NHS Choices

Hormone oestrogen linked to male breast cancer

NHS Choices - Behind the Headlines - Tue, 12/05/2015 - 14:00

"Men with high oestrogen more likely to develop breast cancer," reports the Daily Telegraph.

This headline is based on an international study looking at potential risk factors for male breast cancer. This is a much rarer cancer compared to female breast cancer – an estimated 350-400 UK cases per year for men compared to 50,000 cases in women.

It is known that the hormone oestrogen can trigger the development of some types of female breast cancer. Men as well as women produce oestrogen, but at much lower levels, so researchers wanted to see if there was a similar connection.

This study compared blood samples taken from 101 men who went on to develop breast cancer, with 217 men who didn’t.

It found that men with the highest levels of one form of the hormone oestrogen were about two-and-a-half times more likely to develop the condition than those with the lowest levels.

The study used a good design and approach, and the findings seem plausible, given what is known in women. However, it is still difficult to say whether a raised oestrogen level is directly raising the risk of breast cancer, or if both could be the result of another underlying factor.

Learning more about the causes of male breast cancer might help to find ways to prevent it or find new treatments in the long term.

 

Where did the story come from?

The study was carried out by researchers from the National Cancer Institute in the US, and other research centres in the US, Europe and Canada. It was part of the Male Breast Cancer Pooling Project, and was funded by various international sources, including the National Cancer Institute in the US, and Cancer Research UK and the UK Medical Research Council.

The study was published in the peer-reviewed Journal of Clinical Oncology.

The Telegraph covers this study reasonably well.

 

What kind of research was this?

This was a nested case-control study looking at whether levels of sex hormones are related to a man’s risk of developing breast cancer.

Breast cancer can occur in men, but is very rare. In the UK, about 350 men are reported to be diagnosed with the condition each year. This makes the condition difficult to study, and this is why researchers came together to form an international collaboration, so that they could identify more cases than they would be able to by working alone.

Men and women both produce the sex hormones oestrogen and testosterone – but at different levels. In women, breast cancer is known to be influenced by these hormones. The roles these hormones play in male breast cancer is not known.

A nested case-control study is the most feasible way of looking for possible risk factors for rare diseases. Being "nested" means that information is collected on risk factors in a prospective fashion in a larger group of people, and then people who develop the condition are identified. These people are the "cases" and a matched group of people with similar characteristics, but without the condition, are the "controls".

 

What did the research involve?

The researchers identified 101 men with breast cancer (cases), and 217 similar men without the condition were selected as controls. They analysed blood samples that had been collected from the men before their diagnosis, and compared hormone levels to see if there were any differences from cases and controls.

The participants were identified through seven cohort studies that recruited men without breast cancer. The men provided blood samples, and these were stored. They were then followed up to see if they developed breast cancer. When a case was identified, the researchers selected up to 40 control men from their cohort who were similar to the affected man in terms of race, year of birth, year they entered the study, and how long they had been followed up for.

The researchers then analysed the stored samples to measure the levels of various forms of the steroid sex hormones oestrogen and testosterone. They compared levels in men who later went on to develop breast cancer and controls, to see if they differed. They took into account factors that might affect results (potential confounders) such as:

  • age when the blood sample was taken
  • race
  • body mass index (BMI)
  • date of the blood sample

 

What were the basic results?

The researchers found that for the male sex hormones (androgens such as testosterone) there were no differences in levels between men who went on to develop breast cancer, and those who did not.

However, men who developed breast cancer did have higher levels of the hormone oestradiol (one form of oestrogen) than controls. Men who had the highest oestradiol levels were about two-and-a-half times more likely to develop the condition than those with the lowest levels (odds ratio (OR) 2.47, 95% confidence interval (CI) 1.10 to 5.58).

 

How did the researchers interpret the results?

The researchers conclude that their results support a role for oestradiol (oestrogen) in the development of breast cancer in men. They report that this is similar to the level of effect seen in postmenopausal women.

 

Conclusion

This study has identified that oestrogen may play a role in the development of breast cancer in men. The study’s strengths include the prospective collection of data, and the relatively large group of cases, given how rare the disease is.

One of the main limitations of this type of study is that other factors may influence results. In this study, this risk was minimised by matching controls to cases within each country, and by adjusting for various confounders in the analyses. Despite this, some unmeasured confounders may still have an effect. For example, breast cancer in a first-degree relative (parent or sibling) was five times more common in men who developed breast cancer, and there was no information on whether any of the men carried a high risk form of the BRCA genes, which increase the risk of cancer.

In addition, only one blood sample appeared to be tested for each man, and at various times before their diagnosis. It is possible that the single sample taken may not be representative of levels over a longer period.

It is difficult to say from this type of study whether oestrogen levels are directly causing an increase in risk. The authors note that it is not clear how higher levels of oestrogen might increase breast cancer risk.

Overall, the findings of this study seem plausible, given what is known about breast cancer in women, and could increase knowledge about possible risk factors for male breast cancer.

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

Links To The Headlines

Men with high oestrogen more likely to develop breast cancer. The Daily Telegraph, May 11 2015

Links To Science

Brinton LA, Key TJ, Kolonel LN, et al. Prediagnostic Sex Steroid Hormones in Relation to Male Breast Cancer Risk. Journal of Clinical Oncology. Published online May 11 2015

Categories: NHS Choices

Scientists 'amazed' at spread of typhoid 'superbug'

NHS Choices - Behind the Headlines - Tue, 12/05/2015 - 13:00

“Antibiotic-resistant typhoid is spreading across Africa and Asia and poses a major global health threat,” BBC News reports.

Typhoid fever is a bacterial infection. If left untreated, it can lead to potentially fatal complications, such as internal bleeding.

Uncommon in the UK (there were 33 confirmed UK cases in the first quarter of 2015 and it is thought most of these were contracted abroad), it is more widespread in countries where there is poor sanitation and hygiene.

The headline is based on a study that looked at the genetics of the bacteria that causes typhoid fever, Salmonella typhi, to trace their origins.

The study analysed genetic data from almost 2,000 samples of Salmonella typhi collected between 1903 and 2013. It was looking for a strain called H58 that is often antibiotic-resistant. It found that this strain was likely to have originated in South Asia around the early 1990s, and has spread to other countries in Africa and Southeast Asia. It accounted for about 40% of samples collected each year. Over two-thirds of the H58 samples had genes that would allow them to be resistant to antibiotics.

It would be complacent to assume that this is just a problem for people in the developing world, as antibiotic resistance is a major threat facing human health worldwide. Studies such as this help researchers to identify and track how such bacteria spread. This may help them to use existing antibiotics more effectively, by identifying where specific types of resistance are common.

 

Where did the story come from?

The study was carried out by a large number of researchers from international institutions, including the Wellcome Trust Sanger Institute, in the UK. The researchers were also funded by a wide range of international organisations, including the Wellcome Trust and Novartis Vaccines Institute for Global Health.

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

The news sources cover this story reasonably. Some reporting implies that it is the H58 strain that is killing 200,000 people a year, but this study has not assessed this.

The 200,000 figure seems to be taken from information provided by the US’s Centers for Disease Control and Prevention (CDC), and is an estimate of all types of typhoid fever, not just the H58 strain.

 

What kind of research was this?

This was a genetic study looking at the origins and spread of the H58 strain of Salmonella typhi – the bacteria that causes typhoid fever. This strain is often found to be antibiotic-resistant.

The typhoid bacteria are spread by ingestion of infected faecal matter from a person with the disease. This means that it is a problem in countries where there is poor sanitation and hygiene. Typhoid fever is uncommon in the UK, and most cases in this country are people who have travelled to high-risk areas where the infection still occurs, including the Indian subcontinent, South and Southeast Asia, and Africa. The researchers say that 20-30 million cases of typhoid are estimated to occur each year worldwide.

Typhoid fever has been traditionally treated with the antibiotics chloramphenicol, ampicillin and trimethoprim-sulfamethoxazole. Since the 1970s, strains of typhoid have started to emerge that are resistant to these antibiotics (called multidrug-resistant strains). Different antibiotics, such as fluoroquinolones, have been used since the 1990s, but strains resistant to these antibiotics have been identified recently in Asia and Africa. One such strain, H58, is becoming more common, and was the focus of this study.

 

What did the research involve?

The researchers used genetic sequence data from 1,832 samples of Salmonella typhi bacteria collected across the world. They used this data to assess when the H58 strain (which has identifiable genetic characteristics) had arisen and how it had spread.

They first identified which of the samples belonged to the H58 strain, and in what year it was first identified. They also looked at what the proportion of samples collected in each year were of this strain, to see if it was becoming more common.

Over time, DNA accumulates changes, and the researchers used computer programmes to analyse the genetic changes present in each sample to identify how each strain is likely to be related to the others. By combining this information with the origin and year of each sample, the researchers developed an idea of how the strain had spread.

 

What were the basic results?

The researchers found that nearly half of their samples (47%) belonged to the H58 strain. The first sample identified as part of this strain was from Fiji in 1992, and continued to be identified up to the latest samples, from 2013. H58 strain samples were identified from 21 countries in Asia, Africa and Oceania, showing that it is now widespread. Overall, 68% of these H58 samples had genes that would allow them to be antibiotic-resistant.

There were some very genetically closely related samples found in different countries, suggesting that there was human transfer of the bacteria between these countries. Their genetic analyses suggested that the strain was initially located in South Asia, and then spread to Southeast Asia, western Asia and East Africa, as well as Fiji.

There was evidence of multiple transfers of the strain from Asia to Africa. The H58 strain accounted for 63% of samples from eastern and southern Africa. The analysis suggested that there had been a recent wave of transmission of the H58 strain from Kenya to Tanzania, and on to Malawi and South Africa. This had not previously been reported, and the researchers described it as an “ongoing epidemic of H58 typhoid across countries in eastern and southern Africa”.

Multidrug resistance was reported to be common among H58 samples from Southeast Asia in the 1990s and, more recently, samples from this region have acquired mutations which have made them less susceptible to fluoroquinolones. These have become more common in the area, and researchers suggested that this is due to the use of fluoroquinolones to treat typhoid fever over this period, leading to these resistant strains having a survival advantage.

In South Asia, there are lower rates of multidrug resistance in recent samples than in Southeast Asia. In Africa, most samples showed multidrug resistance to the older antibiotics, but not fluoroquinolones, as these are not frequently used there.

 

How did the researchers interpret the results?

The researchers say that their analysis is the first of its kind for the H58 typhoid strain, and that the spread of this strain “requires urgent international attention”. They say that their study “highlights the need for longstanding routine surveillance to capture epidemics and monitor changes in bacterial populations as a means to facilitate public health measures, such as the use of effective antimicrobials and the introduction of vaccine programs, to reduce the vast and neglected morbidity and mortality caused by typhoid”.

 

Conclusion

This study has provided information about the spread of a strain of typhoid called H58, which is commonly antibiotic-resistant, by looking at the genetics of samples collected between 1903 and 2013. It has shown that the strain was likely to have arisen in South Asia and then spread to Southeast Asia and Africa. The strain showed different patterns of antibiotic resistance in different regions – likely driven by different patterns in the use of antibiotics.

While this study has not estimated the number of cases or deaths worldwide attributable to this strain specifically, there are reported to be 20-30 million cases of typhoid fever globally each year.

The spread of antibiotic resistance is a major threat to human health, and studies like this can help us to monitor them and target treatment more effectively.

Read more about the battle against antibacterial resistance and how we can all help do our bit.

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

Links To The Headlines

Drug-resistant typhoid 'concerning'. BBC News, May 11 2015

Antibiotic-resistant typhoid spreading in silent epidemic, says study. The Guardian, May 11 2015

Deadly typhoid superbug poses global threat after 'rapidly spreading' through Asia and Africa, experts warn. Mail Online, May 11 2015

Links To Science

Wong VK, Baker S, Pickard DJ, et al. Phylogeographical analysis of the dominant multidrug-resistant H58 clade of Salmonella Typhi identifies inter- and intracontinental transmission events. Nature Genetics. Published online May 11 2015

Categories: NHS Choices

Claims a 'sweet tooth' increases your Alzheimer’s risk too simplistic

NHS Choices - Behind the Headlines - Mon, 11/05/2015 - 13:30

"Could cake and chocolate lead to Alzheimer's disease?" The Daily Telegraph asks.

In a series of animal experiments, researchers attempted to see whether high blood glucose could be involved in the development of amyloid protein plaques in the brain; a characteristic hallmark of Alzheimer’s disease. These plaques are abnormal "clumps" of protein that are thought to gradually destroy healthy brain cells.

Some studies have suggested that people with high blood glucose levels and those with type 2 diabetes may be at greater risk of the disease, and this study aimed to see why that might be the case.

The experiments found that giving the mice a sugar solution over a number of hours led to an increased concentration of amyloid in the fluid surrounding the brain cells. The effect was more pronounced in older mice.

The study has only looked at the short-term effects, and not at whether high glucose levels affected longer-term plaque formation or symptoms in the mice.

At this stage, it is not conclusively proven that type 2 diabetes is a risk factor for Alzheimer’s disease, or that you have increased risk of the disease if you have a high-sugar diet.

However, sticking to current healthy eating and activity recommendations is a good way to increase your chances of staying healthy.

 

Where did the story come from?

The study was carried out by researchers from Knight Alzheimer’s Disease Research Center and Washington University School of Medicine in the US, and was funded by the National Institutes of Health. The study was published in the peer-reviewed Journal of Clinical Investigation. It is an open-access study, so it is free to read online or download as a PDF.

The Daily Express accurately describes the methods of the study, but doesn’t make it clear until later in the research that study was on mice. The Daily Telegraph was more upfront about this fact.

The Telegraph piece also includes information on a related study into green tea and Alzheimer’s disease. We have not analysed the study, so we cannot say how accurate the Telegraph’s reporting of this study was.

 

What kind of research was this?

This was animal research that aimed to look into why there might be a link between blood glucose and risk of dementia, specifically Alzheimer’s disease.

The causes of Alzheimer’s disease are still not fully understood. Increasing age is the most well-established factor to date, and there is the possibility of hereditary factors. The influence of health and lifestyle factors is uncertain. Some previous studies have suggested that glucose levels in the blood may have an impact on the development of the beta-amyloid "plaques" and the tau protein "tangles" in the brain that are the hallmarks of the disease. This is supported by other studies that have suggested people with type 2 diabetes are more likely to develop Alzheimer’s disease. Therefore, this research aimed to look at whether there was a biological reason for this. 

Animal studies can provide a valuable indication of how disease processes may work, but the process may not be exactly the same in humans.

 

What did the research involve?

