the more severe forms of MS. A small number of people with more severe MS were included in the study, but too few to reach any reliable conclusions about this subgroup. Therefore, the results are most applicable to those with non-severe relapsing remitting MS.

The treatment only improved the main outcome (EDSS improvement of 1.0 or more) in 50% of people after two years, meaning it didn’t work in the other half. It worked for slightly more people after four years. It also didn’t work in people with MS over 10 years or those with secondary progressive MS. This suggests that selecting the most appropriate patient group for this treatment will be important. It doesn’t look like it would work for everyone.

These preliminary findings are from an uncontrolled study. This means we don’t know if, or how much, the new treatment is better than any existing treatment, or doing nothing. The treatment was described by a study author in the Telegraph as being very aggressive, and only suitable for people who were fit enough to withstand the effects of chemotherapy. Chemotherapy is not without risk. Further studies will need to pay careful attention to weighing up the benefits and risks of this therapy.

Dr Sorrel Bickley, from the MS Society, cautiously welcomed the results in the Telegraph, saying: "Momentum in this area of research is building rapidly and we're eagerly awaiting the results of larger, randomised trials and longer-term follow-up data.

“New treatments for MS are urgently needed, but as yet there are no stem cell therapies licensed for MS anywhere in the world. This means they aren't yet established as being both safe and effective. This type of stem cell therapy is very aggressive and does carry significant risks, so we would strongly urge caution in seeking this treatment outside of a properly regulated clinical trial."

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

Links To The Headlines

Dancing, walking and running again, the wheelchair-bound MS patients after they were given 'miraculous' stem cell treatment. Mail Online, March 1 2015

‘Miraculous’ stem cell treatment may reverse symptoms of multiple sclerosis. The Daily Telegraph, March 1 2015

Stem cell reboot has MS patients dancing. The Times, March 1 2015

Links To Science

Burt KB, et al. Association of Nonmyeloablative Hematopoietic Stem Cell Transplantation With Neurological Disability in Patients With Relapsing-Remitting Multiple Sclerosis. JAMA, Published January 20 2015

Categories: NHS Choices

Healthy older adults carry leukaemia mutations

NHS Choices - Behind the Headlines - Fri, 27/02/2015 - 13:00

BBC News reports that, according to researchers, “It is ‘almost inevitable’ that your blood will take the first steps towards leukaemia as you age”.

Researchers analysed the blood of 4,219 people, looking for DNA errors (mutations) linked to blood cancers (leukaemia).

The number of mutations in healthy older people without the disease was higher than expected. The research focused on 15 genetic hotspots of leukaemia-linked mutations and found them in 0.8% of individuals aged under 60, and 19.5% of those aged 90 or older. 

The media quoted figures suggesting that more than 70% of people in their 90s would have some form of leukaemia-associated mutation. This was based on predictions of the prevalence of other mutations outside of the 15 tested. 

The good news is that this form of age-related leukaemia is highly unlikely to kill you. The bad news is you are far more likely to die of something else before the mutations trigger the onset of leukaemia.

Still, as some are predicting that average lifespans will rise dramatically in the decades ahead, the results of this study could become more of an issue for future generations, and might also apply to other cancer types.

 

Where did the story come from?

The study was carried out by researchers from Wellcome Trust Sanger Institute, Cambridge (UK), and was funded by the Wellcome Trust, Leukaemia Lymphoma Research, the Kay Kendal Leukaemia Fund and the Spanish Ministerio de Economía y Competitividad  Subprograma Ramón y Cajal.

The study was published in the peer-reviewed medical journal Cell Reports. It is open-access, so is free to read and download online.

Generally, the media reported the story accurately. The Independent quoted Dr Vassiliou, senior author of the study, reassuring readers that: “These mutations will be harmless for the majority of people, but for a few unlucky carriers, they will take the body on a journey towards leukaemia. We are now beginning to understand the major landmarks on that journey”.

One small gripe is with the choice of figures used. The main study result was that leukaemia-linked mutations were found in 0.8% of under-60s and 19.5% of over 90s. This was based on studying 15 leukaemia-linked hotspots. 

Both the Independent and the BBC quoted figures suggesting that 20% of 50 to 60 year olds, and over 70% of over 90s, had dormant leukaemia-linked mutations. These much higher figures come from the study discussion and were not directly tested in the current research. They were figures based on assumptions about combining results from the 15 hotspots with other non-hotspot mutations from previous studies. We are not able to appraise the non-hotspot mutations studies, so we don’t know how accurate these figures are.

 

What kind of research was this?

This was a genetic study investigating how common small, leukaemia-linked DNA changes were in cancer-free adults.

Cancers, including leukaemia, develop through the combined action of mutations that are acquired over time. The researchers say that leukaemia-associated DNA mutations can occur without evidence of the disease. They wanted to find out how common these were in healthy people, and how common they were as people got older.

 

What did the research involve?

The researchers analysed DNA samples at 15 pre-defined leukaemia-associated mutation hotspots, using highly sensitive tests. They analysed the DNA of 4,219 people aged 17 and over.

The majority of DNA tests were on healthy people, but for comparison, they analysed the genes of a number of blood cells from people with myeloid leukaemia.

The production of the range of different types of mature white blood cells starts with a small number of stem cells. More specialised cells develop from these, like tree branches. The stem cells replicate themselves, producing clones. Some of these clones receive signals from the body, causing them to replicate and develop (differentiate) into more specialised white blood cells. Different signals produce different types of cells. The researchers were looking at what stage in the production process the mutations were occurring. If the mutations happened early in the differentiation process, they would be found in many downstream white cell types. If they occurred later, then they would be found in fewer cell types.

 

What were the basic results?

The main results were that age-related leukaemia-linked mutations were much more common than previously predicted.

Using only the 15 hotspots studied, they identified leukaemia-linked mutations in 0.8% of individuals under 60, rising to 19.5% of those aged 90 years and over. Coupling these estimates with other mutation rates from previous studies (outside of the 15 hotspots tested) they came up with much higher estimates. They predicted that more than 70% of people aged 90 or older would have some form of leukaemia-associated mutation. The 70% figure made it into the media coverage; the 19.5% was not mentioned.

On closer inspection, they found that mutations DNMT3A-R882 were most common and, although their prevalence increased with age, were found in individuals as young as 25. By contrast, mutations affecting spliceosome genes SF3B1 and SRSF2, closely associated with the myelodysplastic syndromes, were identified only in those aged over 70 years, with several individuals harbouring more than one mutation.

Myelodysplastic syndrome is an uncommon condition of unknown cause, that can lead to a drop in the number of healthy blood cells being produced. In some cases, it can progress into acute myeloid leukaemia.

Mutations in gene NPM1 were not seen in the group. This gene is thought to act as a “gatekeeper” to leukaemia. If it goes wrong, your risk of leukaemia rises considerably. As the group were symptom-free, it is not surprising that this gene was not affected in most people.

 

How did the researchers interpret the results?

The study group said: “individuals without overt features of a haematological [blood] disorder may harbor hemopoietic cell clones [blood stem cells] carrying leukemia-associated mutations” and that accumulating these mutations “is an almost inevitable consequence of aging in humans”

 

Conclusion

This study estimated that 0.8% of individuals under 60, and 19.5% of those aged 90 years and over, had leukaemia-linked mutations. These mutations caused no immediate harm and the people didn’t have leukaemia. The mutations were lurking in the background, but could have the potential to contribute to leukaemia in the future.

The research primarily focused on 15 genetic hotspots of leukaemia-linked mutations.

However, in their discussion, they predicted that more than 70% of people aged 90 or older would have some form of leukaemia-associated mutation. This formed the basis of their comment that these mutations seem an inevitable part of ageing. It is important to realise that this much higher estimate was not directly tested in the study. That is not to say it is not true, but we can’t confirm or refute it either way. Further research could confirm this prediction.

Scientists know that cancer is caused by the accumulation of genetic mutations over many years. This is why most cancers occur in older people, and the risk of cancer increases with age. What is surprising about this study is the relatively high prevalence of leukaemia-linked background mutations in healthy adults. The implication is that if people were to live a lot longer, say 150 years, they might expect to get leukaemia. In theory, this could also apply to some other types of cancer.

This is all largely theoretical. The impact on the average person is minimal, though if lifespans continue to increase, it could be a potential problem for your grandchildren.

It’s important to remember that we can all reduce our risk of cancer by making some simple changes to our lifestyle.

For example, healthy eating, taking regular exercise and stopping smoking will help to lower your risk.

Read more about how a healthy lifestyle can help to reduce your chances of developing cancer

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

Links To The Headlines

DNA develops to acquire genetic mutations linked with cancer as you get older, says study. The Independent, February 26 2015

Leukaemia mutations 'almost inevitable', researchers say. BBC News, February 27 2015

Links To Science

McKerrell T, Park N, Moreno T, et al. Leukemia-Associated Somatic Mutations Drive Distinct Patterns of Age-Related Clonal Hemopoiesis. Cell Reports. February 26 2014

Categories: NHS Choices

Does deadly diet drug DNP defeat diabetes?

NHS Choices - Behind the Headlines - Fri, 27/02/2015 - 11:30

"A chemical [DNP] which caused munitions factory workers to lose weight inexplicably in the First World War could cure diabetes," The Daily Telegraph reports. The banned weight loss drug looked effective and safe when given in a modified form to rats bred to have diabetes.

The potential benefits of DNP surfaced in WW1 munitions workers who lost a lot of weight after being exposed to it. DNP sped up their metabolism, leading to rapid weight loss. After being made into a weight loss drug in the 1930s, it was quickly withdrawn, as it was proven highly toxic.

The problem was that it sped up the metabolism to a dangerously high rate, causing a range of serious side effects, and some deaths. Illegal sales of the drug have caused a number of deaths in the UK in recent years.

Researchers at Yale University wanted to see if it was possible to harness DNP’s metabolic properties, while removing the toxic effects.

They created a slow-release version of DNP, called CRMP, which improved the way the liver processed fat and improved other measures linked to type 2 diabetes risk in rats. As it delivered DNP at a much lower dose over time, there were no toxic effects.

This is encouraging research that should lead to further studies.

The version of DNP that is available through illegal sales, typically via the internet, is toxic, even in tiny amounts. Do not take it under any circumstances.

 

Where did the story come from?

The study was carried out by researchers from Yale University and was funded by United States National Institutes of Health and Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Denmark.

Yale University has applied for a patent-related to the use of CRMP and things working in a similar way for the treatment of metabolic diseases, including non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes.

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

The Daily Telegraph’s coverage was factually accurate. They made it clear the research was in rats, but also explained how: "the [research] team is confident that the research would translate to humans and are keen to start trials".

 

What kind of research was this?

This was an animal study investigating potential new uses for the banned chemical DNP for non-alcoholic fatty liver disease, which in turn, is a major risk factor for type 2 diabetes. Alternatively, both conditions can develop in tandem.

DNP has a murky past. Starting life as an ingredient of explosives in WW1, its potential use as a weight loss drug was recognised in workers handling the agent. They sweated profusely, had sky-high temperatures and lost a lot of weight. In the 1930s, it was sold as a wonder weight loss drug. However, it was quickly withdrawn, because it was highly toxic, causing side effects and, in some cases, death. 

DNP was also linked to deaths in 2013, after a resurgence among bodybuilders. This lead to the Food Standards Agency issuing a public warning about the risks of DNP, saying that: “DNP is an industrial chemical that is extremely dangerous to human health.” 
 
NAFLD is the term used when there is a build-up of fat within the liver cells that is not caused by alcohol intake. It is usually seen in people who are overweight or obese, and is associated with metabolic syndrome. A healthy liver should contain little or no fat. Most people with NAFLD do not develop serious liver problems and just have stage 1 of the disease (simple fatty liver). The most important thing that people with NAFLD can do is to go on a gradual weight loss programme and exercise regularly.

It is known that DNP has benefits on NAFLD, obesity and regulating blood glucose, but is usually too toxic to be used as a treatment. The chemical targets the mitochondria in cells. These are the little "batteries" responsible for making energy in cells, which is essential for life.

