An 83-year-old woman has been implanted with the world’s first “3D printer-created jaw”. Using cutting-edge laser manufacturing techniques, doctors and metal experts were able to build up layers of titanium to form a custom metal jawbone to exactly fit her face. The metal jawbone was then inserted into her lower jaw, replacing a large section of bone that was destroyed by a chronic infection.

The technique of 3D printing has been used to build prototype products for some time, but in recent years scientists have begun experimenting with the medical possibilities offered by the process. In this case, a specialist metalwork company called Layerwise was able to translate 3D bone scans into a custom jaw. The company had previously used the process to make bone-shaped prostheses and dental implants. To make a full jawbone, the implant team had to overcome a number of challenges, such as how to encourage muscles to attach to the implant and how to incorporate the nerves necessary for normal movement of the jaw.

While 3D printing is still very much an experimental medical technique, scientists are even currently devising ways in which they might use it to produce whole organs, which are either “printed” by sandwiching layer after layer of living cells on top of each other or created by building scaffolds for cells to grow on.

 

Why did the woman need a new jaw?

The woman had a condition called osteomyelitis, a type of damaging bone infection usually caused by bacteria or, less often, by a fungal infection. It can occur when infections in nearby skin, muscle or tendons spread to a bone, or when an infection spreads from another part of the body through the blood stream. Depending on the nature of the infection and the health of the patient, osteomyelitis  can cause permanent damage to bones. The condition can be treated with antibiotics to get rid of the infection and prevent further damage, but sometimes surgery will be needed to remove dead bone tissue from around the site of the infection.

If a section of bone tissue is removed, surgeons can close the space by grafting in bone taken from elsewhere in the body or by inserting specialised filler materials that promote regrowth of the surrounding bone.

In this case, the patient had a progressive, chronic form of osteomyelitis which affected nearly her whole jawbone. This meant that she experienced permanent destructive changes which could not be treated by antibiotics alone. Because of the patient’s age, reconstructive surgery using conventional methods would have been risky. Therefore, her medical team decided to attempt to use a bespoke titanium-based implant to replace nearly her entire lower jaw.

 

What is 3D printing?

3D printing broadly encompasses a variety of different techniques. All the techniques involve using computers to knit together layers or particles of materials to form a new 3D structure. At present, doctors, scientist and technicians use 3D print technology to build implants out of metals, plastics and ceramics and are experimenting with making 3D structures using synthetic bone materials  and even living cells.

It can have several advantages over traditional manufacturing techniques, most notably the ability to create highly accurate bespoke structures such as dental implants. In the case of the new jaw implant, the process offers the option to create a structure that can perfectly fit the dimensions and contours of the patient’s face. Given the complexity involved, using an off-the-shelf implant is not practical.

To create the implant, the manufacturer Layerwise used a type of 3D printing called “selective laser melting”. During the process, heat-producing lasers are focussed on a bed of metal powder so that particles are precision-fused to form a 3D structure. This process is different to traditional metalwork, in which a shape is created by starting with a solid block and removing metal, similar to sculpting. Instead, the 3D printing process allows a shape to be built by adding tiny, intricate layers of particles, much like building a structure layer-by-layer from microscopic building blocks.

 

Has it been used medically before?

Doctors have previously used 3D-printed metal implants for dentistry and small bone prostheses, but this was the first time it was used to make a full jawbone. The benefit is that these custom-made prostheses can be modelled and shaped to fit the unique structure of someone’s surrounding bones. The surgeons revealed that surgery to implant the jaw took less than four hours and that the patient could speak and swallow again the day after surgery. This rapid recovery of function is encouraging.

It is likely that this technique will be investigated by other surgical groups, but the current reports relate only to the treatment of a single patient with chronic bone infection. It is not yet known whether it could be successful in wider facial reconstructive surgery, for example following trauma.

 

What might it be used for in the future?

While there are no guarantees that experimental lab techniques can be turned into usable treatments, medical 3D printing has been a hot topic in the news in recent years.

For example, in November 2011, BBC News reported that a team of scientists from Washington State University had used “a bone-like ceramic powder” to make a bone-like material that acts as a scaffold for new cells to grow. However, his experimental technique had not been used in people at the time of reporting.

Scientists are also looking at whether it is possible to use 3D printing to create important structures such as heart valves and even whole organs. A variety of systems is being tested in the lab, from creating 3D scaffolds for cells to populate to layering cells themselves.

Much of this cutting-edge technology is years away at the very least, but the possibilities are great and very exciting, as highlighted during a talk by Dr Anthony Atala at last March’s TED conference.

Links To The Headlines

World's first 3D printer-created jaw fitted to 83-year-old. Daily Mail, February 7 2012

Transplant jaw made by 3D printer. BBC News, February 7 2012

3D printer builds new jaw bone for transplant. The Daily Telegraph, February 7 2012

“Diabetic mothers-to-be have high risk of giving birth to children with congenital abnormality,” The Guardian said today.

The news is based on UK research that compared the rates of birth defects in women with and without diabetes. It found that about 7% of pregnancies in women with diabetes were affected by birth defects that were not caused by problems with the number or structure of the chromosomes. This was 3.8 times higher than the rate in women without diabetes. The study also found that women who have worse control over their blood sugar around the time of conception were at greater risk.

It has been known for some time that diabetes in pregnancy is associated with a higher risk of various complications, and this large study provides further evidence on the link between diabetes and birth defects. UK medical guidance already addresses this risk, and recommends that from adolescence onwards, women with diabetes should be routinely given information on the importance of planning any future pregnancies and on getting specialist care and advice when they decide to have a baby. Women with very poor control of their diabetes are also advised not to become pregnant until their blood sugar control has improved.

Women with diabetes are likely to already be aware of these risks. However, this study provides another reminder that diabetic women who are thinking about becoming pregnant should discuss their options with their doctor first.

 

Where did the story come from?

The study was carried out by researchers from Newcastle University, the Regional Maternity Survey Office in Newcastle, and the South Tees NHS Trust. It was funded by Diabetes UK, the Department of Health, the Healthcare Quality Improvement Partnership, and the four primary care trusts in northeast England. The study was published in the peer-reviewed medical journal Diabetologica.

The Guardian provided good coverage of this story, and put it into context of what is already known about how a woman’s diabetes can affect her pregnancy. The shorter news article in The Independent covered the basics of the story, but could be taken to suggest that the study was the first to discover the risk. In fact, this risk has been known for some time.

 

What kind of research was this?

Pregnancies in women with diabetes are already known to be at increased risk of various complications, including stillbirth and birth abnormalities. This cohort study aimed to clarify the extent to which diabetes increases the risk of major birth defects, and how this risk is affected by other factors such as maternal age, smoking and socioeconomic status.

A cohort study is the best way to assess this type of question, which could not be answered by a randomised controlled trial. Clearly, women with diabetes differ from women without diabetes in terms of their medical condition, but the two groups may also vary in other ways. It is important that researchers take such differences into account during their analyses.

 

What did the research involve?

The researchers used data collected on approximately 401,000 pregnancies that occurred between 1996 and 2008. They looked at whether mothers had diabetes, and if their babies had birth defects. The researchers then looked at whether birth defects were more common in babies born to mothers with diabetes.

The researchers obtained their data from the north of England, collected by the Northern Diabetes in Pregnancy Survey (NorDIP) and the Northern Congenital Abnormality Survey (NorCAS). NorDIP contains data on pregnancies in women diagnosed with diabetes at least six months before conception. It does not include women with gestational diabetes (diabetes that only occurs in pregnancy).

