East Cambridgeshire District Council

“Parents will receive text message and email advice on how to bring up their children after David Cameron said it was ‘ludicrous’ that people get more training in driving a car,” the Daily Mail has reported.

The story, covered in much of the media, is based on the launch of a new interactive service providing information and advice to parents.

 

Why is this in the news?

Launched today by the prime minister David Cameron, the NHS Information Service for Parents gives mums, dads and parents-to-be advice on issues around staying healthy in pregnancy, preparing for birth and looking after their baby. It includes:

• advice via email and text messages (SMS)
• short film clips of advice from midwives and parents
• online advice from the NHS

 

Why has this service been launched?

The three initiatives are reportedly being launched because of the impact a child’s care early in life has on their health, behaviour and ability to learn throughout their lives. A 2010 Department for Education survey of 2,319 parents of under-threes, found that 85% wanted practical help with caring for their baby.

 

What can mums and dads and parents-to-be expect from the service?

The free Information Service for Parents emails and texts contain NHS-approved advice and will be sent every week from five weeks pregnant through to four weeks after the birth of your baby. Fathers-to-be can sign up for advice specifically aimed at them. The email and text service is expected to offer more advice for parents of older children in the future.

The videos available from the Information Service for Parents demonstrate practical advice for parents and parents-to-be, including:

• how much weight should I put on during pregnancy?
• what’s involved in a caesarean section?
• how do I know if I have postnatal depression? 
• how can I get my baby to sleep?

There are already around 670,000 visits per month to the pregnancy and baby webpages on NHS Choices.

 

How can I sign up to this service?

Visit www.nhs.uk/parents to sign up to the service or find out more information. Alternatively, you can sign up at a midwife appointment or at pregnancy, child or parenting support organisations such as NCT, as well as a host of websites.

 

What else has been announced for parents today?

The NHS Information Service for Parents was announced alongside a trial of free parenting classes for all parents of children aged five years and under in:

• Middlesbrough
• High Peak (Derbyshire)
• Camden (London)

Mums and dads will be able to use vouchers to pay for the parenting classes, which are being offered by a large group of children’s and parenting charities. These parenting class vouchers are available from Boots stores, children’s centres and health visitors.

The government has also launched a trial of subsidised relationship support sessions to help expectant mothers and fathers, and those with children up to the age of two. These sessions are being offered in York, Leeds, North Essex, Hackney and City of London, by Relate, The Tavistock Centre for Couple Relationships and the Fatherhood Institute. The sessions are set to include help with:

• managing new roles and responsibilities in your relationship
• dealing with the emotional impact of having a child
• learning negotiating and compromising skills
• balancing your role as a parent and as a partner
• coping with issues such as lack of sleep and mess

Links To The Headlines

No 10 guide to changing nappies and baby talk. The Daily Telegraph, May 18 2012

No 10 scheme will text and email parents with child-rearing tips from choosing baby names to changing nappies. Daily Mail, May 18 2012

Marriage counselling for tired new parents. The Independent, May 18 2012

“Dieting in pregnancy is good for you,” according to The Independent, while the Daily Mail has warned pregnant women not to eat for two since “piling on the pounds during pregnancy” increases the risk of complications.

Both these news stories are based on a study that compared ways to manage weight during pregnancy, but did not tell women to diet or look at the effects of overeating, as the headlines implied. Instead, the research reviewed previous studies to look at how diet, exercise or a combination of the two affected maternal weight gain and the risk of health problems for babies. In particular, it found that compared to other interventions such as exercise, following a diet plan (not a weight-loss diet) during pregnancy was more effective at reducing the amount of weight mothers gained. This had no adverse effect on the baby and reduced the risk of pre-eclampsia, diabetes, high blood pressure and premature birth.

This large study comes in the wake of concerns about the growing problem of obesity in pregnancy, which can cause serious problems for the mother and is a risk factor for later obesity in the child. It has found that dieting during pregnancy to maintain a healthy weight is safe, effective and has no effect on the baby’s birth weight, a factor which many woman worry about.

Currently, pregnant women are advised not to “eat for two” or reduce their calories, but to follow a healthy, varied diet with plenty of fruit and vegetables and a minimal intake of foods that are high in fat and sugar. Women who suspect they are overweight or obese are advised to talk to a dietitian, who will help them with a weight management programme.

 

Where did the story come from?

The study was carried out by researchers from several institutions in Europe, including Queen Mary University of London and the University of Birmingham. It was funded by the National Institute for Health Research’s Health Technology Assessment Programme.

Predictably, many newspapers made a meal of reporting this research, warning women not to “eat for two” even though women have been advised against doing this for several years now. The Metro’s headline that expectant mothers were being “urged to go on a diet” was also misleading. The study did not advise all women to follow a calorie-controlled diet but instead suggested that dietary interventions should be targeted at women who are obese or overweight. The paper’s photo of a pregnant woman holding weights was also misleading, since the study found diet to be more effective than exercise at reducing weight in pregnancy.

 

What kind of research was this?

This meta-analysis combined the results of randomised controlled trials which had looked at the effects of diet, exercise or a combination of the two on weight gain in pregnancy. Researchers also explored whether such interventions had any other effects during pregnancy and birth, and whether they affected the weight of the baby.

The researchers point out that obesity is a “growing threat” to women of childbearing age, with half the population being either overweight or obese. In Europe and the US, 20–40% of women gain more than the recommended weight during pregnancy. The researchers say that excessive weight gain during pregnancy is associated with adverse pregnancy outcomes, while for the children maternal obesity is a risk factor for obesity during childhood, which can persist into adulthood.

The authors argue that there is a need to identify safe and effective ways to help women manage their weight during pregnancy.

 

What did the research involve?

The authors analysed the results of 44 randomised controlled trials involving over 7,000 women.

They conducted searches of several electronic databases to find trials on the subject of pregnancy and weight. They also searched for relevant unpublished studies in sources of information such as conference databases. From these, they selected randomised controlled trials that tested the effects of dietary or lifestyle interventions on maternal and baby weight, as well as maternal and foetal outcomes.

The interventions in the trials were classified into three groups: mainly diet-based, physical activity-based, or based on both diet and physical activity. Studies were assessed for the quality of their design and methods to minimise the risk of bias.

The main outcome assessed was weight-related changes in the mother and baby, but researchers also looked at whether diet or exercise were associated with the risk of other critical pregnancy outcomes, including gestational diabetes, pre-eclampsia (a dangerous complication of pregnancy), premature delivery, stillbirth and shoulder dystocia (an emergency during childbirth where one of the baby’s shoulders becomes stuck behind the mother’s pubic bone). They summarised the strength of the evidence for these outcomes using an established system for grading evidence.

To explore possible further adverse effects, they undertook a separate search and review of the safety of diet and exercise in pregnancy, based on established methods. They analysed the data from the selected trials using standard statistical methods.

 

What were the basic results?

The researchers’ analysis included 44 randomised controlled trials involving 7,278 women, looking at the effects of diet, exercise or a combination of the two.

The researchers compared the outomes seen in women who were assigned interventions and women in control groups (who were not offered any interventions). They found that:

• Women who dieted, exercised or did both gained on average 1.42kg less than women in the control groups (95% confidence interval [CI] 0.95 to 1.89kg).
• Dieting, exercising, or doing both had no significant effect on the baby’s birth weight (mean difference -50g, 95% CI -100 to 0g), or whether babies were large or small for gestation age (the amount of time they had spent in the womb).
• On its own, physical activity was associated with a reduced birth weight of 60g on average (95% CI -120 to -10g).
• Diet, exercise, or both reduced the risk of pre-eclampsia (relative risk [RR] 0.74, 95% CI 0.60 to 0.92) and shoulder dystocia (RR 0.39, 95% CI 0.22 to 0.70), with no significant effect on other critically important outcomes.
• Dietary intervention resulted in the largest reduction in mothers’ weight gain during pregnancy. Compared with controls, women following dietary interventions were 3.84kg lighter and had better pregnancy outcomes than with other interventions (95% CI 2.45 to 5.22kg).

The overall evidence rating for the underlying studies was reported as low to very low for important outcomes such as pre-eclampsia, gestational diabetes, gestational hypertension and preterm delivery.

 

How did the researchers interpret the results?

The researchers concluded that diet and exercise can reduce maternal weight gain and improve outcomes for both mother and baby, with dietary intervention being the most effective. The diets in the trials included:

• a conventional balanced diet (based on an energy intake of 18–24kJ per kg of body weight)
• a low-glycaemic diet with unprocessed whole grains, fruits, beans and vegetables
• a diet with a maximum of 30% fat, 15–20% protein and 50–55% carbohydrate

Based on their findings, the researchers suggest that regular advice on planned nutritional intake should be provided to woman from early pregnancy onwards, targeting overweight and obese women who they say would benefit most.

 

Conclusion

This study has found that dieting during pregnancy to maintain a healthy weight is safe, effective and has no consequential effect on the baby’s birth weight, a factor which many women worry about.

It’s important to correct some of the inaccurate news coverage of this research. The research highlights the importance of eating healthily during pregnancy, but does not mean that all pregnant women should be put on diets. Nor does it recommend a reversal of the current advice that women should not eat for two, which has long been discouraged.

While putting on too much weight can affect a woman’s health and increase the risk of complications, gaining too little weight can also cause problems and mean the body is not storing enough fat. The current advice is not to go on a weight-loss or calorie-restricted diet during pregnancy, although a woman’s midwife or GP may have special advice if she weighs more than 100kg. Instead, current advice is based on eating a balanced diet and managing weight at an appropriate level. While it’s unlikely to make juicy headlines, the simple fact is that women should eat a normal amount and a balanced range of nutrients.

Weight gain in pregnancy varies greatly, although most pregnant women can expect to gain 8–14kg, most of it after week 20, as the baby grows and the body lays down enough fat to make breast milk after the baby is born. The medical team supporting a woman during pregnancy will monitor her changes in weight and diet, and will make appropriate suggestions to help her and her baby be as healthy as possible.

Links To The Headlines

Pregnant women should not 'eat for two'. The Daily Telegraph, May 18 2012

Mums-to-be urged to go on a diet rather than 'eat for two'. Metro, May 18 2012

Now dieting in pregnancy is good for you. The Independent, May 18 2012

DON'T eat for two: Piling on the pounds during pregnancy increases risk of diabetes and high blood pressure. Daily Mail, May 18 2012

Links To Science

Thangaratinam S, Rogozińska E, Jolly K et al. Effects of interventions in pregnancy on maternal weight and obstetric outcomes: meta-analysis of randomised evidence. BMJ 2012; 344

“Good cholesterol” doesn’t lower heart attack risk, the Daily Mail has reported.

A great deal of research has previously suggested that higher levels of “good” HDL cholesterol reduce your risk coronary heart disease, while higher levels of “bad” LDL cholesterol increase your risk of a heart attack. However, it has been hard to tell whether HDL cholesterol directly reduces coronary heart disease risk as other medical, biological or lifestyle factors could be involved. To get round this, researchers have conducted a complex study identifying genes that raise levels HDL cholesterol, and then in turn looking at whether carrying these genes influences heart disease risk.

Researchers first identified genetic variants associated with high HDL levels and tested for them in several thousand people, including some who had had a heart attack. They found that carrying these ‘HDL cholesterol genes’ had no effect on the risk of a heart attack. From this, the researchers concluded that there is no direct relationship between HDL cholesterol and coronary heart disease, and therefore that other factors must be involved.

This is a complex study that challenges the commonly held belief that having higher HDL cholesterol will reduce heart attack risk. However, as it only looked at a particular set of genetic variations, it cannot provide the whole answer and tell us whether HDL cholesterol does or does not affect coronary heart disease, and how this effect might come about. An important question is whether things that increase HDL cholesterol levels during our lifetime (i.e. after our genetics are determined), such as exercise and certain medications, can then improve our heart disease risk.

 

Where did the story come from?

The study was carried out by researchers from Harvard Medical School and was funded by the US National Institutes of Health, Wellcome Trust, European Union, British Heart Foundation and German Federal Ministry of Education and Research. The study was published in the peer-reviewed medical journal The Lancet.

The media generally oversimplified what is a complex analysis. Also, captions referring to cholesterol intake through diet have no direct relevance to this research, which examined the genetic factors that determine HDL cholesterol levels and not the influence of dietary sources.

 

What kind of research was this?

There are two broad types of cholesterol in the body that are each associated with altered risk of cardiovascular problems: high-density lipoprotein (HDL) and low-density lipoprotein (LDL). LDL cholesterol is often referred to as “bad” cholesterol, as research has found that raised levels of LDL are associated with an increased risk of heart attacks. Conversely, previous observational studies have tended to show that people with higher levels of HDL (“good”) cholesterol have a lower risk of coronary heart disease (CHD).

However, it is difficult to prove that HDL cholesterol directly lowers people’s risk of CHD. For example, other factors in a person’s health and lifestyle might influence both HDL levels and CHD risk, so could be responsible for the apparent relationship between the two.

This study used a complex genetic analysis concept, called “mendelian randomisation analysis”, to investigate the relationship between genes, HDL cholesterol and CHD. Broadly speaking, Mendelian randomisation analysis looks at whether genetics that determine one factor (such as HDL cholesterol levels) are directly associated with the risk of an outcome (such as heart disease).

In this case, the researchers considered the theory that if increased HDL directly reduces CHD risk, then carriers of genetic variants that confer a high concentration of HDL cholesterol should have a reduced risk of CHD. If genetic determinants of HDL cholesterol had no relationship to CHD risk, then there isn’t a causal relationship between the two and other factors are likely to be involved.

This mendelian analysis has the important limitation that in looking at purely genetic factors, it does not look at how environmental, health and lifestyle factors then influence both HDL levels and CHD risk - basically, all the other things in our lifetime that occur after our genetics are determined at conception.

 

What did the research involve?

The researchers first identified a certain rare form of a gene called the endothelial lipase gene (LIPG Asn396Ser). This particular form of the gene, carried by about 2.6% of the population, was associated with levels of HDL cholesterol. Carriers of this gene variant had consistently higher levels of HDL (good) cholesterol compared to non-carriers, but no difference in their levels of LDL (bad) cholesterol or other blood fat levels. Based on the influence that carrying this LIPG variant had on HDL cholesterol levels, the researchers calculated that if the relationship between HDL cholesterol and CHD was causal, then they would expect carriers of this variant to have a 13% reduced risk of CHD.

To test whether carrying the gene variant had this great an effect, they used a case-control study that included 20,913 people who had had a heart attack (the cases) and 95,407 control participants. They examined whether, as they expected, carriers of the variant had around a 13% reduced risk of being among the cases and to have had a heart attack.

In another part of the study, they examined further gene variants in what they called a “genetic score”. They identified the 14 gene variants that were most commonly associated with HDL cholesterol levels, and the 13 gene variants that were most commonly associated with LDL cholesterol. They tested these variants in a further 12,482 cases who had had a heart attack and 41,331 controls.

 

What were the basic results?

Carriers of the LIPG genetic variant (Asn396Ser) had HDL cholesterol levels that were slightly higher than people who did not carry this gene (about 0.14mmol/L higher). However, while this led researchers to  expect that people carrying this variant would have around a 13% reduced odds of having had a heart attack, they found that carrying this variant had no significant effect on risk of a heart attack (odds ratio [OR] for heart attack 0.99, 95% confidence interval [CI] 0.88 to 1.11).

Following this phase, the researchers looked at a person’s carriage of up to 14 variants that were associated with higher HDL cholesterol levels. They once again found that an increased ‘HDL genetic score’ was not significantly associated with odds of having a heart attack. However, when they examined the LDL genetic score (based on a person’s carriage of up to 13 variants associated with higher LDL cholesterol levels), they found that this was associated with increased odds of having a heart attack (OR 2.13, 95% CI 1.69 to 2.69). In short, genetic variants that increased a person’s LDL cholesterol level were associated with higher CHD risk, as expected.

 

How did the researchers interpret the results?

The researchers concluded that certain genetic variants that raise blood HDL cholesterol do not seem to be related to the risk of heart attacks. They said that this data “challenges the concept” that raising HDL cholesterol levels will directly translate into reduced risk of a heart attack.

 

Conclusion

Previous research has tended to show that HDL cholesterol is “good” for you and higher levels reduce your risk coronary heart disease, while LDL cholesterol is “bad” for you and higher levels increase your risk of a heart attack. This complex research aimed to avoid the problem of the influence of other medical, biological or lifestyle influences by concentrating on genetics linked to HDL cholesterol and how closely they related to the risk of heart disease. If HDL cholesterol is directly related to CHD risk, then genes associated with high HDL levels should be directly associated with lower heart attack risk. Researchers carried out their study based on the theory that because our genetics are randomly assigned, participants can be considered to be randomly allocated to their circumstances and, therefore, equal.