The researchers carried out experiments to control the blood glucose level of a genetically engineered mouse model of Alzheimer’s disease and looked at the effect on the composition of the fluid surrounding the brain cells.

The research involved three-month-old mice, who would normally be too young to have beta-amyloid protein deposits in the brain. Under anaesthetic, the researchers gained access to the large vein and artery in the neck, and then a catheter was guided through the blood vessel into one region of the brain (the hippocampus). Once the mice were awake again, these tubes allowed the researchers to infuse glucose into the brain, and to sample the fluid around the brain cells while the mice were still awake and moving around.

In their experiments, the researchers withheld food from the mice for several hours before a glucose solution was gradually infused into the brain over four hours.

Fluid around the brain cells was sampled every hour during the infusion to look at levels of glucose, beta-amyloid protein and lactate (a compound involved with the metabolism of the brain) – the latter was used as a marker of brain cell activity. The brain was also examined after death.

Other experiments included infusing older, 18-month-old, mice that would already be expected to have some beta-amyloid build-up.

They also tried infusing different drugs to examine in more depth precisely what biological mechanisms were occurring in the brain that could be causing these effects.

 

What were the basic results?

In the main experiments in younger mice, the glucose infusion almost doubled glucose concentration in the brain fluid and increased the concentration of beta-amyloid by 25%. Lactate levels also increased, suggesting an increase in brain cell activity.

In the older mice, glucose infusion raised the concentration of beta-amyloid even higher – by around 45%.

 

How did the researchers interpret the results?

The researchers found that increased blood glucose levels affect brain cell activity glucose, leading to increased beta-amyloid in the fluid surrounding the brain cells in young mice that would normally have minimal beta-amyloid. In aged mice, the effect was even more pronounced.

They further suggest that "during the preclinical period of Alzheimer’s disease, while individuals are cognitively normal, our findings suggest that repeated episodes of transient [high blood glucose], such as those found in [type 2 diabetes], could both initiate and accelerate plaque accumulation".

 

Conclusion

This animal study supports the theory that elevated blood sugar might influence the development of beta-amyloid plaques in the brain – one of the characteristic hallmarks of Alzheimer’s disease. As the researchers say, glucose could similarly be involved in their development in humans.

However, at this stage, we cannot extrapolate these short-term results in mice much further. While animal studies provide a valuable indication of how disease processes may work in humans, the process may not be exactly the same. The study has not looked at the long-term effects of raised glucose on plaque formation in these Alzheimer’s-model mice, and how long raised levels need to be present to have an effect.

Even if the development of amyloid plaques in the human brain could be affected by levels of glucose, we don’t understand the intricacies of how this might happen or whether it can be avoided. Body cells – particularly those in the brain – need glucose, so clearly it cannot be avoided.

Currently, it has not been conclusively proven that type 2 diabetes is a risk factor for Alzheimer’s disease, or that you have increased risk of disease development by having a high-sugar diet. However, high-calorie diets are well established to be a risk factor for overweight and obesity, which are linked to many chronic health conditions, including type 2 diabetes. Sticking to current diet and activity recommendations can help to maintain good health.

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

Links To The Headlines

Could cake and chocolate lead to Alzheimer's disease? The Daily Telegraph, May 6 2015

Got a sweet tooth? It could put you at risk of Alzheimer's. Daily Express, May 6 2015

Links To Science

Macauley SL, Stanley M, Caesar EE, et al. Hyperglycemia modulates extracellular amyloid-β concentrations and neuronal activity in vivo. The Journal of Clinical Investigation. Published online May 4 2015

Categories: NHS Choices

Overweight diabetics 'live longer' than slimmer diabetics

NHS Choices - Behind the Headlines - Mon, 11/05/2015 - 13:00

“Overweight diabetics are 13 per cent less likely to die prematurely than those of a normal weight or those who are obese,” the Mail Online reports.

A new study followed over 10,000 English older adults with type 2 diabetes for 10 years. It examined how their body mass index (BMI) was linked to risk of later cardiovascular disease events such as heart attack and stroke, and death from any cause.

It found that overweight people had a 13% reduced risk of death compared with people who had a normal BMI. Risk of death was no different between obese people and those with a normal BMI.

However, it also found that people who were overweight or obese had an increased risk of cardiovascular disease events that required hospitalisation.

Great care must be taken before jumping to the conclusion that being overweight could be good for people with type 2 diabetes. As seen in this study, being overweight or obese increased the risk of diabetes complications, which could have an adverse impact on quality of life, even if not fatal.

The findings could also have been influenced by various factors other than BMI, including how well people’s diabetes is controlled. Further study is needed to uncover the biological mechanism, if there is a real link.

Current advice remains the same – whatever your current health, aim for a healthy BMI through a balanced diet and regular exercise.

 

Where did the story come from?

The study was carried out by researchers from University of Hull, Imperial College London and Federico II University in Naples, Italy. Financial support was provided by National Institute for Health Research, Hull York Medical School at the University of Hull, and Imperial College London.

The study was published in the peer-reviewed journal Annals of Internal Medicine.

The Mail’s coverage takes the findings at face value, suggesting that being overweight or obese could prolong life for people with type 2 diabetes. However, the study does not prove this and there are known adverse health risks of being overweight or obese.

 

What kind of research was this?

This was a prospective cohort study that aimed to investigate whether body weight has an influence on prognosis (what happens to health over time) in people with type 2 diabetes.

The link between obesity and increased risk of cardiovascular disease is well established. However, some other studies have suggested that in people with established cardiovascular disease, obesity could somehow offer a survival advantage. This observation has been named the "obesity paradox" – as it goes against what one would expect. The researchers wanted to investigate whether a similar link might be seen between obesity and survival in people with type 2 diabetes. The main limitation of this type of study is that there may be unmeasured confounding factors influencing any apparent relationship.

 

What did the research involve?

The study included adults diagnosed with type 2 diabetes who attended the outpatient clinic of a single NHS hospital in England, with a follow-up period of around 10 years. The researchers analysed whether participants’ BMIs were linked to their risk of cardiovascular events or death from any cause.

The participants had attended the clinic between 1995 and 2005, and had their data entered into a patient registry. A total of 10,568 people with type 2 diabetes (54% men) were included.

At the first visit data was collected on age, duration of diabetes, height, weight, blood pressure, smoking history and other significant illnesses (eg cancer, lung or kidney disease). All of these factors were adjusted for in analyses, to try to remove their effects.

Participants were followed for an average of 10.6 years, to end-2011. The main outcome examined was all-cause mortality (death from any cause). Cardiovascular events, such as heart attack, stroke or heart failure, were also examined.

 

What were the basic results?

Average BMI at the study's start was 29, which is in the overweight range, and participants had an average [median] age of 63 years.

During follow-up, 35% of participants died, 9% had a heart attack, 7% a stroke and 6% had heart failure. Overweight or obese participants (BMI >25) had a significantly higher risk of heart attack or heart failure than people of normal BMI (18.5 to 24.9). Risk of stroke was significantly increased in obese people (BMI >30), but not those who were overweight.

However, all-cause mortality risk was not increased for people who were overweight or obese.

Obese people had no significant difference in mortality risk compared with people with a normal BMI. Meanwhile, overweight people actually had decreased mortality risk compared with people with a normal BMI (hazard ratio (HR) 0.87, 95% confidence interval (CI) 0.79 to 0.95).

Meanwhile, underweight people had increased mortality risk compared with people with a normal BMI (HR 2.84, 95% CI 1.97 to 4.10), though there was no difference in their risk of cardiovascular disease events.

 

How did the researchers interpret the results?

The researchers conclude: "In this cohort, patients with type 2 diabetes who were overweight or obese were more likely to be hospitalised for cardiovascular reasons. Being overweight was associated with a lower mortality risk, but being obese was not."

 

Conclusion

This large prospective cohort following over 10,000 older adults with type 2 diabetes for 10 years has found that while being overweight or obese is linked to increased risk of cardiovascular events, being overweight is linked to reduced risk of death. This is similar to the "obesity paradox" seen in some other studies, where being overweight or obese is associated with a survival benefit in people with established cardiovascular disease.

The researchers note that 16 other studies have assessed the same question and found conflicting results. Their study aimed to improve on the methods in these studies, and its large sample size and prospective design, following people for 10 years, are strengths. However, caution must be taken before concluding from the findings of this cohort that "being FAT", as Mail Online states, is a good thing for people with type 2 diabetes.

There are important points to note:

  • The cohort demonstrated significantly increased risk of cardiovascular disease events, such as heart attack and heart failure, for overweight or obese people with type 2 diabetes compared to healthy weight individuals. This is consistent with what is already known about the risks of overweight and obesity for cardiovascular disease.
  • The researchers adjusted their analyses for various factors, including age, blood pressure, other illnesses and smoking history. However, other unmeasured confounding factors (confounders) could still be influencing the association between mortality and BMI – for example, other lifestyle factors (exercise, diet and alcohol) or health (including mental health), disability and quality of life factors. We also don’t know about diabetes medications each person was taking or how well controlled their diabetes was. If these factors differed between people with different BMIs, these could be influencing results rather than BMI itself.
  • The study has also only looked at BMI but not at other measures of body fat, such as distribution of fat mass, or body weight in terms of fat mass and non-fat mass. Analysing these measures might be a way to confirm whether the BMI findings seem robust.
  • As the researchers say, they have not specifically examined cause of death. An analysis of causes of death might help to understand why this difference is seen, and whether being overweight is having some protective effect.
  • The study has looked at cardiovascular diseases and mortality only; the researchers have not looked at the development of other overweight- and obesity-linked diseases that may have had a detrimental effect on health.
  • Though a large sample size, this is still a sample of older people with diabetes from a single UK region. Different results may have been obtained from other, more diverse, samples.

The reasons behind the apparent link are not yet known, and further study is needed into the possible biological mechanism. This study does not prove that being overweight is having a direct beneficial effect on risk of death in people with type 2 diabetes. The authors themselves caution against "promoting preconceptions about the ideal BMI" until further research is done to untangle the "obesity paradox".

For now, the advice regarding weight remains the same – whatever your current state of health, aim for a healthy BMI through a balanced diet and regular exercise.

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

Links To The Headlines

Could being FAT help diabetics live longer? Those who are overweight are 13% less likely to die early than their slimmer counterparts. Mail Online, May 5 2015

Links To Science

Costanzo P, Cleland JGF, Pellicori P, et al. The Obesity Paradox in Type 2 Diabetes Mellitus: Relationship of Body Mass Index to Prognosis: A Cohort Study. Annals of Internal Medicine. Published online May 5 2015

Categories: NHS Choices

Eating little and often 'no better for dieters than fewer feasts'

NHS Choices - Behind the Headlines - Fri, 08/05/2015 - 11:01

"Eating little and often – like Jennifer Aniston – could help dieters achieve a healthy weight loss," reports the Mirror. Meanwhile, the Mail Online urges us to "Forget three square meals a day – eating six smaller portions is better for your waistline".

But don't rush to change how often you eat: the claims are based on a tiny study that has been overstated and misinterpreted by the media. In fact, women lost a similar amount of weight regardless of the number of daily meals they ate.

In the study, 11 obese women ate the same low number of calories in either two meals or six meals a day. They lost around the same amount of weight with both diets.

They did retain their non-fat mass (the weight of the body in muscle, organs and bone) better when they were on six meals a day, but the authors warn against drawing firm conclusions from this.

The two-meal pattern seemed to improve levels of "good" cholesterol more than the six-meal pattern. Whether either of these differences would lead to any health benefits for the women was not assessed.

Overall, this study is too small to prove whether six or two meals a day is better for dieters. What is important is to choose an approach to weight loss or healthy weight maintenance that works for you that you can stick to.

Where did the story come from?

The study was carried out by researchers from California State University and other research centres in the US. It was funded by the University of New Mexico.

Nutrisystem Inc, a commercial weight loss company that provides home delivery of calorie-controlled food portions for weight loss, donated all food products used in the study.

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

The Mirror and the Mail Online have very similar coverage, suggesting that the stories may be based on the same press release. They both say that, "Those who ate six meals a day had healthier levels of glucose, insulin and cholesterol". But this is not true.

When the women ate two meals a day, they had better levels of "good" cholesterol than when they ate six meals a day. The levels of other blood fats, glucose and insulin were generally very similar between the groups, and any slight differences were not large enough to rule out having occurred by chance.

What kind of research was this?

This was a crossover randomised controlled trial assessing whether splitting calories into two or six meals had different effects on body composition and blood markers of health.

In crossover trials, the same group of people received both of the interventions being compared in a random order.

This approach is suitable if the effects of the interventions are not long lasting; therefore, it is likely to be a better way to look at short-term effects on blood markers than the long-term effect on weight loss.

What did the research involve?

The researchers recruited 15 adult women who were obese but not diabetic. They randomly assigned them to eat a reduced-calorie diet as either two or six meals a day over two weeks. They then had a two-week break before switching to the other meal pattern.

The researchers measured various blood markers and the women's body compositions during the different parts of the study.

In each part of the study, the food products were the same and delivered to participants in pre-packaged portions. The meals gave about 1,200 calories per day.

During the break, the participants ate four times a day (three meals and a snack). Fluid consumption was not strictly controlled during the trial.

What were the basic results?

Eleven women (73%) completed the study, and four withdrew because they did not comply with the diet, time constraints, or had family issues.

Overall, the women lost weight during the study and reduced their body mass index (BMI), waist circumference, fat mass and percentage of body fat. Their calorie intake reduced from an average of 2,207 calories a day to 1,200 calories.

Women lost similar amounts of weight after the two meals a day period (2.7% loss) and the six meals a day period (2.0% loss). When the women ate two meals a day, they lost more fat-free mass (3.3% loss) than when they ate six meals a day (1.2% gain).

The researchers did not find any difference between fat mass loss, resting metabolic rate, or the levels of insulin, glucose or most fats in the blood when the women were on the different meal frequencies.

"Good" cholesterol (HDL, or high-density lipoprotein) levels increased more when the women were eating two meals a day (1.3% increase) than when they were eating six meals a day (0.12% increase).

How did the researchers interpret the results?

The researchers concluded that calorie restriction was an effective way of losing weight.

Consuming these calories in two meals a day was associated with improved "good" cholesterol levels.

Conversely, consuming the calories in six meals a day preserved fat-free mass during weight loss. Whether either of these changes would have a beneficial impact on health is unclear.

Conclusion

This small crossover trial found little difference between eating the same low number of calories over six meals a day as opposed to two meals a day.

Both patterns resulted in similar weight loss, but the six meal a day group lost less non-fat weight from their bodies, suggesting that they may have, for example, lost less muscle.

However, the authors themselves suggest their body composition findings should be interpreted with care. They did not impose strict fluid replacement rules, and the method they used for measuring body composition could have been affected by how hydrated the women were during the trial.