The study excluded multiple pregnancies (twins or triplets) and included pregnancies where the baby died at or before 20 weeks of pregnancy, or where the pregnancy was terminated due to a foetal abnormality. It included all eligible births in the study region in the study period. Abnormalities were classified according to standard definitions, and could be recorded up to the age of 12 years. Some birth abnormalities are caused by problems with the number or structure of chromosomes (the structures in the cell that contain our DNA). These abnormalities were looked at separately.

The researchers looked at the effect of various diabetes-related factors including how well the woman’s blood sugar was controlled at around the time of conception, whether she had type 1 or type 2 diabetes, and diabetes complications diagnosed before pregnancy (such as kidney or eye problems). They also looked at the effect of maternal age at the time of delivery, gestational age at time of delivery, folic acid intake before conception, foetal gender, number of previous babies, pre-pregnancy care, and smoking during pregnancy. Any significant factors were taken into account in the analyses to determine the effect of the individual factors.

 

What were the basic results?

Among the 401,149 pregnancies, 1,677 were in women with pre-existing diabetes. Most of these women (78.4%) had type 1 diabetes. Overall, 9,488 pregnancies were affected by at least one major birth defect, and 129 of these were in women with diabetes.

In women with diabetes, 71.6 per 1,000 pregnancies were affected by non-chromosomal major birth defects. This was 3.8 times higher than the rate in women without diabetes. Women with diabetes did not have an increased risk of having a baby with birth defects caused by chromosomal abnormalities.

When looking at specific factors linked to the risk of birth defects, the researchers found that women who had worse blood sugar control at around the time of conception were at increased risk of having babies with birth defects. Blood sugar control is often calculated using a measure called HbA1c level. This represents the levels of haemoglobin in the blood with a sugar molecule attached.

Doctors generally try to keep HbA1c levels below 7%. In this study, each increase of 1% in HbA1c over 6.3% was associated with a 30% increase in the odds of birth defects (odds ratio [OR] 1.3, 95% confidence interval [CI] 1.2 to 1.4). Women who already had kidney problems as a result of their diabetes also had an increased risk of having babies with birth defects (OR 2.5, 95% CI 1.1 to 5.3).

Some other factors were associated with an increased risk of birth abnormalities when looked at in isolation, such as low intake of folic acid and lower socioeconomic status. However, once all other factors were taken into account, these were no longer statistically significant.

 

How did the researchers interpret the results?

The researchers concluded that the main modifiable factor associated with birth defects in women with diabetes is their blood sugar control at around the time of conception. They say that the association with diabetes-related kidney problems needs to be studied further.

 

Conclusion

This study supports the existence of an association between maternal diabetes and increased risk of birth abnormalities, and helps quantify the size of the association. The study’s strengths include its large size and ability to include the entire population in the study area. However, there are a number of points to note:

• The researchers took into account various factors that could influence the results. However, as with all studies of this type, it is possible that unknown or unmeasured factors, other than maternal diabetes, could have affected the risk of birth defects.
• From this study we cannot say what effect diabetes arising in pregnancy (gestational diabetes) might have on risk of birth defects, as these women were not included in this analysis.
• The study relied on registry-recorded data, and there may be some omissions or inaccuracies in this data. That said, the registries used standard systems for recording data that should increase the reliability of their records.

The link between maternal diabetes and an increased risk of birth defects is already established. Better blood sugar control can help reduce this risk, although it cannot eliminate the risk completely. The National Institute for Health and Clinical Excellence (NICE) recommends that women with diabetes who are trying to conceive should aim for an HbA1c of less than 6.1%, if this can be achieved safely. It also suggests that women with an HbA1c of over 10% should avoid becoming pregnant.

NICE also recommends that:

• Women with diabetes who are planning to become pregnant should be informed of the need to establish good blood sugar control before conception, and that maintaining it throughout pregnancy will reduce the risk of miscarriage, birth defects, stillbirth and neonatal death. They also say that it is important for healthcare providers to explain that these risks can be reduced, but not eliminated entirely.
• The importance of avoiding unplanned pregnancy should be an essential component of diabetes education from adolescence onwards for women with diabetes.
• Women with diabetes who are planning to become pregnant should be offered pre-conception care and advice before they stop using contraception.

This study supports the need for specialist information and planning for pregnancy in women with diabetes. Women with diabetes who are thinking about becoming pregnant should discuss this with their doctor if they have not already done so.

Links To The Headlines

Women with diabetes warned to take precautions when having a baby. The Guardian, February 6 2012

Diabetes lifts birth defect risk. The Independent, February 6 2012

Diabetes quadruples birth defects risk, say researchers. BBC News, February 6 2012

Mothers-to-be with diabetes ‘four times more likely to have baby with birth defects’. Daily Mail, February 6 2012

Links To Science

Bell R, Glinianaia SV, Tennant PWG et al. Peri-conception hyperglycaemia and nephropathy are associated with risk of congenital anomaly in women with pre-existing diabetes: a population-based cohort study. Diabetologia (awaiting publication)

A “single genetic mutation can double your risk of stroke”, the Daily Mail has reported. The newspaper added that scientists hope the discovery could lead to tailored treatments for the condition.

The news is based on research which looked for genetic variations that were more common in people who had had an ischaemic stroke than in people who had not had one. Ischaemic strokes occur when the blood flow to a part of the brain is blocked. They account for 80% of stroke cases. By testing the DNA of several thousand participants, the researchers identified a new genetic variant that was associated with increased risk of a type of ischaemic stroke called a “large vessel stroke”. In large vessel strokes, one or more of the arteries supplying blood to the brain become blocked. People can carry up to two copies of the variant, and the study’s authors estimated that each copy of the variant a person carried was associated with about a 42% increase in the odds of a large vessel stroke. However, it is not yet known whether this genetic variant raises the risk of a stroke, or if it is found near to another variant that is responsible for the increased risk.

This well-designed study has identified a new association between a genetic variation and strokes. However, the study cannot confirm whether the variation itself causes the increased risk of a stroke. This key issue will need to be clarified before these findings can contribute to the development of the new treatments that many newspapers optimistically predicted.

 

Where did the story come from?

The study was carried out by researchers from the University of Oxford, St George’s, University of London, and a number of other UK and international universities and research institutes. It was funded by The Wellcome Trust. The study was published in the peer-reviewed scientific journal Nature Genetics.

This study was covered by a number of newspapers. In general, the coverage of the research was good, although many news stories focused on its potential to lead to the development of screening tests and new treatments. However, there is no guarantee that this research will lead to such advances. If it does, they are likely to be some way off.

 

What kind of research was this?

This case-control study aimed to identify genetic factors that are associated with an increased risk of ischaemic strokes. Ischaemic strokes occur when there is a blockage of blood flow to part of the brain. This can deprive brain cells of vital oxygen and nutrients. Around 80% of strokes are ischaemic. The remainder are haemorrhagic strokes, caused by a blood vessel rupturing in or around the brain.

To find genetic variants associated with strokes, the researchers read the DNA sequences of a group of patients who had had an ischaemic stroke. They compared them to the sequences of a group of healthy people. Their theory was that genetic variations that were more common among the stroke group could potentially be linked to stroke risk. To verify whether the variants they initially identified in these groups were associated with strokes, the researchers tested if the same pattern was seen when another group of stroke patients were compared with another group of healthy individuals (controls). This is an accepted method that is used when performing genetic studies of this type.