DNP speeds up the metabolism; however, our metabolic system operates at the rate it does for a reason – it is safe. Speeding up the metabolism may help burn off fat, but it can also trigger a number of dangerous side effects and potentially cause death.

This research team tried to devise a way to harness the benefits of DNP, while minimising its toxic side effects. All their experiments were in rats. This is the usual approach when testing chemicals to treat diseases, particularly dangerous ones. People and rats, both mammals, share lots of common biology, but there are differences.

 

What did the research involve?

The researchers gave groups of rats low levels of DNP and monitored its effect on fat content in the liver and other measures linked to a higher risk of type 2 diabetes. They were looking to confirm the benefits reported in previous studies.

After encouraging results, they modified DNP to create CRMP (controlled-release mitochondrial protonophore). They fed this to rats in small amounts of peanut butter to see whether it had the same benefits, with fewer side effects.

The benefits and side effects of DNP were compared with CRMP in a range of experiments lasting up to six weeks. During the experiments, rats were fed a high-fat diet and the researchers paid particular attention to changes in the function of the liver in dealing with this fat.

 

What were the basic results?

The main result was that CRMP caused fewer side effects than raw DNP, while maintaining similar benefits, including burning lots of fat, improved glucose tolerance and lower insulin levels.

When testing for specific effects, CRMP prevented the development of the rat version of NAFLD in rats fed a high-fat diet for two weeks. Similarly, it seemed to improve blood glucose regulation when given to rats with diabetes for two weeks, also improving their blood fat levels.

CRMP released the DNP-active chemical at a more gradual rate, and over a longer period, than giving straight DNP. This meant the levels in the blood did not spike as much and were lower overall. This seems to be the key to avoiding some of the worst side effects.

One of the biggest side effects of DNP was that it caused a potentially fatal very high temperature. The researchers were able to find a dose of CRMP that was beneficial to the liver, without causing a huge rise in temperature.

 

How did the researchers interpret the results?

The researchers said: "we have shown that altering the pharmacokinetics of DNP to promote a low sustained systemic release can increase the therapeutic window of this agent by more than 500-fold. Daily CRMP administration reversed NAFLD, insulin resistance, T2D [type 2 diabetes], and liver fibrosis in rats without detectable toxicity".

They added: "These data support the potential utility of mitochondrial protonophores and other mitochondrial uncoupling agents for the treatment of the related epidemics of NASH, metabolic syndrome and T2D."

 

Conclusion

This study created a slow release version of DNP, called CRMP, that improved the way the liver processed fat and improved other measures linked to type 2 diabetes risk in rats. It did this when given for up to six weeks without the toxic side effects known to be associated with unmodified DNP.

This is encouraging research, which appears to have partially tamed some of the toxic effects of DNP, while protecting its benefits. Researchers will build on this in further studies in rats and possibly people, if these results are confirmed in more studies.

However, the current version of DNP that is available for sale illegally online is toxic to humans, even in tiny amounts, and has been linked to a number of deaths. Do not take it under any circumstances.

The study used a chemically-modified version of DNP, called CRMP, in rats. DNP on its own remains as dangerous as ever to people. CRMP’s safety in humans has not yet been tested.

This study showed proof of the concept that DNP can be modified to make it safer in rats, while maintaining its benefits. This has not yet been proven in humans.

The authors are planning further safety studies, reporting in the Telegraph that: "Given these promising results in animal models of fatty liver disease and type 2 diabetes, we are pursuing additional preclinical safety studies to take this approach to the clinic."

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

Links To The Headlines

First World War explosive could reverse diabetes, says Yale University. The Daily Telegraph, February 26 2015

Links To Science

Perry RJ, Zhang D, Zhang X, et al. Controlled-release mitochondrial protonophore reverses diabetes and steatohepatitis in rats. Science. Published online February 26 2015

Categories: NHS Choices

Over two hours screen time a day may raise a child’s blood pressure

NHS Choices - Behind the Headlines - Thu, 26/02/2015 - 11:50

"Watching TV for more than two hours a day increases the risk of raised blood pressure in children," The Daily Telegraph reports.

A large study, involving more than 5,000 children who were followed up over two years, found a link between time sitting in front of a screen and an increase in blood pressure rates.

It found that a worryingly high number of children – more than one in 10 – developed high blood pressure, a major risk factor for cardiovascular diseases (CVDs) in later life. CVDs are conditions that can damage the heart and blood vessels, such as a stroke.

Children who spent more than two hours a day on “screen time” over the two years were at increased risk, as were those with low levels of physical activity.

This study supports previous evidence that a sedentary lifestyle and low levels of physical activity are associated with high blood pressure, although it does not prove that the former causes the latter.

There are many factors that can affect blood pressure, including genetics, development in the womb, socioeconomic status and weight.

That said, the more time your child spends watching TV or playing on their PlayStation 4, the less time they are physically active.

In the UK, children aged five to 18 are advised to do at least 60 minutes of physical activity a day.

 

Where did the story come from?

The study was carried out by researchers from several academic centres worldwide, including the University of Glasgow in the UK. It was funded by the European Community Sixth Research, Technological Development and Demonstration Framework Programme.

The study was published in the peer-reviewed medical journal International Journal of Cardiology.

Both The Daily Telegraph’s and the Daily Mail’s reporting was fair, although neither paper included comment from independent experts, and they failed to explain the fact that this kind of study cannot prove cause and effect.

 

What kind of research was this?

This was an observational cohort study looking at the incidence of pre-high blood pressure and high blood pressure in children in Europe and any association between blood pressure, levels of physical activity and sedentary behaviour.

The study’s authors say high blood pressure is one of the most important factors for cardiovascular disease, and studies have shown that blood pressure levels in children and adolescents are linked to high blood pressure in adulthood. However, little is known about the risk factors for high blood pressure in childhood. Their hypothesis is that low levels of physical activity (and high levels of sedentary behaviour may contribute to the development of high blood pressure.

Sedentary behaviour was classified as the amount of time parents reported their children spending in front of a screen – whether watching TV, videos or playing computer games. It did not include other kinds of sedentary activity – such as reading.

Blood pressure is measured in millimetres of mercury (mmHg) and is recorded as two figures:

  • systolic pressure – the pressure of the blood when your heart beats to pump blood out
  • diastolic pressure – the pressure of the blood when your heart rests in between beats, which reflects how strongly your arteries are resisting blood flow

In children, high blood pressure is defined as blood pressure greater than the 95th percentile for their age, height and gender.

 

What did the research involve?

The researchers used data from a study of 16,224 children from eight European countries (Spain, Germany, Hungary, Italy, Cyprus, Estonia, Sweden and Belgium) looking at the effects of diet and lifestyle on health. The current analysis was based on 5,221 children who were between two and 10 years old at the start of the study, for whom all data was available. Of these, 5,061 children were re-examined two years later.

The children had their systolic and diastolic blood pressure measured at the start of the study and at two years follow-up. Pre-high blood pressure was defined as systolic or diastolic blood pressure from the 90th to 95th percentile for their age and height; and high blood pressure was defined as systolic or diastolic blood pressure above the 95th percentile for age and height.

Physical activity in the children was measured using an accelerometer – an electronic device which measures the intensity of exercise. The unit had to be worn for at least six hours a day, for at least three days during one week (two weekdays and one weekend day).

From this, the researchers calculated the time children spent in moderate physical activity and in vigorous physical activity. Moderate activity includes activities such as cycling, while vigorous activity includes running, football and energetic dancing.

The children were classified into two groups – those who met current physical activity guidelines – doing at least 60 minutes of physical activity daily – and those who did not meet the guidelines. They were further classified as to whether changes in physical activity levels had taken place over the two years.

The children’s parents were asked to fill in a questionnaire on their children’s sedentary behaviour, as measured by hours of TV/DVD/video viewing and computer/games-console use for both typical weekdays and weekend days. Researchers used this information to calculate the children’s “total screen time” per day. Participants were classified into two groups – those who met (US) guidelines on total screen time (two hours or less a day) and those who did not. Researchers also calculated changes in sedentary behaviour at two years.

They also included a range of potential confounders, including season, sex, age, parental education and waist circumference.

Researchers estimated the relationship between physical activity levels, reported screen time and the risk of developing high blood pressure or pre-high blood pressure. 

 

What were the basic results?
  • Researchers found that the yearly incidence of pre-high blood pressure was 121 per 1,000 children, and high blood pressure was 110 per 1,000 children.
  • Children who maintained sedentary behaviour of more than two hours a day during the two year follow-up had a 28% higher risk of having  high blood pressure (relative risk (RR) 1.28, 95% confidence interval (CI) 1.03 to 1.60).
  • Children not performing the recommended amount of physical activity (60 minutes a day) at the start of the study had a 53% higher risk of high blood pressure (RR 1.53, 95% CI 1.12 to 2.09).
  • There was no association between pre- high blood pressure and children’s behaviours.

 

How did the researchers interpret the results?

The researchers say that the incidence of pre-high blood pressure and  high blood pressure is high in European children, with those doing less than 60 minutes of physical activity daily or spending two hours or more per day in front of a screen at higher risk. They say that the results suggest regular physical activity should be promoted and sedentary behaviour discouraged in children to prevent high blood pressure and its consequences in adulthood.

 

Conclusion

The study found a worryingly high incidence of high blood pressure in children of just over 10%, instead of the expected 5%. It also found that low levels of physical activity and high levels of “screen time” raised the risk.

Although researchers adjusted their analysis for a range of other factors which might affect blood pressure (called confounders), it is always possible that other unmeasured factors could have affected the results. In addition, the study was reliant on parental estimates of the amount of sedentary behaviour their children had per day, which may be an over- or underestimate. Wearing the accelerometer may also have influenced the amount of physical activity that was performed on those days, which could also affect the results.

It’s generally agreed that many of today’s children spend too much time in front of a screen – and too little on physical activity. The real question is – what can we do about it?  

Children are more likely to accept changes to their lifestyle if they involve the whole family.  Read more about getting healthy as a family.

Also, evidence has shown that placing limits on the use of any type of screen equipment in the hours before bedtime can improve the quality of their sleep. This could then help them improve their energy and activity levels during the day.

Read more about how TVs, phones and screens impair kids' sleep.

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

Links To The Headlines

Too much TV could raise a child’s blood pressure: Watching more than two hours a day ‘makes them 30% more likely to have condition’. Mail Online, February 26 2015

Children who watch TV for more than two hours a day 'at greater risk of high blood pressure'. The Daily Telegraph, February 26 2015

Links To Science

de Moraes ACF, Carvalho HB, Siani A, et al. Incidence of high blood pressure in children — Effects of physical activity and sedentary behaviors: The IDEFICS study: High blood pressure, lifestyle and children. International Journal of Cardiology. Published online November 26 2014

Categories: NHS Choices

Longer sleep linked to stroke

NHS Choices - Behind the Headlines - Thu, 26/02/2015 - 11:00

“Too much sleep could kill you,” is the baseless and needlessly alarmist headline on the front cover of today’s Daily Express.

The study it is reporting on actually showed that people who sleep for more than eight hours a night had a 46% increased risk of stroke over the following 10 years, compared with people sleeping six to eight hours.

While these results certainly warrant further investigation, it does not show that the increased sleep caused strokes, let alone death.

The researchers assessed the usual sleep patterns of nearly 10,000 adults in 1998 and again in 2002, looking for associations between the amount of sleep and the number of people having a stroke over the next 10 years.

They also pooled the results from similar studies. These also showed a 45% increased risk for people who sleep more than eight hours.

When the results were analysed by sex, the link was statistically significant for women, but not men. This wasn’t made clear in the UK media coverage. Women’s risk was 80% higher, which is almost double the 46% risk when the sexes were combined.

The study took into account cardiovascular risk factors such as high blood pressure and cholesterol, but not other illnesses. Without accounting for other illnesses, it is not clear what association the length of sleep has with risk of stroke from these studies. As that widely used, though valid, scientific cliché goes: “further research is needed”.

 

Where did the story come from?

The study was carried out by researchers from the University of Cambridge and the University of Warwick. It was funded by the Medical Research Council and Cancer Research UK.

The study was published in the peer-reviewed medical journal Neurology. The study was published on an open-access basis, meaning that anyone can read and download it for free online. There is also a related editorial.