However, the research did not find that HDL genetics determines the risk of heart disease. Instead, the gene variants that were associated with higher HDL cholesterol levels had no association with heart attack risk. This suggests that there may be no direct relationship between HDL cholesterol and coronary heart disease and, therefore, that other factors must be involved.

When the researchers examined gene variants that caused a person to have higher LDL (“bad”) cholesterol levels, they found that carriers of these variants were more likely to have had a heart attack than people without the variants. This would suggest that there is a direct causal relationship between LDL cholesterol and coronary heart disease, but not HDL cholesterol.

This is a complex study that challenges the commonly held belief that having higher HDL cholesterol will reduce heart attack risk. However, this study alone cannot provide the whole answer and tell us whether HDL cholesterol has any effect at all on coronary heart disease, and how this effect might be medicated. Also, only a few gene variants were examined and there may be many other genetic influences on HDL cholesterol and other blood fats.

Importantly, while our genetics are determined at conception, the environment that we live in for the remainder of our lives is likely to have an influence. Therefore, it is not possible to say how much our genetics influence our cholesterol compared with the many other risk factors for heart disease (such as diabetes and lifestyle factors including smoking, alcohol and exercise). Exercise in particular is thought to raise HDL levels during our lifetime, regardless of our genetic assignment at conception. This study cannot tell us how raising HDL cholesterol levels in adult life could influence coronary heart disease risk.

Analysis by Bazian

Links To The Headlines

'Good' cholesterol is not so great for you as study finds it doesn't lower heart attack risk. Daily Mail, May 18 2012

Eating 'good cholesterol' could be a waste of time. Metro, May 18 2012

Links To Science

Voight BF, Peloso GM, Orho-Melander M, et al. Plasma HDL cholesterol and risk of myocardial infarction: a mendelian randomisation study. Lancet. Published online May 17 2012

Everyone over the age of 50 should be given statins because the “cholesterol-busting” drugs reduce the risk of a heart attack even in healthy people, according to the Daily Telegraph and many other newspapers.

The story is based on a systematic review of 27 studies that looked at the effect of lowering “bad” cholesterol (low-density lipoprotein or LDL) using statin therapy in 175,000 people. It found that for every reduction in cholesterol of 1.0mmol/L, taking statins reduced the risk of heart attacks, strokes and other “major vascular events” by about a fifth (21%), even among people without vascular disease or who were at low risk of developing it.

Current guidelines recommend prescribing statins for people who have at least a 20% chance of developing cardiovascular disease within 10 years. Doctors normally calculate this risk by looking at a range of factors including the patient’s age, blood pressure, cholesterol levels, whether they smoke and whether they have diabetes.

This large review of studies suggests the cholesterol-lowering drugs are suitable for people who don't have heart or vascular disease and those who are not considered at high risk of developing it. The 21% reduction in risk of heart disease and stroke sounds impressive.

However, the number of people who stand to benefit from statins gets smaller as the risk threshold for treatment is reduced. For example, one thousand people at low risk would need to be treated (have a 1mmol/L reduction in bad cholesterol) for five years for 11 of them to benefit. This suggests that someone at low risk may wish to consider whether the possible benefit of taking statins would outweigh the inconvenience.

An editorial accompanying the review argues that the current guidelines should be revised so that age is used as an indicator for taking statins (over 50 years old), rather than using expensive screening tests. The commentary forms part of a running debate as to whether middle-aged people without any known risk of cardiovascular disease should be “medicated”, and, if so, how much (whether with statins, aspirin or a “polypill”, as previously suggested).

 

Where did the story come from?

The study was carried out by researchers from Oxford University and the University of Sydney. It was funded by several institutions including the British Heart Foundation, the UK Medical Research Council and Cancer Research UK. The study was published in the peer-reviewed medical journal The Lancet.

The study – in particular the commentary arguing for all over-50s to take statins – was covered widely and accurately in most of the media.

 

What kind of research was this?

This was a meta-analysis of individual patient data from 27 trials, which looked at the effects of lowering LDL cholesterol with statin therapy. It included trials of people without vascular disease or at low risk of cardiovascular disease.

The authors pointed out that their previous analysis of studies suggested that statin therapy to reduce LDL cholesterol in people without a history of vascular disease ultimately reduced their risk of heart attacks and strokes by about a fifth. However, uncertainty remains as to whether statins have an overall “net benefit” in this group, given that they are at low risk to begin with. The authors said that at least half of all heart attacks and strokes (vascular events) occur among individuals without previous disease.

The authors said they have now taken individual patient data from each trial within the database, allowing a more complete assessment of the effects of lowering LDL cholesterol in low-risk individuals.

 

What did the research involve?

The researchers conducted a meta-analysis of data from 175,000 participants in 27 randomised trials, to explore the effects of lowering LDL cholesterol with statin therapy. Trials were included if:

• they included at least one treatment where the main effect was to lower LDL cholesterol
• there were no other differences in treating risk factors
• at least 1,000 participants were recruited for a duration of at least two years’ treatment

The “major vascular events” the researchers looked at included heart attacks and deaths from heart attacks, strokes and coronary revascularisations (surgery to unblock coronary arteries). They also looked at rates of cancer and the cause of any death that occurred.

They grouped the participants into five categories depending on their risk of a vascular event within five years and compared those taking a statin with control groups or with group taking a lower-dose statin. The risk categories were:

• less than 5%
• 5% to less than 10%
• 10% to less than 20%
• 20% to less than 30%
• 30% or more

The researchers analysed the results using standard statistical methods.

 

What were the basic results?

The researchers found that:

• Reducing LDL cholesterol with a statin reduced the risk of major vascular events (relative risk [RR] 0.79, 95% confidence interval [CI] 0.77 to 0.81 per 1.0 mmol/L reduction), largely irrespective of age, sex, baseline LDL cholesterol or previous vascular disease, and of vascular mortality and all-cause mortality.
• The reduction in major vascular events was at least as big in people in the two lowest risk categories as those in the higher risk categories.
• For strokes, the reduction in risk in participants with a five-year risk of major vascular events lower than 10% (RR per 1.0 mmol/L LDL cholesterol reduction 0.76, 99% CI 0.61 to 0.95) was also similar to that seen in higher-risk categories.
• In participants without a history of vascular disease, statins reduced the risks of deaths from vascular disease and any other cause (RR 0.91, 95% CI 0.85 to 0.97).

There was no evidence that reducing LDL cholesterol with a statin increased cancer incidence, death from cancer, or deaths from other non-vascular causes.

 

How did the researchers interpret the results?

The researchers calculated that in people with a five-year risk of major vascular events lower than 10%, each 1mmol/L reduction in LDL cholesterol produced an absolute reduction in major vascular events of about 11 per 1,000 over five years. They said this benefit “greatly exceeds any known hazards of statin therapy”.

They also pointed out that, under present guidelines, such individuals would typically not be regarded as suitable for statin therapy.

They concluded: "The present report shows that statins are indeed both effective and safe for people with a five-year risk of major vascular events lower than 10% who would typically not be judged suitable for statin treatment … and, therefore, suggests that treatment guidelines might need to be reconsidered."

 

Conclusion

Current guidelines recommend statins for people who have a 20% or greater chance of developing cardiovascular disease within 10 years. This large review of studies, which further assessed previous research, suggests they may also benefit those without existing cardiovascular disease and those who are not considered at high risk of developing it.  However, the individual benefit for those at low risk may be small.

Although the study looked at whether statins increased the risk of cancer and death from other causes, it did not include possible adverse effects. Statins are safe drugs that have been associated with a small risk of side effects. As the authors stated, the risk of side effects when giving statins to everyone over the age of 50 would have to be taken into account when calculating the overall benefit.

Current guidelines on statin therapy from the National Institute for Health and Clinical Excellence (NICE) will reportedly be updated soon, at which point NICE will take this and any other new evidence into account.

There is good existing evidence that a healthy lifestyle (including regular exercise, stopping smoking and a healthy diet) are important factors in cardiovascular health. This study helps answer previous uncertainty about whether apparently healthy individuals could benefit from taking statins.

Links To The Headlines

Give statins to everyone over 50. Daily Express, May 17 2012

NHS 'should consider giving statins to healthy people'. BBC News, May 17 2012

Statins could benefit health of millions. The Guardian, May 17 2012

All over 50s should be taking statins. The Daily Telegraph, May 17 2012

Statins 'could benefit the healthy'. The Independent, May 17 2012

Why EVERYONE over 50 needs to be taking statins: Cholesterol-busting pills cut risk of heart attack or stroke. Daily Mail, May 17 2012

Links To Science

Cholesterol Treatment Trialists' Collaborators. The effects of lowering LDL cholesterol with statin therapy in people at low risk of vascular disease: meta-analysis of individual data from 27 randomised trials. The Lancet, May 17 2012 (published online)

The Daily Telegraph boldly and erroneously reports that “women really do have a 'gaydar' which allows them to tell someone's sexuality 'in the blink of an eye'”, while the Sun informs us that “most people have a ‘gaydar’”.

This story is based on a study that looked at how accurately people can judge someone’s sexual orientation from their face. In two experiments, researchers investigated how accurately US college students judged whether someone was ‘gay’ or ‘straight’ after quickly glancing at a photo. The research found that students were able correctly to determine sexual orientation slightly more often than could be put down to chance. It found that students were able to identify a woman’s sexuality correctly 65% of the time, and a man’s sexuality correctly 57% of the time. The research suggests that people may unconsciously make judgements about sexual orientation when seeing a face for the first time.

Based on this study, the headline that "most people have a gaydar" is misleading. Limited conclusions can be drawn from this small and highly artificial study as accuracy was only just better than chance. In order to draw firm conclusions, larger studies that include people of different ages and from different backgrounds are required. The type of study used does not consider the influence of other factors that could contribute to how a person makes quick decisions about another person’s sexuality and it is not clear whether quick judgements about a person’s sexuality occur in real life.

It is important to note that guessing another person’s sexuality may be a sensitive area. This study does not explore the consequences of making quick judgements about another person’s sexuality. It does show that a subjective snap judgement of someone’s sexuality based on their appearance has a good chance of being wrong. Making decisions on such snap judgements is ill advised, even if you think you have a great ‘gaydar’.

 

Where did the story come from?

The study was carried out by researchers from the University of Washington and Cornell University, US. It was funded by grants from the US Association for Psychological Science, Cornell University’s Einhorn Family Charitable Trust Endowment, the Cognitive Science Program, and the College of Arts and Sciences. The study was published in the peer-reviewed online journal Public Library of Science (PLoS) ONE.

This study was picked up by a variety of papers and online media and most had attention-grabbing headlines like “gaydar exists”. Apart from the overblown headlines, the Daily Mirror and the Sun reported the details of the study accurately. However, both The Daily Telegraph and Metro misleadingly suggest that the research showed women could judge another person’s sexuality better than men. In fact, the research showed that people were better able to judge whether women were gay or straight, not that women were better able to judge sexuality.

 

What kind of research was this?

This was an observational study that aimed to investigate how people make a judgement about someone’s sexuality based on their face. This was a relatively small study that only investigated the judgements of college students from one US university.

Previous research has indicated that there are two ways in which a person perceives a human face – “featural processing” and “configural processing”:

• featural processing involves looking at facial features such as the nose or eyes
• configural processing involves looking at the relationship between facial features, such as the distance between the eyes

 

What did the research involve?

Researchers undertook two experiments. In the first experiment, they recruited 24 University of Washington students (19 women) in exchange for extra course credits. The students viewed 96 photos of young adult men and women who identified themselves as gay or straight. The participants categorised each face as either straight or gay as quickly and accurately as possible. The photographs were of “white-looking” faces of people reportedly aged 18–29 gathered from Facebook. They included individuals living in 11 major US cities. Photographs were digitally altered to remove hairstyles so that only faces were visible. Faces with facial hair, make-up, glasses and piercings were excluded so as to limit any potential prejudice. Photos were flashed up on a screen for 50 milliseconds (approximately a third of the time it takes to blink the eye).

In the second experiment, comprising 129 students (92 women and 37 men), participants were randomly assigned to judge faces that were either upright or upside down. This experiment was designed to judge whether ability to read sexual orientation depends on configural processing (the relationship between features).

Results were analysed using statistical methods to determine whether the results were achieved by accurate judgement or whether similar results could have occurred by chance.

 

What were the basic results?

The main finding of this small study was that students were able to determine sexual orientation from glancing at a photo more often than could be put down to chance. (By chance alone it is assumed that people would be correct 50% of the time, like the toss of a coin.) It found that, in the first experiment students were able to identify the sexuality of women’s faces 65% of the time, while they were correct 57% of the time when viewing men’s faces. In the second experiment, the researchers found that when the picture was glanced at upside down, the success rate was less accurate (61% for women and 53% for men).

The researchers report that the increase in accuracy for judging upright faces suggests that the ability to read sexual orientation from men’s and women’s faces relies on configural face processing (relationships of facial features) as well as featural face processing (facial features). They say the results also indicate that reading sexual orientation from faces of women is easier than from faces of men.

 

How did the researchers interpret the results?

The researchers conclude that configural face processing significantly affects a person’s perception of sexual orientation and that sexual orientation is easier to detect in women’s faces than men’s faces.

The lead researcher, Joshua Tabak, is reported as having said that "we were surprised that participants were above-chance judging sexual orientation based on upside down photos flashed for just 50 milliseconds, about a third the time of an eyeblink". He went on to say that “people of older generations or cultures where homosexuality is not recognised may find it harder to make ‘gaydar’ judgments”.

 

Conclusion

This small study, carried out in highly artificial conditions, shows that students were able to judge sexuality with greater accuracy than could be put down to chance, and that women’s sexuality was judged more accurately than men’s sexuality. Despite these findings, the study should not be misinterpreted to mean that women are better at accurately judging a person's sexuality than men.

The participants' judgement was only just better than the results that could have been expected to have been achieved by chance and larger studies that include people of different ages and backgrounds are required to verify these results.

It is important to note that, in this study, students were instructed to make forced decisions about a person’s sexuality. It is unclear whether these quick decisions are made in real life situations. In addition, this study does not explore the consequences of making quick judgements about another person’s sexuality.

Guessing another person’s sexuality can be a sensitive area. This study highlights the importance of not making snap decisions based on your own subjective judgement of someone else’s sexuality because of the high chance that you may be wrong.

It is also worth noting the inaccurate reporting in both The Telegraph’s and Metro’s stories on this research. While the Mirror and the Sun also featured exaggerated headlines, their reporters did a better job of presenting the research.

Analysis by Bazian.

Links To The Headlines

Gaydar exists: we can tell who is gay and who is straight in the blink of an eye. Daily Mirror, May 18 2012

Gaydar quick as eye's blink. The Sun, May 18 2012

Study claims females really do have a 'gaydar'. Metro, May 18 2012

Women really do have a 'gaydar'. The Daily Telegraph, May 18 2012

Links To Science

Tabak JA, Zayas V. The Roles of Featural and Configural Face Processing in Snap Judgments of Sexual Orientation. PLoS One. Published online May 16 2012

“NHS ban on pill to treat prostate cancer is lifted,” the Daily Express has said, while the Daily Mail has warned that a “prostate cancer wonder drug” was set for approval “south of border but turned down by Scotland”. The stories focus on the fact that the prostate cancer drug abiraterone may soon be available on the NHS in certain circumstances.

These stories are based on a revised decision on draft guidance published by The National Institute for Health and Clinical Excellence (NICE), which makes recommendations about which treatments should be available on the NHS in England and Wales. It recommends that abiraterone (brand name Zytiga) be made available for the treatment of advanced prostate cancer that has not responded to chemotherapy.

Previous draft NICE guidance published in February rejected the use of abiraterone, concluding that it was not cost-effective. The new draft guidance has reconsidered this decision following an offer from the drug manufacturer to make the drug available at a lower price to the NHS.

The Scottish Medicines Consortium (SMC), which advises NHS bodies in Scotland about the status of new treatments, published guidance in March that rejected making abiraterone available. The SMC is currently considering further evidence and is due to publish further guidance this summer.

 

What is abiraterone used for?

Abiraterone is a type of hormone therapy for cancer that has spread beyond the prostate to other parts of the body (metastatic prostate cancer). It is a tablet taken once a day in combination with a steroid drug (prednisolone or prednisone), which reduces inflammation.