Although this was a well-designed study, genetic studies like this one can only show that a particular genetic variant is associated with a disease. Further experiments are required to see if the variants identified have a role in causing strokes, or if they lie close to other genetic variants that have this effect. What these variants do still needs to be identified, so media claims that this research could lead to potential new treatments seem premature.

It is also important to remember that genetic, medical and lifestyle factors are likely to contribute to a person’s risk of a stroke. It should not be assumed that a person’s genetics mean that they will definitely have a stroke. Equally, people without high-risk genetics may still be at risk of a stroke risk because of lifestyle factors, such as smoking.

 

What did the research involve?

In the first phase of the study, researchers recruited 3,548 individuals who had had an ischaemic stroke (the cases) and 5,972 healthy individuals (the controls). The researchers looked for genetic variants that were more common in the stroke group. In a second phase, the researchers confirmed their findings in a new group of 5,859 cases and 6,281 controls.  The new genetic variation they identified was then re-confirmed in a further 735 cases and 28,583 controls.

 

What were the basic results?

The researchers identified genetic variants at three locations that have been associated with different subtypes of ischaemic stroke in previous studies (near the genes PITX2 and ZFHX3, and on the short arm of chromosome 9). In addition, they identified a genetic variant at a new position within the HDAC9 gene, which was associated with a subtype of ischaemic stroke called large vessel stroke. In large vessel strokes, one or more of the large arteries supplying blood to the brain become blocked. This variant in HDAC9 occurs on about 10% of chromosomes in people in the UK. Humans have two copies of each chromosome, and therefore we can carry up to two copies of this variant (one on each chromosome). The researchers calculated that each copy of the variant that a person possessed was associated with a 42% increase in the odds of having a large vessel stroke (odds ratio 1.42, 95% confidence interval 1.28 to 1.57 for each copy).

 

How did the researchers interpret the results?

The researchers concluded that they have “identified a new association with the HDAC9 gene region in large vessel stroke”. They also stated that “the mechanism by which variants in the HDAC9 region increase large vessel stroke risk is not immediately clear.”

 

Conclusion

In this study, researchers have identified a genetic variant in the HDAC9 gene that is associated with a subtype of ischaemic stroke called a large vessel stroke. Large vessel strokes occur when one or more of the arteries supplying blood to the brain become blocked.

In this type of study, the genetic variants identified as being associated with a condition are not necessarily the cause of the increase in risk. Instead, they may lie near another variant that is responsible for the effect. In order to unlock the role of the HDAC9 gene, researchers will now need to study it and the region surrounding it more closely, both to confirm whether the variation in this gene is responsible for the increase in stroke risk and, if so, how it has this effect.

Genetic, medical and lifestyle factors are likely to contribute to stroke risk. In addition, multiple genetic factors may potentially contribute to the risk. It’s important to note that although having higher-risk genetic variants increases the risk of having a stroke, it does not guarantee that a person will have one. Equally, people who do not have any associated variants can still be at risk of a stroke because of lifestyles factors such as smoking, drinking and their diet.

This well-designed study found an association between a new genetic variant and one type of stroke. As yet, it is not possible to say whether this finding will lead to the development of new treatments for large vessel strokes.

Links To The Headlines

New genetic discovery could boost treatment for stroke patients. The Independent, February 6 2012

Mutant gene clue to beat strokes. Daily Express, February 6 2012

Links To Science

The International Stroke Genetics Consortium (ISGC), the Wellcome Trust Case Control Consortium 2 (WTCCC2), Bellenguez C et al. Genome-wide association study identifies a variant in HDAC9 associated with large vessel ischemic stroke. Nature Genetics, February 5 2012 (published online)

A new study has found that “patients are more likely to die in hospital if they are admitted at the weekend”, according to BBC News. The broadcaster said the research backs up previous studies suggesting patients admitted to hospital at the weekend have a lower chance of survival.

The new study in question looked at over 14 million admissions to English NHS hospitals over the financial year of 2009/10. Researchers looked at risk of patients dying from any cause within 30 days of admission taking into account various other factors that could influence the risk, such as age, reason for admission, and other medical illnesses.

During the year there were 187,337 deaths that occurred within 30 days of admission, equating to 1.3% of all those hospitalised. When they looked at factors associated with risk they found a person admitted on a Sunday had 16% increased risk of dying following admission compared to a person admitted on a Wednesday. Conversely, patients were more likely to die on a mid-week day rather than a Saturday or Sunday.

While the study has found a pattern relating to admission day and the risk of dying, the reasons for this are unknown and it should not be assumed that the pattern is due to staffing levels or the availability of senior staff. There could be various reasons for the relationship. For example, it may be that people who need to see the doctor and be admitted on a weekend have more severe illness than people who would wait until the following Monday to be admitted.

While this very large study found a pattern, it will take further delving to unlock the reasons why, which are likely to be more complex than simply the availability of staff.

 

Where did the story come from?

This study was authored by researchers from University College London and various other institutions in the UK. The study was published in the Journal of the Royal Society of Medicine and received no outside funding.

 

What kind of research was this?

This was a retrospective cohort study aiming to see if being admitted at the weekend carried a higher risk of mortality than admission on a weekday. To do so the researchers looked at all hospital admissions that occurred within the NHS over the 2009/10 financial year. It was concerned with ‘30-day mortality’, that is, deaths occurring within 30 days of a hospital admission (either in or out of hospital).

The researchers adjusted their analysis to account for various factors that could have affected this risk, but do not describe how the severity of patients’ conditions was taken into account. This means it is difficult to tell how effectively this potentially major confounder has been accounted for. The severity of a patient’s illness, the type of care provided to them and the differences in their outcome are likely to relate to each other in complex ways, and so the topic will need further careful analysis.

 

What did the research involve?

The researchers analysed all admissions to the English National Health Service (NHS) during the financial year 2009/10. They linked admission records to official mortality data from the Office of National Statistics to identify all deaths that occurred within the 30 days following an admission (both those occurring in or out of hospital).

Using their data the researchers then developed statistical models to account for risk of death following admission. In their main model they adjusted for factors that were likely to have a strong effect on mortality risk:

• age
• sex
• ethnicity
• whether or not the admission was an emergency
• source of admission (for example, from home or transfer from another hospital)
• diagnosis
• number of previous emergency admissions
• number of previous ‘complex’ admissions
• medical co-morbidities
• social deprivation
• hospital trust
• day of the year (seasonality)
• day of the week admission occurred on

They looked at both risk associated with being admitted over the weekend, and with staying in hospital over the weekend (admitted during the week but being an inpatient over the weekend).

 

What were the basic results?

There were 15,061,472 admissions to the NHS in England over this one-year period, and the researchers had information on 30-day mortality and other patient characteristics for 14,217,640 of them (95% of all admissions). There were 187,337 deaths in hospital within 30 days of admission. Admission on weekend days was associated with an increased risk of 30-day death compared with admission on weekdays:

• Sunday admissions were associated with a 16% increased risk compared to those on a Wednesday (hazard ratio [HR] 1.16, 95% confidence interval [CI] 1.14 to 1.18)
• Saturday admissions were associated with an 11% greater risk versus Wednesday admissions (HR 1.11, 95% CI 1.09 to 1.13)

Conversely, deaths were more likely to occur during the week than at the weekend. Staying in hospital on a Sunday was associated with a slightly lower risk of death than staying in hospital on a Wednesday (HR 0.92, 95% CI 0.91 to 0.94), as was staying in hospital on a Saturday (HR 0.95, 95% CI 0.93 to 0.96).