The quality of the UK media's reporting of the study was mixed. The Independent and The Daily Telegraph took a measured approach, making clear the uncertainties of the study.

The Daily Mirror somewhat contradicted itself, saying first that: “Shock study reveals sleeping for longer than eight hours 'could cause a stroke'.” Whereas later on, it correctly says: “Importantly, the study only found an association between sleep length and risk of stroke. It did not find that sleeping for too long actually causes stroke.”

The Daily Express and the Metro said that increased sleep causes strokes, when this is not actually what the study found.

At most, the study found that increased sleep is associated with an increased risk of stroke in women, but it did not take illnesses other than diabetes, high blood pressure and previous stroke into account, which could have affected the results.

A lot of the media carried a useful quote from Yue Leng, from the University of Cambridge, saying: “It’s apparent both from our own participants and the wealth of international data that there’s a link between sleeping longer than average and a greater risk of stroke. What is far less clear, however, is the direction of this link. Whether longer sleep is a symptom, an early marker or a cause of cardiovascular problems.”

 

What kind of research was this?

This was a cohort study, which aimed to see if there was an association between sleep duration and risk of stroke. The researchers also performed a systematic review to find other relevant research, and pooled all the results in a meta-analysis.

A cohort study is the most appropriate type of study when looking at the long-term effect of sleep patterns, as it would not be feasible or ethical to conduct a randomised controlled trial over a long time period. Combining the results with other similar studies in a meta-analysis increases the strength of the evidence. However, due to the nature of the study types, they can only show an association between sleep duration and risk of stroke – they cannot prove that sleep duration causes a stroke.

 

What did the research involve?

The researchers assessed the regular sleep patterns of nearly 10,000 adults, looking for links between the amount of sleep they got and the number of people who had a stroke over the next 10 years. They systematically searched for similar studies and pooled their own results with these others in a meta-analysis.

The researchers recruited 9,692 participants from a larger longstanding study called the European Prospective Investigation of Cancer-Norfolk cohort, EPIC-Norfolk. They were given a questionnaire in 1998-2000, and again in 2002 to 2004, asking how much sleep they usually have over a 24-hour period, with the following options:

  • less than four hours
  • four to six hours
  • six to eight hours
  • eight to 10 hours
  • 10 to 12 hours
  • more than 12 hours

They were also asked if they sleep well, to which they could respond “yes” or “no”.

Participants were excluded from the study if they had already had a stroke. The researchers then obtained all cases of stroke from the National Health Services district database and the UK Office of National Statistics up until March 2009.

They analysed the results according to the average sleep duration, or the change in sleep duration between the two questionnaires. They also took into account all of the following potential confounding factors:

  • age
  • sex
  • social class
  • education
  • marital status
  • smoking
  • alcohol intake
  • hypnotic drug use (sedatives and “sleeping tablets”)
  • family history of stroke
  • physical activity
  • major depressive disorder in the previous year
  • previous heart attack
  • diabetes
  • use of blood pressure medication
  • body mass index (BMI)
  • blood pressure
  • cholesterol

Finally, they performed the systematic review and meta-analysis using all available trials up until May 2014.

 

What were the basic results?

The average age of the participants at the start of the study was 62, and ranged from 42 to 81 years. Most of them slept between six and eight hours per day (69%), with 10% sleeping for more than eight hours. In total, 346 people had a stroke during the 9.5-year follow-up period.

After adjusting for all of the confounding factors listed above, sleep of more than eight hours:

  • increased the risk of stroke by 46% (hazard ratio (HR) 1.46, 95% confidence interval (CI) 1.08 to 1.98)
  • increased the risk of stroke in women by 80% (HR 1.80, 95% CI 1.13 to 2.85)
  • was not associated with stroke in men

There was no statistically significant association between sleep of less than six hours and stroke.

The systematic review identified 11 relevant studies, including 559,252 participants from seven countries. They were followed up for between 7.5 and 35 years. The pooled relative risks for sleep duration and stroke were:

  • increased risk of 15% for sleep of less than six hours (relative risk (RR) 1.15, 95% CI 1.07 to 1.24)
  • increased risk of 45% for sleep of more than eight hours (RR 1.45, 95% CI 1.30 to 1.62)

 

How did the researchers interpret the results?

The researchers concluded that this study, “suggested a significant increase in stroke risk among long sleepers and a modest increase among short sleepers”. They say that, “the underlying mechanism needs further investigation”.

 

Conclusion

This cohort study found that, overall, people who sleep for more than eight hours have a 46% increased risk of stroke. When analysed separately, there was no statistically significant association for men, but a much higher increased risk for women, of 80%.

A major strength of the study is the number of potential confounding factors that the researchers tried to account for, including many cardiovascular risk factors. However, it did not account for other illnesses such as sleep apnoea or cancer, which may have had an effect on the amount of sleep and risk of stroke.

In addition, the study is reliant on the information provided in the questionnaires, which may not be entirely accurate:

  • alcohol intake is famously under-reported
  • perception of sleep duration and actual duration may be different and could be affected by illness and memory problems

The results of the meta-analysis were in line with the results of this study, though they also found an increased risk for people who have less than six hours sleep.

Professor Kay-Tee Khaw, senior author on the study, said in the Mirror that: “We need to understand the reasons behind the link between sleep and stroke risk”. She added that, “With further research, we may find that excessive sleep proves to be an early indicator of increased stroke risk, particularly among older people.”

In conclusion, without accounting for other illnesses, it is not clear what association the length of sleep has with risk of stroke from these studies. Known modifiable risk factors that can reduce your risk of stroke are to stop smoking, eat healthily, do physical exercise, and keep blood pressure and cholesterol within normal limits through lifestyle and use of medication where required.

If you are concerned that your normal sleep patterns have changed for no apparent reason, visit your GP.

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

Links To The Headlines

Weekend lie-in danger: Sleeping for eight hours can increase the risk of a stroke - especially for women over 63. Mail Online, February 26 2015

People who sleep more than eight hours are more likely to have a stroke, research shows. The Independent, February 25 2015

Sleeping more than eight hours raises stroke risk, Cambridge University warns. The Daily Telegraph, February 25 2015

Shock study reveals sleeping for longer than eight hours 'could cause a stroke'. Daily Mirror, February 25 2015

Sleeping too much ‘increases your risk of having a stroke’, study reveals. Metro, February 25 2015

Too MUCH sleep could KILL YOU: More than eight hours a night can double risk of stroke. Daily Express, February 26 2015

Links To Science

Leng Y, Cappuccio FP, Wainwright NWJ, et al. Sleep duration and risk of fatal and nonfatal stroke. Neurology. Published online February 25 2015

Categories: NHS Choices

'Game changer' HIV drug cuts infection risk by 86%

NHS Choices - Behind the Headlines - Wed, 25/02/2015 - 13:00

"Scientists hail discovery of 'game-changer' that cuts the risk of infection among gay men by 86%," The Independent reports. The drug, Truvada, has proved very successful in a "real-world" trial involving 545 participants.

Truvada is currently used as part of a treatment plan for people with HIV. It stops the virus from replicating, which helps protect the immune system.

Researchers wanted to see if it could also prevent the infection taking hold in the first place and have now presented initial results at a conference.

They recruited gay men, other men who have sex with men (MSM) and transgender women who were HIV negative and at high risk of HIV infection from 13 sexual health clinics in England. They randomly assigned them to either immediately start taking Truvada each day, or to wait and start taking it 12 months later.

The researchers also wanted to see if taking the medication made people more likely to increase their sexual risk-taking behaviour because they thought they were protected.

It is reported that both groups had the same rate of other sexually transmitted infections (STIs), an indication that sexual risk-taking did not change. The incidence of HIV infection in their first year of the study was much smaller in the Truvada group, at three people compared to 19 in the group who had to wait for a year before starting taking Truvada.

The researchers plan to submit the study to a peer-reviewed journal in April and are working with a range of stakeholders to determine whether a Truvada service could be commissioned across the NHS for high-risk individuals.

 

Where did the story come from?

The study was carried out by researchers from the Medical Research Council Clinical Trials Unit at University College London, Public Health England and 12 NHS trusts across England. It was co-funded by the Medical Research Council and Public Health England.

The results of the study were presented at the Conference on Retroviruses and Opportunistic Infections in Seattle, Washington. The study has not yet been published, so has not gone through external peer review to ensure the methodology and findings are reliable. The Medical Research Council reports that the study will be submitted to a peer-reviewed journal in April.

As the study has not yet been published, this article is based on the information so far released from the Medical Research Council and Public Health England.

Most of the UK media’s reporting of the study is accurate. An exception to this is the headline from The Daily Telegraph – "HIV drug taken before and after sex cuts risk by 86pc", which is misleading as it implies that Truvada could be taken like a morning after pill, but this has not been tested.

It is highly likely that taking it in this manner would not be effective.

 

What kind of research was this?

This was a randomised controlled trial that aimed to see if Truvada was effective in reducing the incidence of HIV infection in gay and other MSM, and trans-women.

The use of drugs such as Truvada to prevent infection, rather than treat infection, is known as Pre-Exposure Prophylaxes (PrEP). Truvada is an anti-retroviral (anti-HIV) drug, which is usually used to treat HIV. It contains two antiviral compounds called emtricitabine and tenofovir disoproxil fumarate. The drug is taken once a day. Anti-retrovirals work by stopping the virus replicating in the body, allowing the immune system to repair itself and preventing further damage. They have proved very successful, though resistance can be a problem, so people with HIV are usually required to take a combination of drugs.

Truvada has already been shown to be effective in reducing the incidence of HIV infection compared to placebo (dummy pill). The purpose of this study was to see if taking Truvada changed sexual risk-taking behaviour, by making people feel that they were less likely to be infected and thus increasing their exposure to HIV.

This kind of research is important because among gay men, MSM, and trans-women in the UK the rate of HIV infection remains high at 2,800 in 2013.

 

What did the research involve?

The researchers recruited 545 gay men, MSM, and trans-women who were HIV negative into the PROUD study (Pre-exposure Option for reducing HIV in the UK: immediate or Deferred). The participants were randomly assigned to have Truvada immediately (N=276) or to wait and have it after 12 months (N=269).

The participants were recruited from 13 sexual health clinics in England between November 2012 and April 2014. People were eligible to be included in the study if they had reported having anal sex without a condom in the previous three months and planned to do so again in the near future. This put them in the very high risk category.

Participants in both groups were advised to continue other risk prevention strategies such as condom use. They were also asked to keep a short diary, fill out a monthly questionnaire and attend a clinic appointment every three months.

 

What were the basic results?

Those taking Truvada were 86% less likely to be infected with HIV:

  • HIV infection occurred in three people taking Truvada compared to 19 in the group who had to wait for a year.
  • The infection rate in the Truvada group was 1.3 people infected per 100 people followed up for one year (100 person-years).
  • The infection rate in the waiting group was 8.9 per 100 person-years.

Sexual risk-taking behaviour was judged not to have increased in the Truvada group as there was no difference between the groups in terms of the number of participants who had a sexually transmitted infection (STI).

No results were provided from the diaries or questionnaires.

 

How did the researchers interpret the results?

The chief investigator of the study, Sheena McCormack, is reported to have said: "These results are extremely exciting and show PrEP is highly effective at preventing HIV infection in the real world." They are now working with a range of stakeholders to determine whether a PrEP service could be commissioned across the NHS.

 

Conclusion

The results of this unpublished study were presented at a conference in Seattle and have been reported by the Medical Research Council, who helped fund it. As it has not been published, some important details are not yet known, such as:

  • The researchers report that there was "high adherence" to taking the medication, but it is not known how regularly it was taken, or how many people stopped taking it and why.
  • No details have been provided about any side effects experienced on the medication.
  • The incidence of STIs was used to determine whether taking Truvada changed sexual risk-taking behaviour. It is currently unclear which STIs were compared between the two groups. Three common STIs are viral (genital herpes, genital warts and human papilloma virus), so it is possible that the Truvada reduced their incidence in addition to HIV. This could be an added bonus, but we will need to await publication of the study to look at this.