Hormone treatments for prostate cancer aim to block the production of certain male hormones (androgens) that stimulate prostate cancers to grow. Although there are already hormone treatments for prostate cancer, the new drug works in a different way by blocking cytochrome P17, an enzyme that enables the body to make androgens.

Abiraterone was licensed by the European Medicines Agency (EMA) in September 2011. After price changes made the drug more affordable, NICE guidance recommended abiraterone for use within certain circumstances. NICE said it is suitable is for men with:

• metastatic prostate cancer that has not responded to castration (either surgical where the testes are removed, or where medical treatments are used to block male hormones); and
• metastatic prostate cancer that has not responded to a chemotherapy regimen that contains docetaxel (a chemotherapy drug licensed for hormone-resistant prostate cancer)

NICE added that abiraterone should be used in combination with the anti-inflammatory drug predisnolone (or prednisone) in both these cases.

Alternative treatment options for men with metastatic prostate cancer, whose disease still progresses after treatment with docetaxel, include a drug called mitoxantrone, supportive care and re-treatment with docetaxel (which is not recommended in current NICE guidance).

 

How effective is it?

NICE has concluded that abiraterone is an effective second-line treatment for advanced (metastatic) prostate cancer.

Evidence for its effectiveness comes from a large randomised controlled trial carried out in 13 countries including the UK, from May 2008 to April 2009. The trial aimed to find out how well abiraterone worked for men who had already had other types of hormone therapy and chemotherapy for advanced prostate cancer.

One group of men in the trial took abiraterone once a day together with prednisolone, while the other group took a placebo plus prednisolone.

A primary analysis of the results showed that, on average, men who had abiraterone survived about four months longer than those in the placebo group (14.8 months compared with 10.9 months, hazard ratio 0.65, 95% confidence interval 0.54 to 0.77). The trial was stopped early once the benefits of the drug became clear.

The study also included analysis of a subgroup that had received one course of chemotherapy only (as opposed to more than one). It found that in this group, men who took abiraterone lived significantly longer than men who took the placebo (17.0 months compared to 11.7 months, hazard ratio 0.71, 95% confidence interval 0.60 to 0.86). NICE said that this group is likely to be treated with abiraterone in clinical practice and would have better treatment outcomes because they had less advanced disease.

Experts also told NICE that the most important benefits were extension to life and improved quality of life, including less pain and improved mental and physical health. NICE also concluded that the drug has the benefit of being in tablet form, which means patients can take it at home. It added that abiraterone is generally safe and any adverse reactions were tolerable.

 

Why was the drug previously turned down by NICE?

NICE had previously said that abiraterone should not be made available on the NHS because it was not cost-effective. NICE uses a measure called the quality-adjusted life year (QALY) to assess the value for money of a medical intervention. QALY is based on the number of years of life that would be added to a patient’s life, as well as the improvement in the quality of their life in that time added by any treatment. Each year of life is assigned a value.

NICE had previously said that although the drug had survival benefits, it did not feel the drug provided enough benefit to patients to justify the price the NHS was being asked to pay, even with an (undisclosed) discount on the list price then offered by the manufacturer, Janssen. It concluded that the most plausible cost per quality adjusted life year would be at least £63,000.

The list price of abiraterone is £2,930 for a 30-day supply of 120 tablets.

It also said that the drug did not meet its criteria for an end-of-life treatment as it did not consider the population for which the drug is licensed to be small.

 

What has changed now?

The manufacturer of abiraterone, Janssen, has offered the NHS a further undisclosed discount on the list price of the drug. Janssen also offered further information on which patients would benefit most (the subgroup who received only one course of chemotherapy), and clarified how many patients would receive the drug as an end-of-life treatment.

This has enabled NICE to conclude that the plausible cost per quality adjusted life year for this subgroup would be less than £50,000. In coming to this revised figure, NICE also took into account that abiraterone has other quality-of-life benefits, such as being an oral drug. It also meets the criteria for an end-of-life treatment which are:

• it would be used for men who would have a short life expectancy without treatment - less than 24 months 
• providing treatment would provide at least three months extension to life.

 

Is it definitely going to be made available?

NICE will now consult with interested parties on the new draft guidance recommending abiraterone, before it makes a final decision in June. Until then, NHS bodies are advised to make decisions locally on the funding of specific treatments.

Links To The Headlines

Prostate drug abiraterone 'set for NHS use'. BBC News, May 16 2012

England benefits from NHS postcode lottery at long last - as prostate cancer wonder drug looks set for approval south of border but not in Scotland. Daily Mail, May 16 2012

Prostate cancer: health watchdog reverses NHS guidance on drug. The Guardian, May 16 2012

Nice 'to reverse ban on prostate cancer drug'. The Daily Telegraph, May 16 2012

NHS ban on pill to treat prostate cancer is lifted. Daily Express, May 16 2012

         

Links To Science

NICE. Prostate cancer (metastatic, castration resistant) - abiraterone (following cytoxic therapy): final appraisal determination guidance. Published May 16 2012

Revolutionary surgery has given a paralysed man the ability to move his arms and hands again, it has been widely reported. The surgery, which made global news, has shown that rewiring nerves may allow surgeons to restore basic arm and hand control after serious spinal cord injuries.

A 71-year-old patient had been left paralysed from the neck down after the base of his neck was injured in a traffic accident. In a world first, surgeons were able to successfully bypass the injury site by grafting arm nerves from below the injury to nerves originating above the site of his injury. The surgery was given 23 months after his accident, and after several more months of therapy and training the man can handle objects, feed himself and even do basic writing.

This success story is clearly of massive significance to the man involved but also provides a blueprint for other surgeons around the country for how this technique may be applied in similar situations.

However, despite this fantastic success, it is important to bear in mind that this was an individual case, and it is not clear whether this technique will be equally successful in other patients with different types of spinal injuries or circumstances. The severity and location of the spinal cord injury are likely to be important factors in the success of this type of operation.

 

Where did the story come from?

The research was detailed in a report written by researchers from the Division of Plastic and Reconstructive Surgery and the Department of Neurological Surgery at Washington University School of Medicine in St Louis, Missouri in the US. The case report was published in the peer-reviewed Journal of Neurosurgery. The report did not specify any sources of funding for the research.

This story received widespread media coverage and many papers reported on the restoration of function in a previously paralysed man. The coverage of the story was generally well balanced and reflected the case report accurately.

 

What kind of research was this?

This case report described a surgical technique designed to restore nerve function to the arms and hands of a 71-year-old man who had been injured in a road traffic incident and left paralysed. The patient had experienced severing of the spinal cord at the top of his spine, causing him to be paralysed below the site of his injury. This meant the paralysis affected his arms and hands, as the nerves that control the arms are situated below the site of his spinal cord damage.

In this cutting-edge research surgeons created a 'nerve bypass' by grafting a working nerve originating in the spine above the injury site to the nerves in the lower arm originating below the injury site to restore some level of control lost following the injury.

Spinal cord injury (SCI) is devastating for the individuals affected and their families. Recovery from a complete SCI is rare, leaving most patients with significant permanent disability affecting the area below the site of the SCI. Despite advances in understanding the processes that occur in short- and long-term SCI, corresponding advances in surgical techniques or applications to repair them have so far lagged behind.

Case reports are often published that share interesting developments or new techniques in a particular medical field, in this case surgery. Case reports provide a detailed description of the background of a single person and the treatment they received, along with how effective the particular treatment course has been. They do not necessarily reflect what will be seen in all patients treated with the same techniques in the future, but still provide a good insight into new or experimental techniques.

 

What did the research involve?

The right-handed 71-year-old man presented to a surgical department 22 months after he was injured in a motor vehicle accident. He had sustained a spinal injury to the lower part of his neck, called the C7 vertebra. This caused extensive paralysis below the injury site. The strength and mobility of his limbs were extensively assessed to see if surgery might be able to help. Before surgery, he could flex his right wrist only weakly and could not pinch or grip with either hand. He could also not move his fingers on either hand.

A month after his initial assessment, the patient had surgery on both arms in a bid to restore some of the function of his hands. This was based on the concept that a working nerve originating in the spine above the injury site could be grafted onto the nerves in the lower arm to restore some of the control lost after the injury.  The 'nerve transfer' surgical technique involved taking a working nerve in the upper arm that originates from the C6 vertebral level (above the site of the injury), and joining it to the nerve system in the arm that originates from the C7 vertebra (the site of the injury).

This 'nerve rewiring' allowed working nerves above the spinal injury site to artificially connect with nerves below the injury site, which were previously unable to receive a signal due to the injury. Nerve transfer for spinal injuries is not new, but its application has so far been relatively limited.

After the surgery, the patient received continued hand physiotherapy to aid recovery and rehabilitation of the wasted hand muscles due to the injury.

 

What were the basic results?

During the operation, the surgeons stimulated the newly rewired nerves to check they were working and found that the nerve responses were essentially normal for the rewired nerves feeding the hand.

Eight months after the operation, the patient was able to move his left thumb and perform a pinching motion with his fingers and thumb in his left hand. The same increase in movement was achieved in the right hand after 10 months.

The authors report that he can now use his right hand to perform simple 'hand to mouth movements', and with his left hand he can feed himself and perform rudimentary writing activities. Recovery in the right hand has been slower than in the left.

Videos made available by the study group show that the man is now able to handle a ball with both hands, touch his fingers against his thumb in a pinching motion and feed himself. These were all activities he could not do before the surgery.

 

How did the researchers interpret the results?

The researchers said that, to their knowledge, this is the first reported case of restored nerve control of the thumb and finger flexing movement after a spinal cord injury.

They also said the patient’s 'function has improved significantly with his ability to feed himself'.

 

Conclusion

This case report represents the positive experience of a paralysed 71-year-old man who has been granted some manual control after a serious spinal injury to his neck. Before surgery, he could only make minimal arm movements controlled by the nerves above his injury site, but no lifting or fine hand movements as they are controlled by nerves joined lower down the spine, below the site of his injury.

While the nerve transfer technique given to this patient is not new, its application is not widespread and the authors say this is the first time it has been used to successfully rewire the nerves supplying a hand. Furthermore, these gains occurred after surgery that was carried out 23 months after the injury was sustained. This suggests that surgery does not have to be performed immediately, and that it may be possible to carry out the technique in people who have been paralysed for some time.

In addition to the hugely significant benefits to the man involved, this success story has also created a blueprint for other surgeons around the country for how this technique may be applied in similar cases.

However, it is important to bear in mind the limitations of the surgery and the evidence of its effectiveness. This case report represents the experience of just one individual. Therefore, it is not clear whether this technique will be equally successful in other patients with different types of injuries or circumstances. The severity and location of the spinal cord injury are likely to be important in determining the relative success of this type of operation. Also, the level of strength and control achieved in this case did not appear to represent a complete restoration of arm function, although it was clearly still a massive improvement.

Analysis by Bazian. Edited by NHS Choices.

Links To The Headlines

Prostate drug abiraterone 'set for NHS use'. BBC News, May 16 2012

For once England benefits from NHS divide as Nice set to approve prostate cancer drug turned down by Scotland. Daily Express, May 16 2012

Prostate cancer: health watchdog reverses NHS guidance on drug. The Guardian, May 16 2012

Prostate drug u-turn by NICE. The Daily Telegraph, May 16 2012

Nice 'to reverse ban on prostate cancer drug'. The Daily Telegraph, May 16 2012

NHS ban on pill to treat prostate cancer is lifted. Daily Express, May 16 2012

Links To Science

Mackinnon SE, Yee A, Ray WZ. Nerve transfers for the restoration of hand function after spinal cord injury. Journal of Neurosurgery, Published online May 15 2012.

New research has mapped the way that MRSA “superbug” bacteria spread, BBC News has reported. The results suggest that antibiotic-resistant bacteria may often spread from large, inner-city hospitals to smaller regional ones when patients are transferred.

The way that superbugs spread has been researched as part of an intricate study conducted by Scottish researchers, who looked at samples taken across the UK over 53 years. The researchers used genetic techniques to scan patterns and mutations within the various samples and to build up a “family tree” showing how a particular strain (called EMRSA-16) has spread between different hospitals across the country. They found that EMRSA-16 has generally spread by transmission from hospitals in large population centres in London and Glasgow to regional healthcare settings. The researchers suggested that patients’ referrals are an important cause of the spread of this bug across the country.

This type of study can provide useful estimates of transmission routes of MRSA, although there is still a need for further research incorporating a larger number of sampled hospitals to determine the wider UK pattern.

MRSA can be prevented through effective hand washing and screening before hospital admission. Find out more about preventing MRSA.

 

Where did the story come from?

The study was carried out by researchers from the University of Edinburgh and was funded by various research grants, as well as US governmental organisations including the National Institute of Allergy and Infectious Diseases, the National Institutes of Health and the Department of Health and Human Services. The study was published in the peer-reviewed journal Proceedings of the National Academy of Sciences USA (PNAS).

The story was covered accurately by BBC News.

 

What kind of research was this?

This study used genetic analysis of bacteria samples to map the way a particular form of MRSA spread between patients and hospitals across the UK. It collected information from infected patients in the UK over 53 years and looked at the emergence and transmission of EMRSA-16, a major clone (type) of MRSA. The study identified genetic elements and mutations of EMRSA-16 that allowed it to spread between patients and hospitals across the county.

MRSA (meticillin-resistant staphylococcus aureus) is a type of bacterial infection that is resistant to a number of widely used antibiotics. It is often referred to as a “superbug”. MRSA infections are more common in hospitals because patients often have an entry point, such as a surgical site, which allows the bacteria to enter the body. Also, bacteria can easily spread through direct contact with other patients and staff or contaminated surfaces.

Proper hand washing and screening are effective methods used to prevent MRSA infections from occurring. Rates of MRSA have fallen in recent years because of increased awareness of infection by both medical staff and the general public. However, it still places a considerable strain on the health system as it is more difficult to treat than other types of bacterial infection. Currently, all patients who go to hospital for a planned procedure are offered a swab test to see whether they are carrying MRSA bacteria.

 

What did the research involve?

Researchers looked at the genetic make-up of more than 80 variations of a major clone of MRSA called EMRSA-16 found in hospitals. Samples were collected from infected patients during a 53-year period. The EMRSA-16 clone of MRSA predominantly occurs in hospitals, and the researchers estimated that it has been present in UK hospitals for about 35 years. Researchers then identified genetic elements and mutations in the bug and tracked how these spread between patients and hospitals across the country.

Researchers used a specialist approach to map part of the genetic make-up of each sample, looking for changes and patterns in its genetics. In effect, this allowed them to build up a “family tree” showing how different strains had developed.

 

What were the basic results?

The key finding of this study was that EMRSA-16 has spread within the UK by transmission from central hospitals serving large populations to smaller, regional healthcare settings. It found that Glasgow in west Scotland was a hub for transmission to 16 surrounding regions in the north and east of Scotland. Similarly, in London EMRSA-16 spread from large city hospitals to smaller surrounding hospitals in south and southeast England.

 

How did the researchers interpret the results?

Study lead Dr Ross Fitzgerald reported that “our findings suggest the referral of patients to different hospitals is a major cause of MRSA transmission around the country.” He also said that “variants of MRSA circulating in regional hospitals probably originated in large city hospitals.”

The researchers concluded that these findings could help prevent the spread of drug-resistant infections such as MRSA.

 

Conclusion

This study estimates how a strain of MRSA (EMRSA-16) may spread from hospitals in major UK cities to smaller regional healthcare settings. Findings from this study are supported by findings of a recent US study, which estimated high transmission routes from large hospitals to long-term care facilities.

The researchers note that the dataset used is limited by the relatively small number of hospitals sampled. Despite its interesting findings, further research is required that incorporates a larger number of sampled hospitals to determine the pattern of spread elsewhere in the UK.

Collecting data on the prevalence and spread of superbugs such as MRSA (medically known as surveillance) plays an important role in containing and eradicating potentially harmful bacteria in medical settings, and ultimately reducing the number and severity of hospital-acquired infections. When used strategically, data of this type, along with simple but effective measures such as thorough hand washing, can make a difference to the spread of infections, as illustrated by the recent fall in MRSA in NHS hospitals.

Analysis by Bazian

Links To The Headlines

Large city hospitals 'breed and spread' MRSA. BBC News, May 15 2012

MRSA outbreaks start at major city hospitals. Daily Express, May 15 2012

Links To Science

McAdam PR, Templeton KE, Edwards GF et al. Molecular tracing of the emergence, adaptation, and transmission of hospital-associated methicillin-resistant Staphylococcus aureus. PNAS, Published online before print May 14 2012

“Overweight mothers-to-be could be condemning their unborn children to decades of ill health,” the Daily Mail reported.