There were 284,852 deaths overall – both in an out of hospital – and 34% of people that died did so after they had been discharged from hospital. Results for the researchers’ subsequent model, examining all deaths, not just those occurring in a hospital, were similar.

 

How did the researchers interpret the results?

The researchers conclude that admission to hospital at the weekend is associated with increased risk of dying within 30 days of admission. However, death is more likely to occur on a mid-week day than a weekend.

 

Conclusion

The main finding of this study was that being admitted to hospital at the weekend (Saturday or Sunday) is associated with a significant increased risk of death over the following 30 days. This study has strengths in that it has used an extremely large and reliable data set representative of almost all hospital admissions within the NHS in England during one financial year. The researchers’ model also accounted for a wide range of medical and sociodemographic factors and characteristics of admission that could have influenced the risk of death.

While the researchers’ models adjusted for a variety of important confounders, it is difficult to see from the report how they did this, making it difficult to decide whether all relevant factors have been appropriately adjusted for. Most importantly, this study has not examined the reasons why there may be increased risk of death with weekend admission, so no assumptions should be drawn about staffing levels or the availability of senior staff.

It is important to be aware that an increased risk of subsequent death of 16% (Sunday compared to Wednesday) is a relative measure, representing an increase of only about two extra deaths for every 1,000 people admitted on a weekend compared to a week day (a x 0.16 relative increase beyond a 13 per 1,000 average baseline risk of death).

The researchers do offer some potential reasons for the patterns seen, putting forward the hypothesis that patients admitted at the weekend may include patients whose illness may have been severe enough to justify not waiting until a week day, while those who were less ill may have waited rather than going to the hospital at the weekend.

This is an interesting and indeed plausible theory but it is not clear how the researchers adjusted severity of illness in their analysis, and therefore it is not possible to confirm if this phenomenon accounts for the small absolute difference in deaths seen.

Links To The Headlines

You ARE more likely to die if taken to hospital at weekend: Study confirms that NHS care is worse on a Saturday and Sunday. Daily Mail, February 2 2012

Hospital patients more at risk at weekends. The Guardian, February 2 2012

Risk of dying 'significantly' higher if you go into hospital on Sunday. Metro, February 2 2012

Links To Science

Freemantle N, Richardson M, Wood J, et al. Weekend hospitalization and additional risk of death: An analysis of inpatient data. Journal of the Royal Society of Medicine. Published online on February 2 2012

“Malaria deaths twice as high as was thought,” The Independent has reported today. Many newspapers have covered research that found that malaria claimed 1.2 million lives worldwide in 2010. The Guardian also reveals that the study “demolishes conventional thinking” that almost all malaria deaths are in babies and small children under the age of five.

Malaria-related deaths in the UK were not examined in this study. Malaria is not generally present in the UK, but this preventable disease is commonly contracted by unprepared travellers visiting tropical and subtropical regions. In recent years, newspapers have reported several cases of high-profile people who have caught malaria, including pop star Cheryl Cole and Premiership footballer, Didier Drogba.

The headlines are based on a disease-modelling study that examined a large database, alongside a systematic review of other studies, to identify deaths due to malaria across 105 countries over the past 30 years. The research found that malaria in 2010 was the cause of death for 1.2 million individuals, including 714,000 deaths in children younger than five years and 524,000 in individuals aged five years or older. The results tend to show an increase in mortality from 1980 to peak levels in 2004, but since then a clear decline.

The researchers say that the recent decrease in malaria mortality in Africa in particular is due to an increase in measures to control the disease, which has been supported by international help. They say that support from international donors needs to increase if malaria is to be eradicated.

However, the primary aim of this study was to predict trends over time in malaria mortality, not to try to find causes for malaria mortality or to examine the effectiveness of different solutions to the problem.

 

Where did the story come from?

The study was carried out by researchers from the University of Washington, Seattle, and the University of Queensland in Australia, and was funded by The Bill & Melinda Gates Foundation.

It was published in the peer-reviewed medical journal The Lancet. The papers accurately reflected the findings of the research.

 

What kind of research was this?

This was a modelling study that involved collecting all available data on malaria mortality between 1980 and 2010. During the past 10 years, efforts to tackle malaria have increased. This study aimed to assess the trends in malaria mortality in order to check the progress of these efforts, and to identify areas that need future attention. To do this, the researchers developed a range of models to estimate mortality by age, sex, country and year.

 

What did the research involve?

As part of the Global Burden of Disease 2010 Study, all available data for mortality by cause from 1980 to 2010 are being systematically collated, and the researchers used this along with the Malaria Atlas Project (MAP). The MAP monitored the levels of transmission of Plasmodium falciparum (the parasite that causes the most severe form of malaria) in different countries.

The researchers describe how they used a large database to identify systematically all data for deaths classified as due to malaria. The researchers restricted their analyses to 105 countries that had information on malaria transmission during the 30-year period of interest. For countries that had eliminated malaria during this period, they identified the year of elimination and estimated the number of malaria deaths for the period when transmission was still occurring.

The researchers supplemented the information identified with a search of the global literature to identify published and unpublished ‘verbal autopsy’ studies. These record the probable cause of death based on the deceased's symptoms and likely medical diagnosis. They were population-based studies that covered a period of at least one year and provided the number of deaths by cause according to verbal autopsy. The verbal autopsy method tends to be used in countries that lack a formal and reliable system for registering deaths.

In order to develop their models they divided the world into three groups:

• countries from sub-Saharan Africa and Yemen (45 countries)
• countries outside of sub-Saharan Africa (45 countries)
• countries with only Plasmodium vivax malaria (15 countries)

Malaria deaths in countries that only have Plasmodium vivax malaria are lower than others, so for these countries the researchers simply modelled malaria death rate by age. For the other 90 countries the researchers tested different predictive models, including:

• looking separately by sex
• looking separately by age group (less than five years and five years and older)
• looking at the transmission intensity of Plasmodium falciparum malaria, which is a key predictor of the number of malaria deaths

 

What were the basic results?

The study provides extensive mortality data by country. Overall, the researchers observe a fluctuation in the number of malaria deaths worldwide over the 30-year period:

• 995,000 deaths in 1980 (95% confidence interval CI 711,000 to 1,412,000)
• a peak level of 1,817,000 deaths in 2004 (95% CI 1,430,000 to 2,366,000)
• a decrease to 1,238,000 deaths in 2010 (95% CI 929,000 to 1,685,000)

In Africa there were:

• 493,000 deaths in 1980 (95% CI 290,000 to 747,000)
• an increase to 1,613,000 in 2004 (95% CI 1,243 000 to 2,145,000)
• about a 30% decrease to 1,133,000 in 2010 (95% CI 848,000 to 1,591,000)

Outside of Africa, malaria deaths have steadily decreased:

• 502,000 in 1980 (95% CI 322,000 to 833,000)
• down to 104,000 in 2010 (95% CI 45,000 to 191,000)

The researchers suggest that there have been more deaths in people aged five years or older than previous studies have estimated. In 2010 there were 435,000 deaths in over-fives in Africa (95% CI 307,000 to 658,000) and 89,000 deaths in over-fives outside of Africa (33,000–177,000). The comparative 2010 figures for under-fives are 699,000 deaths (95% CI 415,000 to 1,112,000) in Africa and 15,000 deaths (95% CI 4,300 to 31,000) outside of Africa.