This was also a very small study (15 obese women), and almost a quarter dropped out before the study finished. The study size may have limited its ability to identify important differences between the groups.

The study was also very short, with each meal frequency tested over a fortnight. The results may not be representative of what would be seen in more diverse groups of people, over a longer period of time, or what would happen if people had to prepare their own meals.

While the news has suggested the findings show that six meals a day is "better", it is not possible to clearly say this from the results. It is unclear whether the difference in body composition seen is reliable and would have any effect on health.

The only other difference was that women had increased levels of "good" cholesterol during the two meal a day period. While this seems to favour the two-meal pattern, whether this difference would be maintained or have a beneficial impact on health is not clear.

Overall, very little can be concluded from this study. What we can say is that obese women eating a calorie-controlled diet can lose weight, and how they split these calories up does not seem to have much impact on their weight loss in the short term.

Some of the participants reported being more "comfortable" with the two meals a day pattern, while others reported the opposite. Reaching and maintaining a healthy weight brings health benefits, and people should use whatever meal frequency they find helps them achieve this. 

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

Links To The Headlines

Want to lose weight? Eat SIX small meals a day say nutrition experts in new study. Mirror Online, May 7 2015

Forget three square meals a day - eating SIX smaller portions is better for your waistline, say experts. Mail Online, May 8 2015

Links To Science

Alencar MK, et al. Increased meal frequency attenuates fat-free mass losses and some markers of health status with a portion-controlled weight loss diet. Nutrition Research. Published March 17 2015

Categories: NHS Choices

Media hypes molecular blood pressure regulation discovery

NHS Choices - Behind the Headlines - Fri, 08/05/2015 - 10:35

The Mail Online hails a "breakthrough in treating high blood pressure", saying scientists have discovered how the body regulates it, which could "slash risk of heart attacks and stroke".

But there's a hint of hype around this news as, perhaps surprisingly, the research that prompted this story did not test any new treatments for high blood pressure.

Instead, studies in the laboratory and in mice found genetically engineered mice lacking a protein called ERp44 had low blood pressure. This led the researchers to do other experiments, showing how the protein works with another protein called ERAP1, which is involved in controlling blood pressure.

Overall, this finding has increased researchers' knowledge of how blood pressure is controlled at a molecular level. While it is likely these processes in mice are similar to those of humans, further study would be needed to confirm this.

Even if it is confirmed, as yet the researchers have developed no drugs to target these proteins. Any new treatment aiming to do so would need to be thoroughly tested in the laboratory before it would be safe enough to test on humans. 

Where did the story come from?

The study was carried out by researchers from the RIKEN Brain Science Institute and other research centres in Japan.

It was funded by JST International Cooperative Research Project-Solution Oriented Research for Science and Technology, the Japan Society for the Promotion of Science, Scientific Research C, The Moritani Scholarship Foundation, and RIKEN.

The study was published in the peer-reviewed journal Molecular Cell.

The Mail Online headline overstates these findings in two ways – first, this experiment is only in mice and needs to be confirmed in humans. Second, we don't yet know if these findings will lead to treatments for human high blood pressure or other conditions. 

What kind of research was this?

This laboratory and animal research studied the function of a protein known as ERp44. Researchers wanted to know more about this protein, which is already known to be involved in helping make sure other cell proteins are made properly and controlling how they are secreted from the cell.

Often, when the function of a protein is not fully understood, researchers start by genetically engineering mice to lack the protein. They then look at what happens to these mice to find out more.

This is what this study has done. This type of study can suggest ways human diseases might be treated, but is at a very early stage and no drugs were involved. 

What did the research involve?

The researchers genetically engineered mice to lack the ERp44 protein. They studied the health and development of these mice, and looked at exactly what knock-on effect a lack of ERp44 had on the cells.

They also identified which proteins ERp44 was normally interacting with and studied the effect of removing this protein in the mice lacking the ERp44 protein. 

What were the basic results?

The researchers found baby mice that lacked the ERp44 protein produced less urine and had changes in the internal structure of their kidneys. Adult mice lacking ERp44 had low blood pressure.

These findings were similar to those known to occur in mice with low levels of the blood pressure-controlling hormone angiotensin. The researchers found angiotensin was being broken down more quickly than normal in ERp44-lacking mice.

The researchers then looked for proteins that interacted with ERp44. They found a protein called ERAP1 and showed how this protein formed a bond with the ERp44 protein. Experiments in cells in the lab suggested ERp44 was stopping ERAP1 from being released from the cells.

This led the researchers to believe that more ERAP1 would be released in ERp44-lacking mice, and this could be responsible for the breakdown of the angiotensin.

To test this, they removed the ERAP1 from blood samples from ERp44-lacking mice using antibodies. As they expected, these ERAP1-depleted samples did not show as much breakdown of angiotensin.

The researchers also found that in mice experiencing severe infection (which usually causes a large drop in blood pressure), the cells produce more ERp44 and ERAP1, and these form more of the ERp44-ERAP1 "complex".

These mice have less of a drop in their blood pressure than mice genetically engineered to have half the normal levels of ERp44. This suggests the extra ERp44-ERAP1 complex helps normal mice stop their blood pressure dropping too low during infection. 

How did the researchers interpret the results?

The researchers concluded they had showed that, "ERp44 is required for suppressing the release of excess ERAP1 into the bloodstream in order to prevent unfavourable [low blood pressure]."

They reported how variations in the gene encoding ERAP1 have been associated with low blood pressure, psoriasis and a skeletal problem called ankylosing spondylitis, and that, "development of specific drugs targeting ERAP1 activity may contribute to treatment of these diseases". 

Conclusion

This animal research has identified a role for certain proteins in controlling blood pressure. Studies like this give clues as to how human biology works and how it can be fixed when it goes wrong.

While the researchers suggest drugs targeting the proteins identified could help develop drugs to treat abnormal blood pressure, these drugs have not yet been developed.

Researchers will need to develop such chemicals and thoroughly test their effects in animals first before they can be tested in humans.

As such, this is early stage research, and there has not been a "treatment breakthrough" yet, because no treatment exists. 

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

Links To The Headlines

Breakthrough in treating high blood pressure, as scientists discover how the body regulates it - and say discovery could slash risk of heart attacks and stroke. Mail Online, May 7 2015

Links To Science

Hisatsune C, et al. ERp44 Exerts Redox-Dependent Control of Blood Pressure at the ER. Molecular Cell. Published May 7 2015

Categories: NHS Choices

Probiotic yoghurts 'may help' hay fever

NHS Choices - Behind the Headlines - Thu, 07/05/2015 - 13:00

"Is YOGURT the secret to easing hay fever? Probiotics can 'relieve sneezing and itchy eyes','' the Daily Mail reports. New research found initial, but not definitive, evidence that probiotics may offer some relief from this common allergic condition for some people.

Hay fever affects around one in five people, causing frequent sneezing, a runny nose and itchy eyes. It happens when an allergic irritant sets off an immune response in the mucosa of the nasal passages, causing an allergic reaction. Most often, people are sensitive to seasonal allergens such as pollen, hence the name hay fever. However, some people can get symptoms all year round (this is known as allergic rhinitis).

There has been a lot of interest in whether probiotics – "healthy" bacteria that live in the gut – can relieve symptoms.

This review identified 23 trials investigating the effect of probiotic supplements on hay fever. These studies were highly variable in terms of their study populations, the probiotics used, outcomes measured and, importantly, results. While most studies found some benefit for at least one outcome, others found no benefit at all.

The authors concluded that probiotics may have a beneficial effect when added to other hay fever treatments, but that higher-quality, larger studies with standardised measures of effects are still needed.

 

Where did the story come from?

The study was carried out by researchers from the University School of Medicine in Nashville, US. The study's funding is not mentioned. It was published in the peer-reviewed medical journal International Forum of Allergy and Rhinology.

Most of the UK media coverage reported the study’s headline results uncritically, suggesting that yoghurt could be a cure for hay fever symptoms. However, not all yoghurt is probiotic, and it is not clear whether the people in these studies were taking these probiotics in the form of yoghurt or capsules. The study was not specific to people with hay fever, as it included people with allergic rhinitis not associated with seasonal allergens. The study did not find an overall effect on standard symptom scores, and the study authors did not recommend probiotics as a standalone cure.

 

What kind of research was this?

This was a systematic review that has searched the literature to identify randomised controlled trials (as well as two randomised crossover studies) that investigated the effects of probiotics on allergic rhinitis. Hay fever is a type of allergic rhinitis that medical specialists refer to as "seasonal allergic rhinitis".

Where study designs and measured outcomes were similar enough, it pooled the results of these studies in meta-analysis. The review aimed to see whether probiotic supplements helped people with allergic rhinitis.

Systematic reviews of randomised controlled trials are usually a good source of reliable evidence to show whether a treatment is helpful. However, the review is only as good as the studies that have been carried out.

 

What did the research involve?

Researchers searched for randomised controlled trials that studied the effect of probiotics on allergic rhinitis, according to pre-defined specifications, and summarised the results of the studies that came up to their quality standards. They then did a meta-analysis, where they pooled the results of those studies that had used standardised clinical measures for allergic rhinitis treatment, to get an overall picture of treatment effect.

The researchers found 153 studies, 42 of which were relevant. They excluded 19 studies, mainly because they didn't give results using standardised clinical outcome measures. The remaining 23 studies were mostly double-blind randomised controlled trials, with two randomised crossover studies. These studies, which included 1,919 participants, were included in the review.

The outcomes measured included two measures of symptom control. These were the Rhinitis Quality of Life Questionnaire (RQLQ), which includes questions about how much symptoms affect people's daily activities, and the Rhinitis Total Symptom Score (RTSS). Some studies had also measured blood levels of immunoglobin E (IgE) – a naturally occurring antibody involved in allergic reactions.

Where possible, they pooled trial results for these different measures to get an overall picture of the effect of probiotics.

 

What were the basic results?

The review found that 17 of the 23 studies reported a significant improvement in at least one of the outcomes measured for people taking probiotics, while six studies showed no benefit from probiotics.

Results of the meta-analysis were mixed. The only measure that showed a clear beneficial effect from taking probiotics was the RQLQ. When the results were pooled from the four studies that measured RQLQ in a way that allowed direct comparison, the study found a mean reduction in score compared to placebo of -2.23 points (95% confidence interval (CI) -4.07 to -0.4). The researchers say a reduction of 0.5 or more is considered important.

The researchers found no statistically significant difference between placebo and probiotic treatment for the RTSS (pooled analysis of four trials) or IgE scores (from eight trials).

 

How did the researchers interpret the results?

The researchers were cautious about the results. They said that differences between the studies, such as different types of probiotic used and different sizes in the study populations, meant it was possible that the positive effect of probiotics on quality of life they found "may be at least partially due to confounding factors and differences between studies". They point out that the two older, smaller studies showed a bigger effect, while two bigger, more recent studies found no effect or a small effect.

They say their meta-analysis "suggests that probiotics have the potential to alter disease severity, symptoms and quality of life" for people with allergic rhinitis, but that the evidence is not strong enough to recommend using probiotics alone to relieve it.

 

Conclusion

This review has identified 23 trials investigating the effect of probiotics upon allergic rhinitis, which most people experience as hay fever. Overall, it found some evidence that taking probiotic yoghurts or supplements could improve the quality of life of people with allergic rhinitis, compared to taking placebo. However, it didn't find a direct effect on overall symptoms, or on levels of IgE in the blood.

The review of the data showed some of the problems with research into probiotics in relation to allergies. Many different strains of probiotic organisms were used in the study, although most were from the families Bifidobacterium or Lactobacillus. It's possible that some strains work well and others don't work at all. It’s also unclear from the review what form these probiotics were being taken in – for example, in the form of yoghurt or yoghurt drinks, or as capsules or tablets. This could affect absorption and effects.

The populations included in these studies are also likely to be highly variable. The age categories, for example, ranged from young children in some, to middle-aged adults in others. We also don’t know what they were specifically suffering from. For example, some could have had hay fever, while others could have had an allergy to dust mites or animal fur.

Only a few studies reported their results using standardised measures, making it hard to pool data from different studies. Though 23 studies were identified, pooled analyses for effects on symptoms and quality of life came from only four studies each.

The review showed that 17 of the 23 studies included found at least one positive clinical outcome for patients taking probiotics. However, this did not translate into convincing results on symptom scores when results from four of these studies were pooled. Pooled results on quality of life were positive, though without further information it is not possible to tell how much effect there may be on the person’s daily life. The researchers say that a reduction of 0.5 or more is considered important, so the 2.23 reduction in score should make a difference. However, if probiotics had no effect on rhinitis symptoms, it would be interesting to know in what ways they were helping a person’s quality of life.

Allergic rhinitis, or hay fever specifically, is a common problem in the UK, and treatments don't help everyone. While the evidence for probiotics is not strong enough to recommend them as treatment, the researchers said that few people reported any adverse effects from taking them. Some people taking probiotics reported diarrhoea, abdominal pain or flatulence (wind), but so did similar numbers of people taking placebos.

Overall, the review cannot answer with certainty how much benefit probiotics may have, and as the researchers say, better-quality evidence is needed.

Other treatments for hay fever, such as antihistamine medication, have proved to be effective for many people.

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

Links To The Headlines

Is YOGURT the secret to easing hay fever? Probiotics can 'relieve sneezing and itchy eyes'. Daily Mail, May 7 2015

Could probiotic yoghurt be the key to fighting hay fever? The Daily Telegraph, May 6 2015

Eating a pot of yogurt could keep hay fever symptoms at bay. Daily Express, May 6 2015

Links To Science

Zajac AE, Adams AS, Turner JH. A systematic review and meta-analysis of probiotics for the treatment of allergic rhinitis. International Forum of Allergy & Rhinology. Published online April 20 2015

Categories: NHS Choices

Smartphone app used to scan blood for parasites

NHS Choices - Behind the Headlines - Thu, 07/05/2015 - 13:00

"A smartphone has been used to automatically detect wriggling parasites in blood samples," BBC News reports. It is hoped the customised device could help in programmes to get rid of parasites in parts of Africa.

In certain regions of Africa, two parasitic diseases – river blindness and elephantiasis – are a major health problem affecting millions. Both of these diseases can be treated with a drug called ivermectin.

But if you give somebody ivermectin and they also have high numbers of a less harmful parasite called Loa loa (African eye worm) inside their body, it can trigger potentially deadly side effects.

This has hampered large-scale ivermectin treatment programmes aimed at eradicating river blindness and elephantiasis in some areas,  as people need to have time-consuming tests for Loa loa levels before they can be treated.