The news is based on the results of large, long-term research that examined mothers’ body mass index (BMI) before and during pregnancy and how this was linked to various indicators of their children’s health when their children reached 32 years of age. These indicators included BMI, waist size and levels of fat and sugar in the blood, which are associated with the risk of conditions such as diabetes and heart disease.

Researchers found that higher maternal BMI before pregnancy was associated with increased BMI in children, as well as larger waistlines, raised blood pressure and increased blood levels of insulin and fat. Greater maternal weight gain during pregnancy was also associated with increased BMI, waist size and levels of fat in the blood.

This study adds to a growing body of evidence that mothers’ weight before and during pregnancy may affect a range of health-related factors in their children, perhaps even in the long-term. That said, this study’s design means that on its own it cannot prove that a mother’s weight or weight gain during pregnancy are responsible for the health effects seen in their grown-up children. For example, many complex environmental, social and genetic influences are known to determine who develops obesity.

Although the long-term effects of maternal weight are unclear from this study, excess weight is known to increase the risk of complications during birth, as well as making it harder to conceive in the first place. This study highlights the importance of maintaining a healthy weight for these reasons, rather than the potential long-term ones.

The Daily Mail also reported that “concern about the issue is so high that British doctors have started to medicate babies in the womb.” The newspaper appears to be referring to ongoing research into treating women for high blood sugar during pregnancy. This valuable study primarily aims to treat mothers, rather than their unborn babies, to cut potentially dangerous complications, rather than to improve their children’s long-term health.

 

Where did the story come from?

The study was carried out by researchers from the Hebrew University-Hadassah in Israel and the University of Washington in the US. It was funded by the US National Institutes of Health and the Israeli Science Foundation. The study was published in the peer-reviewed medical journal Circulation.

The story was accurately covered by the Daily Mail. However, it should be noted that this study measured factors that can contribute to various diseases, but did not determine the rates of negative health outcomes such as heart attacks, diabetes and strokes mentioned in the news coverage.

 

What kind of research was this?

This cohort study examined how mothers’ BMI and weight changes during pregnancy were associated with various markers of disease in their children once they reached adulthood. The disease markers of interest were waist circumference, BMI, blood pressure and levels of glucose, insulin, fats and lipoproteins in the blood. These were measured once the children reached 32 years of age. Maternal BMI and weight changes during pregnancy were reported by mothers in interviews conducted by nurses while they were in hospital after having their baby.

This is the ideal study design to examine a possible association between maternal weight and children’s health. The study’s strengths also included its large size and long follow-up. However, this type of study can only find associations between factors, and cannot prove a cause-and-effect link. This is because researchers cannot exclude the possibility that another factor is responsible for the association seen.

 

What did the research involve?

This research drew on data from a large, long-running study called the Jerusalem Perinatal Study. The research collected the following information on births in Jerusalem between 1974 and 1976:

• demographic and socioeconomic information
• medical conditions of the mother during current and previous pregnancies and gynaecological history
• smoking status of the mother
• height, pre-pregnancy weight and end-of-pregnancy weight of the mother
• child’s birth weight and gestational age

This information was obtained from maternity ward logbooks, birth certificates and interviews with mothers while they were hospitalised after having their baby.

In this study, a sample of 1,400 individuals born during this period was interviewed and examined again between 2007 and 2009 (when they reached 32 years of age). Individuals who had been born as part of a multiple birth, who were premature or who had congenital malformations were excluded. The researchers collected data on:

• height
• body weight
• waist circumference
• blood pressure
• levels of glucose, insulin and fats in the blood

The researchers looked at associations between maternal pre-pregnancy BMI and weight gain during pregnancy and children’s outcomes at 32 years of age. During their calculations, they accounted for gender, ethnicity and other factors that could explain any relationship seen, including:

• how many previous pregnancies a mother had had
• the mother’s age at the birth
• maternal smoking, and smoking status of the children as adults
• socioeconomic status
• maternal education, and education of the children
• maternal medical condition
• the children’s birth weight and gestational age
• physical activity of the children 

 

What were the basic results?

The researchers found that greater maternal BMI before pregnancy was associated with the following factors in grown-up children at the age of 32:

• increased BMI
• increased waist circumference
• increased blood pressure
• increased blood levels of insulin and fat 
• lower levels of high-density lipoprotein cholesterol

These associations were independent of weight gain during pregnancy (i.e. were evident regardless of how much weight a mother gained during pregnancy).

Greater weight gain during pregnancy was associated with:

• increased BMI
• increased waist circumference
• increased blood levels of fat 

When calculating these various associations, the researchers split mothers into four evenly sized groups, based on their pre-pregnancy BMI. They found that, on average, the adult children of women in the group with the greatest BMI (maternal BMI more than 26.4kg/m2) went on to have a BMI of  five units (kg/m2) higher than the children of mothers in the lowest quarter (maternal BMI less than 21.0kg/m2).

 

How did the researchers interpret the results?

The researchers concluded that “maternal size both before and during pregnancy is associated with cardiometabolic risk factors in young adult offspring.”  In other words, mothers who have a high BMI before pregnancy or who gain a lot of weight during pregnancy are more likely to have children who have risk factors for various metabolic and heart-related health problems in adulthood.

The researchers added that these associations appear to be driven mainly by children’s body fat during adulthood.

 

Conclusion

The link between pregnant women’s weight and the health of their children has been in the public eye several times in recent months, with high-profile news stories questioning whether our mothers can “programme us to be fat” and the need to “treat babies for obesity while still in the womb”.

This latest study analysed potential links between mothers’ excess weight around the time of pregnancy and “cardiometabolic risk factors” in their children decades later. Cardiometabolic risk factors are factors such as raised BMI and blood sugar, which signal that a person has a higher risk of conditions such as diabetes and heart disease.

The study found a long-term relationship, with higher maternal weight (assessed using BMI) and greater weight gain during pregnancy associated with a number of factors in the mothers' children at the age of 32. These included increased BMI, waist circumference, blood pressure and blood levels of insulin and fats, and decreased levels of high-density lipoproteins (“good cholesterol”) in children. As the authors state, this study “adds to and extends accumulating evidence” of this relationship, as similar findings have been reported in other studies.

This study has shown associations between maternal weight and children’s later health, but it cannot show cause and effect. This is because it cannot rule out the possibility that another factor is responsible for the association seen. Also, both pre-pregnancy weight and weight gain were not directly measured but were reported by mothers in interviews conducted by nurses after delivery. This may have led to some inaccuracy in the calculation of BMI and makes the results less reliable.

The average pre-pregnancy BMI of women in this study was 24kg/m2 (within the healthy range) in mid-1970s Jerusalem. This population may not be typical of pregnant women in the UK today.

In addition, the exact mechanism by which maternal pre-pregnancy weight and weight gain during pregnancy might cause increased levels of cardiometabolic risk factors in children remains to be determined. Several mechanisms, including shared genetic and environmental characteristics or changes caused by exposures in the womb, have been proposed, although none is completely clear.

Analysis by Bazian

Links To The Headlines

Obesity legacy of mums-to-be: Carrying too many pounds in pregnancy can give your baby a life of weight problems. Daily Mail, May 15 2012

Links To Science

Hochner H, Friedlander Y, Calderon-Margalit R et al. Associations of maternal prepregnancy body mass index and gestational weight gain with adult offspring cardiometabolic risk factors/clinical perspective : The Jerusalem perinatal family follow-up study. Circulation, February 17 2012, 2012;125:1381-1389 (published online before print)

Women concerned about PIP breast implants can find all the latest NHS information about the issue in our Health A-Z section on PIP implants.

Worries about the implants have emerged since news of a major investigation into them in France was widely covered in the media in December 2011.

Initially it was thought that around 40,000 women in the UK had the implants but on March 15 the Department of Health said new evidence meant a further 7,000 women in the UK might have them. About 95% of the implants were provided privately for purely cosmetic reasons.

The French implants caused global concern after it was revealed they contained industrial silicone rather than medical-grade fillers and that they may be more prone to rupture and leakage than other implants.

Initially reports also linked the implants to a rare form of cancer known as ALCL. This cancer link has been now been firmly discounted by medical experts here and in Europe.

 

What type of implants are involved?

The implants involved are called Poly Implant Prosthèse (PIP) and were made by a French company of the same name.

In a Medical Device Alert in March 2010, the Medical and Healthcare products Regulatory Agency (MHRA) said: " ... most
breast implants manufactured by the company since 2001 have been filled with a silicone gel with a composition different from that approved".

That alert was based on advice from French regulators. However, after an investigation by the MHRA, the French authorities reported in March 2012 that PIP implants made before 2001 may also contain unauthorised silicone gel.

PIP gained approval to market its silicone implants in 1997 but it is not clear when it began using a cheap type of silicone gel intended for making mattresses.

The marketing, distribution and use of the PIP implants was suspended in March 2010.

 

Do the implants have to be removed early?

About one breast implant in five needs replacing within 10 years, whatever the make, so it is unlikely that all the 7,000 women who had PIP implants before 2001 still have the same implants.

An expert committee was set up recently to examine the specific risks associated with PIP implants. It concluded that there was not enough evidence to recommend their early removal. That advice has not changed. For more details, read the expert review group's report (PDF, 159kb).

Links To The Headlines

No Routine Removal For PIP Breast Implants. Sky News, January 6 2012

NHS will remove implants free of charge for their patients but private clinics must pay for operations themselves, Government says. Daily Mail, January 6 2012

Government will pay for women who had breast implants on NHS to have them removed. The Daily Telegraph, January 6 2012

Clinics 'should remove implants'. BBC News, January 6 2012

The NHS “spends £1m a week on repeat abortions”, the Daily Mail reported. The newspaper claimed that single women are using terminations “as another form of contraceptive”, and that some will have “seven, eight or even as many as nine terminations in their lifetime”.

The Mail’s coverage seems to be a response to a request for data on repeat abortions that was made in parliament in April 2012. The article appears to draw on 2010 abortion statistics available from a Department of Health report. The annual report provides data on the number of abortions (medically termed “termination of pregnancy”) performed in the UK, and includes a section on repeat abortions.

Despite the Daily Mail's headline, the report does not provide any data or information on women’s reasons or motivations for seeking an abortion. The “abortion as contraception” claim appears to be an interpretation of the data provided by campaign groups and abortion legislation critics. Also, the data suggest that only a tiny fraction of abortions were in women who have had seven or more previous abortions – 85 procedures out of the 189,574 performed in 2010.

 

What is a repeat abortion?

Much as the term implies, a repeat abortion is an abortion in a woman who has had one or more previous abortions. The Department of Health has recorded the rate of repeat abortions for many years, and includes a section on repeat abortions in its annual report on abortion statistics.

 

How many repeat abortions are happening each year?

According to the Department of Health’s abortion statistics report, in 2010 there were 189,574 abortions in England and Wales (data are available on residents of England and Wales only). Approximately 64,445 (34%) of these were repeat abortions. The percentage of repeat abortions was found to increase with age: 8% of those under 18 years old had a repeat abortion compared with 44% of women over the age of 35. While it may initially seem puzzling why older women have more repeat abortions, a logical, cumulative effect of ageing is responsible. Put simply, the longer a woman has been alive, the greater time she has had to undergo a repeat abortion.

The Department of Health report also provides data on the percentage of abortions that are repeat abortions in women aged under 25. In 2010 in England and Wales, this figure was 24.8%, with the figure varying across difference primary care trusts (range 15% to 41%).

The Department of Health reports that “repeat unintended pregnancy and subsequent abortion is a complex issue associated with increased age”, as increasing age allows for a longer time at risk for becoming pregnant.

 

Are repeat abortions increasing?

Full sets of annual data have so far been published up to 2010, with figures for 2011 scheduled for publication in the near future. Between 2000 and 2010, there was a small rise in the number of total abortions, up from 175,542 to 189,574. The 2010 figure was, however, slightly lower than the peak number seen in 2007, when there were 198,499 abortions.

The Department of Health data also indicate that the proportion of all abortions that are considered repeat abortions has increased from 30% to 34% since 2000. In absolute terms, this was estimated to equate to 52,663 repeat abortions in 2000 and 64,445 in 2010.

 

Why have these figures come to light now?

It is not immediately clear from the Mail’s coverage why these figures are making headlines today. On April 16 2012, the Labour MP Diane Abbot asked the secretary of state for health to provide estimates on the number of repeat abortions performed in 2010, 2011 and 2012. She asked that these figures be provided based on the marital status and age of the women across each primary care trust.

However, as abortion figures are published a year in arrears, the 2012 figures will not be published until 2013. Also, the 2011 figures are not scheduled for official publication until the end of May 2012, meaning that only figures up to 2010 are available at this time. The House of Commons website also reports that the 2010 statistics provide information on the number of repeat abortions by age, but not marital status. The Daily Mail, however, quoted statistics based on both age and marital status, and it is unclear how these have been derived.

 

Is abortion used as a 'form of contraception'?

In the UK, abortion is legal if one of several conditions apply:

• continuing the pregnancy would involve risk to the life of the woman
• termination of the pregnancy is required to prevent serious permanent injury to the woman
• the pregnancy has not gone beyond 24 weeks, and continuing would involve risk to the physical or mental health of the woman, greater than if the pregnancy was terminated
• the pregnancy has not gone beyond 24 weeks, and continuing would involve risk to the physical or mental health of any existing children, greater than if the pregnancy was terminated
• there is a significant risk that the child would suffer physical or mental abnormalities leading to serious handicap
• emergency situations to save the life of the woman
• emergency situations to prevent serious permanent injury to the woman

The Department of Health report on abortion statistics provides information on which of these conditions applies to each registered abortion. It does not, however, provide any specific data on the reasons why women decided to seek an abortion. The idea that abortion is used “as contraception”, as reported in the Daily Mail, appears to be an interpretation of the abortion statistics data by critics of the current legislation, with the newspaper quoting pro-life campaign groups and critics of current abortion legislation.

 

Who can give advice about reproductive health and contraception?

People seeking advice on reproductive health and contraception can speak with their GP or a community family planning clinic. GUM (genitourinary medicine) clinics, which are often located in hospitals, can also provide contraceptive services and sexual health advice. For younger adults in particular, voluntary organisations such as Brook advisory centres also provide a wide range of sexual health services.

Links To The Headlines

NHS spends £1m a week on repeat abortions: Single women using terminations 'as another form of contraceptive'. Daily mail, May 14 2012

NHS 'spends £1m on repeat abortions'. The Daily Telegraph, May 14 2012

Repeat abortions cost NHS £50m a year. Daily Express, May 14 2012

Cholesterol-lowering statin drugs “could more than halve the risk of bowel cancer”, according to the Daily Mail.

Millions of people take statins in a bid to prevent problems such as heart attacks and strokes, but several recent studies have looked at whether they might also cut the risk of cancer. This latest news is based on a study of statin use in people with and without bowel cancer. It looked at use of the drug in a group of 101 bowel cancer patients and 132 people without cancer. It found that statin users had a lower risk of developing bowel cancer, and that higher doses and longer duration of statin use were associated with a greater reduction in the odds of having the disease.

Previous research into the potential effect of statins on bowel cancer has had mixed results. Some studies have suggested that the drugs have a protective effect, and others have found no clear association between statin use and bowel cancer risk. It is important to note that this latest study is small, so its results may be inaccurate. This means the results need to be replicated in much larger samples of people. Also, all patients in this study – with or without cancer – were included because they were undergoing colon examinations for bowel symptoms, so they may not represent the general population.

Nevertheless, this small study adds to the mounting evidence that stains may have an effect in protecting against the development of certain cancers. However, more research is needed to confirm the findings and establish how large this protective effect may be.

 

Where did the story come from?

The study was carried out by researchers from the University of East Anglia and the Norfolk and Norwich University Hospital. It was funded by the Norwich Medical School.
 
The study was published in the peer-reviewed journal Biomed Central Gastroenterology.

This research was covered appropriately by the media, with the Daily Mail reporting that previous studies have found conflicting results and that additional research is needed. The newspaper also reported the possible side effects of statin use.

 

What kind of research was this?

This case-control study examined the association between statin use and bowel cancer. Case-control studies are a useful way of examining some types of association. They recruit and compare two groups of participants who either have or don’t have a particular disease or condition. For example, this study compared the histories of people with bowel cancer to those of similar participants without the condition. This allows researchers to study a relationship without having to recruit a large number of participants and follow them up over a long period.

Case-control studies have weaknesses, however, including relying on participants to accurately recall their past behaviour and exposures, often over many years. This can introduce bias into the results as such recollection can be difficult, particularly if someone is trying to understand why they have developed a condition such as cancer. Overall, the limitations of case-control studies mean they are considered to show only associations between two factors, and not that one factor causes the other.