Deaths in both under- and over-fives have been decreasing over the past five years. However, the trend of deaths for countries within Africa is different from that for countries outside Africa: in Africa deaths have declined in both the under- and over-fives in the past five years, though deaths in the under-fives still remain clearly higher than those in the over-fives; outside of Africa deaths in both age groups have also steadily declined, though here the mortality rate in the over-fives is higher than in under-fives.

 

How did the researchers interpret the results?

The researchers conclude that their findings show that the global malaria mortality burden is larger than previously estimated, especially in adults. They say that the recent decrease in malaria mortality in Africa is due to more measures being taken to control the disease, which has been supported by international help. However, they say that support from international donors needs to increase if malaria is to be eradicated.

 

Conclusion

This study has looked at a large amount of data and used systematic methods to examine trends in malaria mortality over the past 30 years. It shows that malaria in 2010 was the cause of death for 1.2 million individuals, including 714,000 deaths in children younger than five years and 524,000 in individuals aged five years or older. The results tend to show an increase in mortality from 1980 to peak levels in 2004, but since then a clear decline.

The researchers say that the recent decrease in malaria mortality in Africa in particular is due to malaria control activities being increased, supported by international help. They say that support from international donors needs to increase further if malaria is to be eradicated.

However, the primary aim of this study was to predict trends over time in malaria mortality, not to try to find causes for malaria mortality or to examine the effectiveness of different solutions to the problem.

Links To The Headlines

Malaria is twice as deadly as first thought after disease claims 1.2million lives in a year. Daily Mail, February 2 2012

Malaria death toll far higher than previously thought. The Daily Telegraph, February 2 2012

Malaria kills 1.2m worldwide - double the level feared. Metro, February 2 2012

Malaria kills twice as many people as previously thought, research finds. The Guardian, February 2 2012

Malaria deaths twice as high as was thought. The Independent, February 2 2012

Links To Science

Murray CJL, Rosenfeld LC, Lim SS, et al. Global malaria mortality between 1980 and 2010: a systematic analysis. Lancet 2012; 379: 413–31

Editorial: New estimates of malaria deaths: concern and opportunity. The Lancet, 2012:379;385

Britain is in the grip of a new “flesh-eating bug spread by sneezes and coughs”, according to the front page of today’s Metro. The newspaper says that the bacteria are spreading across Britain, as they can be caught through people coughing and sneezing on crowded trains and buses.

This unsettling news put some of the Behind the Headlines team off grabbing their free copy of the Metro at the station this morning, not because of the fear of catching deadly germs from the paper, but because its report was alarmist and overblown. The basis of this news was a laboratory study that investigated why healthcare-acquired meticillin-resistant staphylococcus aureus (MRSA) bacteria rarely cause infections in healthy individuals. The study found that healthcare-acquired MRSA has a high level of antibiotic resistance, but that this property comes at a cost of reduced virulence (being less able to cause infection). Conversely, the study found that the type of MRSA that is usually caught in a community setting is more virulent, but weaker against treatment with antibiotics.

This study has not investigated the transmission, effects or number of cases of community-acquired MRSA in the UK, the discussion of which formed the basis of many news reports on the research. The researchers state that MRSA outside the healthcare system and in the community is a growing concern, but cases are still very rare. This interesting research contributes to our knowledge of MRSA, rather than warning us of an invasion of airborne superbugs.

 

Where did the story come from?

The study was carried out by researchers from the University of Bath and the University of Nottingham in the UK; University College Dublin in Ireland; and Texas A&M Health Science Centre and the University of Texas in the US. It was funded by the UK Medical Research Council and a Biotechnology and Biological Sciences Research Council Studentship. The study was published in the peer-reviewed Journal of Infectious Diseases.

This story was widely covered. Most reports were alarmist, concentrating on the supposed emergence of a dangerous, highly infectious new form of community-acquired MRSA. Many newspapers suggested that transmission is easy, that it can lead to a “flesh-eating form of pneumonia”, and that cases are on the increase. These claims seem to be based on the press release for the research rather than the research paper itself. The study was actually laboratory-based research that had investigated why healthcare-acquired MRSA bacteria rarely cause infections in healthy individuals. Although there was some investigation of community-acquired MRSA, the results do not justify the news coverage.

 

What kind of research was this?

This was a laboratory-based study. It aimed to examine why healthcare-acquired MRSA bacteria rarely cause infections in healthy individuals. Healthcare-acquired, or hospital-acquired, means that the bacteria cause infections that mostly occur in healthcare environments.

The researchers initially covered the nature of MRSA and how it resists certain types of antibiotics. It is already known that MRSA is resistant to the antibiotics meticillin and oxacillin because it has acquired a piece of DNA called a ‘mobile genetic element’. Meticillin is an old antibiotic that is now no longer used and has been replaced by flucloxacillin.

Many staphylococcus aureus bacteria have now also developed resistance to the penicillin group of antibiotics (because they produce enzymes that can make penicillin inactive), but they are usually still susceptible to the antibiotic flucloxacillin. MRSA, however, does not have this susceptibility to flucloxacillin, and is, therefore, harder to treat than most staphylococci bacteria, needing stronger antibiotics still.

One particular genetic element that is key for deciding the properties of MRSA is called the ‘staphylococcal cassette chromosome mec’ (SCCmec). There are several different versions of this cassette, which each provide bacteria with slightly different properties. The researchers state that healthcare-acquired MRSA have type I, II or III SCCmec elements, whereas community-acquired MRSA have type IV and V elements. These different cassettes all contain a gene (mecA) that codes for a protein called PBP2a, located in the cell wall of the bacteria. PBPs (penicillin binding proteins) are a normal part of the cell wall of many bacteria. Many antibiotics work by inactivating PBPs, which cause the bacteria to die. However, the version of PBP encoded by mecA, PBP2a, is less sensitive to antibiotics, allowing the bacteria to survive.

 

What did the research involve?

The researchers initially determined whether deleting the mecA gene, which encodes the PBP2a cell wall protein, affects the toxicity of MRSA. They then took a healthcare-acquired MRSA strain and a version of this strain that they genetically modified to delete the mecA gene, and performed tests to see how each was able to break up a type of immune cell called a T cell in the laboratory.

The researchers then investigated the ability of the different strains to respond to ‘signalling molecules’, which normally cause the bacteria to activate their production of toxins. The virulence of these strains was confirmed using mouse experiments.

The researchers then compared the production of the PBP2a cell wall protein, T-cell toxicity and the resistance of healthcare-acquired MRSA to antibiotics, compared with community-acquired MRSA.

 

What were the basic results?

The researchers found that deleting the mecA gene caused the MRSA to become more toxic. This was because the expression of mecA results in cell wall changes that interfere with MRSA’s ability to detect or respond to signals to switch on toxin expression. MRSA with mecA deleted was also more virulent in a mouse model, causing mice to lose weight or die.

The researchers then compared MRSA strains with different SCCmec elements: those with type II elements (typical of healthcare-acquired MRSA) and those with type IV elements (typical of community-acquired MRSA). They found that typical community-acquired MRSAs had lower resistance to the antibiotic oxacillin, were more toxic to the immune system’s T-cells and expressed less PBP2a.

 

How did the researchers interpret the results?