The new device – a standard iPhone hooked up to a specially designed lens module – allows people with minimal training to quickly measure Loa loa levels in a sample of blood.

This study found the device performed similarly to standard, more time-consuming, laboratory tests performed by trained technicians.

But this was a small pilot study in just 33 people, and larger studies are needed to confirm the technique's accuracy.

The development of a technique that could be carried out quickly in the field without much specialised equipment could be an important step forward in treating these parasitic diseases.

The researchers speculate the device could also be used to detect other moving disease-causing parasites in the blood. 

Where did the story come from?

The study was carried out by researchers from the University of California, the National Institute of Allergy and Infectious Diseases in the US, the Centre for Research on Filariasis and other Tropical Diseases, and the University of Yaoundé, Cameroon and the University of Montpellier, France.

It was funded by the Bill and Melinda Gates Foundation, the University of California, the US Agency for International Development, the Purnendu Chatterjee Chair Fund, and the National Institute of Allergy and Infectious Diseases.

Some of the researchers hold patents or have applied for patents relating to this new approach, and two hold shares in the company that developed the device.

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

The BBC's coverage was fair and included a comment from an independent expert in the UK. 

What kind of research was this?

This laboratory study looked at whether a mobile phone video microscope could accurately detect and measure the amount of a parasitic worm called Loa loa (African eye worm) in a drop of a patient's blood.

In certain regions of Africa, parasitic diseases are a major public health problem affecting millions of people. In particular, an infection called onchocerciasis, or river blindness, is the second most common cause of infectious blindness worldwide, and can also result in disfiguring skin disease.

Lymphatic filariasis leads to elephantiasis, which is marked by disfiguring swelling and is the second leading cause of disability worldwide.

Both these diseases can be treated with the antiparasitic drug ivermectin, but this can have dangerous side effects for patients who are also infected with Loa loa.

When there are high numbers of microscopic Loa loa worms in a patient's blood, treatment with ivermectin can lead to severe and sometimes fatal brain damage. The authors say this has led to suspension of mass public health campaigns to administer ivermectin in central Africa.

At present, the standard method of assessing Loa loa levels involves trained technicians manually counting the worms using conventional laboratory microscopes. This process is impractical for health professionals working in communities where they do not have access to labs, or in large ivermectin treatment campaigns.

This study tested a new method researchers developed for detecting Loa loa, which uses a smartphone camera and avoids the need to send samples to a lab. 

What did the research involve?

To test the accuracy of the new technique, researchers compared it with gold standard microscope analysis in a laboratory. They did this for blood samples taken from 33 people in Cameroon, who were all over the age of six and were potentially infected with Loa loa.

The new technique uses a mobile phone-based video microscope that automatically detects the tell-tale wriggling movement of the worms. It examines a fingerpick sample of blood using time lapse photography and uses this characteristic movement to count the worms.

The process uses an iPhone 5 camera attached to a 3D-printed plastic base, where the sample of blood is positioned. Control of the device is automated through an app the researchers developed for the purpose.

The patients' blood was taken from a finger prick and then loaded into two rectangular capillaries to obtain duplicate measurements. A series of videos was taken of each sample by the mobile phone software.

The researchers say it takes a minute to prick the finger and load the blood on to the capillary, and the whole process takes two minutes maximum, starting from the time the sample is inserted to the phone displaying results.

In total, 5 or 10 videos were taken of each sample, resulting in some 300 videos. Sixteen of these were excluded from the analysis either because of inconsistent counts or device malfunction.

Blood was also taken from each patient for gold standard laboratory analysis for Loa loa worms. These samples were transported to a central laboratory for assessment by two independent technicians.

The counts from this analysis were used to assess whether the Loa loa worm count was below the level at which it was safe to treat patients with ivermectin. This was called the treatment threshold.

The researchers then compared results from the smartphone microscope with those from the laboratory.   

What were the basic results?

The researchers found the Loa loa worm count measured by the mobile phone video was very similar to the results from the laboratory. Compared with the laboratory analysis, among the smartphone samples:

  • there were no false negatives – that is, there were no patients who had a worm count above the safe treatment threshold of gold standard methods who were incorrectly identified as safe for treatment by the smartphone technique
  • there were two false positives – that is, two patients whose worm count fell below the safe treatment threshold by gold standard methods were incorrectly identified as not safe for treatment by the smartphone technique

This meant the mobile phone device had:

  • 100% sensitivity – this measures how good the test is at identifying those with an unsafe worm count and who should not be treated with ivermectin
  • 94% specificity – this measures how good the test is at identifying those with a safe worm count who could be treated with ivermectin; this means 6% of people tested would be told their worm levels were unsafe when in fact they were safe  
How did the researchers interpret the results?

The researchers say this new technology could be used at the point of care to identify patients who could not be treated safely using ivermectin.

They say this would allow the mass drug treatment for both river blindness and elephantiasis in central Africa to be resumed.   

Conclusion

This study suggests a new smartphone-based approach could provide a quick way of measuring levels of infection with the Loa loa worm in blood samples, and with a high level of accuracy.

This technique could allow assessment of people's infection in communities without easy access to the laboratory testing that is usually used to detect the worms.

This is important, as people with high levels of this infection can suffer potentially fatal side effects with the drug ivermectin, which is used to treat two other parasitic infections.

It's worth bearing in mind that this was a pilot study in only 33 people using a prototype device. The new device will require more refinement and testing to make sure it performs well enough before it can be put into practice. 

The test seemed to correctly pick up all people with worm levels that would make ivermectin unsafe, but did class 6% of people as having unsafe levels when in fact laboratory tests found they had safe levels. This means that 6% of people might miss out on ivermectin unnecessarily.

If its accuracy is confirmed, this new approach could allow health workers to quickly determine on site whether it is safe to give someone ivermectin for the treatment of river blindness or elephantiasis.

Elephantiasis is a leading cause of preventable disability in the developing world, while river blindness is the second leading cause of infection-related blindness. Approaches that allow cheap, effective and safe mass treatment programmes could have an important impact on health.

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

Links To The Headlines

Smartphone 'scans' blood for parasites. BBC News, May 7 2015

Links To Science

D'Ambrosio MV, Bakalar M, Bennuru S, et al. Point-of-care quantification of blood-borne filarial parasites with a mobile phone microscope. Science Translational Medicine. Published online May 6 2015

Categories: NHS Choices

Infection clue points to causes of rheumatoid arthritis

NHS Choices - Behind the Headlines - Wed, 06/05/2015 - 09:46

"Infection could trigger arthritis," claimed a headline in the Daily Express today. But you needn't worry that a cough or cold will cause you crippling joint pain: the headline is an oversimplification of some fascinating – if early stage – research.

The research in question focused specifically on the causes of rheumatoid arthritis – a painful long-term condition that causes swelling and stiffness in the joints. It is caused by the body's immune system attacking the joints.

In a series of laboratory experiments, scientists singled out a form of a protein called vinculin as playing an important role in how the immune system is triggered to attack the body in rheumatoid arthritis.

A tiny section of the vinculin protein acted as a target for the immune attack. The same target was found in common bacteria, leading to speculation that bacteria infection might sensitise some people to develop the disease later. While this is plausible, it was not proved to be the case in this study, so is largely speculative at this stage.

While further research might be able to prove if this is true, the immediate implications, including ways of preventing or treating rheumatoid arthritis, are zero. 

Where did the story come from?

The study was carried out by researchers based in medical centres in the Netherlands, Cyprus and Greece, and was funded by the Netherlands Organization for Scientific Research, the Innovative Medicines Initiative and the University of Cyprus.

It was published in the peer-reviewed journal Nature Communications.

The first sentence in the Express' story seems overenthusiastic. It is a bit early to say to what extent this finding represents a genuine "breakthrough". 

What kind of research was this?

This was a laboratory study looking at the biological disease processes involved in rheumatoid arthritis.

Rheumatoid arthritis is a long-term condition that causes pain, swelling and stiffness in the joints. It is caused by the body's immune system attacking the joints and sometimes other parts of the body. It is not yet known what specifically triggers this self-attack.

Most people with rheumatoid arthritis have special antibodies known as anti-citrullinated protein antibodies (ACPA). Citrullination is a normal chemical modification of a protein, but it seems in the case of rheumatoid arthritis this modification singles it out for attack.

These ACPAs are thought to be involved in directing the body's immune system to attack itself, which causes rheumatoid arthritis symptoms.

This process is not well understood, so the researchers wanted to find out what the ACPAs were targeting in the joints, to help them understand how to come up with treatments for rheumatoid arthritis.

Laboratory studies are very useful in the early stages of understanding disease processes, because scientists can control the conditions precisely and manipulate them as they choose.

However, disease processes in the lab are not the same as those in the body, so once an initial understanding is developed, studies in humans usually follow. 

What did the research involve?

The study involved biochemical experiments on human and lab-grown cells taken from people with rheumatoid arthritis, as well as healthy volunteers.

The experiments focused on understanding the behaviour of the immune cells involved in the disease process and the antibodies involved in orchestrating the self-attack. 

What were the basic results?

The researchers found that a citrullinated form of the protein vinculin was a target for ACPAs. It was also a target for the immune system cells – called T cells – involved in the self-attack.

The ACPAs and T cells appeared to recognise part of the vinculin protein that was also present in common bacteria, as well as in another protein that occurs naturally in some people, giving them some protection against rheumatoid arthritis. When this "protective" protein was absent, T cells targeted the part of vinculin found earlier. 

How did the researchers interpret the results?

The results as a whole led the researchers to conclude they had found a molecular basis for protection against rheumatoid arthritis involving these two proteins. 

Conclusion

Through a series of laboratory experiments, this research pinpointed a protein called vinculin as an important autoimmune target in rheumatoid arthritis.

Much of the media reporting focused on the idea that being exposed to bacteria with the same target sequence as vinculin might sensitise someone to develop the disease later.

The research team did discuss how infection might lower the threshold at which the T cells are activated to self-attack and might prime the immune system for self-attack. While this is plausible, it was not proved to be the case in this study, so this is largely speculative.

This research furthers our understanding of rheumatoid arthritis, which may one day lead to treatment improvements. However, the immediate implications, in terms of treatments or prevention, are minimal.

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

Links To The Headlines

Infection 'could trigger arthritis'. Daily Express, May 5 2015

Links To Science

van Heemst J, et al. Crossreactivity to vinculin and microbes provides a molecular basis for HLA-based protection against rheumatoid arthritis. Nature Communications. Published May 5 2015

Categories: NHS Choices

Appetite for apples? How fruit sugars may not suppress hunger

NHS Choices - Behind the Headlines - Wed, 06/05/2015 - 09:44

Are you tempted to avoid eating fruit "because the sugar in it triggers cravings," as the Mail Online suggests today? If you are, it's worth having a look at some of the reassuring facts that can keep you chomping cherries and guzzling grapefruit.

The news – covered by the Mail and the BBC – stems from a laboratory study of just 24 young, healthy volunteers. These volunteers were given cherry-flavoured drinks containing either fructose ("fruit sugar", not real fruit juice) or glucose.

Brains scans showed that those who had a fructose drink had more brain activity when shown pictures of high-calorie food than when they were given glucose. They also said they were hungrier when they saw pictures of the food in question.

The researchers suggest that in real life, people might be more likely to seek out food and eat more after having fructose. But as the study didn't test this directly, we can't conclusively say this is true. Also, the results from this small sample of young people may not be representative of the population at large.

We know that eating or drinking fructose in isolation, as in this study, is very different from eating it as part of whole fruit, where other nutrients and fibre interact and affect how it is digested. It's worth bearing such facts in mind when reading media stories casting doubt on generally healthy foods. 

Where did the story come from?

The study was carried out by researchers from the University of Southern California, and was funded by a Doris Duke Charitable Foundation Grant, the American Heart Association, and the Southern California Clinical and Translational Science Institute.

It was published in the peer-reviewed science journal, Proceedings of the National Academies of Science of the USA.

Generally, the media reported the story accurately. The BBC reminded readers that drinking fructose in a drink, as in the experiment, is not the same as eating it from whole fruit.

However, the Mail's suggestion that advice to get your 5 A DAY of fruit and veg should carry "a word of warning – to steer clear of the sugar, fructose" takes the implications of the research too far. 

What kind of research was this?

This was a small, double-blind randomised controlled trial (RCT) looking at the effect of the sugars fructose and glucose on hunger and desire for food. The study team say fructose, a fruit sugar, may not suppress appetite as strongly as glucose, a different form of sugar.

The researchers wanted to measure the effect of fructose and glucose on brain, hormone and appetite responses to food cues. They also wanted to see whether it had any effect on "food-seeking behaviour".

An RCT is an effective way of proving cause and effect. However, this particular one didn't involve many people, so may not be applicable to the UK population at large. 

What did the research involve?

Researchers recruited 24 healthy volunteers. These volunteers had two separate brain scans to measure their brain activity after drinking a cherry-flavoured drink containing either fructose or glucose.

The brain scans, called functional (f)MRI, happened as participants looked at sets of images of high-calorie foods and non-food items. After each set of images, participants rated their hunger and desire for food.

The volunteers also completed a task where they chose between immediate food rewards and monetary reward in a month's time.

The researchers measured the volunteer's levels of the hormones insulin and glucagon (both involved in food metabolism) before having the sugary drink, and again 30 and 60 minutes after the drink. As a control group, 18 volunteers were also given a cherry drink without fructose or glucose.

The study used a crossover design, meaning a volunteer would be tested and scanned after drinking a glucose drink on one day and a fructose drink on a different day.

The study was double blind, meaning neither the volunteers nor those analysing the brain scan results knew which drink the participants had been given. This helps to reduce the chance of bias and confounding factors influencing the results. 

What were the basic results?

Compared with drinking glucose, drinking fructose resulted in smaller increases in blood insulin hormone levels.

It also resulted in greater brain reactivity to food cues in areas of the brain called the visual cortex and left orbital frontal cortex, which is thought to be involved in attention and reward processing.

Fructose also led to greater ratings of hunger and desire for food, and a greater willingness to give up long-term monetary rewards to obtain immediate high-calorie foods, compared with glucose. 

How did the researchers interpret the results?

The researchers concluded: "These findings suggest that ingestion of fructose relative to glucose results in greater activation of brain regions involved in attention and reward processing, and may promote feeding behaviour." 

Conclusion

Can we conclude from this evidence that fruit makes you hungry, as the Mail Online suggested? No.

This small double-blind RCT showed that young adults who consumed a fructose-sweetened drink had more brain activity in attention and reward centres in response to pictures of food, compared with the same drink sweetened with glucose. There were signs this also affected food-seeking behaviour in a somewhat artificial laboratory test.