Arguably, as both statin use and bowel cancer are fairly common among the general population, it would be possible to conduct a cohort study to examine bowel cancer development in a large sample of statin users and non-users. A study of this type would take a large group of participants using statins and follow them over time to see which of them developed cancer. It would then examine differences between the participants that may have contributed to the development of cancer. Alternatively, a carefully controlled randomised controlled trial would be the best way to examine this question, although it would need to be carried out over a long period as bowel cancer can take many years to develop.

As mentioned above, case-control studies cannot prove that a particular exposure (such as statin use) causes a particular outcome (such as a reduction in bowel cancer). They are, however, still a useful way to explore potential relationships, and are often conducted as a way to justify attempting large cohort studies or randomised controlled trials. In short, they provide useful initial data that will need to be corroborated through more intensive types of research.

 

What did the research involve?

The research included people who had undergone a colonoscopy at the Norfolk and Norwich University Hospital between September 2009 and May 2010. All the participants had bowel symptoms which led them to be referred to the hospital for a diagnostic colonoscopy examination. A colonoscopy involves inserting a long, flexible camera into the bowel to look for abnormalities such as tumours, pre-cancerous cells or damage. The study excluded patients who received a colonoscopy for surveillance of current or previous illnesses (such as inflammatory bowel disease), and symptomless patients who received a precautionary screening colonoscopy because they were considered to be at higher risk of bowel cancer (for example, those with a strong family history of bowel cancer).

Bowel cancer cases were identified based on a positive result during a diagnostic colonoscopy test, and control subjects were drawn from patients who had a negative test result. All the participants completed an interview during which information on statin use was collected. The researchers also collected information on other known risk factors for bowel cancer, which were adjusted for during the statistical analysis.

The researchers compared the percentages of cases and controls who reported taking statins, and determined whether the odds of having bowel cancer changed depending on statin use. They performed further analysis to determine whether or not the dose, duration or type of statin used was associated with differing risk of developing bowel cancer. All analyses were presented as odds ratios (OR). This is an appropriate statistical method to use in case-control studies. Odds ratios compare the odds of an outcome in an exposed group (statin users) with the odds of the same outcome in an unexposed group (non-users).

 

What were the basic results?

The research included 101 patients with bowel cancer and 132 cancer-free controls. There were some differences between the two groups. Cases were more likely to be male, older and to drink more alcohol during the course of a week. Controls were more likely to have diabetes and to have previously used aspirin (some research has linked long-term aspirin use to a reduced risk of bowel cancer). These factors were considered to be potential confounders and were controlled for in the statistical analysis.

The researchers found that previous statin use for at least six months was associated with significantly reduced odds of being diagnosed with bowel cancer (OR 0.43, 95% confidence interval [CI] 0.25 to 0.80).

When the researchers performed subgroup analysis based on the duration of statin use, they found that longer statin use was associated with a greater protective effect:

• 8 cases and 14 controls had used statins for less than 2 years. There was no significant difference in the odds of a bowel cancer diagnosis between statin users and non-users (OR 0.66, 95% CI 0.21 to 1.69).
• 7 cases and 23 controls had used statins for 2 to 5 years. There was no significant reduction in odds of bowel cancer diagnosis (OR 0.38, 95% CI 0.14 to 1.01).
• 5 cases and 31 controls had used statins for over 5 years. This was associated with an 82% reduction in the odds of being diagnosed with the disease (OR 0.18, 95% CI 0.06 to 0.55). This particular association was statistically significant.

When the researchers performed subgroup analysis based on the statin dose, they found larger doses were associated with a greater protective effect:

• 12 cases and 28 controls used a dose of less than 40mg a day. There was no significant reduction in odds of bowel cancer diagnosis at this dose (OR 0.51, 95% CI 0.21 to 1.24).
• 8 cases and 40 controls used a dose of 40mg or greater a day. This was associated with an 81% reduction in the odds of being diagnosed with the disease (OR 0.19, 95% CI 0.07 to 0.47).

 

How did the researchers interpret the results?

The researchers concluded that statin use was associated with a reduction in bowel cancer diagnosis, and that this reduction was largest at higher doses and with longer duration of statin use.

 

Conclusion

This study suggests that stains, a commonly prescribed class of cholesterol-lowering drugs, may protect against bowel cancer. However, further research with more participants and a more robust study design will be needed to confirm its findings.

This was a relatively small study, which was further divided during subgroup analysis. Analysing small numbers of participants increases the possibility that any risk associations calculated could be inaccurate. Larger studies are needed to verify the associations found in this research.

The researchers report that one of their study’s strengths is that a comprehensive drug history was available, both through prescription records and patient reports. This increases the likelihood that exposure to statins was correctly classified. Additionally, all the participants underwent the same diagnostic testing to confirm or rule out the presence of bowel cancer.

There were, however, limitations to the study. For instance, all the participants had symptoms that indicated the need for a colonoscopy. Given that the control group may have had health issues relating to their bowels, the results may not reflect the risk of bowel cancer in the wider population. Further studies including participants receiving a screening, rather than diagnostic, colonoscopy could help address this potential bias.

When being used to treat or prevent cardiovascular problems, statin drugs may be given as part of a package of treatments including dietary changes and salt reduction. It’s possible that people with the greatest need for cholesterol-lowering statins may also modify their diet alongside their use of statins. Given that diet is associated with bowel cancer risk, dietary changes (and not just the use of statins) may have played a role in the association. This study did not investigate the participants’ dietary habits. Future studies could examine this risk factor.

The researchers say that the protective effect seen in their study was greater than that seen in other studies with similar results. They also point out that not all previous research has found a protective effect, and that there are inconsistent findings across the field. They say that these inconsistencies may be due to differences in the populations studied, or the duration of statin use. Given the variability in results, more research is needed before we can be confident that statins are indeed associated with a reduced risk of developing bowel cancer. Ideally, this research should be a prospective cohort study or randomised controlled trial.

Overall, this case-control study adds to the existing evidence that statin use has a potential protective effect against the development of bowel cancer. Further research is needed to confirm the findings, and the risks associated with statin use will need to be weighed up against any benefits before the drugs are considered for cancer-prevention.

Analysis by Bazian

Links To The Headlines

Statins 'cut risk of bowel cancer': Danger 'halved' by cholesterol-busting pills. Daily Mail 11, May 2012

Links To Science

Broughton T, Sington J, Beales ILP. Statin use is associated with a reduced incidence of colorectal cancer: a colonoscopy-controlled case-control study. BMC Gastroenterology. April 24 2012

“Women using a vaginal ring or skin patch for contraception are at around double the risk of a blood clot compared to those taking the Pill,” the Daily Mail has reported.

The news is based on a large Danish study that looked at contraceptive use in more than 1.5 million women. The study looked at how different hormone-based methods such as implants, the patch and the pill related to the risk of blood clots. Between 2001 and 2010 researchers recorded a total of 3,434 blood clots, also known as venous thromboembolisms or VTE. The background rate of VTE among women not using hormonal contraception was 2.1 per 10,000 woman-years (for example, 2.1 would occur if 1,000 women were followed for 10 years). The highest rate of VTE was among women who used the contraceptive patch, with 9.7 per 10,000 woman-years. Women using a common oral contraceptive pill experienced a rate of 6.2 per 10,000 woman-years.

Despite what some news coverage might suggest, hormonal contraceptives containing oestrogen ( the combined oral contraceptive pill, transdermal patch and the vaginal ring) are already recognised as increasing the risk of VTE, although the risk is very low. Instead of discovering a new danger from using hormone-based contraceptives, the research simply refines estimates of the clot risk associated with different methods.

Women should be fully informed of the potential risks and benefits of any contraceptive option that they choose. They can talk to their GP or nurse about these. Despite the small increase in risk associated with the patch or vaginal ring compared with the combined oral contraceptive pill, there may be women for whom this is still an appropriate choice.

 

Where did the story come from?

The study was carried out by researchers from the University of Copenhagen and did not receive external funding. It was published in the peer-reviewed British Medical Journal.

News coverage generally failed to reflect the true context of this research. It is already known that there is a clot risk associated with use of oestrogen-containing contraceptives, and this research has helped to analyse some of the finer points around the issue rather than revealing any previously unknown risk. This research provides valuable quantification of the possible risk among users of hormonal contraception but the findings are not as unexpected as the media implies.

In particular, the Daily Mail’s headline is misleading and may scare women: ‘Women using alternative contraception to the Pill are at double the risk of blood clot’. This might suggest to readers that any alternative option to the combined oral contraceptive pill doubles the risk. This is not true. The oestrogen-containing patch or vaginal ring increase risk slightly more than the oestrogen-containing pill, but the pill itself actually significantly increases risk of VTE compared with non-use, or use of progestogen-only contraceptives or barrier methods.

 

What kind of research was this?

This was a large, national cohort study that compared contraceptive use and VTE risk among more than 1 million Danish women. It used four national registries in Denmark to look at all non-pregnant women aged 15-49 (who were free of cancer or thrombotic disease) and collected data on their contraceptive use over the period 2001 to 2010. From these data, researchers were able to see how the rate of VTE among users of non-oral hormonal contraceptives compared with the rate in users of the oral contraceptive pill, as well as in women who didn’t use hormonal contraception.

A cohort study is a good way of evaluating whether a certain exposure increases risk of a certain outcome. The researchers of this cohort study when conducting their analyses have attempted to adjust for some of the possible confounding factors that could be affecting the results.

 

What did the research involve?

Data available in Danish registries allowed for 1,626,158 non-pregnant women to be followed between January 2001 and December 2010. The researchers were only interested in first-ever events of VTE, so excluded women who had had any type of thrombotic event in their veins or arteries before the study period (assessed by checking medical registries from 1977 to 2000). They also excluded those with cancer, those who had had a hysterectomy or both their ovaries removed and those who had been sterilised.

Since 1995 the registries consulted by the study have recorded all filled prescriptions, and so the researchers were able to obtain information on all hormonal contraceptives prescribed between 1995 and 2010. They recorded the products according to progestogen type, oestrogen dose, method of administration and duration of use. The registry also records all hospital admissions.

Any hospital admission for suspected VTE (a clot in a vein or blood vessel) or pulmonary embolus (a clot in the blood supply to the lungs) was confirmed by examining prescribed anticoagulation therapy recorded in the national registry of medicinal products for at least four weeks after the diagnosis. Fatal VTEs were captured by the national causes of death registry.

The researchers also obtained information on some possible confounders that could influence VTE risk, such as educational status, age and calendar year (contraceptives prescribed or healthcare in general may have changed subtly over the nine-year study period). However, they didn’t have information on other relevant confounders such as smoking.

 

What were the basic results?

The researchers had 9,429,128 woman-years of follow-up data (for example, 90 woman-years of follow-up could be 90 women followed for one year, or nine women followed for 10 years). Over this period there were 3,434 confirmed first-event VTEs.

The researchers then calculated the VTE rate according to use of different contraceptive types:

• not using hormone-based contraception: women not using any hormone-based contraception experienced a background rate of 2.1 events per 10,000 woman years (for example 2.1 would occur if 1,000 women were followed for 10 years)
• contraceptive patch: a rate of 9.7 per 10,000 woman years
• vaginal ring: a rate of 7.8 per 10,000 woman years
• combined oral contraceptive pill (30-40 micrograms of oestrogen in combination with levonorgestrel): a rate of 6.2 per 10,000 woman years
• combined oral contraceptive pill (30-40 micrograms of oestrogen in combination with norgestimate): a rate of 4.5 per 10,000 woman years
• progestogen implant: a rate of 1.7 per 10,000 woman years
• progestogen-releasing intrauterine system: a rate of 1.4 per 10,000 woman years

The researchers calculated that, after adjustment for confounders, the risk of confirmed VTE among users of the contraceptive patches was 7.9 times that of women not using hormonal contraception (95% confidence interval 3.54 to 17.65), and 2.3 times that of users of the combined oral contraceptive pill (95% CI 1.02 to 5.23).

The risk of confirmed VTE among users of the vaginal ring was 6.5 times that of non-users, and 1.9 times that of users of the combined oral contraceptive pill. Compared with women who did not use hormonal contraception, women who used the combined oral contraceptive pill had around a trebled risk of VTE.

Compared with women who did not use hormonal contraception, users of the progestogen implant or progestogen-releasing intrauterine system had no increased risk of VTE.

 

How did the researchers interpret the results?

The researchers conclude that “women who use transdermal patches or vaginal rings for contraception have [respectively] a 7.9 and 6.5 times increased risk of confirmed venous thrombosis compared with non-users of hormonal contraception of the same age”. Respectively, this equates to 9.7 and 7.8 events per 10,000 woman-years (for example, for the transdermal patch a rate of 9.7 events among 1,000 women followed for 10 years).

 

Conclusion

This large study provides valuable information on the rate of VTE that may be experienced among users of hormonal contraception.

However, the findings are not completely surprising. Oestrogen-containing hormonal contraceptives are already known to increase the risk of VTE, and medical professionals already consider this potential side effect when prescribing contraception and monitoring patients. Instead of revealing some new or major danger, this study provides a good indication of how the risks compare for a variety of different contraceptive methods.

The oestrogen-containing contraceptives currently available are the combined oral contraceptive pill, the transdermal patch (of which there is one licensed product – brand name Evra) and the vaginal ring (of which there is one licensed product – brand name NuvaRing). There are many different preparations of combined oral contraceptive pill that contain different strengths and forms of oestrogen and progestogen. Different progestogens contained in combined oral contraceptive pills are considered to have a differing effect on risk of venous thromboembolism. This study chose to look separately at VTE rate among users of combined oral contraceptive pills containing levonorgestrel or norgestimate, but there are various other types of progestogen contained in other combined pills, and this study has not examined those.

Progestogen-only contraceptives are not known to increase risk of VTE, and this study supports this. Users of implants and the progestogen-releasing intrauterine system had no higher risk than non-users of hormonal contraception. Information was not available for progestogen-only pills or injections.

There are some further points to note about the study:

• This was a cohort study looking at associations within a large population using contraception in an everyday setting rather than in the artificially controlled setting of a clinical trial. As such, the method of contraception used will have been down to the woman’s personal choice in consultation with her doctor, and there may be health and lifestyle factors that have influenced the choice of contraceptive and that could also influence risk of VTE. The researchers adjusted their results for possible confounders of age, education and calendar year, and also excluded women who may be at particularly increased risk of VTE. However, information on other relevant confounders such as smoking or body mass index was not available.
• Use of contraception was determined by looking at filled prescriptions. Although the women are likely to have used the method prescribed for them, and for the prescribed time period, this may not always have been the case.
• There were far fewer women in the study using the patch (6,178 woman years) or vaginal ring (50,334 woman years) compared with the combined oral contraceptive pill (530,241 woman years). The event rate of VTE among users of the patch or vaginal ring was correspondingly low (six events among users of the patch; 39 with the ring). Therefore, although the ring and patch were calculated to give double the risk of the combined oral contraceptive pill, the low event rates mean that the risk figures are only estimates, and may not be completely accurate. This is reflected by the wide confidence intervals. In other words, even a small spike in cases could inflate the rate seen.

Overall, the study highlights the importance of women being fully informed of the potential risks and benefits of any contraceptive option that they choose. Despite the small increase in risk associated with the patch or vaginal ring compared with the combined oral contraceptive pill, there may be women for whom this is still an appropriate choice and for whom the benefits, such as not having to take a daily pill, outweigh the small extra risk.

Analysis by Bazian

Links To The Headlines

Skin patch contraceptive linked to high blood clot risk: research. The Daily Telegraph, May 11 2012

Women using alternative contraception to the Pill 'are at double the risk of a blood clot'. Daily Mail, May 11 2012

Links To Science

Lidegaard Ø, Nielsen LH, Skovlund CS, Løkkegaard E. Venous thrombosis in users of non-oral hormonal contraception: follow-up study, Denmark 2001-10. BMJ. Published May 10 2012

The NHS is set to use Botox injections to treat chronic migraines, it has been widely reported today. The muscle-paralysing injections are popular as a cosmetic treatment but, due to its nerve-blocking effects, Botox also has a role in treating certain medical conditions.

The move to use Botox to prevent migraines is based on new guidance published today by the National Institute for Health and Clinical Excellence (NICE), which looks likely to come into force in the near future. NICE recommends that Botox can be considered as an option for the prevention of headaches for people who have chronic migraine (headaches on at least 15 days of every month, at least eight days of which are migraine) that has not responded to at least three prior preventative drug treatments.