A limitation of the study is the amount of contact the participants had with the sexual health clinics. They were asked to fill out monthly questionnaires and attend a clinic every three months. It is possible this frequent contact with services caused this particular group to be more aware of the risks of HIV infection.

The researchers plan to submit the study to a peer-reviewed journal in April. In the meantime, they are working with a range of stakeholders to determine whether a PrEP service could be commissioned across the NHS. It has been suggested that men may wish to take PrEP during periods in their life when their sexual risk is highest, rather than continuously. This will no doubt be among the many considerations that will be taken into account.

In conclusion, the researchers report that PrEP reduced HIV infection by 86% in this very high risk group when it was taken on a daily basis. Full publication of this study, and any further developments, are awaited.

The most effective method of reducing your risk of HIV if you are sexually active – and whether you are gay, bisexual, trans or straight, is to always use a condom.

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

Links To The Headlines

HIV pill: Scientists hail discovery of 'game-changer' that cuts the risk of infection among gay men by 86%. The Independent, February 24 2015

Daily pill Truvada cuts spread of HIV by 86%, study shows. The Guardian, February 24 2015

'Give HIV drugs to healthy gay men'. BBC News, February 24 2015

HIV Drug: 'Game Changer' Hopes For Gay Men. Sky News, February 25 2015

Healthy gay men should be given HIV treatment to PREVENT infection, 'game-changing' trial suggests. Mail Online, February 24 2015

Healthy gay men 'should be offered HIV drugs'. ITV News, February 25 2015

HIV drug taken before and after sex cuts risk by 86pc. The Daily Telegraph, February 25 2015

Categories: NHS Choices

Depression linked to violent crime

NHS Choices - Behind the Headlines - Wed, 25/02/2015 - 10:30

"Depressed people are three times more likely to commit a violent crime," the Daily Mirror reports. Research into Swedish crime and medical data found that depression was linked with an increased risk of a person committing a violent crime.

It is important to stress from the outset that while the number of depressed people involved in a violent crime was above average, it was still small.

3.7% of men and 0.5% of women were convicted of committing a violent crime after being identified as clinically depressed, compared to 1.2% of men and 0.2% of women in the general population.

This was a well-designed study, but it’s important that the findings are not misinterpreted or used to add to the stigma of depression.

Also, the study does not show that depression causes crime. It only found an association between depression and a criminal conviction. It is possible that a third factor – such as poverty, unemployment or early trauma – can explain this link.

The study only included patients diagnosed and treated for depression by outpatient psychiatric services. People who required inpatient admissions and those treated by their GPs were excluded, so it may not be representative of people with different severities of depression.

If you are suffering from symptoms of depression, it is important to talk to your GP, especially if you find yourself lashing out at people. It’s important to remember that depression is treatable.

 

Where did the story come from?

The study was carried out by researchers from the University of Oxford and funded by the Wellcome Trust and the Swedish Research Council. Two authors declare financial ties with pharmaceutical companies, including Shire, Eli Lilly, Servier, Cephalon/Teva, Merck and GlaxoSmithKline. 

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

Most of the UK media’s coverage was fair and included comments from independent experts. 

The exception was The Daily Telegraph, as its headline, "Depression to blame for 46,000 violent crimes a year", was dangerously misleading. This headline does not relate to the results of the study, which was conducted in Sweden. In addition, the study found an association between depression and convictions for crime, but it did not show that depression was "to blame".

 

What kind of research was this?

This was an observational study that looked at the risk of violent crime in people with depression. In a second study, the authors investigated the association between depressive symptoms and violent crime in a cohort of twins, to assess the potential role of genetic and environmental factors.

The authors say that depression is associated with a wide range of adverse outcomes, including suicide, self-harm and early death, but any association with violent crime is uncertain.

 

What did the research involve?

The authors conducted two studies on people from Sweden. The first compared the rates of violent crime in people with depression and their siblings, compared to the general population. The second study followed a cohort of twins, assessed any symptoms of depression in 2005, and followed them up to see if any committed a violent offence.

The first was a population study in Sweden of 47,158 people diagnosed with at least two episodes of depressive disorders between 2001 and 2009. Those requiring inpatient admission were excluded, as were those with other psychiatric diagnoses. They were age- and sex-matched to 898,454 people in the general population, to compare the odds of their being convicted of violent crime. They analysed the results, taking account of various factors – low income, immigrant status, history of self-harm, previous criminality, and drug and alcohol abuse.

Data on convictions for violent crimes was obtained from the country’s national Crime Register and defined as:

  • homicide
  • attempted homicide
  • aggravated assault
  • common assault
  • robbery
  • arson
  • any sexual offence
  • illegal threats or intimidation

Researchers also compared the odds of violent crime conviction among 15,534 half-siblings and 33,516 full siblings of depressed people, compared to the general population.

In the second study, they looked at a sample of 23,020 adult twins born between 1959 and 1986, who had participated in an adult or child and adolescent Swedish Twin study. They were asked to fill in a questionnaire in 2005 to measure depressive symptoms using a recognised depression scale, and they were then followed for any violent outcome through linkage to the Crime Register. The aim of this second study was to assess whether any association between depression and violent crime could be due to common genetic or environmental factors.

 

What were the basic results?

In the first study, researchers identified 47,158 individuals (17,249 men and 29,909 women) with outpatient diagnoses of depression between 2001 and 2009. The average age of diagnosis was 32 years for men and 31 for women. They were followed for an average of three years.

During the follow-up period, 641 men (3.7%) and 152 (0.5%) women with depression were convicted of committing a violent crime, compared with 1.2% of men and 0.2% of women in the general population.

After adjusting for various sociodemographic factors, they calculated that individuals with depression were three times more likely to be convicted of a violent crime compared to people in the general population (odds ratio (OR) 3.0, 95% confidence interval (CI) 2.8 to 3.3). 

In people with either a previous criminal history, or a history of substance abuse or self-harm, the risk of being convicted for a violent crime was highest.

The odds of violent crime in brothers and sisters of people with depression were also significantly higher than in the general population, after adjusting the results to take into account age, sex, low family income and being born abroad:

  • half-siblings (adjusted OR 1.2, 95% CI 1.1-1.4)
  • full siblings (adjusted OR 1.5, 95% CI 1.3-1.6)

This, say the researchers, suggests that family background may be a confounding factor (confounder) in association between depression and a criminal conviction.

In the twin study, 88 violent crimes were recorded in the 5.4 years of follow-up.

Depressive symptoms were associated with a slightly increased risk of violent crime (hazard ratio (HR) 1.09, 95% CI 1.06 to 1.13).

 

How did the researchers interpret the results?

The researchers say that even after adjusting their findings for possible confounders, such as genetics and early family background, a diagnosis of depression modestly increased the risk of violent crime.

They argue that clinical guidelines should consider recommending violence risk assessment in certain subgroups with depression.

 

Conclusion

This was a large, well-conducted study that found an association between depression and violent crime. However, there were several limitations. As the authors point out, it did not include people who only go to their GPs – rather than psychiatric services – with depressive symptoms, or people who required inpatient admission for depression, so the results may not represent all people with depression.

Also, it was only conducted in one country, so the findings may not be generalisable to others.

As the authors say, they had no information about the treatment their patients had or were undergoing, so we cannot know how much treatment for depression was a factor in the findings.

The study did its best to take account of confounders that might influence the risk of violent crime, or explain both a diagnosis of depression and the likelihood of committing a crime, including family background. It is always possible that both measured and unmeasured confounders, such as early trauma or poor care as a child, can influence the results.

It’s also worth noting that depressed people were found to be more likely to be convicted of crimes – not that they actually committed more crimes. Given the nature of depression, which is associated with feelings of guilt and hopelessness, it is possible that depressed people are less likely to try to avoid being caught and less likely to try to avoid a conviction – for example, by seeking legal advice.

The results of this study would appear to suggest that current UK clinical guidelines on depression may benefit from being amended, by including advice on the small risk of violence in depressed people. They certainly shouldn’t be taken as "proof" that all depressed people are dangerous.

If you or someone you know is suffering from symptoms of depression, it is important to talk to a healthcare professional. 

Find information on mental health services 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

Depressed people are three times more likely to commit a violent crime, research shows. Daily Mirror, February 25 2015

Depression linked to violent crime, study finds. BBC News, February 25 2015

Depression to blame for 46,000 violent crimes a year, says Oxford University. The Daily Telegraph, February 25 2015

Links To Science

Fazel S, Wolf A, Chang Z, et al. Depression and violence: a Swedish population study. The Lancet – Psychiatry. Published online February 25 2015

Categories: NHS Choices

Peanut butter for non-allergic babies may reduce later allergies

NHS Choices - Behind the Headlines - Tue, 24/02/2015 - 07:32

"The cure for peanut allergy – peanuts, from the age of four months," says The Guardian.

This is dangerous headline advice, potentially leading parents to think they can simply give peanuts to an allergic child and cure them. This is irresponsible. Parents are also advised not to give peanuts – or any whole nuts – to children under the age of five, because of the risk of choking.

There are ongoing trials to assess whether medically supervised gradual introduction to peanut protein can help children with a peanut allergy – but the study on which the headline is based did not do this. It looked at whether foods containing peanuts, such as peanut butter, may play a role in helping to reduce the risk of children developing a peanut allergy.

The news is based on a well-designed trial in 640 infants aged between four and 11 months, who were not already allergic to peanuts, but were at increased risk of developing allergies due to having other food allergies or eczema. It compared the effects of giving the infants regular small amounts of peanut protein (in the form of smooth peanut butter or snacks containing peanut butter) or avoiding peanuts altogether up to the age of five.

It found that early introduction of peanut products (not whole nuts) reduced the proportion that developed a peanut allergy by age five, compared to those avoiding peanuts completely.

It is important to know that this study was not about treating infants or children who already have a peanut allergy. All children had a skin prick test before starting the trial, and those who showed an allergic reaction to peanut protein were excluded. Those who developed an allergic reaction stopped eating the products.

If your child shows signs of a peanut allergy, you should not try to feed them peanuts, and should instead consult your GP.

 

Where did the story come from?

The study was carried out by researchers from King’s College London, Guy’s and St Thomas' National Health Service Foundation Trust, and other research centres in the UK and US. It was funded by the US National Institute of Allergy and Infectious Diseases, Food Allergy Research and Education, the UK Medical Research Council, Asthma UK, the UK National Institute for Health Research, the US National Peanut Board and the UK Food Standards Agency.

The study was published in the peer-reviewed New England Journal of Medicine, and has been made open access, so is available for free online.

Other than the Guardian’s print and The Daily Telegraph's headlines (both referring to "peanuts" rather than peanut products), the media generally reported on this study well. It’s worth noting that the headline slips might be due to a King's College London press release entitled "Eating peanut at an early age prevents peanut allergy in high-risk infants", which is not as clear as it could be.

Other sources avoided saying that the infants were fed "peanuts" in their headlines. For example, the Mail Online avoided a sensationalist headline and gave sensible warnings to parents not to try this at home.

 

What kind of research was this?

This was a randomised controlled trial (called the Learning Early about Peanut Allergy (LEAP) trial) looking at whether introducing children to peanuts at an early age could reduce the risk of them developing a peanut allergy.

Peanut allergy in children is reported to have doubled in westernised countries in the past decade, with between one in 100 and three in 100 children being affected. Peanut allergy is the most common cause of anaphylactic shock and death due to food allergy.

UK and US guidelines have in the past recommended pregnant and breastfeeding women and infants at high risk of allergy to avoid "allergenic" foods such as peanuts. However, this was not shown to reduce the likelihood of developing food allergies, so this recommendation was withdrawn.

It is still not clear whether avoiding or introducing allergenic foods early on is a better way to avoid food allergies later in life. Researchers in the current study wanted to compare these strategies to find out which might be better for reducing the chance of developing a peanut allergy.

A randomised controlled trial is the best way of comparing different interventions or approaches. Assigning people randomly should ensure that the groups are well balanced, and therefore any differences between the groups should be due to the different interventions.

 

What did the research involve?

The researchers enrolled infants aged between four and 11 months of age with severe eczema, egg allergy, or both, and randomly assigned them to either peanut exposure or peanut avoidance.