The research team took this to mean that the volunteers might be more likely to seek out food and eat more in a real-life scenario. But the study didn't test this directly, so it remains unproven.

Numerous factors influence what and how much you eat in the real world, such as food availability, whether you have company, boredom and the time of day. From this study alone, we can't tell how important fructose is in influencing how much people eat, or what they eat.

The randomisation and double blinding in the study mean that bias and confounding factors are not likely to affect the results. But the study was small, only involving 24 healthy adults aged around 21.

It doesn't tell us much about how fructose affects people's appetite or food-seeking behaviour in other groups – for example, the over-60s or people with chronic diseases.

The best way to find out is to do a larger study using a more diverse group that is more representative of the UK population.

This RCT tested fructose and glucose in isolation in a drink. But some of the media coverage gave this the label "fruit sugar", perhaps giving the impression that fruit should be avoided if you want to reduce your hunger and, as an inevitable result, your calorie intake.

However, sugar in fruit is digested by the body in a different way from fructose in a drink. For example, having a whole apple is better for you than having juice made from the same apple. The whole fruit contains vitamins, minerals and fibre, and allows your body to absorb the sugar slower than in a "free" juice form.

As Priya Tew from the British Dental Association explained to the BBC: "Eating fructose and glucose in isolation is very different to eating them within the context of a food, where we have other nutrients that interact and can affect digestion.

"For example, fructose in fruit is tied up within the cellular structure of that fruit, and the fibre content slows down the release of the fructose into the bloodstream. Fruit also has a high water content and takes a while for us to chew and digest, so the fructose is not instantly released."

Find out about 5 A DAY portion sizes

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

Links To The Headlines

Eating fruit could make you MORE hungry because the sugar in it triggers cravings, experts warn. Mail Online, May 5 2015

Fruit sugars 'may worsen food cravings'. BBC News, May 5 2015

Links To Science

Luo S, et al. Differential effects of fructose versus glucose on brain and appetitive responses to food cues and decisions for food rewards. Proceedings of the National Academies of Science of the USA. Published May 4 2015

Categories: NHS Choices

Heart failure drug digoxin linked to premature death

NHS Choices - Behind the Headlines - Tue, 05/05/2015 - 13:30

"A heart drug taken by 250,000 Britons can actually hasten death," the Mail Online warns today. An analysis of previous research on digoxin, used to treat heart failure and heart rhythm abnormalities, suggests that it can raise the risk of premature death.

The analysis pooled the results of 19 different studies investigating whether digoxin – used in the treatment of heart failure and atrial fibrillation – increases the risk of death from any cause.

Overall, the review found that people taking digoxin had a 21% higher risk of death from any cause compared to people not taking the drug.

The risk increase was slightly higher for people taking digoxin for atrial fibrillation (29%) than for heart failure (14%).

Though an effective drug, digoxin has long been known to have potentially serious adverse effects and always needs to be used with care. However, in this analysis, it is difficult to know how much of the higher risk of death is due solely to digoxin, and how much is due to health differences between the people who were and were not taking the drug. People who were prescribed digoxin may have had more severe health problems and these may have increased their mortality risk.

If you are taking digoxin and you have any concerns, or any new or worsening symptoms, do not stop taking your medication, but contact your health professional as soon as possible.

 

Where did the story come from?

The study was carried out by researchers from Goethe University in Germany. No sources of funding are reported, though one of the authors declares receiving consulting fees from various pharmacological companies.

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

Unsurprisingly, the UK media was vigorous in highlighting the potential dangers of digoxin. However, they did take the responsible step of advising readers not to stop taking digoxin without first consulting their GP. 

The Express’ headline of "Popular heart pill raises death risk by a third" was a little misleading. This figure actually refers to the risk in people with atrial fibrillation (29%). The overall figure, for atrial fibrillation and congestive heart failure combined, was slightly lower, at just over a fifth (21%).

What kind of research was this?

This was a systematic review that searched for all relevant studies looking at the link between digoxin use and mortality risk. They pooled the results in a meta-analysis.

Digoxin is a heart drug that increases the strength of each heartbeat. It also controls the rate that electrical impulses signalling the heart muscle to contract are transmitted through the heart chambers. For this reason, it can be used in the control of fast and irregular heartbeats such as atrial fibrillation, and is also sometimes used in the treatment of heart failure.

However, digoxin has side effects. It takes a long time for the drug to be broken down by the body, so it can sometimes have toxic effects, particularly at high blood concentrations. Side effects often centre upon heart function, so it can sometimes be difficult to distinguish between what are direct side effects of the drug and what is due to the worsening clinical condition.

Various studies are said to have caused uncertainty over the side effects of digoxin, with some suggesting it could increase mortality risk. The researchers therefore aimed to carry out a systematic review to pool the evidence on the safety of the drug, particularly looking at mortality effects. 

 

What did the research involve?

The researchers searched two literature databases (Medline and Cochrane) up to November 2014 to identify English language publications looking at the effect of digoxin on all-cause mortality (death from any cause) in people taking the drug for heart failure or atrial fibrillation.

There were 19 studies included, nine of which included people with atrial fibrillation, seven of people with heart failure, and three studies that included a combination of the two. These studies included a total of 235,047 people with atrial fibrillation and 91,379 with heart failure. Study duration ranged from less than one year to 4.7 years (average 2.5 years). Only one of the studies was a randomised controlled trial, the rest were observational studies. All studies were assessed to be of high quality.

Results were pooled and took into account the differences between study results, due to their different study design (heterogeneity).

 

What were the basic results?

In a pooled analysis of all 19 studies, people taking digoxin had a 21% increased risk of all-cause mortality compared with people not taking this drug (hazard ratio (HR) 1.21, 95% confidence interval (CI) 1.07 to 1.38). When separately analysed by condition, people with atrial fibrillation had a slightly higher risk of all-cause mortality (HR 1.29, 95% CI 1.21 to 1.39) compared to people taking the drug for heart failure (HR 1.14, 95% CI 1.06 to 1.22).

 

How did the researchers interpret the results?

The researchers conclude: "The present systematic review and meta-analysis of all available data sources suggests that digoxin use is associated with an increased mortality risk, particularly among patients suffering from AF."

 

Conclusion

This is a valuable systematic review that has searched the global literature to investigate the link between digoxin use and death from any cause in people with atrial fibrillation or heart failure.

Overall, it found that people taking the drug had increased risk of death from any cause. People who were taking the drug for atrial fibrillation had a slightly higher risk than those taking it for heart failure.

These are important findings in terms of trying to quantify the size of the increased risk. However, there are points to consider:

  • The researchers report how the individual studies had adjusted their results for potential confounders that could be influencing the results. However, the factors adjusted for are likely to have differed between studies, and we do not know how completely they will have taken into account all of the differences in characteristics between people who were and weren’t taking digoxin. This means it's still not clear how much of the increase in mortality risk is due directly to digoxin, and how much could be due to the health differences between the people studied.
  • As the researchers also noted, the studies provided limited information on how mortality risk was associated with a particular therapeutic dose of digoxin, or with blood concentration levels. As such, it is difficult to know of a particular "toxic dose" when it comes to increased overall mortality risk.
  • This study has also only focused on all-cause mortality. It has not investigated the underlying reasons for death. Therefore, the review cannot inform us on the reasons why digoxin could be increasing mortality risk (for example, by causing adverse effects on the way the heart functions).

Digoxin is already recognised by the medical profession to be a drug with potential serious adverse effects, and one that needs careful monitoring. This review again highlights the delicate balance there may be between its beneficial therapeutic effects upon conditions such as atrial fibrillation and heart failure, and its possible risks.

It is reported that the Medicines & Healthcare Products Regulatory Agency (the government body that regulates medicines and medical devices in the UK) is now looking at the evidence provided by this new analysis.

People taking digoxin should discuss with the doctor in charge of their care if they have any concerns, or any new or worsening symptoms. These could include lethargy or fatigue, feeling lightheaded or dizzy, or sickness.

However, it is important not to suddenly stop taking digoxin without having an alternative treatment plan, as there could be serious risk from the untreated heart problem.

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

Links To The Headlines

Irregular heartbeat drug taken by 250,000 Britons 'can raise risk of death'. Mail Online, May 5 2015

Popular heart pill raises death risk by a third. Daily Express, May 5 2015

Links To Science

Vamos M, Erath JW,  Hohnloser SH. Digoxin-associated mortality: a systematic review and meta-analysis of the literature. European Heart Journal. Published online May 4 2015

Categories: NHS Choices

New test could improve diagnosis of ovarian cancer

NHS Choices - Behind the Headlines - Tue, 05/05/2015 - 13:10

"New ovarian cancer test twice as effective as existing methods," The Guardian reports, after new research proved relatively successful in diagnosing ovarian cancer.

This study hasn't identified a new blood test for cancer as such – instead, it is a refinement of existing diagnostic methods. The blood test looks at levels of the protein CA125, long recognised as a marker for ovarian cancer.

But this marker is not very reliable – some women with ovarian cancer don't have raised levels, and levels can also be raised in non-cancerous conditions.

This study has developed a new algorithm called the risk of ovarian cancer algorithm (ROCA), which categorises cancer risk according to CA125 levels measured every year.

Around 50,000 women aged 50 or over were screened using ROCA:

  • women at normal risk carried on with annual screening
  • women at intermediate risk had CA125 repeated at 12 weeks
  • women at elevated risk had CA125 repeated at six weeks and a transvaginal ultrasound scan

High-risk women would then be referred for further assessment and surgery as needed. The algorithm accurately detected 86% of women with ovarian cancer, and ruled out almost 100% of women who were cancer-free.

The study suggests the new algorithm could be a valuable way of assessing risk of ovarian cancer, a cancer with notoriously non-specific symptoms. A reliable method of early diagnosis could save some women's lives.

But this is the key thing the research team still has yet to examine – whether screening using this method actually does save lives. Results for this are expected in the autumn.

Screening isn't a "magic bullet", and there has to be careful assessment of the risks of misdiagnosis and any cost implications. 

Where did the story come from?

The study was carried out by researchers from University College London, among various other hospitals and academic institutions in the UK.

It was funded by the Medical Research Council, Cancer Research UK, the Department of Health and the Eve Appeal.

Two study authors are co-inventors of the risk of ovarian cancer algorithm (ROCA), which is patented and licensed to Abcodia Ltd. Two other study authors also declare financial interests through Abcodia Ltd.

One of the authors declared a consultancy arrangement with Becton Dickinson in the field of tumour markers. The remaining authors declare no conflicts of interest.

The study has not yet been published online.

The media generally reported the findings accurately, though some reports give the impression a new test has been developed. This isn't technically a new test – it's a new way of interpreting the results.

The media also failed to mention that it isn't clear yet whether this could be introduced as a screening test, as there are many issues to consider.

Professor Usha Menon of University College London told the BBC News website that, "It's good, but the truth lies in whether we've picked up the cancer early enough to save lives", adding that they don't know this yet. 

What kind of research was this?

This was a randomised controlled trial (RCT) looking at whether annual blood tests for a biomarker of ovarian cancer might be a useful cancer screening tool. The biomarker being examined is called CA125. It has long been recognised that levels of this marker can be raised in ovarian cancer.

However, it's not a specific marker for ovarian cancer as it can also be raised by other conditions, such as infection or inflammation. Also, some women with ovarian cancer don't have raised CA125, so it isn't very good at picking up ovarian cancer on its own.

The research team devised a new way of looking at changes in levels of CA125 over time using an algorithm. 

This publication reports on women in the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) who were allocated to the multimodal screening arm of the trial. These women had their CA125 levels measured every year and interpreted using the risk of ovarian cancer algorithm (ROCA).

Other arms of the trial not reported here included a group who received screening by ultrasound scan (around 50,000 women) and a control group who received no screening (around 100,000 women).  

What did the research involve?

A total of 46,237 women aged 50 years or older were involved in the multimodal screening arm of the trial. Each year, their CA125 levels were measured. Based on these levels, their risk of ovarian cancer (ROC) was interpreted on the algorithm as:

  • normal – return to annual screening
  • intermediate – repeat CA125 in 12 weeks (repeat level I screen)
  • elevated – repeat CA125 and transvaginal ultrasound in six weeks (level II screen) with earlier screens arranged where clinically suspicious

A transvaginal ultrasound scan (TVS) uses high-frequency sound waves to create an image of the ovaries. This image can show the size and texture of the ovaries, plus any cysts or other swellings present.

The way the ROC risk categories were set meant about 15% of all screened women would be in the intermediate ROC category and 2% would be in the elevated ROC category.

For the minority of women in the elevated category, follow-up actions after the level II screen six weeks later would be as follows:

  • TVS normal and normal/intermediate ROC – return to annual screening
  • TVS normal and elevated ROC – repeat level II screen six weeks
  • TVS unsatisfactory, regardless of ROC – repeat level II screen six weeks
  • TVS abnormal – clinical referral

Women with a high ROC risk were recommended to be referred for further investigation and surgery as required.

Participants were followed up using national cancer and death registries. 

What were the basic results?

Overall, there were 296,911 annual screens carried out over an average of three years of follow-up. In this study arm, 640 women underwent surgery, 133 of whom were found to have ovarian cancer.

The researchers calculated that multimodal screening had a 85.8% sensitivity for ovarian cancer. This is the proportion of women with ovarian cancer who were correctly identified as being at risk by the ROCA algorithm.

The specificity was even better at 99.8%, the proportion of women without ovarian cancer who would be correctly identified as not being at risk by the algorithm. For each single case of ovarian cancer identified, 4.8 operations were performed.

However, the researchers also found that basing risk on a fixed CA125 cut-off level was much less accurate, and only would have identified about half of the women with ovarian cancer. 

How did the researchers interpret the results?

The researchers concluded that, "Screening using ROCA doubled the number of screen-detected ovarian cancers compared to a fixed [CA125] cut-off."

They also said that, "In the context of cancer screening, reliance on predefined single threshold rules may result in biomarkers of value being discarded." This implies that CA125 is a valuable biomarker when used in the right way. 

Conclusion

This is a valuable study that has reported the results for around 50,000 women aged 50 or over who were allocated to one arm of a larger trial. They had their ovarian cancer risk assessed annually using the risk of ovarian cancer algorithm (ROCA).

When CA125 levels were used to categorise cancer risk alongside this algorithm, the algorithm was able to accurately identify 86% of women with ovarian cancer. Encouragingly, it ruled out almost 100% of women who were cancer-free. This means these women would not undergo unnecessary further investigation and surgery.

The study suggests the new algorithm could be a valuable way of assessing ovarian cancer risk. This cancer has notoriously non-specific symptoms often only first detected when it is at an advanced stage.