This latter point is key – although this treatment will be available on the NHS very few people may actually be eligible. The treatment will be available for people whose migraine is debilitating enough to require preventative treatment to be taken, and then for only the small proportion of those who have not responded to other standard preventative drug options.

 

What is a migraine?

There are many different types of headache. A migraine is a type of headache where the person often has an intense throbbing headache and additional symptoms such as nausea, vomiting or increased sensitivity to bright light, noise or smell.

There are two recognised forms of migraine. A migraine is often described as a classic migraine with ‘aura’ if the person gets some form of visual distortions prior to the headache. These visual distortions are often in the form of zigzag or flashing patterns across their vision. Non-classic or common migraine does not have this aura.

Migraines are thought to be caused by changes in the chemicals of the brain, in particular serotonin. Serotonin levels are believed to decrease during a migraine, which can cause the blood vessels in the brain to spasm and then dilate, causing the headache. Other triggers can be hormonal changes, certain food items, environmental situations, emotions, stress and physical triggers (for example muscular tension or poor sleep).

Acute migraines are usually treated using painkillers and anti-sickness medications. For people whose migraine does not respond to over-the-counter medications, stronger painkillers may be prescribed by a doctor. If a person suffers from regular debilitating migraines they may need to be prescribed preventative (prophylactic) medications, which they take to stop them getting migraines. There are various drugs currently prescribed for migraine prophylaxis, including beta-blockers and certain antidepressants or anticonvulsants.

 

What is botulinum toxin type A (Botox)?

Botulinum toxin type A, or Botox as it is commonly known, is a purified neurotoxin (nerve toxin) derived from the bacterium Clostridium botulinum. It works by paralysing the nerve supply to muscles, thereby restricting their movement.

The reasons why Botox might aid migraine are not clear, and several theories have been put forward. At various points it has been suggested that:

• Botox might relax muscles around the head and thereby reduce blood pressure within the brain
• Botox might reduce the nerves’ ability to send pain signals during a migraine
• Botox might prevent the nerves from sending signals that will lead to a migraine

While the mechanism behind any effect is not clear, NICE feels the results of research indicate Botox should be considered as a potential treatment for migraine. Under the new guidelines Botox for the treatment of chronic migraine would be given (to those eligible) by intramuscular injection to between 31 and 39 sites around the head and back of the neck. A new course of treatment can be administered every 12 weeks.

 

How effective is Botox for migraine?

NICE looked at a systematic review that had identified all randomised controlled trials comparing botulinum toxin type A with placebo for people with chronic headache. Two large trials were identified, and in both of these trials Botox injections reduced the frequency of headache days, which was the main trial outcome that the researchers were interested in. Botox also helped to improve quality of life on validated scales, but was no more effective than placebo in reducing the use of painkillers to treat acute pain.

 

Is Botox safe for migraine?

In the reviewed trials the most frequently reported adverse reactions in the Botox group were neck pain, headache, migraine, eyelid drooping, muscular stiffness and muscular weakness. Neck pain was the only adverse effect that occurred at a rate of 5% or more in the Botox groups compared with the placebo groups. Other recognised adverse effects of Botox are itching, injection site pain and other muscular effects such as aching, tightness or spasms.

The manufacturer’s summary of product characteristics states that “in general, adverse reactions occur within the first few days following injection and, while generally transient, may have a duration of several months or, in rare cases, longer”.

 

What does the guideline say?

The guideline says that botulinum toxin type A may be prescribed on the NHS for the prevention of chronic migraine, but only if specific criteria are met. These are as follows:

• The person has chronic migraine, defined as headaches on at least 15 days a month, of which at least eight days are with migraine.
• The person has not responded to at least three drug-based treatments intended to prevent migraines.
• The person is being appropriately managed for medication overuse. The regular use of painkillers to treat headaches can lead to withdrawal headaches as the effect of the painkillers wears off. For some people with chronic headaches this compounds the problem.

If botulinum toxin type A is prescribed, NICE recommends that it should then be stopped if the following criteria are met:

• the person is not adequately responding to treatment (defined as less than a 30% reduction in headache days per month after two treatment cycles)
• the headache has changed from chronic to episodic migraine (defined as fewer than 15 headache days per month) for three consecutive months

 

What sort of guidance is this?

NICE produces many different types of evidence-based appraisals evaluating the evidence on treatments or interventions for different conditions. Their aim is to ensure that treatments offered are of the highest quality and the best value for money. Rather than being a full guideline that covers all the different ways to manage migraine, the current publication is a ‘technology appraisal’ specifically assessing Botox use for the prevention of headaches in adults with chronic migraine. Technology appraisals evaluate when and how new and existing medicines and treatments should be used in the NHS.

 

Will Botox definitely be made available?

The current publication is NICE’s final recommendation on the use of botulinum toxin type A for the prevention of headaches in adults with chronic migraine. It is not completely approved as it is currently open to appeal, a process NICE allows with all evaluations. Unless there is later a successful appeal against the decision to approve Botox for migraines, the guidance will be adopted for people with chronic migraine who meet the specific criteria as outlined above.

Links To The Headlines

Botox given go-ahead for migraine sufferers. The Guardian, May 11 2012

Botox migraine jab set to be offered on NHS, says NICE. BBC News, May 11 2012

Botox to be the new treatment for chronic migraine. The Independent, May 11 2012

Hope for thousands who suffer migraines as treatment involving botox is given the green light. Daily Mail, May 11 2012

Free Botox on the NHS... but only for those with chronic migraines. Daily Mirror, May 11 2012

Botox jabs on the NHS to bash migraine on the head. Metro, May 11 2012

Migraine sufferers to get botox jabs on NHS. Daily Express, May 11 2012

Links To Science

NICE. Migraine (chronic) - botulinum toxin type A: final appraisal determination. Published online May 10 2012

Thousands of heart attack survivors are too worried to have sex because they fear it will trigger another attack, the Daily Mail has reported today.

The story is based on a US study that looked at patients’ sexual activity both before their heart attack and in the year that followed. The study looked at the factors that affected whether people were still sexually active. It found that almost half of men and nearly 60% of women were less sexually active after a heart attack than previously, and that about one in ten who had been sexually active before a heart attack did not have sex in the year afterwards.

The study also found that only a third of women and 47% of men reported receiving any counselling about resuming sexual activity on leaving hospital. Those who had not received counselling were more likely to report reduced sexual activity in the following year. The study also found that patients who had sex in the year following a heart attack were no more likely to die than those who were sexually inactive, with mortality rates among both groups being similar.

Although it did not explore the reasons why some people were less sexually active after a heart attack, this study suggests that lack of any advice on the topic may leave patients fearing that sexual activity could put them at risk of a repeat heart attack, and that the issue needs to be addressed.

Most people value sexual activity as an important part of life, whatever their health. In the UK, the current advice is that anyone who has had a heart attack should be able to have sex without risk to their heart once they are fit enough to walk briskly up two flights of stairs without getting chest pains or becoming out of breath. This is usually about four weeks after having a heart attack. At this point, having sex will not put you at further risk of another heart attack.

 

Where did the story come from?

The study was carried out by researchers from the University of Chicago, the University of Missouri and Yale University. It was funded by the US National Heart, Lung and Blood Institute, and the non-profit corporation Cardiovascular Outcomes Inc. The study was published in the peer-reviewed American Journal of Cardiology.

The research was reported accurately in the Daily Mail, which pointed out that men having heart attacks during sex is rare, despite what “dramatic movie scenes” might suggest. To aid readers in the understanding of this complex medical issue the paper featured a run down of a famous coital heart attack on film, experienced by Jack Nicholson’s character Harry Sanborn in the film Something’s Gotta Give. The Daily Telegraph combined its report of the study with comments from a doctor explaining that TV programmes often mislead people into thinking heart attacks after sex are common. The doctor gave the examples of the TV shows Downton Abbey and Mad Men, which both “feature dramatic scenes where philandering men suffer heart attacks in bed”.

 

What kind of research was this?

This was an observational study that looked at sexual activity among 1,879 heart attack patients both before their heart attack and in the following year. It also looked at whether these patients received any instructions on the subject when being discharged from hospital, and whether any information provided covered sexual activity. Finally, it looked at any association between sexual activity and mortality rates within a year of having a heart attack.

 

What did the research involve?

The study, which was part of a larger study monitoring the health of heart attack patients, began in 2007. It included 1,879 patients (1,274 men and 605 women) who were followed for a year after they had been admitted to hospital with a heart attack.

Patients included in the study were first interviewed at the bedside by trained staff within 24 to 72 hours of the event, and the details gathered were added to information from their medical records. Data collected by the interviewers included information on income and social class, depression, severity of their disease and physical functioning.

Patients who took part in the sexuality study were interviewed by telephone at one month and 12 months after being enrolled. They were asked a series of questions including whether they had been sexually active in the year before having a heart attack, and whether they had had sex since having a heart attack (asked at both one and 12 months). Those who reported being sexually active before their heart attack were also asked whether they had had sex with more, less or the same frequency afterwards. 
Patients were also asked if they had received any instructions at hospital discharge about when to resume sexual activity, and whether they had discussed sex with their doctor during the period after being in hospital.

The researchers obtained mortality data on the patients through social security records at 12 months.

They analysed the findings to assess any factors associated with “loss of sexual activity” 12 months after heart attack.

 

What were the basic results?

The study featured 1,274 men and 605 women, with average ages of 58.6 years and 61.1 years, respectively. Researchers found that:

• Forty-four per cent of women and 74% of men were sexually active in the year before hospitalisation and 40% and 68% were sexually active afterwards.
• Of these groups, 48% of men and 59% of women reported less-frequent sexual activity in the 12 months after a heart attack.
• About one in 10 patients who were sexually active before their heart attack were not active in the subsequent year.
• One-third of women and 47% of men reported receiving hospital discharge instructions about resuming sex.
• Those who did not receive instructions were more likely to report loss of sexual activity (women, adjusted relative risk 1.44, 95% confidence interval 1.16 to 1.79; men, adjusted relative risk 1.27, 95% confidence interval 1.11 to 1.46).
• One-year mortality after heart attack was similar in those who reported sexual activity in the first month after their attack (2.1%) and those who were sexually inactive (4.1%). This suggests that whether or not people are sexually active has little bearing on their risk of death following a heart attack.

The study also found that men who had discussed sex with their doctor following their heart attack were less likely to be sexually active. The researchers say this could be because men who are anxious about having sex after a heart attack may be more likely to initiate a discussion with their doctor.

While nearly half of patients who were married and sexually active received no counselling about resuming sexual activity, two-thirds of unmarried patients who were sexually active, did not receive counselling.

Other factors such as age, marital status, depression and severity of heart disease were not associated with loss of sexual activity.

 

How did the researchers interpret the results?

The researchers conclude that, although many patients were sexually active before their heart attack, only a minority received counselling about resuming sexual activity at their discharge from hospital. Lack of counselling was associated with loss of sexual activity one year later. Mortality was not significantly increased in patients who were sexually active soon after their heart attack.

They say the study indicates that counselling may be an important factor in the likelihood of being sexually active after a heart attack, and that men and women can benefit equally.

They also argue that sexually inactive older adults with chronic illness value sexuality as an important part of life and that sexual inactivity before a heart attack should not exclude patients from receiving counselling in this area. “Profiling” patients for counselling based on previous sexual activity or on marital status, they argue, will exclude some patients who could benefit from this information.

 

Conclusion

This study had a number of limitations, including its reliance on patients recalling both their sexual activity in the year following their heart attack and also whether they received advice or counselling on the topic when discharged from hospital. This reliance on patients self-reporting past events could affect the reliability of the results, particularly as they were estimating these factors in the wake of a potentially life-changing heart attack.

Also, the researchers did not objectively measure whether it was patients or staff who initiated counselling on this topic at the time of discharge. Although counselling is likely to be initiated by hospital staff, it is possible that patients who were more interested in resuming sexual activity may also have been more likely to ask for counselling.

Previous research has already established the extremely low risk of a heart attack from having sex, and this study raises a number of important issues including a possible lack of medical advice causing heart attack patients to be anxious about resuming sexual activity. This is unlikely to be good for people’s sex life or their peace of mind as they recover.

Most people value sexuality as an important part of life, whatever their health. In the UK, the current advice is that anyone who has had a heart attack should be able to have sex without risk to their heart once they are fit enough to walk briskly up two flights of stairs without getting chest pains or becoming out of breath. This is usually about four weeks after having a heart attack for most patients. Having sex will not put you at further risk of having another heart attack, although you can speak to your doctor or read NHS Choices’ guide to sex after a heart attack if you require further information.

Links To The Headlines

Sex after heart attacks 'not the preserve of Mad Men'. The Daily Telegraph, May 10 2012

It is safe to have sex with a heart condition, say doctors (as long as patients can climb a flight of stairs). Daily Mail, May 10 2012

Links To Science

Tessler Lindau S, Abramsohn E, Gosch K et al. Patterns and Loss of Sexual Activity in the Year Following Hospitalization for Acute Myocardial Infarction (a United States National Multisite Observational Study). American Journal of Cardiology, Volume 109 Issue 10 , Pages 1439-1444, May 15 2012

“A simple drawing test may help predict the risk of older men dying after a first stroke,” says BBC News. The test asks participants to draw lines between a series of ascending numbers in as short a time as possible. The aim of the test is to indicate how well their minds are working.

In a new study published this week researchers looked at whether performance in the test could predict the risk of dying after suffering a stroke. In the study, the test, known as the Trail Making Test, was given to 919 older men at the start of the research. The participants were then followed using medical records for the next 14 years. In total, 155 participants had a stroke, of whom 84 died. When researchers examined the risk of dying in relation to men's cognitive test scores they found that doing poorly on the test was associated with an increased risk of dying following a stroke. The researchers say that the Trail Making Test offers an easy-to-use option for predicting death after a stroke.

Overall, this small study suggests that the simple test may offer an additional tool for identifying individuals at high risk of death from stroke. Given that the test does not require specialised equipment or extensive training it may, in theory, be helpful when used alongside other diagnostic techniques such as brain scans. However, the mechanism that explains the predictive power of this test is still uncertain, and the idea would benefit from testing in a more diverse group.

 

Where did the story come from?

The study was carried out by researchers from Uppsala University in Sweden and was funded by Uppsala University and the Swedish Stroke Association (STROKE-Riksforbundet). The study was published in the peer-reviewed American Journal of Cardiology.

The media reported the story appropriately, with the BBC pointing out that the study was relatively small and that the underlying causes of poor performance on the test are not known.

 

What kind of research was this?

This was a prospective cohort study in which a group of men were given a cognition test. The results were then analysed to assess how they related to the participants’ risk of dying from a stroke in the years that followed.

The researchers initially recruited 919 white men who had never had a stroke and asked them to complete the Trail Making Test (TMT), a simple cognitive test that involves drawing lines between numbers and letters in ascending order as quickly as possible. Participants performed two slightly different versions, A and B (TMT-A and TMT-B). TMT-A simply involves joining up ascending numbers scattered randomly across a page, while TMT-B adds letters to the task, and involves alternating between letters and numbers in ascending order, again, as quickly as possible. Requiring a long time to complete the tests is considered to reflect impairment in movements associated with mental activity.

The participants were then followed over time to see how their performance in the TMT tests related to their risk of dying of a stroke.

A prospective cohort study is necessary to determine the predictive or prognostic ability of a test. During research of this type, researchers can require participants to complete the test while healthy, and then follow them up to assess how their health changes. In this study that means the researchers were able to assess how well the TMT-A and TMT-B test predicted the participants’ risk of future stroke.

 

What did the research involve?

The research included 919 men between the ages of 69 and 75. At the beginning of the study information was also collected on medical history, alcohol habits, demographic factors and physical health status. Participants who had had a previous stroke were excluded from entering the study. The participants then completed the TMT-A and TMT-B, and their times were recorded.

The researchers followed the men for up to 13.6 years (median follow-up 11.2 years) and, using hospital discharge records and cause of death registries, recorded:

• how many participants had a stroke during follow-up
• how many of those who had a stroke died within two and a half years of it occurring

The researchers then compared the risk of dying among stroke patients according to TMT-A and TMT-B test performances at the start of the study. To do this, they split the cohort into three groups (or tertiles), with tertile 1 comprised of the men with the best (fastest) scores on the TMT-A and TMT-B tests, tertile 2 comprised of the men with intermediate scores and tertile 3 comprised of the men who performed the worst (slowest) on the tests.

During this analysis they controlled for multiple variables that had the potential to distort or influence the relationship between test performance and death risk, including age, education, social group and health status.

 

What were the basic results?