Infants in the exposure group who did not show signs of a peanut allergy were given at least six grams (g) of peanut protein a week up to the age of 60 months. Infants in the avoidance group were not given any peanut products. The researchers tested the children during the trial to see if any of them developed a peanut allergy.

Crucially, before starting the trial, they tested the infants using a skin prick test, using peanut protein to identify those who showed signs of an allergic reaction with a wheal (a small raised area of the skin). Those who developed a large wheal (area of raised or reddened skin) at the site of exposure (more than 4mm in diameter), as this is a strong sign of an allergic reaction, were excluded from the study. Those showing a slight reaction (wheals of up to 4mm) were included, but analysed separately to those showing no skin reaction.

Those who had been allocated to the peanut exposure group then had a further "food challenge" test to see if they reacted to eating a small amount of peanut protein (2 to 3.9g). Those who showed a slight reaction to peanuts in the skin prick test were instructed to avoid them, but still analysed as part of the "peanut exposed" group. This was to make sure the groups stayed balanced.

The peanut protein used in the study was a commercially available snack made from peanut butter and puffed maize, called Bamba, or smooth peanut butter (Duerr’s or Sunpat brands) if the infant did not like the snack. The researchers assessed how well the families stuck to the assigned diet for the infants with a standard food questionnaire.

The researchers had telephone calls with the parents every week until the infants were 12 months old, then every fortnight up to the age of 30 months, then monthly. They assessed the infants face-to-face at ages 12, 30 and 60 months, and in any cases where the infant showed signs of a possible peanut allergy. At these visits, they again assessed whether the child showed signs of being allergic to peanuts. This started with a skin prick test with peanut protein.

Those who reacted to the skin prick test, had shown any signs of allergic reaction to peanut protein, sesame or tree nuts, or had an anaphylactic reaction to any food during the study, were given gradually increasing amounts of peanut protein, while being closely observed for any reaction. If they showed a reaction, the test was stopped.

The researchers doing this test did not know which group each infant had been part of. All other children were given 5g of peanut protein and also observed for any reaction. Eleven children who had inconclusive results on the food challenge tests, or who missed the test, were assessed based on their medical history, skin prick test and level of peanut allergy-related antibodies in their blood.

The researchers then compared what proportion of children in each group had developed a peanut allergy, to see if it differed. They looked at children who showed a positive skin prick test at the start of the study and those who showed a negative skin prick test separately.

 

What were the basic results?

Overall, 628 out of the 640 infants recruited (98%) provided enough information for their data to be analysed.

Among the 530 children who were negative on the first skin prick test, 13.7% of those who avoided peanuts had developed a peanut allergy by 60 months, compared to only 1.9% of the peanut exposed group.

Among the 98 children who were positive on the first skin prick test, 35.3% of those who avoided peanuts had developed a peanut allergy by 60 months, compared to 10.6% of the peanut exposed group.

These results were statistically significant, meaning that they were unlikely to have occurred by chance. Similar results were obtained even in a "worst case scenario", where all participants in the peanut exposure group with missing data were assumed to be allergic, and the opposite assumed for the peanut avoidance group.

There were no deaths among the infants in the study, and there was no difference between the groups in serious adverse events or need for hospitalisation. There were more adverse events overall in the peanut exposed group. The events that were more common in the peanut exposed groups included upper respiratory tract infection, viral skin infection, gastroenteritis, urticaria (hives – a raised, itchy rash), and conjunctivitis. These events were generally mild to moderate in severity for both groups.

 

How did the researchers interpret the results?

The researchers concluded that, "the early introduction of peanuts significantly decreased the frequency of the development of peanut allergy among children at high risk for this allergy".

They say that this, “raises questions about the usefulness of deliberate avoidance of peanuts as a strategy to prevent allergy”.

 

Conclusion

This well-designed randomised controlled trial has found that the early introduction of regular small amounts of peanut protein to infants at high risk of having allergies reduced the proportion who developed a peanut allergy by age five, compared to avoiding peanuts completely.

The study looked at a group of infants who were at a particularly high risk of going on to develop food allergies, because they already had severe eczema or an allergy to eggs, or both.

It is important to know that this study was not about treating infants or children who already had a peanut allergy. Those who showed a strong reaction on a skin prick test were excluded from the study, and those who showed an allergic reaction to eating peanut protein during the study were advised not to eat them. The results of this study do not apply to this group, and the researchers say they don’t know if their approach would work and be safe in this group.

The main limitation to the study was that parents and children could not be blinded to which group they were part of. However, the use of objective tests for allergic reactions should mean that their views cannot influence this outcome. There appeared to be a high level of compliance with the group allocations, but this was largely based on reports from the parents, so may not be fully accurate.

Overall, this study suggests that eating peanut products early in life may reduce the risk of children with a tendency towards allergies developing a peanut allergy up to age five. The researchers now plan to follow the participants for longer to see if the effects are maintained over time, even if they stop eating peanut products. As a number of experts point out in the media, this is not yet at a stage where it could be recommended to families to try at home.

If your child shows signs of a peanut allergy, do not try to feed them peanuts, and instead consult your GP. 

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

Links To The Headlines

Feed babies peanut products to reverse rise in allergy, say scientists. The Guardian, February 23 2015

What to know about new research on babies, peanut allergies. Mail Online, February 23 2015

Feeding peanuts to babies protects from peanut allergies, scientists find. The Daily Telegraph, February 23 2015

Peanut allergy 'cut by early exposure'. BBC News, February 23 2015

Links To Science

Du Toit G, et al. Randomized Trial of Peanut Consumption in Infants at Risk for Peanut Allergy. New England Journal of Medicine. Published online February 23 2015

Categories: NHS Choices

Anger possibly linked with non-fatal heart attacks

NHS Choices - Behind the Headlines - Tue, 24/02/2015 - 07:32

"'Plate-throwing rage' raises heart attack risk nearly 10 fold," The Daily Telegraph reports, slightly inaccurately.

This headline reports on a study that found that just seven out of 313 people had felt "very angry" in the two hours before a heart attack – compared to their normal levels of anger. Despite the headline, none of the participants had felt furious or angry to the point of throwing plates or any other objects.

The participants in the study had all been admitted to a cardiac unit following a heart attack. They completed questionnaires to estimate their levels of anger in the 48 hours before the heart attack and their usual levels in the preceding year.

Anger was assessed on a seven-point scale, and seven people reported being "very angry, body tense, maybe fists clenched, ready to burst" (a score of five) in the two hours before the heart attack. This level of anger was associated with 8.5 times the risk of a heart attack in the next two hours than other times.

This type of study alone cannot prove that anger caused the heart attack. And as so few people reported feeling angry before the heart attack, the results are not precise.

The study also relies on accurate recall not only of the period before the heart attack, but also of the usual levels of anger that were reached during the preceding year. People may be more likely to remember anger associated with a dramatic event like a heart attack than anger at other times, and this would affect results.

 

Where did the story come from?

The study was carried out by researchers from the Royal North Shore Hospital in Sydney and the University of Sydney. There was no external funding.

The study was published in the peer-reviewed medical journal Acute Cardiovascular Care on an open-access basis.

The media headlines exaggerated the findings of this study, with the Mail Online inaccurately reporting that anger "can cause" a heart attack.

This type of study cannot prove cause and effect. The Daily Mirror failed to explain that the results were only based on seven people.

 

What kind of research was this?

This was a case crossover study looking at whether episodes of anger are associated with an increased likelihood of heart attack shortly after they occur.

This type of study is uncommon, and aims to assess whether a brief condition or set of circumstances has a temporary impact on risk of an outcome shortly after they occur. It is similar to a case control study, but each case acts as its own control. Case crossover studies then look at how likely the outcome was to occur just after the circumstances occur, compared with any other time.

 

What did the research involve?

The researchers recruited people admitted to a cardiac unit with suspected heart attack. The participants reported on how angry they were over the previous 48 hours, and also their usual levels of anger. The researchers then looked at whether people were more likely to have had their heart attack in the four hours after an angry episode than at other times in the year.

They also looked at the likelihood of having high levels of anger or anxiety just before the heart attack compared to at other points in the year.

All people admitted to a single cardiac unit (in Sydney, Australia) with suspected heart attack between 2006 and 2012 were eligible for the study. The final 313 participants were those who had evidence of a blockage in an artery supplying the heart (coronary artery) found during angiography (a procedure that looks at the blood flow to the heart).

These participants completed a detailed questionnaire within four days of admission, which included questions about their activities in the 48 hours before the heart attack. They were also asked to rate their level of anger in this period, describe any events that caused it, and estimate how frequently they experienced each level of anger per year, using the following seven-point scale:

  1. calm
  2. busy, but not hassled
  3. mildly angry, irritated and hassled, but it does not show
  4. moderately angry, so hassled it shows in your voice
  5. very angry, body tense, maybe fists clenched, ready to burst
  6. furious, forced to show it physically, almost out of control
  7. enraged, out of control, throwing objects, hurting yourself or others

They also filled out another standard questionnaire about their level of anger and anxiety. They analysed the results comparing the likelihood and level of anger two hours before the heart attack and two to four hours before with their usual yearly estimated likelihood and levels of anger. They also compared the likelihood and level of anger and anxiety in the preceding two hours with the level 24 to 26 hours before.

 

What were the basic results?

The average age of the participants was 58 and most of them were male (85%). No one reported anger levels of above five (“very angry, body tense, maybe fists clenched, ready to burst”) – so despite the headlines, no-one threw anything.

In the two hours before heart attack:

  • seven people reported an anger level of five 
  • the risk of experiencing a heart attack within two hours of an anger level of five or more was raised by 8.5 times compared with other times (relative risk (RR) 8.5, 95% confidence interval (CI) 4.1 to 176)
  • two people had an anger level of four, and this was not associated with a significant increase in risk of heart attack in the next two hours (RR 1.3, 95% CI 0.3 to 5.1)

In the two to four hours before the heart attack:

  • one person reported an anger level of five or more, but this was not significantly associated with risk of heart attack
  • three people had an anger level of four, which was also not associated with an increased risk

When looking at the levels of anxiety in the two hours before heart attack compared to the level at the same time the previous day, people whose anxiety was in the top 75% of levels (75th percentile) had an increased relative risk of heart attack (RR 2.0, 95% CI 1.1 to 3.8) and this increased for those in the top 90% of levels (RR 9.5, 95% CI 2.2 to 40.8).

 

How did the researchers interpret the results?

The researchers concluded that episodes of intense anger, defined as being "very angry, body tense, clenching fists or teeth", are associated with increased risk of a heart attack within two hours. Anxiety was also associated with increased risk of heart attack in the next four hours.

 

Conclusion

This study found that an anger level of five of more (according to their scale) was associated with 8.5 times the risk of a heart attack than at other times. However, there are a number of limitations when considering this result.

Firstly, very few people reported feeling angry shortly before the heart attack – just seven people out of the 313 participants. Therefore the confidence interval for the main result is wide, meaning the results are not particularly precise, and we can’t be certain of the size of the association with risk.

Secondly, the study relies on accurate recall, not only of the period before the heart attack, but also of the usual levels of anger that were reached during the preceding year. As well as the potential for misremembering, it is open to what is called "recall bias". This is where someone is more likely to remember the anger they experienced just before their heart attack if they think it may have contributed to it, than anger at other times in the year.

In conclusion, the study by itself does not prove that increased levels of anger or anxiety directly cause heart attacks. However, a recent systematic review (that we have not assessed) suggests that similar studies also support an increase in risk shortly after outbursts of anger.

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

Links To The Headlines

'Plate-throwing rage' raises heart attack risk nearly 10 fold. The Daily Telegraph, February 24 2015

Malcolm Tucker style rants can increase risk of a heart attack. Daily Mirror, February 24 2015

Losing your temper CAN cause a heart attack: Being angry increases the risk eightfold. Daily Mail, February 24 2015

How anger raises heart attack risks. Daily Express, February 24 2015

Links To Science

Buckley T, et al. Triggering of acute coronary occlusion by episodes of anger. Acute Cardiovascular Care. Published February 23 2015

Categories: NHS Choices

Many deaths of mentally ill in custody 'avoidable'

NHS Choices - Behind the Headlines - Mon, 23/02/2015 - 16:00

“Hundreds of deaths in mental health units ‘were avoidable’,” says a report on the front page of today’s Independent. The Guardian highlights 662 mentally ill detainee deaths from 2010 to 2013.