But before any new screening test is introduced there has to be careful assessment of its risks and benefits. These include comparing it with other methods of detecting ovarian cancer based on an assessment of symptoms, clinical examination and investigation findings.

This study did not compare outcomes with the large number of women in the other two screening arms of the trial – those in the control group and those being screened by transvaginal ultrasound. Other issues also need to be considered, including resource implications.

This research doesn't yet say whether the screening saved any lives by detecting the cancer earlier so it could be treated more effectively.

On this point, Professor Usha Menon from University College London told the BBC News website: "There is no screening at the moment, so we are awaiting the results [on whether lives have been saved] before the NHS can decide. Many people would have to be screened, so it really needs to translate to lives saved."

BBC News reports the results of screening this are expected in the autumn. We will provide an update once these become available.

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

Links To The Headlines

New ovarian cancer test twice as effective as existing methods. The Guardian, May 4 2015

Ovarian cancer trial boosts hope of screening programme. The Daily Telegraph, May 4 2015

Blood test 'boost' in ovarian cancer fight. BBC News, May 5 2015

Ovarian cancer blood tests breakthrough: Huge success of new testing method could lead to national screening in Britain. The Independent, May 5 2015

New Test May Double Detection Of Ovarian Cancer. Sky News, May 5 2015

New ovarian cancer screening test 'more accurate'. ITV News, May 5 2015

New test hope for detecting ovarian cancer. The Times, May 5 2015

Links To Science

Menon R, Ryan A, Kalsi J, et al. A risk algorithm using serial biomarker measurements doubles the number of screen-detected cancers compared to a single threshold rule in the United Kingdom Collaborative Trial of Ovarian Cancer Screening (UKCTOCS). Journal of Clinical Oncology. Study not yet available online

Categories: NHS Choices

Replacing sugary drinks with water may reduce diabetes risk

NHS Choices - Behind the Headlines - Fri, 01/05/2015 - 13:30

"Swapping orange squash for a cup of tea cuts diabetes risk," The Daily Telegraph reports.

This widely-reported news is based on a major UK study, involving around 25,000 adults, which looked at the association between drink choices and the risk of type 2 diabetes. It found that those who consumed more of their calories through sugary drinks, and those who drank more soft drinks or sweetened milk drinks, were more likely to develop type 2 diabetes.

The study has a number of strengths, including its large size and use of multiple approaches to identify people who developed diabetes. But its main limitation is that other factors may be contributing to the effect seen, even though the researchers did try to reduce this as much as possible.

Based on their data, the researchers estimated that swapping water or unsweetened tea or coffee for soft drinks or sweetened milks could potentially reduce the number of new diabetes cases by up to 25%.

We know being overweight or obese is a major risk factor for type 2 diabetes, and ensuring we maintain a healthy weight will help reduce your diabetes risk.

Some sugary drinks contain a surprisingly high amount of calories – for example, a 330ml can of coke contains 139 calories, which would take around an hour of dog walking to burn off.

Reducing your calorie intake by swapping sugar-sweetened drinks for unsweetened drinks, such as tap water, could be one way to help achieve this goal. 

Where did the story come from?

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

It was published in the peer-reviewed medical journal Diabetologia.

The UK media's coverage of the study was accurate.

What kind of research was this?

This was an ongoing prospective cohort study called the European Prospective Investigation into Cancer and Nutrition (EPIC)-Norfolk study.

The current analysis looked at whether the amount of sugar-sweetened beverages (SSBs), artificially sweetened beverages (ASBs) and fruit juice a person drank was linked to their risk of developing type 2 diabetes. The researchers also wanted to estimate what impact swapping non-sweetened beverages for these sweet beverages would have.

A previous statistical pooling of prospective studies found that higher SSB consumption was associated with greater diabetes risk, while studies have had varying findings for ASBs and fruit juice.

However, the researchers note that these studies have largely relied on food frequency questionnaires, which do not collect very detailed information on drinks. They wanted to use food diaries (where people are asked to record their food consumption on a daily basis) in their study to better assess drinks intake.

This is the best way to assess this question, given that it would be unethical to randomly assign people to drink a lot of sugary drinks over a long period of time.

The main limitation of this type of study is that healthy (and unhealthy) behaviours and environments tend to cluster together, so picking apart their effects is difficult. 

What did the research involve?

The researchers recruited adults in the UK who did not have diabetes and had them record their food and drink consumption over a week.

They then followed them up over almost 11 years to see who developed type 2 diabetes, and analysed whether people who drank more sweet beverages were at increased risk.

Using their results, they then calculated what impact it would have if people swapped non-sweetened drinks, such as water, for these sweet beverages.

The 25,639 participants in the study were recruited in the 1990s, when they were aged 40 to 79 years old. They filled out a food diary for a week, and the researchers used these to determine how much of the following they drank:

  • soft drinks – squashes and juice-based drinks sweetened with sugar
  • sweetened tea or coffee
  • sweetened milk beverages – such as milkshakes, flavoured milks, and hot chocolate
  • artificially sweetened drinks (ASBs) – such as diet sodas
  • fruit juice

The first three categories were classed as SSBs. The participants also provided other information on their lifestyles. During the study, they had health checks and filled in follow-up health and lifestyle questionnaires.

The researchers followed participants up until 2006, and identified anyone who developed type 2 diabetes through the health checks, questionnaires, and medical records. If a person reported they had diabetes but this could not be confirmed with medical records, they were not counted as having the condition.

The analyses included the 24,653 participants who did not have diabetes or a family history of diabetes and had reported all the information the researchers needed. The researchers looked at whether the number of servings of the individual drinks consumed was linked to the risk of developing type 2 diabetes during the study.

These analyses took into account a range of factors that could influence the results (potential confounders), such as:

  • age
  • gender
  • socioeconomic status
  • physical activity
  • smoking
  • intake of other sweet beverages
  • total calorie intake
  • body mass index (BMI)
  • waist circumference

The researchers used standard methods to estimate what impact it would have if people stopped consuming SSBs, based on their findings. They also calculated the potential impact of swapping water or ASBs for SSBs. 

What were the basic results?

During the study, 847 participants (3.4%) developed type 2 diabetes.

After adjustment for all of the potential confounders, including total energy intake and BMI:

  • each additional serving of soft drinks was associated with a 14% increase in the risk of developing diabetes (hazard ratio [HR] 1.14, 95% confidence interval [CI] 1.01 to 1.32)
  • each additional serving of sweetened milk drinks was associated with a 27% increase in the risk of developing diabetes (HR 1.27, 95% CI 1.09 to 1.48)
  • sugar-sweetened tea and coffee, ASBs, fruit juice and water were not associated with type 2 diabetes risk

Overall, consuming more sweet drinks (measured as what percentage of a person's calorie intake came from these drinks) was associated with increased type 2 diabetes risk.   

Substituting one serving a day of water or unsweetened tea or coffee for soft drinks or sweetened milk drinks was estimated to have the potential to reduce the number of new cases of type 2 diabetes by 14-25%. Substituting ASBs for SSBs was not estimated to have a significant effect.

If people who drank sweet beverages reduced their intake of these drinks so they accounted for less than 2% of their total calorie intake, this was estimated to have the potential to prevent 15% of new diabetes cases.

How did the researchers interpret the results?

The researchers concluded that, "The consumption of soft drinks, sweetened milk beverages and energy from total sweet beverages was associated with higher type 2 diabetes risk independently of adiposity [BMI and waist circumference]".

They suggest that, "Water or unsweetened tea/coffee appear to be suitable alternatives to SSBs for diabetes prevention", and feel their findings are of public health importance. 

Conclusion

This cohort study has found an association between sugar-sweetened drink consumption and the risk of type 2 diabetes. It estimated that swapping water or unsweetened tea or coffee for these beverages could have the potential to reduce the number of new diabetes cases by up to 25%.

The study has a number of strengths, including its large size and prospective collection of data. It also used multiple approaches to identify people who developed diabetes, which should help to make sure that most, if not all, cases were identified.

People also used a food diary to record food and drink intake, which is reported to provide more detailed information than the questionnaire-based methods used in many previous studies.

As with all studies of this type, the main limitation is that it is difficult to single out the impact of one factor and be sure that no others are contributing to the link seen.

For example, people who drank more sweetened tea or coffee and sweetened milk beverages tended to have less healthy diets overall.

The researchers did take into account a range of factors, such as diet and physical activity in their analyses, to reduce this as much as they could, but it could still be having some effect.

Another limitation is that the researchers only assessed drink intake once, at the start of the study, and this may have changed over time.

The figures for the percentage of cases of type 2 diabetes that could be prevented are estimates. They are based on the assumption that the risk factor (sugar-sweetened drinks in this case) is directly causing the entire link seen, which may not be the case.

This method can overestimate the impact of individual factors. However, these types of estimates are used to help public health policy makers decide which disease risk factors are most important for them to target.

Overall, we know that being overweight or obese is a major risk factor for type 2 diabetes. Maintaining a healthy weight will help to reduce this risk.

Reducing your calorie intake by swapping sugar-sweetened drinks for unsweetened drinks could work towards this goal. And given that UK tap water is cheap, calorie-free and safe to drink, it would seem the obvious choice for a sugar swap.

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

Links To The Headlines

Choosing water instead of sugary drinks could cut diabetes 2 risk by a quarter. The Guardian, April 30 2015

Swapping orange squash for a cup of tea cuts diabetes risk. The Daily Telegraph, April 30 2015

Cutting out one fizzy drink a day slashes diabetes risk by 25%: Replacing sugary beverages with unsweetened tea or coffee could combat epidemic. Mail Online, May 1 2015

A glass of water a day 'can cut diabetes risk by a quarter'. Daily Express, May 1 2015

Links To Science

O'Connor L, Imamuara F, Lentjes MAH, et al. Prospective associations and population impact of sweet beverage intake and type 2 diabetes, and effects of substitutions with alternative beverages. Diabetologia. Published online April 30 2015

Categories: NHS Choices

Texting may help relieve pain during minor surgery

NHS Choices - Behind the Headlines - Fri, 01/05/2015 - 11:45

"Need pain relief for surgery? Try a text," the Daily Mail reports. The advice was prompted by a small study that found people who used a mobile phone during minor surgery were less likely to require additional pain medication.

During surgery, participants in this study were allocated to texting a close friend or family member, texting a research assistant they did not know, playing Angry Birds, or receiving usual care.

Researchers found patients who used a mobile phone to text someone were less likely to need additional painkillers during surgery. Interestingly, people who texted a research assistant tended to need slightly less painkillers than those who texted somebody that they knew.

The researchers speculate this could be because the conversations with the research assistant were not about their surgery, so this may have helped take their mind off the experience.

While the study was well designed, it was relatively small and may not be representative of all people having this type of surgery, or be able to detect small effects.

Larger studies assessing a wider variety of pain-related outcomes, such as the patient's own rating of their pain, are needed to confirm the findings.

Distraction techniques and social support can be useful self-help methods for coping with pain

Where did the story come from?

The study was carried out by researchers from Cornell University in the US and McGill University and LaSalle Hospital in Canada, and was funded by Cornell University. It was published in the peer-reviewed journal, Pain Medicine.

The Daily Mail covered the story reasonably, but does not highlight any of the study's limitations. The Daily Telegraph's headline, "Angry Birds could reduce pain during surgery, study finds", is misleading. There was no statistically significant difference between the "Angry Birds" group and the "no special activities" group in terms of their need for the painkiller.

It would be a shame if the paper just included the term to create an eye-catching headline rather than trying to report the study accurately.  

What kind of research was this?

This was a randomised controlled trial (RCT) looking at whether text messaging or playing a mobile phone game during minor surgical procedures could reduce patients' need for a strong painkiller.

Having social support has been reported to have a number of benefits, including reducing a person's pain sensation and making them able to bear pain for longer (in childbirth, for instance).

Distraction techniques, such as listening to music or using virtual reality simulations, have also been reported to help reduce anxiety and people's need for anaesthesia.

The researchers were interested in whether social support (in the form of text messaging) would have a greater effect than just being distracted (in the form of a game).

They also tested whether there was a difference between texting a friend or family member, who might be anxious about the person's surgery, and texting a stranger. An RCT is the best way to compare the effects of different interventions.  

What did the research involve?

The researchers recruited 98 adults scheduled to undergo minor surgery with regional, rather than general, anaesthesia. They allocated them at random to perform one of four things just before and during their surgery:

  • texting a close friend or family member
  • texting a research assistant they did not know about their hobbies and interests, for example
  • playing Angry Birds on a phone
  • no special activities (usual care)

The participants had the normal pre-surgery procedures, including being given their anaesthesia and initial dose of painkillers.

All except one of the anaesthetists (the doctors who give anaesthetic during surgery) did not know the aim of the study or what it was measuring. They knew whether the patient had a phone with them, but were not told what the patient had been asked to do with it.

The anaesthetists asked patients if they were in pain after the first surgical incision was made, then again within the first 5-10 minutes of surgery and throughout the procedure. If the patient reported pain, the anaesthetist could give them the painkiller fentanyl or sedation as they judged appropriate.

The researchers then compared the groups to see if they differed in terms of how much fentanyl was needed during the surgery.

What were the basic results?

The patients in the four groups did not differ in their anxiety levels before surgery, or the type of surgery or how long they were in the operating room. Only about a quarter of the patients (27.6%) needed extra fentanyl during the surgery.

The researchers found that:

  • patients who texted a close friend or family member during their surgery needed less fentanyl than those who did not do any of the activities
  • patients who texted the research assistant needed less fentanyl than those playing the game and those who did not do any of the activities
  • patients in the two texting groups did not differ significantly in their need for fentanyl
  • patients in the game group and those who did not do any of the activities did not differ significantly in the amount of fentanyl they needed

The researchers also analysed the odds of needing additional fentanyl during surgery. They report that those doing nothing were four times more likely to need more fentanyl than those texting friends or family, and six times more likely than those texting the research assistant.

Looking at the text conversations, those who texted the research assistants tended to be more positive, while the texts with a friend or family member tended to use more biological terms, so seemed to focus on the surgery itself. 

How did the researchers interpret the results?

The researchers concluded that their study "provides the first evidence of the analgesic-sparing benefits of social support from text messaging in a surgical setting". 

Conclusion

This relatively small study suggests text message conversations during minor surgery may reduce the need for painkillers, and are more effective than playing the game Angry Birds.

The study was an RCT, the best design for comparing different interventions, which should ensure the groups were well balanced. This means any differences in the patients' outcomes should be the result of the interventions.

