NHS Choices

Targeting 'addiction switch' may help combat alcoholism

NHS Choices - Behind the Headlines - Wed, 31/08/2016 - 17:30

"Alcoholics are missing 'vital chemical in their brain' that helps control addiction," the Daily Express reports.

Research carried out on rats suggests that low levels of the PRDM2 enzyme could trigger self-destructive addictive behaviour associated with alcohol dependency; leading people to continue to drink even though it is causing them physical and mental stress.

The studies showed that levels of this enzyme were lower in brain cells of the frontal lobe in rats that had previously been made dependent on alcohol, through being made to inhale alcohol vapour. These rats showed signs of addiction such as increased drinking of alcohol, even when it was mixed with bitter quinine, and seeking alcohol when stressed by being given electric shocks.

The researchers then found that rats which had not been exposed to alcohol vapour showed similar behaviour, after being treated to prevent them from producing PRDM2. They say this shows that the enzyme is important in controlling impulsive behaviour, which is difficult for people with alcohol addiction.

The obvious caveats about extrapolating animal research to humans apply.

The lead researcher said he hoped the findings would lead to medicines that can help people recover from alcoholism.

Current treatment options for alcohol dependency include talking therapies, group therapy, and medication that can help relieve cravings and prevent relapses.

To keep your risk of alcohol-related harm low, the NHS recommends not regularly drinking more than 14 units of alcohol a week.

If you are worried about your alcohol consumption, speak to your GP to find out more about treatment options.

Where did the story come from?

The study was carried out by researchers from Linköping University in Sweden, University of Miami Miller School of Medicine, National Institute on Alcohol Abuse and Alcoholism, and the University of Georgia, all in the US. It was funded by the National Institute on Alcohol Abuse and Alcoholism, the Swedish Research Council and United States Department of Defense.

The study was published in the peer-reviewed journal Molecular Psychiatry on an open-access basis so it is free to read online.

The Times says that cancer drugs "could help alcoholics give up drink." This claim seems to be based on interviews with researchers, rather than anything in the study, which did not look at any medicines that might reverse the effects of the enzyme found to be lower in alcohol-dependent rats. The headline could raise hopes that a treatment for alcoholism is closer than it actually is.

The Daily Express fails to make it clear in its report that there is no direct evidence from this study that lack of PRDM2 is responsible for alcoholism in humans. This may be because the researchers' press release was headed: "People with alcohol dependency lack important enzyme," and doesn't mention animal research until the seventh paragraph.

 

What kind of research was this?

This was a series of animal experiments on rats in a laboratory, including manipulation of genes responsible for producing the enzyme PRDM2. These types of studies are helpful to understand molecular pathways behind diseases like alcoholism, but they do not investigate cures. Also, findings that apply to animals do not always translate to humans.

 

What did the research involve?

Researchers did a series of experiments involving rats that had been exposed to breathing alcohol vapour for 14 hours a day over seven weeks. This makes them "dependent" on alcohol. The researchers studied their behaviour in a series of behavioural experiments, including seeing whether they continued to drink alcohol when it was mixed with bitter-tasting quinine.

The researchers examined brain tissue cells for production of enzymes including PRDM2 and carried out DNA sequencing to examine the function of nerve cells affected by these enzymes. They used DNA analysis and cell chemistry techniques to look at expression of PRDM2 and behavioural experiments to examine the effects of changing this enzyme expression. They then carried out behavioural experiments on rats that had not been exposed to alcohol vapour, but which had been genetically manipulated not to produce PRDM2.

The behaviour of these rats was compared to rats with normal PRDM2 expression.

The researchers wanted to understand the role of different enzymes, and whether specific enzymes could be identified that affected alcohol addiction or produced behaviour similar to that shown by rats dependent on alcohol.

 

What were the basic results?

Researchers found that rats with alcohol dependency, as shown by their behaviour, had lower levels of the enzyme PRDM2 produced in their prefrontal cortex cells, weeks after they had stopped receiving alcohol.

In the second series of experiments, rats engineered not to produce PRDM2 showed similar behavioural signs of alcohol dependency, despite not having been exposed to alcohol vapour. Compared to rats with normal PRDM2 production, they were likely to drink more alcohol, to drink compulsively despite the bitter quinine taste, and to drink alcohol in response to electric shock stress. They were no more likely than normal rats to drink more sugar solution, suggesting that the effects of PRDM2 were specific to alcohol.

 

How did the researchers interpret the results?

In their paper, the researchers said "these observations suggest that long-term repression of PRDM2 is a key epigenetic mechanism contributing to a cluster of behaviours thought to be at the core of alcohol addiction." Epigenetics is the way in which genes are switched on and off, in response to external stimuli including enzymes.

They concluded that this gave a "strong rationale to explore PRDM2 or some of its downstream targets as candidate targets for novel alcoholism medications." They say that reversing the changes seen in alcoholism where the cells stop producing PRDM2 might "promote a transition back to a preaddicted state."