Both stories follow an inquiry by the Equality and Human Rights Commission (EHRC) into the deaths of people with mental health conditions while detained in police custody, prisons or psychiatric hospitals.

The inquiry looked at whether people who were detained had been treated correctly according to EHRC guidelines. The inquiry focused on two basic rights: the right to life and the right to non-discrimination.

Over the period 2010 to 2013, there were 367 deaths from non-natural causes of adults with mental health conditions while detained in psychiatric wards and police custody. A further 295 adults died in prison, many of whom had mental health conditions.

The inquiry identified many areas of concern, including a lack of information sharing between professionals, insufficient involvement of family members, inappropriate use of restraint, and failure to learn from past incidents.

The Commission recommends that rigorous systems are put in place to ensure that any incidents are thoroughly and transparently investigated, and acted upon.

 

What did the EHRC investigate?

The Commission’s report looked into deaths in detention for those with mental health conditions. The inquiry looked at the period 2010 to 2013 in three detention areas:

  • Psychiatric hospitals. Detention in hospital means being held under the Mental Health Act, which is sometimes referred to as being “sectioned”. In 2012/13, there were said to be over 50,000 such detentions and the number has since been increasing.
  • Police custody. The Mental Health Act allows for a person “in crisis in a public space” to be held in police custody as a “place of safety” when there is insufficient other health-based support available. In 2012/13, there were reported to be 7,761 occasions when the Act was used to hold an individual in police cells.
  • Prisons. The prison service does not record the number of imprisoned people who have mental health conditions; however, they are likely to affect a large proportion of inmates. The most recent data – from 1997 – reported that 92% of male prisoners were suffering from psychosis, neurosis, personality disorder, alcohol misuse or drug dependence.

The Commission wanted to establish the extent to which there has been compliance with Article 2 (the right to life) and Article 14 (the right to non-discrimination) of the European Convention on Human Rights. It wanted to see whether improved compliance with these civil rights rules could reduce deaths in psychiatric hospitals, prisons and police custody.

 

What did the inquiry find about deaths in detention?

From 2010 to 2013, there were 367 deaths from non-natural causes of adults with mental health conditions while detained in psychiatric wards and police custody. A further 295 adults died in prison, many of whom had mental health conditions.

The inquiry found that the same mistakes are being repeated across prisons, police cells and psychiatric hospitals. This includes, for example, the failure to appropriately monitor patients and prisoners at serious risk of suicide, even in cases where their records recommend constant or frequent observation. It also includes failure to remove “ligature points” in psychiatric hospitals, which are known to be often used in suicide attempts.

According to the inquiry report, psychiatric hospitals are an “opaque system”. The Commission found it difficult to access information about non-natural deaths in psychiatric hospitals, such as individual investigation reports. This contrasts with prisons and police settings, where there is an independent body in charge of investigating deaths and ensuring that lessons are learnt.

The Commission also found misplaced concerns about data protection, leading to failures to share important information, such as concerns of other professionals about mental health, or suicidal tendencies not being passed on to prison staff. Similarly, failure to involve families to support the person being detained make it difficult for the family to pass on information that might have prevented deaths. Poor communication between staff, including lack of updates on risk assessments after self-harm or suicide attempts, was also highlighted.

Other significant findings included:

  • The availability of drugs, including “legal highs”, in prison.
  • Evidence of bullying and intimidation in prisons in the lead-up to someone talking their own life. This can result in a person being locked up alone in a cell for their own safety, because there is nowhere else for them to go. This can lead to deterioration of the person’s mental state.
  • Inappropriate use of restraint in people with mental health conditions, including “face-down” restraint. There were also increasing reports of police officers being called out to restrain people on psychiatric wards.
  • A high number of deaths occurred shortly after a person ended a period of detention, suggesting insufficient mental health support and follow-up.

 

What does the EHRC recommend?

The EHRC recommends:

  • Structured ways of learning from deaths and near misses in all settings where people with mental illness are detained, to ensure that improvements are made.
  • Individual prisons, hospitals and police settings should focus more strongly on meeting the basic responsibilities of keeping detainees safe. It recommends better staff training, and for the inspection regimes to explicitly monitor this. 
  • The Commission wants more “transparency”, to allow services to be scrutinised and held to account. The Commission suggests that the “statutory duty of candour”, which is being introduced in April 2015 and applies to all NHS bodies in England, could help to achieve this.

 

What happens next?

Mark Hammond, the EHRC’s chief executive says: “This Inquiry reveals serious cracks in our systems of care for those with serious mental health conditions. We need urgent action and a fundamental culture shift to tackle the unacceptable and inadequate support for vulnerable detainees.

“The improvements we recommend aren't necessarily complicated or costly: openness and transparency, and learning from mistakes are just about getting the basics right. In particular, by listening and responding to individuals and their families, organisations can improve the care and protection they provide.”

The Commission says it is now going to follow up its recommendations with the relevant organisations.

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

Links To The Headlines

Mental health deaths in detention 'avoidable'. BBC News, February 23 2015

Hospital psychiatric detainees more at risk of preventable death. The Guardian, February 23 2015

Too many deaths in custody are preventable but staff lack mental health expertise, says human rights body. The Independent, February 23 2015

Categories: NHS Choices

Dementia: researchers tip Mediterranean diet as preventive

NHS Choices - Behind the Headlines - Mon, 23/02/2015 - 15:55

“New diet to fight dementia,” claims the Sunday Express, while The Independent reports: “Mediterranean diet could help beat dementia”.

Despite the media focus on the Mediterranean diet, this was only a small part of a review which aimed to discover whether some modifiable risk factors (such as high cholesterol or high blood pressure) were linked to the risk of developing dementia in people with existing mild cognitive problems.

The review found collated relevant studies, covering a wide variety of potential risk factors, finding the most evidence around diabetes, high blood pressure and mental health.

Researchers found that the evidence suggested diabetes increased the risk of “conversion” from mild cognitive impairment to dementia. However, this increased risk was not adjusted for other potential confounding factors such as physical activity or smoking – which could influence the results.

The researchers found a single study assessing the Mediterranean diet in people with one type of mild cognitive impairment (particular problems remembering specific events). It found that the Mediterranean diet was associated with a reduced risk of developing Alzheimer’s among people with this type of mild cognitive impairment. However, it does not provide strong enough evidence to suggest that following the Mediterranean diet will definitely reduce the risk of a person with mild cognitive impairment developing dementia.

While this review is helpful, there is still a lot to be learned about risk factors for dementia and how to reduce risk.

 

Where did the story come from?

The study was carried out by researchers from University College London and Johns Hopkins Bayview Medical Center, Baltimore, US. One of the authors reported receiving financial support from various sources including the National Institute on Aging and National Institute of Mental Health, as well as various pharmaceutical companies. The other authors reported no financial relationships with commercial bodies.

The study was published in the peer-reviewed medical journal the American Journal of Psychiatry.

The main body of The Independent’s article is quite representative of this study, focusing on links with diabetes and mental health symptoms and risk of dementia. However, the choice to focus the headline on the Mediterranean diet is quite confusing and misleading. The Mediterranean diet was not the main focus of the review or its findings, and the evidence on it in the review comes from only one study. The Express' coverage was similarly skewed in focusing on diet.

 

What kind of research was this?

This was a systematic review that looked at which modifiable behaviours are associated with the development of dementia in people who have mild cognitive impairment (MCI).

The researchers say that recent public health campaigns have increased the recognition and diagnosis of MCI – described as a state between normal ageing and dementia. MCI is where someone (or a relative or doctor) has concerns about their cognitive symptoms, but they have normal functional activities and do not meet a diagnosis of dementia.

Almost half of people with MCI are reported to develop dementia within the following three years. However, ways to prevent the onset of dementia are unclear. The researchers had conducted a previous review of randomised controlled trials investigating treatments for MCI, but they found no consistent evidence that any of the treatments reduced the person’s cognitive decline, or the risk of the person developing dementia.

In the absence of trial evidence, they aimed next to look at observational studies to get an idea of which modifiable risk factors (such as different lifestyle choices) are associated with an increased or reduced risk of dementia. This may help to identify ways people might be able to reduce the risk of dementia developing. 

A systematic review is the best way of gathering all the available evidence on a particular question. However, such reviews are always going to be inherently limited by the quality of the underlying studies identified.

 

What did the research involve?

The researchers searched two literature databases (PubMed and Web of Knowledge) using relevant search terms to identify published longitudinal studies of “potentially modifiable risk factors” in people with MCI that looked at dementia outcomes.

The researchers defined MCI as cognitive impairment identified from objective neuropsychological tests, in the absence of dementia or significant functional impairment. Dementia outcomes were dementia of any cause, or Alzheimer’s dementia specifically.

They assessed the quality of identified studies, specifically looking for studies which recruited a representative sample of the general older population, had followed at least 70% of the included participants for at least one year, and used objective assessment methods for diagnosing MCI and dementia.

They also graded the quality of evidence supporting each of their conclusions as follows:

  • grade 1 evidence: consistent evidence from higher-quality studies
  • grade 2 evidence: evidence from a single higher-quality study or consistent evidence from other studies
  • inconsistent evidence: described as “troublingly inconsistent”

 

What were the basic results?

The search identified 62 relevant studies, nine of which were considered high-quality. 30 of these studies were pooled in meta-analysis. The studies looked at the following risk factors in people with MCI, as follows:

Diabetes

The pooled results of seven of 10 studies (grade 2 evidence) found people with MCI who had diabetes were at increased risk of developing dementia during follow-up compared to those without diabetes (unadjusted odds ratio (OR) 1.65, with a 95% confidence interval (CI) of 1.12 to 2.43).  

High blood pressure

The pooled results of seven of 11 studies (grade 2 evidence) did not find that this was associated with significantly increased odds of dementia (OR 1.19, 95% CI 0.81 to 1.73).

High cholesterol

Two studies (grade 2 evidence) found high cholesterol did not predict development of dementia (OR 0.92, 95% CI 0.50 to 1.68).

Smoking

Three studies (grade 1 evidence) found that smoking seemed to be associated with a decreased risk of dementia, but the relationship was no longer significant in the individual studies after adjusting for age. This suggested that the reason for the association could be due to smokers being more likely to die before they developed dementia.

Alcohol

Three higher-quality studies did not find any clear association between moderate alcohol consumption and development of dementia (grade 2 evidence).

Metabolic syndrome

One identified study (grade 2 evidence) found that metabolic syndrome predicted any-cause dementia in a specific type of MCI, termed "amnestic MCI". This was defined to be, “MCI with progressive symptoms and particular impairment of episodic memory”.

Mental health factors

The pooled results of four studies (grade 2 evidence) found an association between neuropsychiatric symptoms and dementia (OR 3.11, 95% CI 1.38 to 7.02). Pooled results of 13 studies did not find a significant association between depression symptoms and dementia (OR 1.35, 95% CI 0.89 to 2.06).

However, there was variability across studies. The studies following samples from the population that reported conversion from any type of MCI consistently found depressive symptoms were associated with increased risk of development of all-cause dementia (grade 1 evidence). However, the findings of studies in people with amnestic MCI and in groups of people with MCI identified through medical clinics were less consistent.

There was inconsistent evidence on any association with anxiety or apathy.

Dietary factors

The Mediterranean diet was the media focus, but only one study was identified, including 482 people with MCI. It was of high quality, and reported that a Mediterranean diet (low in meat and dairy products; high in fruits, vegetables, legumes, cereals and fish) was associated with a lower risk of conversion from amnestic MCI to Alzheimer’s dementia (grade 2 evidence). Of other dietary factors, three studies found suggestions that lower folate level is associated with an increased risk of conversion to dementia (grade 2 evidence).

Education

Seven studies (grade 1 evidence) found that number of years in education for people with amnestic dementia did not predict dementia.

 

How did the researchers interpret the results?

The researchers conclude that diabetes increases the risk of conversion from mild cognitive impairment to dementia.