But this study does have some limitations:

  • It was relatively small and may not be representative of all people having this type of surgery. The authors suggest the study's small size may also be why they did not find an effect for the Angry Birds intervention.
  • The anaesthetists could not be completely blinded to which group patients were in, as they knew whether the person had a phone with them. They may also have been able to guess what a person was doing (texting or playing a game) based on their hand movements or expression. This might influence their perception of the participants' pain.
  • Being engaged with the phone might affect the frequency anaesthetists asked the participants about their pain. The researchers say they tried to make sure this wasn't the case, but acknowledge this was down to the discretion of the anaesthetists.
  • It only assessed one outcome. Ideally, comparison of the patients' own assessment of pain and satisfaction with the procedure would be an important outcome to assess.

There is interest in developing non-drug-related methods to reduce people's pain and discomfort during surgery or other procedures.

The researchers suggest that texting could be a good approach, as it is simple and doesn't need specialised equipment or input from healthcare staff. However, whether this would be considered acceptable from an infection control perspective is unclear.

Overall, this study suggests that using a mobile phone during surgery has some effect, but larger studies assessing a wider variety of outcomes are needed.

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

Links To The Headlines

Need pain relief for surgery? Try a text: Simple act of writing a message on a mobile phone could significantly reduce patients' discomfort. Daily Mail, May 1 2015

Angry Birds could reduce pain during surgery, study finds. The Daily Telegraph, April 30 2015

Links To Science

Guillory JE, Hancock JT, Woodruff C, Keilman J. Text Messaging Reduces Analgesic Requirements During Surgery. Pain Medicine. Published online December 19 2015

Categories: NHS Choices

Where's your pain?

NHS Choices - Live Well - Fri, 01/05/2015 - 11:37
Where's your pain?

Pain can strike anywhere in the body. Wherever you feel pain, whether it's in your hip, back, foot or head, use this guide to find the information you need.

Head and neck

Chest, shoulders and back

Arms and hands

Abdomen, pelvis and genitals

Legs and feet

Categories: NHS Choices

UK life expectancy expected to rise to late 80s by 2030

NHS Choices - Behind the Headlines - Thu, 30/04/2015 - 12:50

"Life expectancy is rising faster than thought, with 90 expected to become the norm in some affluent areas of the country by 2030," The Guardian reports. The same predictions led the Daily Mail to warn of a "life expectancy timebomb".

A new modelling study looking at trends in life expectancy estimated that male babies born in 2030 could live to an average of 85.7 years, with females living an average of 87.6 years.

The study also flagged up the potential effects of health and socioeconomic inequalities on life expectancy. For example, it estimated life expectancy in the affluent London borough of Kensington and Chelsea would be five to six years higher than the working class area of Tower Hamlets.

It remains to be seen if the increase in life expectancy would be a blessing or a burden. Elderly people contribute to society in many meaningful ways, such as helping out with childcare or volunteering for charity work. But they may also have complex health needs that could require significant resources to treat.

Assuming the model is accurate, the study produces some interesting results about trends in life expectancy and inequalities, and how they may change over time.  

Where did the story come from?

The study was carried out by researchers from the department of epidemiology and biostatistics at the School of Public Health and MRC-PHE Centre for Environment and Health, the UK Small Area Health Statistics Unit, Imperial College London, Northumbria University, and GlaxoSmithKline. It was funded by the UK Medical Research Council and Public Health England.

The study was published in the peer-reviewed medical journal, The Lancet. It has been made available on an open-access basis, so it is free to read online.

Most of the media reported the results of the research well, although they did not question the accuracy of the predictions much. Different outlets focused on different aspects of the research.

The Daily Telegraph and the Mail focused on the headline figure that the study predicted higher life expectancies than official estimates. In its headline, the Telegraph claimed people would live "up to four years longer" than official estimates, although the study shows a difference of 2.4 years for men and one year for women.

BBC News highlighted the narrowing gap between men and women's life expectancies, while The Guardian and The Independent were more concerned with the widening gap between rich and poor.  

What kind of research was this?

This modelling study analysed death rates and population data for 375 districts of England and Wales. Researchers used the data to construct mathematical models to predict life expectancy from 1981 to 2030 for each of the districts, looking at men and women separately.

The study aimed to give reliable district-level information about life expectancy to help with future planning for health, social service and pension needs. The figures are all averages for the districts and cannot be used to predict individual lifespans. 

What did the research involve?

Researchers looked at records of deaths in England and Wales between 1981 and 2012 by local authority district. They combined this with population data to develop five statistical models that could predict future death rates and life expectancy.

The researchers tested the models to see which best predicted actual death rates during the last 10 years of the data, then used the best-performing model to predict future life expectancy at the local and national level.

The data in the study came from the Office for National Statistics. The models incorporated features of death rates in relation to people's age, trends of death rates in people who were born within or close to the same five-year period, changes to death rates over time, and by local area.

The test of the five models found one model, which gave greater importance to trends in those born within adjacent time periods, worked better than the others, with forecast errors of 0.01 years for men and women.

This model was best able to predict death rates for 2002-12 using the first 21 years of the data. The researchers therefore chose this model to predict life expectancy from 2012-30.

While the geographical areas of the districts remained the same over the study, people living in these areas obviously change. The researchers looked at trends for each district, including birth rates and migration, so they could factor this in.

They looked at how relative levels of deprivation for each district affected the mortality rates and life expectancy. Taking account of all this data, they then predicted how life expectancy at birth could change from babies born in 2012 to babies born in 2030.

Rates for men and women were calculated separately, as life expectancy differs by gender. As far as we can tell from the paper, the analysis was done using reasonable assumptions about population trends.  

What were the basic results?

The study found life expectancy in England and Wales is expected to continue to rise from the 2012 average of 79.5 years for men and 83.3 for women, to 85.7 (95% credible interval 84.2 to 87.4) for men and 87.6 (95% credible interval 86.7 to 88.9) for women by 2030.

This is higher than predictions from the Office of National Statistics. However, this will come at the cost of increasing inequality between districts.

Improvements in life expectancy from 1981-2012 varied a great deal between districts. In 1981, men in districts with the best life expectancies could expect to live 5.2 years longer than those in the areas with the lowest life expectancies (4.5 for women).

By 2012, this had increased to a difference of 6.1 years for men and 5.6 years for women. The study says this trend is expected to accelerate, so that by 2030 the difference in life expectancy between the best and worst districts could reach 8.3 years for both men and women.

Most of the districts with the lowest life expectancies now and in 2030 were in south Wales and the northeast and northwest of England. The areas with the highest life expectancy were mostly in the south of England and London. However, London districts varied from the highest to the lowest life expectancy levels.

The gap between men and women's life expectancy is expected to shrink further. It has already shrunk from 6 years in 1981 to 3.8 years in 2012, and by 2030 it could be only 1.9 years. In some areas, there may be no difference between men and women's life expectancy at all.  

How did the researchers interpret the results?

The researchers say their results are a more accurate prediction of how life expectancy will increase than official figures, and are the first to look consistently at changes in life expectancy at the district level over a long period of time.

They say the increase is likely to be the result of better survival in people over the age of 65. They say men's life expectancy will rise faster than women's, partly because of the effect of social trends such as smoking among middle-aged and older women.

The researchers claim the data will allow local authorities to plan better for the future, especially as much health and social care is now the responsibility of local areas. However, they also say the figures provide a warning that inequality in England and Wales will continue to rise.  

Conclusion

This analysis of population data provides some fascinating information about how life expectancy has changed over the past 30 years, and how it may change in the future.

It found life expectancy for men and women will continue to rise. However, it also found the existing trends of the difference in life expectancy between different districts will continue to rise, which is of concern.

Although the data shows more deprived areas have seen less of an improvement in life expectancy, the study cannot inform us what factors are responsible for the differences in life expectancy.

There is one big limitation of any study that predicts life expectancy in the future: the figures are always based on trends from death rates in the past, and assume that past trends will continue into the future.

These types of studies cannot account for unexpected events or major social changes that could have a huge effect on life expectancy. For example, they can't build into their models the potential for unlikely events such as a big natural disaster, changes within the healthcare system, or even a major health breakthrough, such as a cure for heart disease or cancer.

It's worth remembering, too, that life expectancy figures represent the life expectancy of a baby born in that particular year. So the life expectancy figures for 2012 don't represent life expectancy for adults alive in 2012, but for babies born that year. This means the figures for 2030 don't yet apply: they are only predictions for babies born in the future.

The study can't be used by individuals to predict how long they may live, but it does provide useful data to plan for pensions and health and social provisions in the future.

If you are keen to live to 2030 and beyond, your best bet is to take steps to reduce your risk of the five leading causes of premature death:

Read more about the top five causes of premature death.

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

Links To The Headlines

Life expectancy increases but gap widens between rich and poor. The Guardian, April 30 2015

Men near equality with women in life expectancy. The Times, April 30 2015

Men 'catching up' on life expectancy. BBC News, April 30 2015

Britain is facing a life expectancy timebomb: By 2030, the average man will live to 85... and women will reach 87. Daily Mail, April 30 2015

Richest one per cent will live over eight years longer on average than those living in poorest parts of UK by 2030, say experts. The Independent, April 30 2015

Britons to live up to four years longer than official estimates by 2030. The Daily Telegraph, April 30 2015

Why we are all living longer: Life expectancy set to soar for Britons. Daily Express, April 30 2015

Links To Science

Bennett JE, Li G, Foreman K, et al. The future of life expectancy and life expectancy inequalities in England and Wales: Bayesian spatiotemporal forecasting. The Lancet. Published online April 29 2015

Categories: NHS Choices

New prostate cancer treatment has promising results in mice

NHS Choices - Behind the Headlines - Thu, 30/04/2015 - 12:00

"Prostate cancer resistant to conventional treatment could be all but wiped out by a therapy that boosts the immune system," the Daily Mail reports. The therapy, as yet only used in mice, enabled chemotherapy to destroy cancer cells in mice with previously treatment-resistant prostate cancer.

Abnormal body cells will usually be recognised by the immune system and destroyed. However, the fact the cancers develop and progress, and can be resistant to treatment, shows that something is preventing these cells from being destroyed.

Previous study has suggested that immune cells called B cells (which make antibodies) may have a role in making prostate tumours resistant to chemotherapy. This mouse study further investigated this by looking at different ways to suppress these B cells, using immune therapy or genetic techniques. It found that once these B cells were blocked or removed, a chemotherapy drug (oxaliplatin) was then able to attack and destroy mouse prostate tumours.

The researchers have dubbed this approach "chemoimmunotherapy", as it combines chemotherapy with immunotherapy (having an effect on the immune cells).

It is too soon to know whether "chemoimmunotherapy" could be the answer for progressive and treatment-resistant cancer in humans – prostate or any other type of cancer.

However, this study could aid further understanding of how the immune system tackles cancer, potentially leading to new treatment approaches.

 

Where did the story come from?

The study was carried out by researchers from the University of California, Institute of Immunology in Berlin, Medical University of Vienna and the University of Veterinary Medicine in Vienna. There is no information about external funding. 

The study was published as a letter in the peer-reviewed scientific journal Nature (letters are short reports of new research that are of potential interest to other researchers).

Media coverage was fair, but over-optimistic, about the results being applicable to humans. It is exaggerating the results of this very early stage study to suggest that advanced prostate cancer could be “"wiped out", as suggested by both the Daily Telegraph and the Daily Mail.

To its credit, the Mail’s headline made it clear that the experiment was in mice. The Telegraph also mentioned this, below its headline.

 

What kind of research was this?

This was a laboratory experiment using mice, exploring how the body’s immune system deals with cancer.

Abnormal body cells will usually be recognised by the immune system and destroyed. However, the fact the cancers develop and progress, and can be resistant to treatment, shows that something is preventing these cells from being destroyed. The possible reasons are poorly understood.

Previous research suggested that immune system cells, called B cells (which make antibodies), may be involved in making prostate cancer cells progress and become resistant to chemotherapy. As the researchers point out, although early prostate cancer responds well to chemotherapy, this is not the case with advanced or established tumours.

The researchers aimed to look at whether by disabling or blocking the B cells in mice, chemotherapy may be more successful in activating the immune system to fight the cancer. This would be an approach of combined chemotherapy and immunotherapy – known as chemoimmunotherapy.

 

What did the research involve?

The research used mouse models of metastatic prostate cancer that were resistant to the chemotherapy drug oxaliplatin, which is used in the treatment of aggressive prostate cancer in humans.

The researchers looked at different ways of suppressing the development or activity of the B cells that are thought to block the activity of chemotherapy drugs. They blocked or removed the B cells using immune-modulating drugs or genetic engineering techniques. Treated and untreated mice were then given oxaliplatin for a three-week period to look at the effects.

The researchers also investigated which are the crucial B cells that require elimination, including looking at human prostate cancer samples.

 

What were the basic results?

Researchers found that when the B cells were blocked or removed, the mice prostate tumours were successfully treated with oxaliplatin.

The researchers were able to identify the exact type of B cells that were responsible for blocking treatment, and these cells were also found in human prostate cancer samples resistant to chemotherapy.

 

How did the researchers interpret the results?

The researchers say in an accompanying press release that their findings call for clinical testing of "this novel therapeutic approach."

They also point out that in addition to prostate cancer, similar immunosuppressive B cells can be detected in other human cancers. They say this indicates that B cell-mediated immunosuppression might be the reason several other cancers do not respond to treatment, raising hopes that the combination of chemotherapy and immunotherapy could have broader applications for other cancers.

 

Conclusion

This study has built on the findings of previous research that has suggested B immune cells could have a role in making prostate tumours resistant to chemotherapy. This mouse study further investigated this by looking at different ways to suppress these B cells, using immune therapy or genetic techniques. It found that once these B cells were blocked or removed, chemotherapy was able to attack and destroy aggressive prostate cancer cells in mice.

The potential for a new chemoimmunotherapy treatment approach for cancer is promising. However, the study is still at a very early stage. While mice studies can give an indication of how cellular processes work and how a treatment may work in humans, they are only indications, as there are inherent differences between the species. It is often the case that diseases in genetically engineered mice differ in key ways from the same disease in humans, so we can’t say whether the results of this study would be the same for humans.

It is too soon to know whether suppressing the B immune cell response could be the answer for progressive and treatment-resistant cancer in humans – prostate or any other type of cancer. It is also not known whether a safe and effective new immunotherapy treatment for cancer could be developed on the back of these results. Other immunosuppressants can cause a wide range of side effects, so the benefits of this treatment approach could be outweighed by the risks.

However, this study could further understanding of how the immune system tackles cancer, potentially leading to new treatment approaches.