 

Conclusion

It seems likely that many factors influence why some people become addicted to alcohol and not simply a single enzyme. This new study shows that a change in enzyme production by brain cells of rats who have been forcibly exposed to alcohol vapour may be part of the process by which animals become dependent on alcohol. But despite the claims in the press release, this study does not prove anything about human brain cells, enzymes or alcohol addiction.

One researcher expressed the hope that his findings would "do away with the stigmatisation of alcoholism," by showing that it has a biochemical basis. While this is a laudable aim, the research published today does not show that the same mechanisms operational in rat brains operate in human brains. We do not know whether PRDM2 expression is the key to developing alcohol addiction for humans, even if animal research suggests it may be.

The findings open up possibilities for future research in humans, and may even one day lead to new drugs to reverse people's dependency on alcohol. That is still a way off, however, and much more research needs to be done before new drugs are likely to be available.

If you are worried you may have a problem with alcohol, talk to your GP or find out more about getting help with our information on alcohol support.

Links To The Headlines

Alcoholics are missing 'vital chemical in their brain' that helps control addiction. Daily Express, August 31 2016

Cancer drugs could help alcoholics to give up drink. The Times, August 31 2016 (subscription required)

Alcoholics lack a key enzyme in the brain – and this creates a 'vicious cycle' of addiction. Wired, August 30 2016

Links To Science

Barbier E, Johnstone AL, Khomtchouk BB, et al. Dependence-induced increase of alcohol self-administration and compulsive drinking mediated by the histone methyltransferase PRDM2. Molecular Psychiatry. Published online August 30 2016

Categories: NHS Choices

One in three heart attack cases 'misdiagnosed'

NHS Choices - Behind the Headlines - Tue, 30/08/2016 - 16:40

BBC News reports a "third [of people] given wrong initial heart attack diagnosis", while The Sun makes the totally unsupported claim that "Doctors miss heart attacks in women 'because they expect victims to be fat, middle-aged men'."

These headlines are based on a study that analysed a database containing information about nearly 600,000 people in the UK who had been diagnosed with a heart attack over a nine-year period.

Researchers were particularly interested in how a change in the initial and later diagnosis was associated with survival. Overall, a third of people were given the wrong diagnosis initially.

Factors associated with being given the wrong diagnosis were being elderly (over the age of 83), having heart failure and atypical test findings, and – surprisingly – being female. Men were about a third less likely than women to have the wrong diagnosis to start with.

However, this is only observational data. It doesn't look into each individual case and give reasons for the wrong diagnosis or the gender discrepancy, despite what The Sun says. It also can't be assumed that all of these cases are down to clinical errors.

Nevertheless, there is a definite need to now examine the possible reasons behind these results in more depth to ensure people receive the correct care and treatment they need as soon as possible, and maximise the chances of a good outcome.   

Where did the story come from?

The study was carried out by researchers from the University of Leeds and other institutions in the UK, and was funded by the British Heart Foundation and the National Institute for Health Research.

It was published in the peer-reviewed European Heart Journal – Acute Cardiovascular Care.

The study builds on previous work looking at whether clinicians were following best practice when dealing with non-ST segment elevation myocardial infarction (NSTEMI) type of heart attacks.

We discussed this research earlier this year.

The UK media's reporting of the study was generally accurate, but many of the headlines were speculative.

What kind of research was this?

This cohort study aimed to look at the impact of an initial diagnosis of a heart attack in hospital on outcomes.

There are different types of heart attack. The "classic" heart attack most people would be familiar with is medically called ST-elevation myocardial infarction (STEMI).

This is when the person has signs and symptoms of a heart attack, raised heart enzymes on blood test, and elevation of the ST segment on an electrocardiogram (ECG).

Non-ST elevation myocardial infarction (NSTEMI) is where the person similarly has the classic signs and symptoms and blood test findings, but lacks the ST elevation on ECG that indicates a heart artery has been completely blocked.

The two types of heart attack are managed slightly differently. If STEMI is diagnosed early enough, the person can be given clot-busting medication.

Sometimes immediate percutaneous coronary intervention (PCI), where a dye is injected to look at the heart arteries, is combined with breaking up the clot and putting in a flexible metal mesh called a stent to hold the artery open.

An NSTEMI is mainly managed with various medications, but coronary intervention may also be planned at an early stage.  

This cohort study used a large quantity of data from a research database to look at how the initial diagnosis – STEMI or NSTEMI – impacted survival.

What did the research involve?

The study used data from the Myocardial Ischaemia National Audit Project, which included data for 564,412 adults (average age 68, two-thirds male) with STEMI or NSTEMI treated across 243 NHS hospitals in England and Wales between 2004 and 2013.

The researchers used the audit registry to look at the socio-demographics, medical history, clinical presentation and management of these people, including acute treatment at presentation – for example, clot-busting drugs or PCI – and longer-term medications.

The initial diagnosis was given by the treating consultant or medical team. The researchers confirmed this by looking at the European Society of Cardiology, American College of Cardiology and American Heart Association guideline definitions.

They looked at how the diagnosis changed as a result of subsequent tests and findings.

The main outcome of interest was death from any cause one year after hospital discharge, specifically analysing the effect of age and gender.