They report that other potentially modifiable risk factors include the metabolic syndrome, neuropsychiatric symptoms, and low dietary folate. They suggest that dietary interventions and interventions to reduce neuropsychiatric symptoms may decrease risk of onset of new cases of dementia.

 

Conclusion

This was a systematic review that identified longitudinal studies that have looked at the association between modifiable risk factors in people with mild cognitive impairment and the development of dementia.

Despite the media headlines highlighting the Mediterranean diet, this was only a small part of this review – just one study of around 400 people that found the Mediterranean diet reduced risk of conversion from one type of MCI (amnestic MCI) to Alzheimer’s dementia.

So, despite the often-studied potential health benefits of the Mediterranean diet, this single study does not provide firm and conclusive evidence that following the Mediterranean diet will reduce the risk of a person with MCI developing dementia. Ideally, these findings need to be confirmed in other studies.

Such a systematic review is always going to be inherently limited by the underlying quality and methods of the included studies. This research found the largest body of evidence for diabetes, high blood pressure and mental health factors.

The largest body of evidence in this review suggested that diabetes increases the risk of conversion from MCI to dementia. However, even then this increased risk was in analysis that was not adjusted for other potential confounders. For example, with a condition such as diabetes, it’s possible that other cardiovascular risk factors may be involved in any association with the development of dementia, particularly vascular dementia.

It is also important to recognise that while this review did not find association with other factors such as high cholesterol, smoking or alcohol and dementia development, this is not to say these modifiable risk factors are definitely “safe”. The review only found few and variable quality studies addressing these factors.

It is important to note that the researchers’ previous systematic review of randomised controlled trials did not find that any interventions reduced the risk of conversion from MCI to dementia. In the absence of such evidence, observational studies can provide an idea of which factors look like they could be increasing risk. However, we can’t say for sure that changing them will definitely reduce risk.

Overall, this systemic review provides a summary of the currently available evidence on MCI and the risk factors for dementia in people with MCI. However, there is still much to be learned about risk factors for dementia and how to reduce risk.

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

Links To The Headlines

New diet to fight dementia: Best evidence yet that diet of fish & veg can beat the disease. Daily Express, February 21 2015

Mediterranean diet could help beat dementia finds UCL study. The Independent, February 22 2015

Links To Science

Cooper C, et al. Modifiable Predictors of Dementia in Mild Cognitive Impairment: A Systematic Review and Meta-Analysis. American Journal of Psychiatry. Published online February 22 2014

Categories: NHS Choices

New HPV vaccine may protect against 90% of cervical cancers

NHS Choices - Behind the Headlines - Fri, 20/02/2015 - 13:30

"New HPV vaccine stops 90% of cervical cancers," the Mail Online reports. The vaccine, which protects against nine common strains of the cancer-causing human papilloma virus (HPV), has proved both safe and effective in a study involving 14,000 women. HPV is one of the major causes of cervical cancer, as well as genital warts.

The current HPV vaccine, Gardasil, which the NHS offers to all girls aged 12 to 13, protects against the two most common strains associated with cervical cancer, as well as an additional two strains known to cause genital warts. Research suggests Gardasil can prevent around 70% of potential cervical cancers.

The new vaccine covers these four strains and five additional ones. This latest study indicates this may provide protection against 90% of cases. And researchers found the new vaccine reduced the incidence of cancer from these extra five strains to 0.1 cases per 1,000 person-years, compared with 1.6 cases per 1,000 person-years.

It is important to note that the study was conducted in women aged 16 to 26, which is much older than the 12 to 13 age group currently offered vaccination, and may affect the results. In addition, the participants were only followed up for 4.5 years. Longer studies including other age groups are now required.

 

Where did the story come from?

The study was carried out by researchers from universities and institutes in Austria, Norway, Denmark, Germany, the UK, the US, Canada, Brazil, Hong Kong, Mexico, Thailand, Columbia, Taiwan, and Australia.

It was funded by the pharmaceutical company Merck. There are potential conflicts of interest, as many of the authors have affiliations with Merck.

The study was published in the peer-reviewed journal, the New England Journal of Medicine.

The Mail's reporting was confusing as it opened with the incorrect information that the "current vaccine used in the UK, Gardasil, protects against nine HPV strains". If this were the case, there would be no reason to assess the effectiveness of a new vaccine.

The current vaccine actually only protects against two strains that cause 70% of cervical cancers, and two strains that cause genital warts.

And despite the irresponsible suggestion to the contrary, we wouldn't recommend that you decline the offer of a smear test – cervical cancer screening – if recommended.

 

What kind of research was this?

This was a randomised, double-blind clinical trial comparing the effectiveness of a new vaccine against HPV with the current vaccine.

In the UK, around 3,100 women are diagnosed with cervical cancer each year. A major cause of cervical cancer is infection from the human papilloma virus (HPV). There are more than 100 types of HPV, and at least 15 of them are considered to be high risk.

In the UK, the HPV vaccine, which is offered to all girls aged 12 to 13, gives protection against four types of HPV: 6, 11, 16 and 18. Two of these types – HPV 16 and 18 – are believed to cause more than 70% of cases of cervical cancer.

The vaccine also protects against strains HPV 6 and 11, which are responsible for 90% of genital wart cases.

The new 9vHPV vaccine covers these four strains as well as five others (31, 33, 45, 52 and 58). This has the potential to increase the protection against cervical cancer from 70% to 90%, according to the prevalence of these strains in a global study of 10,575 cases of cervical cancer.

 

What did the research involve?

Women aged 16 to 26 were given either the current Gardasil vaccine or the new 9vHPV vaccine, and the rates of HPV infection were then compared.

The study recruited 14,215 women from Asia Pacific, Europe, Latin America and North America, and randomly assigned them to receive three doses of the 9vHPV vaccine or three doses of the current HPV vaccine over the course of six months. Their average age was 22 and the age when they first had sexual intercourse was 17.

Women were eligible for the study if they had:

  • no history of an abnormal smear test result
  • no more than four sexual partners in their lifetime
  • no previous abnormality on cervical biopsy

The women had swabs taken for 14 types of HPV on the day they first received the vaccine and then every six months for 4.5 years. They also had a smear at each visit and, if this was abnormal, they had a colposcopy (a more detailed examination of the cervix).

Statistical analyses were performed comparing the outcomes for women who had no evidence of HPV infection when they were first vaccinated or the subsequent seven months. Additional analyses were performed for those who did have HPV infection during this time.

The outcomes measured were incidences of cervical, vaginal and vulval cancers. They did not directly compare the two vaccines for infection with the four types of HPV.

 

What were the basic results?

For all women who entered the study:

  • The incidence of high-grade cervical, vulval and vaginal disease was 14.0 per 1,000 person-years in women given either vaccine. High-grade disease included invasive cancers and abnormal changes that have a high likelihood of developing into invasive cancer.
  • In women not initially infected with HPV, the incidence was 2.4 per 1,000 person-years in those given the new 9vHPV vaccine compared with 4.2 per 1,000 person-years for those given the current vaccine. This means the new vaccine was 42.5% more effective (95% confidence interval [CI] 7.9 to 65.9) in women who were not infected with HPV at the time they had the vaccination. In women who were already infected with HPV when they had their first vaccine, there was no difference in incidence.

For women who did not have HPV infection for the first seven months of the study who completed the vaccination course and had no study violations, called the per-protocol efficacy population:

  • The incidence of disease from the extra five types of HPV was 0.1 per 1,000 person-years in the 9vHPV group compared with 1.6 per 1,000 person-years in the current vaccine group (1 case versus 30), meaning the vaccine was more effective for these women.

The new 9vHPV caused slightly more pain, swelling and redness than the current vaccine. There were no serious events related to the vaccine in either group.

 

How did the researchers interpret the results?

The authors concluded that the 9vHPV vaccine provided the same amount of protection as the qHPV vaccine for the four vaccines that they both cover.

It also prevented infection and disease related to the five extra strains in susceptible women when compared with the normal qHPV vaccine. The 9vHPV vaccine did not protect against other strains of the virus.

 

Conclusion

This double-blind randomised trial has shown that the new HPV vaccine provides increased protection from additional strains of HPV that cause cervical, vulval and vaginal cancers.

Strengths of the study include:

  • Blinding of the pathologists to the vaccine type, and blinding of the participants (they didn't know which vaccine they had been given), which reduces any bias – a double-blind randomised controlled trial is considered the gold standard of how best to assess a treatment or intervention.
  • The large number of women included in the study, with diverse ethnic backgrounds, makes it likely that the results would be applicable to most women in this age group.

However, there are some limitations:

  • It is widely reported in the media that the two vaccines offer the same protection for the original four HPV strains, but there was no direct comparison between the vaccines for their ability to protect against the four types of HPV virus. The comparison was restricted to incidence of invasive cancers and high-grade abnormalities, which may take longer to occur than the 4.5 years of the study's duration. The researchers acknowledge that longer studies are required, however.
  • The study group were much older than the age of girls who are currently vaccinated, presumably so that they could provide their own consent to participate. This may have a bearing on the results.

Further studies will be required to address these issues before it is known whether there will be a change in the type of vaccine offered in the UK.

While vaccination is an important component in reducing the risk of these types of cancer, it is important to reduce the risk in other ways, too.

This includes not smoking, as this increases the risk of cervical cancer – chemicals from cigarettes have been found in cervical mucus, and it is thought this damages the cervix. Safe sex, such as using condoms, is also important.

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

Links To The Headlines

New HPV vaccine stops 90% of cervical cancers and could mean fewer women need smear tests in future. Mail Online, February 19 2015

Links To Science

Joura EA, Giullano AR, Iversen O, et al. A 9-Valent HPV Vaccine against Infection and Intraepithelial Neoplasia in Women. The New England Journal of Medicine. Published online February 19 2015

Categories: NHS Choices

Sunlight UV damage to skin persists even after dark

NHS Choices - Behind the Headlines - Fri, 20/02/2015 - 12:00

“Moving immediately into the shade does not stop sun damage, as UV rays can continue damaging skin cells hours after exposure,” The Guardian reports. Ultraviolet (UV) light is known to cause damage to DNA in skin cells, which increases the risk of the most serious type of skin cancer: melanoma.

This study aimed to examine the biological mechanisms that may be involved in this process.

Researchers used pigment-producing skin cells from mice (melanocytes) and found that it is the pigment melanin that plays a role in the damage process.

Exposure to UV light causes melanin to produce small molecules, called cyclobutane pyrimidine dimers (CPDs). The CPDs form abnormal bonds between the “building blocks” in the DNA helix. These CPDs are formed at the time of UV exposure, but the research showed that the formation of CPDs also continues for three or more hours after UV exposure has stopped (“after dark”). After this, DNA repair mechanisms step in.

Some tests using human melanocytes were also performed. This was said to similarly demonstrate the continued formation of CPDs after dark, but the effects were much more variable. It is unclear whether the situation in humans is completely identical.

Overall, the findings reinforce the risks of over-exposure to sunlight. It is easy to forget that the sun is a giant nuclear fusion reactor that emits radiation. Therefore, it is important to be sun-smart to reduce your risk of skin cancer.

You don’t need to get a suntan, let alone sunburn, to harvest the vitamin D-boosting effect of sunlight.

 

Where did the story come from?

The study was carried out by researchers from Yale University School of Medicine in the US and other institutions in Brazil, Japan and France. The study was supported by various grants, including those from the Department of Defence and National Institutes of Health. 

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

The UK media’s reporting of the study was accurate, though some of the headlines were potentially confusing. For example, headlines such as The Daily Telegraph’s “Sunlight damages DNA even in the dark” and The Guardian’s “Exposure to sun poses risk of skin cancer even in the dark” could be taken the wrong way. People may be concerned that when they go out at night, the sun is damaging their skin and they need to cover up. The results of the study actually suggest that the damage caused by UV exposure to the skin continues for some hours after the exposure has stopped (e.g. after you have come in for the evening, after a day at the beach). 

 

What kind of research was this?

This was a laboratory study aiming to see by what processes UV light causes damage to the DNA in skin cells.