In all, 155 (16.9%) of the participants suffered a stroke or ‘mini-stroke’ during the follow-up period. A mini-stroke, also known as a transient ischaemic attack or TIA, occurs when the blood supply to parts of the brain is momentarily restricted. The event generally lasts a few minutes and causes similar symptoms to a stroke. Although a TIA can cause lasting effects, most symptoms generally resolve within a day or so. Having a TIA can be a warning sign that a person is at risk of having a stroke in the future.

On average (median) participants were followed for 2.5 years after their first ever stroke or TIA, and during this time 84 of the 155 men who suffered a stroke or TIA died (equating to 54% of patients who had a stroke dying). Twenty-two of the deaths occurred within the first month after the stroke or TIA.

The researchers found that diabetes (Hazard Ratio [HR] 1.67, 95% CI 1.04 to 2.69) and treatment for high blood pressure (HR 1.56, 95% CI 1.02 to 2.40) at the start of the study (the baseline) were significantly related to the risk of death after first ever stroke or TIA. No other variables at baseline were significantly associated with risk of death following stroke.

The researchers first assessed the relationship between performance on the TMT-A test (involving joining numbers only) and fatal stroke. They found that, overall, for each standard deviation increase in test time (about 20 seconds), the risk of dying after a first ever stroke or TIA increased by 88% (HR 1.88, 95% CI 1.31 to 2.71).

When comparing mortality between test time groups, the researchers found that the men who performed worst on the test were nearly three times more likely to have died following a stroke than those who performed the best (HR 2.90, 95% CI 1.24 to 6.77). There was no significant increase in mortality between men in the middle group and the best performers.

The researchers then examined the association between performance in the TMT-B test (involving both letters and numbers) and mortality after a stroke. They found that a standard deviation increase in test time (about 45 seconds) was associated with a significantly increased risk of mortality after a stroke (HR 2.01, 95% CI 1.28 to 3.15).

Compared with the fastest test performers, the slowest group were more than three times more likely to have died after a stroke (HR 3.53, 95% CI 1.21 to 10.34). Once again, there was no significant difference in mortality between the middle group and the fastest group.

 

How did the researchers interpret the results?

The researchers conclude that levels of cognitive functioning before a stroke, assessed using a simple test, predicted survival following a stroke in a sample of elderly men.

 

Conclusion

This study suggests that the results of a relatively simple test given at age 70 could predict the likelihood of dying after a stroke. This particular study did not, however, assess whether or not the TMT-A or TMT-B could itself predict the likelihood of having a stroke, as some internet coverage has suggested.

At present there are many risk factors that are used to identify individuals at an increased risk of having a stroke, including age, family history, ethnicity and medical history, as well as lifestyle factors such as smoking, excessive alcohol consumption and diet. This research suggests that the Trail Making Test may be useful for predicting outcomes after a stroke, although this particular paper did not provide data on the test’s ability to predict who will have a stroke in the first place. That said, the researchers highlight that previous research has shown that the TMT-B is also useful for predicting stroke in elderly men.

The study did have several strengths that allow us to be fairly confident in its results. First, the researchers were able to follow up on all of the study participants, which limits the likelihood of people dropping out of the study, biasing the results. Second, both the TMT test and the outcome of interest (death following a first stroke) were measured in a consistent manner across all the participants, and important potential confounders were accounted for in the data analysis.

The study sample was, however, not completely representative of the people that are likely to take such a test. While the age range of the sample is likely to be similar to that of patients who would be given this test, all of the study participants were white men. It is unclear whether the same or similar results would be seen in women or other ethnicities.

Also, as a test of observation and manual dexterity the TMT test may not be suitable for people with certain conditions such as sight problems or joint problems, which may hinder performance in the test. These are generally more prevalent among older people, who also have a greater risk of stroke, further complicating the issue.

The mechanism underlying this association is unclear, the researchers point out that having dementia before a stroke is known to be a predictor for stroke severity and death from stroke. So it is possible that this cognitive test is identifying early cases of sub-clinical dementia. This theory will, however, need further research.

Analysis by Bazian

Links To The Headlines

Strokes: Drawing test 'may predict risks in older men'. BBC News, May 9 2012

Links To Science

Wiberg B, Kilander L, Sundström J et al. The relationship between executive dysfunction and post-stroke mortality: a population-based cohort study. BMJ Open 2012;2:e000458

“The coil is a much more effective form of emergency contraception than the morning-after pill,” the Metro has reported. The coil, medically known as an intrauterine device or IUD, is often used as a form of long-term contraception, but it can also be implanted after sex to provide emergency protection against pregnancy.

IUDs are in the news as researchers have today published findings on how effectively they prevent pregnancy in women who have them implanted after unprotected sex. Drawing on data from 43 previous studies, the review found women who had an IUD fitted after having unprotected sex had a pregnancy rate of 0.09% – the equivalent of less than 1 pregnancy out of every 1,000 IUDs inserted. Another way of saying this is that 99.91% of women who used an IUD as emergency contraception did not become pregnant.

The study was mainly based on findings relating to IUDs containing copper, rather than all-plastic devices, and the data came largely from Chinese studies. As a consequence, the results may not reflect the effectiveness of other types of coil or use of the IUD in the UK. Also, the research did not directly compare the coil to the effectiveness of emergency contraceptive pills, or examine how easily women could obtain an emergency coil following unprotected sex. These will both be important factors for women deciding which option to use.

 

Where did the story come from?

The study was led by researchers from the University of Princeton USA in collaboration with researchers based in South Africa, China and the UK. It was funded by a grant from Eunice Kennedy Shriver National Institute of Child Health and Human Development, and the researchers declared that they had no conflicts of interest.

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

Some news coverage of this research suggested women should “forget morning-after pills” as a form of emergency contraception, which is somewhat irresponsible as they remain an effective form of emergency contraception for some women. Also, emergency contraceptive pills may be a more practical and accessible option at times.

Women seeking emergency contraception should be informed about the full range of options available to them to help them make a decision about the most appropriate method for them.

 

What kind of research was this?

This research was a systematic review investigating how effective intrauterine devices are at preventing pregnancy when used for emergency contraception.

An intrauterine device (IUD) or ‘the coil’ is a form of birth control that is placed in the uterus of a woman to prevent pregnancy. An IUD is made of copper and plastic and works by physically preventing sperm from fertilising the egg. They can also prevent any fertilised eggs from implanting in the womb. Some devices, known as intrauterine systems, also release hormones that prevent fertilisation, but these were not included in this review and are not recommended for emergency contraception.

A systematic review seeks to identify and summarise all known literature published on a specific topic. It is an effective way of summarising a large body of research to answer a specific research question.

It should also be noted that the study did not directly compare the use of IUDs with the use of the morning after pill, nor did it compare how easily women could access either option after unprotected sex. This means we cannot tell which is a more viable option for women seeking emergency contraception, or say that one is intrinsically ‘better’ than the other based on the study’s results alone.

 

What did the research involve?

The researchers performed searches of research databases to gather all relevant published studies on women being given an IUD after seeking emergency contraception.

Studies were only included if clear information was available on whether the emergency contraception was effective and whether or not the women became pregnant. Only studies published in English or Chinese were included. The authors state that research published in Chinese was included because there is a high volume of contraceptive research taking place in China.

Those studies that met the inclusion criteria were analysed in more detail and data were extracted from them by two reviewers working independently of one another, which is intended to reduce errors and bias during data selection. The authors then described the results from the individual studies.

The researchers then used a simple method to pool the results of the different studies. During this process they combined the number of women seeking contraception and the number who became pregnant from across all the studies, which was intended to estimate the overall effectiveness of IUDs at preventing pregnancy.

 

What were the basic results?

The researchers included 42 studies that provided data on the effectiveness of IUDs in women seeking emergency contraception. These represented studies conducted in six countries between 1979 and 2011, and included 7,034 women using eight different types of IUD. Nearly all the IUDs were devices containing small amounts of copper, and only a small number of plastic-only IUDs were included, in the older pre-1985 studies. Most of the study data came from research based in China.

The main finding was that, out of the total 7,034 IUD insertions after unprotected sex, there were 10 recorded pregnancies. This gave a combined IUD failure rate (failure to prevent pregnancy) of 0.14% (95% CI 0.08 to 0.25%).

The authors commented that a study in Egypt gave a “surprisingly high” failure rate of 2%, which was vastly different from all the other studies. If this single atypical study was excluded the combined failure rate of using an IUD fell to 0.09% (95%CI 0.04 to 0.19%).

This rate means that less than one woman in every 1,000 would fall pregnant using the IUD as an emergency contraceptive. Another way of saying this is that 99.91% of women who used an IUD as emergency contraception did not become pregnant.

The maximum length of time from intercourse to IUD insertion ranged from two days to 10 or more days. Most of the insertions (74% of the studies) occurred within five days of intercourse. However, the studies did not include sufficient detail about the delay between intercourse and insertion of IUD for the researchers to analyse accurately how the effectiveness of the IUD was affected by any delay.

 

How did the researchers interpret the results?

The researchers conclude that “IUDs are a highly effective method of emergency contraception, with a failure rate of less than one per thousand”.

In discussing the different types of IUD they concluded that use of a copper IUD “is by far the most effective emergency contraception option” compared with the non-copper alternatives.

 

Conclusion

This systematic review of IUD use in emergency contraception provides useful estimates of pregnancy rates following insertion after unprotected sex. To assess the issue it drew upon studies in several different countries, although the studies were primarily carried out in China. The results of the study suggest that IUDs are a highly effective form of emergency contraception, with a very low failure rate of around 0.09%.

It should be noted that the research primarily estimates how likely it is that a woman would become pregnant after having unprotected sex and having an IUD fitted. It does not, however, tell us important related factors such as how available IUDs are after unprotected sex, nor does it confirm that they are necessarily a better option than emergency contraceptive pills. For example, women can obtain emergency contraceptive pills from specially trained pharmacists, whereas an IUD needs to be fitted by a trained clinician. This is not to say that either is better or more practical, rather that there are particular considerations to take into account with each form or contraception beyond overall failure rate.

The research also has some limitations, which should be considered when interpreting the results. For example, most of the results included in the review related to the copper coil and some were older devices, so the overall failure rate of 0.09% may not accurately represent the failure rate of newer IUDs or ones that contain hormones (known as intrauterine systems). More data on these devices are needed to establish whether they have a similar failure rate leading to pregnancy as the copper options included in the review. Similarly, most of the data feeding into the 0.09% figure come from studies based in China. Hence, this overall estimate best reflects copper IUD use in Chinese women. The effectiveness in other countries and for other IUDs is less certain based on this study alone.

Also, the research originally set out to assess the effectiveness of IUDs in detail so the researchers could see how many days had elapsed between unprotected sex and insertion of the IUD. However, the studies they identified did not contain sufficient detail for this to be possible. Hence, the combined IUD failure rate represents all cases together regardless of the time between intercourse and insertion of IUD. It is likely that the time between unprotected sex and insertion of the IUD directly influences the effectiveness of the contraceptive device, but this review was unable to analyse this. The recommended maximum interval after unprotected sex is 120 hours (five days) for most currently marketed devices.

As research was restricted to studies published in English or Chinese, this will exclude potentially informative research in other languages. The results of these excluded studies may have influenced the conclusions of this review had they been included.

When discussing their research the authors highlight recent studies exploring attitudes towards IUDs, which identified several potential barriers to a greater use of IUDs as emergency contraception. These included the waiting time (not being able to get a coil on the day emergency contraception is requested), low levels of awareness and understanding among patients, and a lack of understanding among healthcare providers. The results of this study, which show that IUDs are a highly effective option, may renew efforts to increase awareness of IUDs as an emergency contraceptive option. On this note, a spokeswoman for the Family Planning Association is quoted in the Metro as calling for more women to be offered the IUD routinely as a method of contraception.

The Metro’s headline suggesting that women should “forget morning-after pills” is somewhat irresponsible, as morning after pills remain an acceptable and effective method of emergency contraception for some women. A previous systematic review carried out by the Cochrane collaboration in 2008 concluded that drugs (such as the morning after pill) and copper IUDs were both effective and safe methods of emergency contraception.

The risks of sexually transmitted diseases associated with unprotected sex are well known and the coil, whether used as a standard contraceptive or an emergency contraceptive, does not reduce these risks.

Analysis by Bazian

Links To The Headlines

Forget morning-after pills, the coil is far more reliable. Metro, May 9 2012

Coil 'could be a more effective form of emergency contraception than the Morning-after pill'. Daily Mail, May 9 2012

Links To Science

Cleland K, Zhu H, Goldstuck N, et al. The efficacy of intrauterine devices for emergency contraception: a systematic review of 35 years of experience. Human Reproduction, Published online May 8 2012

“One in six cancers caused by preventable infections,” the Daily Mail reported today. The story comes from a study estimating that, of 12.7 million new cases of cancer that occurred worldwide in 2008, about 2 million were caused by infectious diseases.

The infections that cause cancer include Helicobacter pylori (the bacteria that cause stomach ulcers), hepatitis B and C (viruses that cause inflammation of the liver) and human papilloma viruses (sexually transmitted viruses that cause several cancers, notably cervical cancer in women). In women, cancers of the cervix were estimated to account for about half of infection-related cancers and in men, liver and gastric cancers accounted for more than 80%.

This important study suggests that certain treatable infections are a significant cause of cancer worldwide. It implies that tackling these infections (particularly in developing countries) may be a more effective way to reduce the number of global cancer deaths than focusing on treatment for the cancers.

It is of note that the proportion of cancers attributable to infection varied widely according to region, for example, in Europe 7% of cancers were attributed to infection while in sub-Saharan Africa this figure was 32.7%. It should also be noted that the calculations used by the researchers to identify the scale of cancer attributable to infections might be imprecise, partly due to the scarcity of cancer incidence data in some countries.

In the UK, infections such as H. pylori can be treated with antibiotics, vaccination against human papilloma virus (HPV) is offered by the NHS for girls aged 12 and 13, and a vaccine for people considered to be at high risk of hepatitis B is available.

While infections play a role in the development of several cancers, it is important to remember that there are many risk factors that affect how likely you are to develop cancer. These include smoking, diet and family history.

 

Where did the story come from?

The study was carried out by researchers from the International Agency for Research on Cancer, France. It was funded by Fondation Innovations en Infectiologie (FINOVI) and the Bill & Melinda Gates Foundation.

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

Generally, the media reported the story accurately, although headlines focused on the more alarming global figure of one in six cancers caused by infection than the estimated UK figure of 3.1% (just over one in 30).

 

What kind of research was this?

This was a narrative review in which the researchers estimated the proportion of cancers that could be attributed to infection, both worldwide and within eight geographical regions.

The authors point out that infection is recognised as a major cause of cancer worldwide and that prevention and treatment of infectious agents has already had a substantial effect on cancer prevention. Their review is an update of a previous review carried out in 2002.

 

What did the research involve?

The researchers reviewed the infectious agents that have been classified by the International Agency for Research on Cancer as causing cancer in humans and the cancer sites with which they are associated. There are thought to be 10 infections that can cause cancer, including:

• H. pylori (stomach)
• hepatitis B and C (liver)
• HPV (cervix, penis and other sites)
• Epstein-Barr virus (lymphomas and nose/throat)
• human T-cell lymphotropic virus type I (T-cell leukaemia and lymphoma)
• human herpes virus type 8 (Kaposi’s sarcoma)
• Chinese and South Asian liver flukes (gall bladder and bile duct)
• Schistosoma trematode worms (bladder)

The researchers obtained estimates of the number of new cancer cases in 2008 using statistics from an established source, the Globocan 2008 report, which provides age-specific and sex-specific incidence for 27 cancers in 184 countries.

For each of these cancers, they calculated the “population attributable fraction (PAF)”. PAF is an estimate of the proportion of cases of a disease that could theoretically be avoided, either by protection against or treatment of a specific risk factor. For example, H. pylori can be treated with antibiotics before it leads to stomach cancer. PAF uses a formula that combines the size of the effect of a risk factor with the distribution of that risk within a population. The researchers used various sources to calculate the PAF, including studies on risk factors associated with these cancers and the prevalence of infection.

Using the PAF they calculated the number of new cancer cases attributable to infection in 2008 worldwide and in eight geographical regions:

• sub-Saharan Africa
• North Africa and West Asia
• Central Asia
• East Asia
• South America
• North America
• Europe
• Oceania

 

What were the basic results?