What were the basic results?

Overall, 29.9% of the cohort (168,534) had the wrong diagnosis initially.

Characteristics associated with having a STEMI but being wrongly diagnosed initially (either NSTEMI or other chest pain) were ST-depression at presentation, older age (over 83), fast heart rate and having heart failure.

People who had been misdiagnosed often missed out on having immediate aspirin or clot-busting treatment.

Similarly, being an older age, having a fast heart rate and heart failure were also associated with people with NSTEMI being wrongly diagnosed initially. These people often missed out on having coronary angiography.

Men were also significantly less likely than women to be wrongly diagnosed initially.

Compared with women, men had 37% reduced odds of having a wrong diagnosis if they had a STEMI, and 29% reduced odds of being given a wrong diagnosis of NSTEMI.

Pre-hospital ECG was associated with a good chance of having the correct diagnosis.

At one year, the death rate for people with STEMI was 5.6%, compared with 8.4% among those wrongly diagnosed as NSTEMI initially.

NSTEMI patients had 10.7% mortality, but it was 25.5% for those who were not correctly diagnosed with NSTEMI initially.

Overall, however, after adjusting for other factors, having a STEMI and being wrongly diagnosed initially (either NSTEMI or other chest pain) was not associated with significant reduction in time to death.

For NSTEMI, being wrongly diagnosed as having a STEMI was associated with a 10% reduction in time to death (time ratio 0.90, 95% confidence interval [CI] 0.83 to 0.97), as was other initial diagnosis (0.86, 95% CI 0.84 to 0.88).

The researchers calculated that if the 3.3% of patients with STEMI and 17.9% of patients with NSTEMI who were given the wrong diagnosis had been diagnosed accurately, between 33 and 218 deaths a year might have been prevented respectively. 

How did the researchers interpret the results?

The researchers concluded that, "Nearly one in three patients with acute myocardial infarction had other diagnoses at first medical contact …

"There is substantial potential, greater for NSTEMI than STEMI, to improve outcomes through earlier and more accurate diagnosis of acute myocardial infarction." 

Conclusion

This valuable audit looks at nine years' worth of data from NHS hospitals, finding about a third of people with two forms of heart attack – STEMI and NSTEMI – are often wrongly diagnosed initially.

These people are less likely to receive the guideline-indicated treatments they need – and the delay in receiving correct treatment could have a harmful effect.

The study also highlights the factors associated with a wrong diagnosis, including being of an older age, having heart failure, and atypical findings for either diagnosis. Unexpectedly, gender was also associated with a wrong initial diagnosis for women.

The study's findings are based on a very large database and mortality data came from the Office for National Statistics, so information on patient characteristics, presentation and deaths is likely to be fairly reliable.

However, the data has a few limitations. As the researchers say, there was some missing information in some cases, such as timing of the blood test to check the heart enzymes.

They also didn't have much detail on those who were given initial diagnoses of "other" chest pain.

Additionally, the researchers excluded people who died in hospital because they were uncertain of the treatments they were given beforehand.

In doing this they may, as they acknowledge, have underestimated the effects of changing diagnosis because the risk of death from a heart attack is highest in the early stages.

Also, the database does not contain complete data for all people who have had a heart attack in the UK.

This is only observational data, and you can't look in-depth into each individual case and find out exactly why the person was diagnosed and managed in the way they were.

As such, it is difficult to pin definite causes on this and explain reasons for the wrong diagnosis and gender discrepancy.

It may be that because being a man is a known risk factor for heart attack, the diagnosis may be more likely to be missed in women or thought to be other things – but this shouldn't be assumed.

Neither should it automatically be assumed that all of these wrong diagnoses were down to errors on the part of the care system or health professionals.

For example, in some cases the person may have immediately received all the diagnostic examinations, tests and treatments indicated initially, but their condition, signs and symptoms may have evolved over time.

Nevertheless, there is a definite need to now examine the possible reasons behind these results in more depth to ensure people receive the correct care and treatment they need as soon as possible, and maximise the chances of a good outcome. 

You can reduce your risk of having a heart attack by having a healthy diet, maintaining a healthy weight, taking regular physical exercise within your limits, and stopping smoking.

Links To The Headlines

Third 'given wrong initial heart attack diagnosis'. BBC News, August 30 2016

Doctors failing to spot thousands of heart attacks in women – with fatal results. Mail Online, August 30 2016

Women suffering heart attacks 50 per cent more likely to be misdiagnosed, study finds. The Daily Telegraph, August 30 2016

Women 50% more likely to be misdiagnosed after heart attack – study. The Guardian, August 30 2016

Thousands of women with heart attack symptoms misdiagnosed – with fatal consequences. Daily Mirror, August 30 2016

Doctors miss heart attacks in women 'because they expect victims to be fat, middle-aged men'. The Sun, August 30 2016

Links To Science

Wu J, Gale CP, Hall M, et al. Impact of initial hospital diagnosis on mortality for acute myocardial infarction: A national cohort study. European Heart Journal – Acute Cardiovascular Care. Published online August 29 2016

Categories: NHS Choices

Pages