“As a direct result of its high level of antibiotic resistance, healthcare-acquired MRSA is impaired in its ability to cause infection, which can explain its inability to cause infection in community settings, where antibiotic usage and the prevalence of susceptible patients are low.” In other words, healthcare-acquired MRSA makes a trade-off, sacrificing its ability to spread to healthy individuals in order to fight off a greater range of antibiotics.

 

Conclusion

This interesting study helps explain why healthcare-acquired MRSA infections are rarely found in healthy individuals. It found that expression of a gene that produces one of the proteins responsible for MRSA’s antibiotic resistance caused it to be less toxic. It also showed that typical community-acquired MRSA strains express less of this antibiotic-resistance protein, but are more toxic.

However, this intriguing lab study did not investigate the transmission, effects or number of cases of community-acquired MRSA in the UK, the discussion of which formed the majority of the news reports. On this basis, the research itself does not support the claims that we are under siege from an ‘airborne, bacteria-resistant, flesh-eating superbug’, as newspapers have today suggested.

Links To The Headlines

Flesh-eating bug spread by sneezes and coughs. Metro, February 2 2012

Deadly new superbug is heading for Britain. Daily Express, February 2 2012

New deadly MRSA strain on its way to the UK from USA. Daily Mirror, February 2 2012

Super-strong MRSA bug heading to UK. The Sun, February 2 2012

Flesh-eating bug spread by coughs and sneezes spreading across the UK. Daily Mail, February 2 2012

Links To Science

Rudkin JR, Edwards AM, Bowden MG et al.Methicillin Resistance Reduces the Virulence of Healthcare-Associated Methicillin-Resistant Staphylococcus aureus by Interfering With the agr Quorum Sensing System. Journal of Infectious Diseases, February 1 2012

“Sugar is so harmful that it should be controlled and taxed in the same way as tobacco and alcohol,” according to health experts quoted in today’s Daily Express. The researchers say that sugar indirectly contributes to 35 million deaths a year worldwide.

The news is based on a comment article by US health scientists, who argue that there has been a massive rise in diseases such as heart disease, cancer and diabetes since we began eating more sugar contained in processed food. The researchers argue that many of the health effects of excess sugar consumption are similar to those of alcohol, and that sugar should, therefore, be controlled and taxed in a similar way. They advocate introducing a tax on processed foods with added sugar, limiting sales during school hours and placing age limits on purchase. Interestingly, the authors rate sugar as more dangerous to health than saturated fat and salt, which they call dietary “bogeymen”.

It is important to highlight that the researchers’ article is a comment piece and, therefore, primarily reflects their views and opinions, rather than presenting direct research on the issue. While it is certainly an interesting concept, there is still a lack of evidence supporting the effectiveness of such measures and, crucially, whether the public would actually accept them.

 

Where did the story come from?

The article was written by researchers from the University of California. There is no information about any external funding. It was published in the comment section of the peer-reviewed scientific journal Nature.

The article was covered fairly by the papers, many of which included comments from UK experts including the UK Food and Drink Federation, which represents food manufacturers. The BBC also quoted an expert from the British Heart Foundation, who reportedly said that taxing salt and fat alongside sugar should also be considered.

 

What kind of article was this?

This was a comment piece in which experts discuss the global burden of general chronic disease related to sugar consumption and the need to regulate certain dietary items. In particular, the authors draw parallels between the health effects of sugar and the use of alcohol and tobacco, arguing that sugar should be regulated in a similar manner.

It is important to highlight that this was a comment piece only and, as such, it primarily reflects the views and opinions of the authors. A formal systematic review of the literature does not appear to have been conducted and, as such, it is not certain whether all relevant evidence and resources related to sugar consumption and its health effects will have been consulted.

Also, the short piece looks at the issue from a global perspective and, therefore, is not a direct commentary on sugar consumption in the UK. In fact, a map showing average added sugar consumption per day across different nations shows that people in the UK consume a relatively low amount of sugar, at least compared with the rest of the world. Much of the article’s content may be focused on policies suited to the US, which has by far the greatest per-head sugar consumption, at more than 600 calories worth of sugar per day.

 

What does the article say?

The article points out that, for the first time in human history, non-communicable diseases such as heart disease, cancer and diabetes, pose a greater health burden worldwide than infectious disease. While alcohol, tobacco and diet are all targeted as risk factors for these diseases by policymakers, only the first two – alcohol and cigarettes – are regulated by governments to protect public health. (Although, as the report points out, Denmark taxes food high in saturated fats and is now considering taxing added sugar.) The authors argue that fat and salt have become the current “dietary bogeymen” in the US and Europe, but that most doctors no longer believe that fat is the “primary culprit” of such disease. Doctors are apparently calling for attention to be turned towards the dangers of excess sugar consumption.

The authors estimate that over the past 50 years sugar consumption has tripled worldwide, mainly as a result of it being added to cheap processed foods. While excess sugar is thought to be a key cause of the obesity epidemic, they argue that obesity itself is not the root cause of disease but that its presence is a marker for metabolic damage. This, they say, could explain why 40% of those with metabolic syndrome (a collection of the key metabolic changes that lead to heart disease and diabetes) are not obese.

 

Why do they think sugar is dangerous?

The authors say that although sugar is described as “empty calories”, a growing body of evidence suggests that fructose (one component of table sugar) can trigger processes that lead to liver toxicity and a host of other chronic diseases. “A little is not a problem but a lot kills – slowly,” they say.

The authors argue that sugar meets all the four criteria used by health policy makers to justify the regulation of alcohol. These are:

• Unavoidability. While sugar was only available as fruit and honey at certain times of the year to our ancestors, it is now present in nearly all processed foods. In some parts of the world people are consuming more than 500 calories worth of sugar per day.
• Toxicity. There is growing evidence that excess sugar has an effect on human health beyond simply adding calories and can cause many of the same problems as alcohol, including high blood pressure, high blood fats, insulin resistance and diabetes.
• Potential for abuse. The authors argue that, like tobacco and alcohol, sugar acts on the brain to encourage dependence. Specifically, it interferes with the workings of a hormone called ghrelin (which signals hunger to the brain) and it also affects the action of other important compounds.
• Negative impact on society. The economic and human costs of these diseases place excess consumption of sugar in the same category as smoking and drinking.

 

What do they think should be done?

While the authors accept that sugar is “natural” and a “pleasure”, they argue that, like alcohol, too much of a good thing is toxic. Strategies to reduce consumption of alcohol and tobacco show that government controls, such as taxation and imposing age limits, work better than educating people. They make several proposals for controlling sugar, including:

• taxing any processed foods with added sugar, including drinks
• reducing the hours during which retailers can sell food containing added sugar
• tightening the licensing requirements on vending machines and snack bars selling sugary products
• controlling the numbers of fast food outlets and convenience stores
• limiting sales during school hours or imposing an age limit for drinks with added sugar

Finally, they argue that regulating sugar will not be easy, but it can be done with enough pressure for change, citing bans on smoking in public places as an example of what can be achieved.

 

What does this mean for me?

This article will be of interest to food scientists, health policy makers and the public alike, but the use of strategies to restrict the consumption of added sugar is complicated and, indeed, controversial. The implications of such moves would need to be considered in both medical and societal terms. They would need both medical evidence to support their effectiveness and assurance that the public would accept drastic changes, such as age limits on buying sweets. For example, in recent years, Denmark has imposed taxes on fatty foods, a move that has divided opinions greatly.