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

Links To The Headlines

New drug 'helps healthy cells kill prostate cancer': Test carried out in combination with chemotherapy drugs achieve almost complete remission in mice. Daily Mail, April 30 2015

Prostate cancer could be 'wiped out' by new treatment. The Daily Telegraph, April 29 2015

Links To Science

Shalapour S, Font-Burgada J, Di Caro G, et al. Immunosuppressive plasma cells impede T-cell-dependent immunogenic chemotherapy. Nature. Published online April 29 2015

Categories: NHS Choices

Diet swap study highlights bowel effects of western-style diet

NHS Choices - Behind the Headlines - Wed, 29/04/2015 - 13:30

"Diet swap experiment reveals junk food's harm to guts," BBC News reports.

20 American volunteers were asked to eat an African-style diet (high fibre and low fat) while 20 Africans were asked to eat a typical American-style diet (low fibre and high fat). The western diet seemed to contain more red and processed meat.

The researchers found that after just two weeks, both diets led to biological changes in the guts of both groups, such as changes in the microbes present and levels of inflammation.

The African-style diet led to changes that were suggested to possibly contribute to reduced bowel cancer (also known as colon cancer) risk in the long term, while the opposite was true of the western-style diet.

However, it was a very short-term study, which only looked at biological changes in the gut, and the authors say they can’t be certain that these led to the changes in bowel cancer risk.

That said, there is the striking figure that Americans are around 13 times more likely to develop bowel cancer than Africans, with similar rates existing in most western countries. There is also evidence that when non-western populations adopt a more westernised diet, there is a corresponding rise in bowel cancer cases.

The Department of Health advises people who eat more than 90 grams (g) of red and processed meat (cooked weight) a day to cut down to 70g, to help reduce their bowel cancer risk.

 

Where did the story come from?

The study was carried out by researchers from the University of Pittsburgh and other research centres in the US, Europe and South Africa. It was funded by the US National Institutes of Health, the UK National Institute for Health Research, the Academy of Medical Sciences, the Netherlands Organization (de Vos) for Scientific Research, the European Research Council and the Academy of Finland. The study was published in the peer-reviewed journal Nature Communications.

The news headlines generally focus on the effects of these diets on cancer risk – not making it clear that this study was not looking at cancer directly. Instead, it was looking at a range of indicators – biomarkers – that may provide an indication of how healthy a person’s digestive system is.

The BBC bucks this trend, with a more representative headline "Diet swap experiment reveals junk food's harm to gut", although the study was not specifically looking at junk food.

Some sources took a positive interpretation of the results, such as The Independent, which told us that "Adopting high-fibre diet could dramatically cut risk of bowel cancer". Others took a more negative approach, such as the Daily Express, whose headline was "Western diets can raise your cancer risk after just two weeks". While the study did find bowel changes after two weeks, we don’t know if these changes directly raise cancer risk or whether they remained after people changed back to their normal diet.

 

What kind of research was this?

This was an experimental study looking at the effects of two different diets – those of African-Americans and rural Africans – on the gut. Rural South Africans have much lower rates of bowel cancer than African-Americans – with fewer than 5 people per 100,000 affected, as opposed to 65 per 100,000 African-Americans.

Dietary differences are likely to be responsible for this difference, and the researchers wanted to see what the effect of the typical diets of these groups had on the gut. They did this by getting these two groups to effectively switch diets for two weeks and seeing what happened.

This study is appropriate for looking at short-term effects of diet on the gut, which might be related to cancer risk if the diet was maintained in the long term.

However, a long-term study would be unethical, as you would be exposing some people to a diet that you know, or at least strongly suspect, is unhealthy.

 

What did the research involve?

The researchers recruited 20 healthy African-Americans aged 50 to 65 years old, living in the US, and an age and sex-matched group of 20 South Africans living in a rural area. They were first assessed over a two-week period, where they ate their normal diet at home. They then switched to the "opposite" diet – either a western-style diet or a rural African-style diet provided by the researchers. The researchers then assessed what affect this had on their gut.

The rural African-style diet increased average fibre intake among the African-Americans from 14g to 55g per day, and reduced their fat from 35% to 16% of their total calorie intake. The western-style diet reduced fibre intake among the rural Africans from 66g to 12g per day, and increased their fat intake from 16% to 52% of their total calorie intake.

During this part of the study, the participants lived in research facilities and had their meals prepared for them. The meals were also designed to be appealing to participants. While there was some "junk food" in the western-style diet used in the study (hamburger, fries and hot dogs), there were also some healthier meals, such as chilli, rice and stuffed bell peppers. The rural African-style diet also included some foods that would not be traditionally served in Africa – such as vegetarian corn dogs and hushpuppies (a fried or baked ball of cornmeal batter). From the sample menus reported in the study, the western-style menus appeared to include more red and processed meat than the African-style meals – with the latter including more fish.

The investigations the researchers performed included collecting faecal samples to test them for bacteria and chemical by-products of digestion, and carrying out colonoscopies (where a small tube containing a light and a camera is inserted via the rectum to observe the bowel wall).

 

What were the basic results?

In their normal diet, the African-Americans ate two to three times more protein and fat than the rural Africans. In contrast, fibre intake was higher in the rural Africans’ diets. The cells in the walls of the African-Americans’ colons were dividing more than those in the rural Africans.

The researchers found that switching African-Americans to the high-fibre, low-fat diet led to an increase in the fermentation of sugars in their gut. This indicated a change in the microbes in the gut that are responsible for this process, and this was supported by testing which microbes were present.

There was also a reduction in the production of certain bile acids in the rural African diet. Some animal studies have suggested that these bile acids can promote cells to become cancerous, and human studies were also reported to have found that higher levels are linked with increased colon cancer risk. There was also a reduction in signs of inflammation of the walls of the colon, and the cells in the colon wall stopped dividing as quickly. Again, these changes could potentially predict lower cancer risk.

The opposite changes were observed in the rural Africans when they switched to a western-style diet.

 

How did the researchers interpret the results?

The researchers concluded that "in individuals from high-risk and from low-risk cancer populations, changes in the food content of fibre and fat had remarkable effects on their [bowel bacteria and metabolites] within two weeks, and, critically, that these changes were associated with significant changes in inflammation and proliferation [of the bowel lining]". They say these changes may not lead to changes in bowel cancer risk, but state that other studies suggest there could be links.

 

Conclusion

This study aimed to investigate various biological changes to the gut that occur when switching from a western-style low-fibre, high-fat diet to an African-style high-fibre, low-fat diet, and vice versa. These changes may partly explain why African-Americans living in the US have over 10 times the bowel cancer rate of rural Africans.

The differences seen may not solely have been due to the differences in fibre and fat. The western-style diet also appeared to contain more red and processed meat, which have also been linked to increased bowel cancer risk. It is also worth bearing in mind that this study only took place over two weeks, and the longer-term effects of these diets on the colon were not studied. The authors themselves acknowledge that they can’t be sure the changes they saw would directly lead to changes in cancer risk. However, other research suggests they might be if they were present in the long term.

The other limitations are that the study was relatively small and only included healthy middle-aged and older adults of African origin, so may not apply to the wider population. 

Overall, the results do not contradict current advice that consuming a high-fibre diet can reduce your bowel cancer risk. Meanwhile, obesity and a diet high in red and processed meat have been shown to increase bowel cancer risk.

Read more about bowel cancer prevention.

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

Links To The Headlines

Diet swap experiment reveals junk food's harm to gut. BBC News, April 28 2015

Eating a western diet for just TWO WEEKS raises colon cancer risks: US-African diet swap reveals damaging impact of junk food. Mail Online, April 28 2015

Adopting high fibre diet could dramatically cut risk of bowel cancer, says study. The Independent, April 29 2015

Bowel cancer risk may be reduced by rural African diet, study finds. The Guardian, April 28 2015

Why Western diets can raise your cancer risk after just two weeks. Daily Express, April 28 2015

Links To Science

O’Keefe SJD, Li JV, Lahti L, et al. Fat, fibre and cancer risk in African Americans and rural Africans. Nature Communications. Published online April 28 2015

Categories: NHS Choices

Bullying may have worse long-term effects than child abuse

NHS Choices - Behind the Headlines - Wed, 29/04/2015 - 12:10

"Bullied children are five times more at risk of anxiety than those maltreated," reports the Daily Mail. A study looking at both UK and US children found an association between childhood bullying and anxietydepression and self-harm in adulthood.

People bullied by their peers in childhood were found to be more likely to have mental health problems in young adulthood than those who were ill-treated by adults, including their parents.

But the headlines are misleading – this figure only reflects the results of the US study. The results from the UK part of the study, which included more than three times the number of children, were not nearly as dramatic.

There are also some problems with the way this study was designed. It relied on children and parents self-reporting their experiences, which may make the results less reliable. For obvious reasons, parents in particular may have played down their ill-treatment of their children.

Still, the authors' conclusion that schools, health services and other agencies should co-ordinate their response to bullying seems a valid suggestion.

If you are concerned that your child is being bullied, it's essential that you or your child, or both of you, talk to their school. You could ask to see their anti-bullying policy, which every school has to have by law. This will allow you to see how the school plans to prevent and tackle bullying.  

Where did the story come from?

The study was carried out by researchers from the University of Warwick and Duke Medical Centre, both in the UK.

It was funded by The Wellcome Trust, the Medical Research Council, and the Economic and Social Research Council in the UK, and the National Institute of Mental Health, the National Institute on Drug Abuse, NARSAD (Early Career Award), and the William T Grant Foundation in the US.

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

The study was widely covered by the media. However, the Mail's assertion that bullied children are five times more at risk of anxiety than those maltreated by adults is misleading.

This figure was also used in other news sources and in an accompanying press release, but it only reflects the results of a US study. The figures from the UK, which involved more than three times the number of children, were not as striking.

What kind of research was this?

This was a cohort study exploring the long-term mental health effects of bullying in childhood compared with a child's ill-treatment by adults.

The researchers say ill-treatment by adults in childhood, such as neglect, cruelty and sexual abuse, is a matter of intense public concern. It has been shown to increase the risk of mental ill health, substance abuse and suicide attempts.

Verbal and physical abuse (bullying) by other children is also a global issue, with one in three children across 38 countries reporting being bullied. It can also have similar adverse effects in adulthood.

The researchers aimed to find out whether mental ill health is a result of both ill-treatment and bullying, or whether bullying has an independent effect. 

What did the research involve?

The research was based on two large ongoing cohort studies of families. One involved 4,026 children from the UK and the other had 1,420 children from the US.

The UK study aims to look at the health and development of children during childhood and beyond. The participants were pregnant women with an expected delivery date between April 1991 and December 1992.

From the first term of pregnancy, parents in the study completed postal questionnaires about themselves and their child's health and development.

The mother provided information on maltreatment between the ages of 8 weeks and 8.6 years, and their child's reports of bullying when they were aged 8, 10 and 13. The term "maltreatment" was assessed as physical, emotional or sexual abuse, or "severe maladaptive parenting".

Children attended annual assessment clinics, including face-to-face interviews and psychological and physical tests, from the age of seven onwards.

The US study is based on a sample of three groups of children aged 9, 11 and 13 years who were recruited in 1993. The parents and children were repeatedly interviewed and asked about bullying and maltreatment.

This included any physical or sexual abuse, or harsh parental discipline. The children were screened for behavioural problems and mental disorders up until young adulthood.

The researchers controlled the results for factors thought to increase the risk of child abuse and bullying, including the sex of the child, family hardship and the mother's mental health. They assessed for these factors during pregnancy for the UK cohort, and at annual parent and child interviews for the US cohort. 

What were the basic results?

The researchers found that:

  • In the US cohort, children who were bullied were nearly five times more likely to suffer anxiety than children who were maltreated (US cohort odds ratio [OR] 4.9; 95% confidence interval [CI] 2.0 to 12.0).
  • In the UK group, compared with children who were maltreated, children who were bullied were more likely to have depression (OR 1.7, 1.1-2.7) and self-harm (OR 1.7, 1.1-2.6).
  • In the US cohort, children who were maltreated but not bullied were four times more likely to have depression in young adulthood compared with children who were not maltreated or bullied (OR 4.1, 95% CI 1.5-11.7).
  • In the UK cohort, those who were maltreated but not bullied were not at an increased risk for any mental health problem compared with children who were not maltreated or bullied.
  • In both cohorts, those who were both maltreated and bullied were at an increased risk for overall mental health problems, anxiety and depression compared with children who were not maltreated or bullied. In the UK cohort, they were also at risk of self-harm.
  • In both cohorts, children who were bullied by peers but not ill-treated by adults were more likely to have mental health problems than children who were maltreated but not bullied (UK cohort 1.6, 95% CI 1.1-2.2; US cohort 3.8, 95% CI 1.8-7.9).  
How did the researchers interpret the results?

The researchers say that being bullied by peers in childhood had generally worse long-term adverse effects on young adults' mental health than ill-treatment by adults.

The findings have important implications for public health planning and service development for dealing with peer bullying, they argue. 

Conclusion

The two sets of results from differing cohort groups make the findings of this study quite confusing. For example, the abstract and press release highlight the 4.9% increase in anxiety when children had been bullied only, compared with children ill-treated by adults. But this figure only comes from the US cohort.

The confidence interval for this figure is very wide, suggesting it may not be reliable. In the UK cohort, the increased risk for anxiety among those who were bullied was small, but this was not included in the abstract or the press release.

The study relied on both adults and children self-reporting bullying or maltreatment by adults, which may undermine its reliability. Adults especially may be less inclined to report ill-treatment by themselves or a partner, although the authors tried to design the study in a way to guard against this. Also, as the authors point out, the study makes no distinction between abuse by adults and harsh parenting.

In the UK cohort, not all children completed the mental health assessment at 18 years. Those with more family problems were more likely to drop out, which could also make the results less reliable. There may also have been some selection bias of those people who agreed to participate in the study in the first place.

The study also failed to take cyberbullying into account, although the authors say previous studies have shown an overlap between "traditional" forms of bullying and cyberbullying.

Across both cohorts, about 40% of children who were ever maltreated were also bullied. As the authors point out, it is possible that being ill-treated may make children more susceptible to being bullied, or that both types of abuse have common risk factors.

Read more advice about bullying, including spotting the signs and what you can do to help.

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

Links To The Headlines

Childhood bullying has worse long-term negative impact on kids than maltreatment by adults. Daily Mirror, April 28 2015

Children bullied by peers 'at greater mental health risk'. The Guardian, April 28 2015

Being bullied is 'worse than child neglect or abuse': Youngsters tormented at school are much more likely to suffer anxiety, depression or self-harm. Daily Mail, April 29 2015

'Being bullied worse than neglect and abuse,' study says. The Daily Telegraph, April 27 2015

Links To Science

Lereya ST, Copeland WE, Costello EJ, Wolke D. Adult mental health consequences of peer bullying and maltreatment in childhood: two cohorts in two countries. The Lancet Psychiatry. Published online April 28 2015

Categories: NHS Choices

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