Melanin is the pigment in skin and hair cells, which is present in variable amounts across individuals. The amount and type of pigment in your skin, such as pheomelanin and eumelanin, are associated with the risk of developing melanoma – the most serious type of skin cancer.

People with blonde and red hair have higher amounts of yellow pheomelanin relative to brown eumelanin in their skin and hair, which puts them at higher risk than people with darker skin and hair.

Previous research has demonstrated that when melanin, particularly yellow pheomelanin, is exposed to UV light, this produces reactive oxygen species (ROS) – molecules that can cause cell damage and "breaks" in the DNA. Looking at the DNA abnormalities present in melanoma, it seems that in most cases there are distortions to the DNA helix. This is due to the presence of molecules called cyclobutane pyrimidine dimers (CPDs), which cause abnormal bonds between the “building blocks” in the DNA.

Ultraviolet A type radiation (UVA) makes up around 95% of the UV entering the atmosphere. However, the researchers say that although UVA is clearly linked to melanoma, UVA is not very good at making these CPDs directly. The researchers therefore aimed to look at the biochemical pathways that cause the pigment-producing skin cells (melanocytes) to produce CPDs.

 

What did the research involve?

The researchers carried out a variety of laboratory experiments, where melanocytes from mouse and human skin were exposed to UVA and UVB light. They used special laboratory techniques to examine the DNA in the cells, looking for the generation of CPDs at the time of UV exposure and for some time after UV exposure had been discontinued (“after dark”).   

The researchers then carried out further studies to see what biochemical processes may be causing the melanocytes to produce CPDs.

 

What were the basic results?

The researchers showed that exposure to UVA light causes the immediate production of CPDs. Unexpectedly, CPD generation continued for three or more hours after UVA exposure was stopped. After this, the formation of CPDs was offset by DNA repair mechanisms.

Experiments using melanocytes from albino mice suggested that it was the melanin pigment that was involved in the continued production of CPDs after dark, as pigment-free melanocytes did not continue to produce CPDs after UVA had been stopped.

Half of all CPDs produced after UVA exposure to mouse melanocytes were found to be formed in this “after dark” period, when exposure had stopped. Further tests with UVB light showed that most of the CPDs produced occurred after dark. Further tests in the mice suggested that the red-yellow pigment pheomelanin is both a “poorer shield” against the generation of CPDs at the time of UV exposure, and a stronger generator of CPDs after dark.

Tests with the human melanocytes similarly demonstrated the production of CPDs after dark, but in human cells the response was said to be much more variable. The researchers considered that this could be due to genetic differences, though they could not look into this further due to privacy restrictions on the donated skin.

When looking into the underlying biochemical pathways involved in the production of CPDs after dark, they found that this was due to UV-induced reactive oxygen and nitrogen species combining and causing excitation (the application of energy) of an electron in the melanin pigment. The energy produced during this process is transferred to the DNA and causes the formation of CPDs.

 

How did the researchers interpret the results?

The researchers conclude that pigment-producing skin cells (melanocytes) cause the production of “dark CPDs”, even after UV exposure ends. They say that melanin, while it may protect against cancer in one respect (e.g. people with darker skin having lower risk), it may also be cancer-causing (carcinogenic).

They also say that their findings “validate the long-standing suggestion that chemically generated excited electronic states are relevant to mammalian biology”.

 

Conclusion

This laboratory research examined the biochemical processes by which UV exposure causes damage to the DNA in skin cells, and so increases the risk of melanoma.

The research which used mouse pigment cells in the laboratory, confirmed that the melanin pigment plays a role. Exposure to UV light causes melanin to produce CPD molecules, which cause abnormal bonds to form between the “building blocks” in the DNA helix. The research showed that the formation of CPDs continues for three or more hours after UV exposure has stopped (“after dark”) before DNA repair mechanisms step in. The melanin pigment is necessary for the continued formation of CPDs after dark (pigment-free cells did not do this), and there was also the suggestion that different types of melanin could have differing effects. For example, the red-yellow pigment pheomelanin seemed to be a stronger generator of CPDs after dark. 

However, it should be noted that most of these results came from experiments using mouse pigment cells. Although UV exposure to human melanocytes was said to similarly cause the continued formation of CPDs after dark, the effects were reported to be much more variable. The researchers considered that this could be due to genetic differences, but they were not able to explore this further, due to privacy restrictions.

Therefore, these results must be predominantly considered to be applicable to mice. Although this is likely to be a good indication of the biochemical pathways that may occur in human skin cells after UV exposure, it is not know if the results would be completely identical.

Overall, the findings show that at whatever time UV exposure causes most damage to the skin – either at the time of exposure, or in the continuing hours afterwards – it does cause DNA damage to the skin, which is linked to the risk of skin cancer. The study again highlights the importance of safety in the sun, including the use of sunscreen, sunglasses and skin coverage.

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

Links To The Headlines

Exposure to sun poses risk of skin cancer even in the dark, study finds. The Guardian, February 19 2015

Could using sunscreen at NIGHT prevent skin cancer? Damage caused by UV light continues for hours after dark, finds study. Mail Online, February 19 2015

Sunlight damages DNA even in the dark, Yale scientists find. The Daily Telegraph, February 19 2015

A day on the beach can lead to cancer-causing damage AFTER the sun has set. Daily Mirror, February 19 2015

Links To Science

Premi S, Wallisch S, Mano CM, et al. Chemiexcitation of melanin derivatives induces DNA photoproducts long after UV exposure. Science. Published online February 20 2015

Categories: NHS Choices

Nanoparticles used to treat damaged arteries

NHS Choices - Behind the Headlines - Thu, 19/02/2015 - 13:00

“New trials suggest microscopic stealth drones could be used to seek and repair damaged arteries,” The Daily Telegraph, somewhat over-excitedly, reports.

A study in mice has found promising results for a targeted treatment where nanoparticles are used to deliver a "repair protein" to sections of arteries affected by atherosclerosis.

Atherosclerosis occurs when fatty material collects in the lining of arteries, causing inflammation. The body tries to repair this, covering the areas with fibrous tissue, creating “plaques”. Continued fatty build-ups collect on these plaques and eventually the repair system fails, and the plaques rupture. This may cause a blood clot to enter the circulation and cause a heart attack or stroke.

In this study, researchers have identified a protein called annexin A1, which is usually part of the repair process. They took a section of this protein and covered it in a nanoparticle (a microscopic particle). They then attached proteins to the surface that would “stick” to the plaques.

The nanoparticles targeted the plaques in mice with advanced atherosclerosis, where they slowly released the section of annexin A1, which helped to improve the repair system. 

Further studies in pigs and then primates are now planned. If successful, human trials may then be conducted.

 

Where did the story come from?

The study was carried out by researchers from Colombia University in New York, Brigham and Women’s Hospital in Boston, and Barts and the London School of Medicine. It was funded by the US National Institutes for Health, the Wellcome Trust and the David Koch Prostate Cancer Foundation. The authors have disclosed a competing interest, in that an international patent has been filed for the inflammatory resolving nanoparticles.

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

We suspect that somebody at The Daily Telegraph has been reading too much science fiction, which led to their description of “microscopic stealth drones”. Microscopic? Yes. Stealth drones? No.

That aside, the media reported this study accurately, though descriptions of nanoparticles “mending” or “repairing” damaged arteries, are not exactly what occurred. The new technique helped to stabilise plaques and reduce the damaging inflammation, but did not remove them.

 

What kind of research was this?

This was an animal experiment, which aimed to test a new technique to resolve atherosclerotic plaques.

Atherosclerosis (hardening and thinning of the arteries) occurs when fatty material collects in the lining of arteries, causing inflammation. This in turn causes the body to try to repair the area by forming a protective fibrous tissue over the top. These areas, called plaques, continue to build up and restrict blood flow. Eventually, the inflammation continues, but the repair process stops working. The plaques then have a thin layer of this fibrous tissue and so are more likely to rupture, causing a blood clot to break off, which can lead to a stroke or heart attack.

Prevention of atherosclerosis involves a healthy diet, not smoking, and doing exercise, though plaques may still develop. Current treatments aim to reduce the amount of cholesterol in the blood using statins, treating high blood pressure to reduce the likelihood of a plaque rupturing, and drugs such as aspirin to thin the blood and prevent it sticking to the plaques and causing a clot.

The researchers’ main aim was to find a way to reduce the inflammation that is occurring within the plaques as an additional treatment strategy. Other novel attempts, such as with genetic manipulation or immunosuppressant drugs, dampen down the whole immune system, leaving it vulnerable to infection. This new technique, using targeted nanoparticles, means that a limited amount can be circulated in the bloodstream, without affecting the normal immune response.

 

What did the research involve?

The researchers isolated a human protein called annexin A1, which normally helps to resolve inflammation. They took a component of this, called Ac2-26, and covered it in a nanoparticle, which is a microscopic particle with a diameter of 100 nanometers or less. They attached peptides to the surface of these nanoparticles that would effectively “stick” to the plaques.

They injected mice with advanced atherosclerosis once per week for five weeks with either these nanoparticles, a scrambled version of the nanoparticles, Ac2-26, or a control of normal saline (salty water). The researchers then looked at the first part of the aorta (the main artery taking oxygenated blood from the heart to the body) and the main artery that supplies the brain.

 

What were the basic results?

The nanoparticles stuck to the plaques and released the Ac2-26 proteins. Compared to the other mice, those given the nanoparticles had:

  • increased collagen (the protective fibrous layer covering the plaques)
  • reduced reactive oxygen species (these accumulate during acute inflammation, but an excess amount can damage tissues)
  • increased anti-inflammatory cytokines (communication cells of the immune system)
  • 80% reduced area of plaque necrosis (breakdown)

In short, this acted to resolve the inflammation and stabilise the plaques. These changes were not present in the spleen or liver, indicating that the nanoparticles were likely to have just targeted the plaques.

 

How did the researchers interpret the results?

The authors concluded that their animal experiments “tested a proof-of-concept targeted NP [nanoparticles] with one type of proresolving mediator. To bring targeted resolution mediator nanotherapeutics to the clinic for patients at high risk for atherothrombotic vascular events, additional confirmatory studies will be needed, including evaluation in more predictive models, such as fat-fed pigs and non-human primates”. They also acknowledge that “detailed toxicity studies will be needed to show the safety of both the NP material and the resolution mediator cargo”.

 

Conclusion

This exciting study in mice has shown that nanoparticles can be manufactured to target the plaques that form in atherosclerosis, and help stabilise them. It appears that the nanoparticles honed in on the plaques, rather than affecting other organs such as the spleen or liver, which gives an early indication that there may not be substantial side effects. However, it will be necessary to see if the same holds true for other organs.

As with all mice studies, they give an indication of the likely biological effects of a new technique, but they do not provide the full picture of what may happen in humans, especially with regards to more subtle side effects.

The media have rather exaggerated the results of this study by claiming the technique repaired arterial damage. This is not the case; the nanoparticles were able to help stabilise the plaques and reduce the inflammation that is part of the process of plaque formation. However, the study did not show that the arteries went back to normal. The plaques were still present. This technique, if possible in humans, would be an additional strategy for “damage limitation” of atherosclerosis.

Researchers now plan to see if the techniques work in animals with more complicated bodies and biological systems, such as pigs and primates. If these hurdles are successfully passed, human trials may then begin.

Currently, the best way to slow down or try to prevent atherosclerosis is to lead a healthy lifestyle and reduce known risk factors.

This includes stopping smokingweight management and regular exercise. In some cases, cholesterol-lowering medications, such as statins, and blood-thinning medications, such as low-dose aspirin, may also be recommended.

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

Links To The Headlines

Drones could be used to seek out arteries to prevent heart attacks. The Daily Telegraph, February 18 2015

Nano drones mend arteries: Microscopic particles that seek out and repair damage could be future of treatment for heart disease and strokes. Mail Online, February 19 2015

Microscopic DRONES could be used to treat heart and stroke patients in the future. Daily Mirror, February 18 2015

Links To Science

Fredman G, Kamaly N, Spolitu S, et al. Targeted nanoparticles containing the proresolving peptide Ac2-26 protect against advanced atherosclerosis in hypercholesterolemic mice. Science Translational Medicine. Published online February 18 2015

Categories: NHS Choices

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