It is generally accepted that added sugar or excessive sugar consumption is bad for health and dietitians advise restricting sugar intake to the occasional “treat”. However, to what extent sugar is directly to blame for the rise in chronic disease and how much is due to other dietary components, such as saturated fat and salt, is open to debate. The current article does not appear to be a formal systematic review of the literature, and it is not certain whether all relevant evidence and resources related to sugar consumption and its health effects have been consulted. As such, it should be considered primarily to reflect the views and opinions of the authors.

In the UK at present, policymakers generally favour encouraging healthier eating through education and the provision of healthier options. This is carried out through public health campaigns such as 5 A DAY or by introducing new food ranges to schools. Whether this approach alone is adequate and whether healthier eating patterns should be encouraged by government regulation, is a crucial area of debate.

Links To The Headlines

Sugar 'is toxic and must be regulated just like cigarettes', claim scientists. Daily Mail, February 2 2012

Sugar tax needed, say US experts. BBC News, February 2 2012

Tax harmful sugar. Daily Express, February 2 2012

Links To Science

Lustig RH, Schmidt LA, Brindis LD. Public health: The toxic truth about sugar. Nature, February 2 2012

“Mind-boggling! Science creates computer that can decode your thoughts and put them into words,” the Daily Mail’s headline exclaimed today, while The Daily Telegraph heralded an era in which a “mind-reading device could become a reality”.

You’d be forgiven for thinking famous mind readers such as Derren Brown had just produced a telepathy implant. Instead, these reports are from a small study of 15 people that culminated in researchers being able to reconstruct the sound patterns of words using brain activity alone.

This research involved attaching electrical sensors directly to brains of people undergoing brain surgery to understand how they processed individual words that were played to them. The researchers demonstrated that the brain breaks words down into complex patterns of electrical activity. They were then able to create a mathematical algorithm that decoded and translated the brain activity back into a rough version of the original sound.

But the reconstructed words were not of good enough quality to be recognised by a human listener when played. The words were only recognised when the original and reconstructed sound patterns were compared visually.

This exciting and new research does raise the prospect of brain activity one day being translated into words using an implant. Such technology could help the vast numbers of people suffering from problems affecting speech. But it is important to recognise that this research is in its very early stages and a clinically effective implant is likely to be a long way off.

 

Where did the story come from?

The study was carried out by a collaboration of North American universities led by researchers from the University of California, Berkeley. It was funded by several academic grants and was published in the peer-reviewed science journal Public Library of Science (PLoS) Biology.

The researchers report that the human brain has evolved complex mechanisms to decode highly variable sounds into meaningful elements of language, such as words. Understanding this complex decoding in humans has proved difficult, as it requires recording brain activity on the exposed brain (with the skull removed).

This study took advantage of cases of rare brain surgery for epilepsy and brain tumours that allowed researchers to measure brain activity by attaching sensors directly to the brain surface. This provided a unique opportunity to understand how the human brain recognises speech.

This study received wide media coverage due to its futuristic appeal and was often given a sci-fi angle, with some suggesting a “mind-reading device could become reality”. This research does raise the possibility of developing a device that could interpret thoughts into speech in the future. However, it is important to note the authors’ own caution - that the technology of translating thoughts into words needs to be vastly improved before such a device could become a reality.

 

What kind of research was this?

This was a small study of 15 people undergoing brain surgery for epilepsy or brain tumour. It looked at whether the complex brain activity involved in processing spoken words, such as the sound wave form and syllable rate, could be reconstructed using a computer program.

The researchers believe that the brain processes internal thoughts in a similar way to hearing sounds, and hope that this type of technology could eventually be used to help those who cannot talk, such as those in a coma or in the much-feared “locked-in syndrome”.

 

What did the research involve?

Fifteen patients undergoing brain surgery for epilepsy or brain tumour were asked to listen to 47 real or invented words and sentences from different English speakers. All patients had normal language capabilities when they were enrolled in the study.

During this process electrical signals from the brain were recorded using multiple sensors attached directly to the part of the brain called the lateral temporal cortex, which includes the superior temporal gyrus (STG), thought to be very important in the processing of speech.

To understand and mimic the brain activity involved in processing heard words, the researchers used an approach referred to as “stimulus reconstruction”. In this case, the stimulus was hearing a spoken word.

Hearing words causes a large amount of brain activity involved in recognising and processing the different aspects of the sounds of the words, for example the different sound frequencies and timing of syllables. The word reconstruction involved creating a mathematical program (like that used in computer software) capable of decoding the vast amount of brain activity in such a way that it was possible to identify the original words heard by the participant.

The reconstructed signals from different mathematical models (linear and non-linear) were compared to those detected directly from the brain surface to see how good they were at mimicking the brain’s activity when hearing spoken words. The researchers also used the models to identify the most important areas of the brain involved in processing this information and what other factors influenced the accuracy of the sound reconstructions.

 

What were the basic results?

When constructing the mathematical models they found that the STG region of the brain was important in creating an accurate prediction of the sound pattern of the original word.

The sound patterns generated by the mathematical model allowed the identification of specific words to be generated directly from the brain activity of patients listening to the words. These took the form of visual representations of the word sound pattern. A total of 47 words were presented in pairs and, on average, the model correctly identified the word in approximately nine out of every ten instances (89%). This was significantly better than 50% correct identification, which would be seen simply by guessing.

Importantly, however, the quality produced from reconstructing the words was not good enough for them to be recognised by a human listener when played. The words were only recognised when the original and reconstructed sound patterns were compared visually.

The researchers found that different types of mathematical models performed better at reconstructing the sounds of words with particular characteristics.

 

How did the researchers interpret the results?

The authors concluded that their results demonstrated that key aspects of speech signals can be reconstructed from STG activity.

 

Conclusion

This study of 15 people undergoing brain surgery has demonstrated a method of reconstructing the sound of a heard word using only the signals obtained from the brain. This study represents an important progression in the field of speech reconstruction, which has the potential to improve the lives of many who suffer from speech difficulties in the future.

But the words, when reconstructed, were not of good enough quality to be recognised by a human listener when played. The words could only be identified when the original and reconstructed sound patterns were compared visually. The researchers suggest that improving the brain sensors detecting the STG brain activity may, in the future, improve the reconstructed sound to a level that could be understood by a person listening.

The mathematical formula used to reconstruct the words is at a very early stage and would need a significant amount of improvement and development before it could be considered for use in an implant or similar device in the future. Similarly, future speech reconstruction research would need to demonstrate it was effective in a large range of words, sentence patterns and languages. Currently, the mathematical program has only been tested on a limited vocabulary of 47 English words.

This research represents an intriguing first demonstration of the potential of speech reconstruction technology to transform the lives of people with communication problems in the future.

Links To The Headlines

Science decodes 'internal voices'. BBC News, February 1 2012

Mind-reading device could become reality. The Daily Telegraph, February 1 2012

Mind-boggling! Science creates computer that can decode your thoughts and put them into words. Daily Mail, February 1 2012

Mind-reading program translates brain activity into words, The Guardian, February 1 2012

Links To Science

Pasley BN, David SV, Mesgarani N, et al. Reconstructing Speech from Human Auditory Cortex. PloS Biology. Published online January 31 2012

“Heartburn pills taken by thousands of women ‘raise risk of hip fractures by up to 50 per cent’,” the Daily Mail reported today. The headline is based on a large new study of drugs called proton pump inhibitors (PPIs), which are commonly used to treat heartburn, acid reflux and ulcers.