• Researchers found that, of the 12.7 million new cancer cases that occurred in 2008, the population attributable fraction (PAF) for infectious agents was 16.1%, meaning that around 2 million new cancer cases were attributable to infections. This is the one in six figure quoted in the media.
• This fraction was higher in less developed countries (22.9%) than in more developed countries (7.4%), and varied from 4% in North America to 32.7% in sub-Saharan Africa.
• Helicobacter pylori, hepatitis B and C viruses, and human papilloma viruses (HPV) were responsible for 1.9 million cases of cancer, mainly gastric, liver and cervical cancers.
• In women, cervical cancer accounted for about half of the infection-related burden of cancer. In men, liver and gastric cancers accounted for more than 80%.
• Around 30% of infection-attributable cases occurred in people younger than 50 years.

 

How did the researchers interpret the results?

The researchers say that since infection-related cancers have high mortality rates, the proportion of cancer deaths attributed to infections is probably higher than 16.1%. They estimate that of the 7.5 million deaths from cancer in 2008, 1.5 million were caused by infections – roughly one in five cancer deaths worldwide.

Public health measures to prevent infections, such as vaccination, safer injection practice or antimicrobial treatments, could substantially reduce future burden of cancer worldwide, the researchers argue.

 

Conclusion

This important study highlights the potential role played by certain infections in causing cancer. It uses the highest quality available evidence to calculate the proportion of cancer caused by infectious agents, worldwide and by region.

However, as the authors point out, their calculations may be imprecise. For example, many countries have very sparse data on cancer incidence and the prevalence of risk factors for specific cancers. To obtain global estimates researchers had to extrapolate data from other areas. They also say they had to make certain assumptions, for example, that the risk of infection was constant across populations and sexes. They also point out that there was a lack of high quality data from some of the research sites in the studies.

In the UK, a vaccine against strains of HPV that cause cancer (as well as genital warts) is now offered to girls between the ages of 12 and 13. A vaccine for people considered at high risk of hepatitis B is also available. Helicobacter pylori is usually treated with antibiotics when diagnosed. These may all contribute to a further reduction in the proportion of cancers caused by infectious diseases in this country, which may be some way below that suggested in the headlines.

It’s important to bear in mind the other risk factors, such as smoking, diet and family history, that can contribute to your chances of developing cancer.

Links To The Headlines

'One in six cancers worldwide are caused by infection'. BBC News, May 9 2012

One in six cancers are caused by preventable infections. Daily Mail, May 9 2012

One in six cancers 'caused by treatable infections'. The Guardian, May 9 2012

Links To Science

de Martel C, Ferlay J, Franceschi S et al. Global burden of cancers attributable to infections in 2008: a review and synthetic analysis. The Lancet Oncology, Early Online Publication, May 9 2012

Scientists have found that taking zinc tablets “may shorten the duration of a cold”, The Independent reported today.

For many years, laboratory research has suggested that zinc can stop cold viruses from multiplying, but it has not been clear whether this means taking zinc can prevent or ease a cold. To examine the issue, scientists pulled together all relevant studies of zinc as a cold treatment and conducted a thorough range of analyses of their overall findings. They found that zinc lozenges may shorten the length of a cold by one or two days more than taking a dummy placebo treatment, but that taking zinc was also associated with side effects.

Notwithstanding the newspaper’s excitement, the conclusions of this study are not new. A previous systematic review published in 2011 also found that zinc reduced the duration and severity of cold symptoms, although the trials it included varied considerably in methods, study populations and dosage timing. Overall, this variation made the results less reliable.

The common cold is generally a mild illness. Given that zinc carries the potential for side effects such as nausea and an unpleasant taste, zinc supplements are probably not suitable as a treatment for most people. Furthermore, large high-quality trials to assess the effectiveness and safety of zinc for the common cold would be needed before any recommendations could be made. It should be possible for a person to get all the daily zinc they need from a normal balanced diet.

 

Where did the story come from?

The study was carried out by researchers from the Hospital for Sick Children, Toronto, and MacMaster University, Ontario. There was no external funding for this study. The study was published in the peer-reviewed Canadian Medical Association Journal.

The research was accurately reported in The Independent, although the paper may have implied that this was the first time a study on zinc and the common cold had been undertaken. The issue was in fact examined in a recent review conducted by the prestigious Cochrane organisation, which found a modest reduction in the length of cold symptoms among people who had been using zinc supplements over a number of months. Cochrane reviews are generally considered to be among the highest levels of evidence, and draw upon all relevant evidence on a particular topic, rather than just selected studies supporting a particular view.

 

What kind of research was this?

This was a systematic review and meta-analysis of randomised controlled trials evaluating the effectiveness and safety of zinc as a treatment for the common cold. A randomised controlled trial, in which a treatment is compared to a placebo or another intervention, is the best direct way to assess the effectiveness of a treatment as it tests two or more treatments among two or more groups of randomly selected individuals. In a systematic review, researchers search through all relevant literature sources to identify all trials that have assessed the question of interest, and then use rigorous criteria to assess the quality of this evidence. Systematic reviews can also include a meta-analysis, a statistical method that combines the results of all identified studies into a single, larger set of data and results.

The researchers point out that colds are very common: on average, adults get colds two to four times and children eight to ten times a year. Although not serious for most people, colds lead to substantial amounts of time off work and school.

Colds can be caused by several viruses, of which rhinoviruses are the most common. Lab research has shown that the mineral zinc is known to help block replication of rhinoviruses and other viruses which affect the respiratory system, so might be a potential treatment for colds. The authors of this review also suggest that zinc may reduce the severity of cold symptoms by reducing activity in one of the main nerves in the face.

The authors point out that the recent Cochrane review concluded that zinc was effective at reducing the duration and severity of cold symptoms, but that the studies covered in the review varied so much in their design and nature that the results may be unreliable. On this basis, they say, the effectiveness of zinc remains uncertain.

In their own systematic review, the researchers say they tried to improve on the previous review by including more trials and obtaining additional data from the study authors.

 

What did the research involve?

The researchers conducted a search of several electronic databases and other sources for any studies on zinc as a treatment for the common cold, published up to September 2011. They included studies from all years and in any language, and included all randomised controlled trials comparing zinc taken orally with a placebo or with no treatment for common colds. All potentially relevant articles were screened and assessed to decide whether they were eligible for inclusion in the review. Study authors were also contacted for further information when required.

The researchers assessed the studies for any risk of bias using a validated method. Risk of bias occurs if the results of a study are affected by factors such as whether participants know which treatment they are using, which can affect their impressions of how effective a treatment is. They pooled all the relevant data from the studies included and carried out a statistical analysis using validated methods.

The researchers also carried out “subgroup” analyses to assess whether factors such as age, formulation, dosage and timing of treatment, and funding source (whether industry or independent) had any effects on the results.

 

What were the basic results?

The researchers included 17 studies in their review, involving 2,121 participants. The results of 14 of these studies were combined in the meta-analysis. They found that people taking zinc had cold symptoms for an average of one to two days less than patients given a placebo treatment (mean difference -1.65 days, 95% confidence interval [CI] -2.50 to -0.81). However, they pointed out that differences between trials in terms of design, dosages, timing and age of participants make this result less reliable. This problem persisted even after subgroup analyses.

The other findings are summarised below:

• Zinc shortened the duration of cold symptoms in adults by between two and three days (mean difference -2.63, 95% CI -3.69 to -1.58).
• Zinc had no significant effect on duration of cold symptoms in children (mean difference -0.26, 95% CI -0.78 to 0.25).
• Adverse events were more common in the zinc group than in the placebo group. These included unpleasant taste and nausea. The results show that 477 per 1,000 people taking zinc got side effects, compared to 385 per 1,000 in the control groups.
• Higher doses of zinc had greater effects on reducing symptom duration than low doses.

 

How did the researchers interpret the results?

The researchers say they found “moderate quality” evidence to suggest that zinc taken orally reduces the duration of cold symptoms, but that large high-quality trials are needed to properly assess the potential benefits and side effects of taking zinc for a cold. “The questionable benefits must be balanced against the potential adverse effects,” they argue.

 

Conclusion

For many years, it has been suggested that zinc supplements could relieve the symptoms of the common cold, but there was little clarity until a 2011 evidence review. This recent review suggested a modest reduction in the length of symptoms, although the results were not entirely conclusive. In a bid to help clarify the matter, researchers have conducted another review of evidence on this issue.

It suggests that zinc may help shorten the common cold. However, as with the previous reviews, the results are undermined by the high variability between trials in terms of their methods, study population and treatment aspects (such as zinc dosage and when zinc was first taken). In addition, while zinc may help shorten a cold, it also seems to have side effects such as nausea and an unpleasant taste. As the authors point out, large-scale randomised trials would be needed to assess whether the potential benefits of zinc outweigh the side effects, as well as what dose might be optimal. However, colds are a minor illness for most people, so whether such a trial is warranted is debatable.

From a nutritional perspective, the recommended daily intake of zinc is 5.5–9.5mg a day for men, and 4–7mg a day for women. It should be possible to obtain this amount through a normal balanced diet. If supplementary zinc is taken, the Food Standards Agency and Department of Health recommend that no more than 25mg a day is taken, as too much may cause anaemia and weakening of the bones.

Links To The Headlines

Zinc tablets may shorten the duration of a cold. The Independent, May 8 2012

Links To Science

Science M, Johnstone J, Roth DE et al. Zinc for the treatment of the common cold: a systematic review and meta-analysis of randomized controlled trials. Canadian Medical Association Journal, May 7 2012 (published online)

Cochrane review

Singh M, Das RR. Zinc for the common cold. Cochrane Database of Systematic Reviews 2011, Issue 2. Art. No.: CD001364. DOI: 10.1002/14651858.CD001364.pub3

“A blood test for men with prostate cancer could detect if the illness is likely to be life-threatening,” the Daily Mail has reported. In some cases prostate cancer can be benign, but in others it can be life-threatening and require treatment such as surgery or chemotherapy.

The news is based on research that looked at whether scanning for genetic abnormalities in various types of tissue could be used to predict whether prostate cancer would rapidly relapse after treatment. To conduct the research, scientists looked at samples of blood, prostate tumours and healthy prostate tissue from 238 men who had undergone surgery to remove their whole prostate gland. They compared genetic differences to the different outcomes the men experienced.

The researchers found that prostate cancer patients had high numbers of genetic mutations called "copy number variations", in which sections of DNA are abnormally repeated or missing. Particular repeats and deletions were more common in patients who went onto have a rapid relapse, and the size of copy number variations tended to be larger in these patients as well. The researchers then used this information to create prediction models based on the DNA in different types of tissue samples.

This study is exciting because it raises hope that one day a test could help predict the outlook for patients with prostate cancer, which could in turn aid treatment decisions. However, these findings will have to be further validated, and a simple, inexpensive test developed and tested before this is a realistic option for doctors.

 

Where did the story come from?

The study was carried out by researchers from the University of Pittsburgh and was funded by the American Cancer Society, the US National Cancer Institute and the University of Pittsburgh Cancer Institute. The study was published in the peer-reviewed American Journal of Pathology.

The Daily Mail’s coverage of the story was generally accurate, although it may imply that the research could help discern benign prostate tumours from life-threatening ones before treatment. However, the research was conducted in patients after a round of treatment where they had already had surgery to remove all or part of the prostate. Also, the Mail’s headline suggests that the test has been developed and is soon to be implemented, which is not the case. The story correctly stated that “it is likely to be several years before the academics are able to develop a blood test to predict the speed prostate cancer will spread.”

 

What kind of research was this?

Prostate cancer is not typical of most cancers, as men can live with the condition for many decades without any symptoms or the need for treatment. This is because in most cases the cancer progresses very slowly, at such a rate that they will probably die of other causes or even old age before it causes ill effects on their health. However, a minority of men with the disease experience a more rapid progression of their cancer that requires treatment, such as a prostatectomy (surgery to remove all or part of the prostate).

This cohort study of men with prostate cancer examined whether the presence of genetic abnormalities in various types of tissue could predict whether a person with treated prostate cancer would relapse. It looked at the amount of genetic abnormalities in tumour tissue, normal tissue adjacent to a tumour and in blood.

The specific type of genetic abnormality the researchers looked at is called a copy number variation. This occurs when duplications or deletions in the genetic code cause an abnormal number of copies of a region of DNA. The researchers initially looked at samples from 238 men who had had radical prostatectomy (a surgical procedure where part or all of the prostate gland is removed), and three cell lines (a type of isolated cell used in lab research). They then validated their findings on an additional 25 samples.

This study was appropriately designed to see whether patients who have different outcomes have differences in copy number variation. However, before this technique can be used as a test, it will have to be trialled on a much larger cohort of people, so that researchers can get a clearer picture of its use in clinical settings. For example, researchers will need to know how often the test might miss patients that are likely to relapse, and also how often the test incorrectly suggests a person’s cancer is likely to relapse, which could lead them to have unnecessary further treatment. Also, as the authors note, the techniques used in this study need high-quality DNA, so may be difficult and expensive to perform.

 

What did the research involve?

The researchers looked at prostate cancer samples, samples of healthy tissue taken from next to a tumour, and blood from men who had had a radical prostatectomy to treat prostate cancer. The researchers extracted DNA from these samples, and then looked at their genome, the entire genetic code they contained. The researchers then compared the results from this analysis to the outcomes experienced by the prostate cancer patients:

• Approximately one-third of the patients had a relapse soon after surgery, with a median time to progression of 1.9 months.
• One-third had a relapse but much more slowly, with a median time to progression of 47.4 months.
• One-third of patients in the cohort were free of cancer for at least five years.

Based on the associations they found, the researchers developed an algorithm for predicting whether a patient would relapse, and how quickly they would relapse. This was based on whether the genetic code at specific locations was repeated or deleted, or on the size of copy number variation found across a person’s genome. They then tested their prediction model on an additional 25 samples.

 

What were the basic results?

The researchers found that the prostate cancer samples had a large number of genetic abnormalities. Deletions of specific regions occurred at high frequency, and amplification (abnormal repetitions) of other regions occurred in a subset of samples. Healthy tissue adjacent to a tumour also had similar amplification and deletion patterns. The blood of patients with prostate cancer also contained copy number variations, and some of these variations occurred in the same locations within the DNA as they had in the prostate cancer samples.

The researchers then developed a tool to predict whether a cancer would relapse based on DNA regions that had a significant proportion of amplification or deletion in prostate tissue samples (both cancerous and healthy) from patients who relapsed, but not in patients who did not relapse.

• The prediction model looking at cancer tissue samples could predict a relapse correctly 73% of the time. It had a 75% accuracy for predicting rapid relapse (relapse with a short PSA doubling time).
• The prediction model based on examining healthy tissue samples could predict a relapse 67% of the time. It had a 77% accuracy for predicting rapid relapse.

For blood samples, looking at amplification and deletion of specific regions did not distinguish patients who relapsed from non-relapsed patients. Instead, the researchers looked at the size of copy number variations throughout the genome, as they had observed that the size of variations in patients who relapsed was significantly larger.

This blood-based prediction model had an accuracy of 81% for predicting relapse, and a 69% accuracy for predicting rapid relapse.

The researchers then validated their models on a further 25 samples:

• The cancer tissue analysis tool had an accuracy of 70% for predicting relapse, and 80% for rapid relapse.
• The healthy tissue sample tool had an accuracy of 70% for relapse and rapid relapse.
• The blood sample tool had an accuracy of 100% for relapse and 80% for rapid relapse.

 

How did the researchers interpret the results?

The researchers said that copy number variation analysis of blood, normal prostate tissue or tumour tissues “holds promise to become a more efficient and accurate way to predict the behaviour of prostate cancer”.

 

Conclusion

This novel study looked at genetic abnormalities in patients who had prostate cancer and whether they could be used to predict whether the cancer would relapse and, if so, how soon. It found that prostate cancer patients had high numbers of “copy number variations”, where there is an abnormal number of copies of a particular DNA region. These regions were also often large.

By comparing particular amplifications and deletions and the size of copy number variants, the researchers were able to build a prediction model to identify patients who would relapse and those who would relapse quickest (as demonstrated by a rapid increase in PSA levels). The prediction models could be used on DNA extracted from prostate cancer tissue, normal prostate tissue or blood.

This study is exciting because it raises hope that a test may one day predict the prognosis of patients with prostate cancer, which could in turn aid treatment decisions. However, this will only be possible once these findings have been further validated and a simple, inexpensive test developed and tested.

Analysis by Bazian

Links To The Headlines

Blood test for missing or damaged DNA could provide hint of a prostate cancer relapse. Daily Mail, May 7 2012

Links To Science

Yu YP, Song C, Tseng G et al. Genome abnormalities precede prostate cancer and predict clinical relapse. The American Journal of Pathology, 2012;180:2240-2248