The study found that post-menopausal women who regularly took PPIs for at least two years were 35% more likely to suffer hip fracture than non-users, a figure that increases to 50% for women who were current or former smokers. However, although this increase in risk is large, the overall risk of fractures remains small.

This was a large, well conducted study that suggests that long-term use of PPIs is associated with a small increase in risk of hip fracture, although the researchers point out that the risk seems to be confined to women with a history of smoking. Unlike previous research, this study took careful account of other factors that might affect risk such as body weight and calcium intake.

Women who are concerned about their use of PPIs are advised to consult their GP.

 

Where did the story come from?

The study was carried out by researchers from Massachusetts General Hospital, Boston University and Harvard Medical School and was funded by the US National Institutes of Health. The study was published in the peer-reviewed British Medical Journal.

Although the Mail’s headline is technically correct, it gives the impression that these drugs carry a very large increase in the risk of hip fracture. In fact, the study found that, in absolute terms, the increase in risk for regular users was small. Researchers found that among the women in the study who regularly used PPIs, about 2 in every 1,000 fractured a hip each year. In non-users, this figure was about 1.5 in every 1,000. This is a increase of about 5 fractures a year in every 10,000 women taking PPIs.

The Mail did point out this “absolute difference” towards the end of its story. Both the Mail and the BBC included comments from independent experts.

 

What kind of research was this?

The researchers point out that PPIs are among the most commonly used drugs worldwide. In the US they are available over the counter, but in the UK are available only on prescription. They are used for symptoms of heartburn, gastro-oesophageal reflux disease (GORD) and stomach ulcers. PPIs are thought to work by reducing acid production in the stomach. Concern has grown over a potential association between long-term use of these drugs and bone fractures, although the researchers say that previous studies have had conflicting results and many did not take other factors (called confounders) that might affect the risk of fracture into account.

In their cohort study of nearly 80,000 post-menopausal women, the researchers set out to examine the association between long-term use of PPIs and the risk of hip fracture. Unlike a randomised controlled trial, a cohort study cannot prove cause and effect. However, cohort studies enable researchers to follow large groups of people for long periods and they are useful for looking at potential long-term risks and benefits of treatments. The study was prospective, which means it followed participants in time, rather than collecting information retrospectively. This makes it more reliable.

 

What did the research involve?

This study took its data from a large ongoing US study called the Nurses Health Study, which began in 1976 and which sent health questionnaires every two years to 121,700 female nurses aged 30-55.

From 1982 participants were asked to report all previous hip fractures and in each biennial questionnaire, women were asked if they had sustained a hip fracture over the previous two years. Those who reported a hip fracture were sent a follow-up questionnaire asking for more details. Fractures from bad accidents, such as falling down a flight of stairs, were excluded from the study. A review of medical records for 30 of the women validated all self-reported fractures.

From 2000 to 2006 the women were asked if they had regularly used a PPI in the previous two years. In earlier questionnaires (1994, 1996, 1998 and 2000), the women were also asked if they had regularly used other drugs for acid reflux, called H2 blockers.

The biennial questionnaires also included questions on other factors including menopausal status, body weight, leisure activities, smoking and alcohol use, use of hormone replacement therapy (HRT) and other medicines. Researchers used a validated food frequency questionnaire to calculate the women’s total intake of calcium and vitamin D.

They then analysed the data for any association between regular use of PPIs and hip fracture, adjusting their findings for key confounders such as body weight, physical activity, smoking, and alcohol and calcium intake. They also took into account whether the reasons for using a PPI might have affected the results.

Finally, they carried out a systematic review combining their results with 10 previous studies on the risk of hip fracture and the long-term use of PPIs.

 

What were the basic results?

The researchers documented 893 hip fractures during the period of the study. They also found that, in 2000, 6.7% of women regularly used a PPI – a figure that had risen to 18.9% by 2008.

• Amongst women who had regularly taken a PPI at any time, there were 2.02 hip fractures per 1,000 person years, compared with 1.51 fractures per 1,000 person years among non-users.
• Women who regularly used PPIs for at least two years had a 35% higher risk of hip fracture than non-users (age adjusted hazard ratio (HR) 1.35; 95% confidence interval (CI) 1.13 to 1.62), with longer use associated with increasing risk. Adjustment for risk factors, including body mass index, physical activity and intake of calcium did not alter this association (HR 1.36; CI 1.13 to 1.63).

The increased risk did not change when researchers also took into account the reasons for PPI use:

• Current and former smokers who regularly used PPIs were 51% more likely to have a hip fracture than non-users (HR 1.51; (CI) 1.20 to 1.91).
• Among women who never smoked there was no association between PPI use and hip fracture (HR 1.06; (CI) 0.77 to 1.46).
• In a meta-analysis of these results with 10 previous studies, the risk of hip fracture in users of PPI was higher compared with non-users of PPIs (pooled odds ratio 1.30; CI 1.25 to 1.36).

The researchers also found that two years after women stopped taking PPIs, their risk of hip fracture returned to a similar level to that in women who had never taken them. Also, women taking H2 blockers had a “modest” increased risk of hip fracture but the risk was higher in women who took PPIs.

 

How did the researchers interpret the results?

The researchers conclude that their results provide “compelling evidence” of a risk between PPI use and hip fracture. They say the findings suggest that the need for long-term, continuous use of PPIs should be carefully evaluated, particularly among people who have smoked or are still smokers.

They suggest that PPIs may increase the risk of fracture by impairing the absorption of calcium, although in this study the risk of fracture was not affected by dietary calcium intake. The finding that the risk was confined to women with a history of smoking (an established risk factor for fracture) indicates that smoking and PPIs may act together (have a “synergistic effect”) on fracture risk.

 

Conclusion

This large study had several strengths. Unlike some previous studies, it collected information on and took into account other key risk factors for fracture, including body weight, smoking, alcohol use and physical activity. It also looked at the women’s use of PPIs every two years (rather than just asking them once) and took into account variations in use during this time in their analysis.

 

However, as the authors note, it also had some limitations:

• It did not ask about the brands of PPI used, nor the doses of PPI the women took, both of which could affect risk of fracture.
• The information about hip fracture was self-reported and not confirmed by medical records (although a smaller study has found self-reporting of hip fracture to be reliable).
• Also, the study did not record the women’s bone mineral density (BMD). Low BMD is an important risk factor for fracture and adding a measure of this could have strengthened the study.

Finally, because this was a cohort study, other factors both measured and unmeasured may have affected the results, even though researchers took many of these into account in their analysis. Socio-economic status and education, for example, were not established. Because this was a study of registered nurses, the applicability of the results to other socio-economic groups might be limited.

This study found that the long-term, regular use of these drugs is associated with a small increased risk in hip fracture among older women, a risk that seems to be confined to past or current smokers. Women who regularly take PPIs and who are concerned about these findings are advised to talk to their GP. Whether any change in use of this commonly prescribed drug is needed requires further study. 

Links To The Headlines

Indigestion drugs taken by millions linked to hip fractures. The Daily Telegraph, February 1 2012

Heartburn pills taken by thousands of women 'raise risk of hip fractures by up to 50 per cent'. Daily Mail, February 1 2012

Ulcer drugs 'link to fractures'. BBC News, February 1 2012

Links To Science

Khalili H, Huang ES, Jacobson BC, et al. Use of proton pump inhibitors and risk of hip fracture in relation to dietary and lifestyle factors: a prospective cohort study. British Medical Journal. Published online January 31 2012

 

“Drinking just one glass of milk a day could boost your brain power,” the Daily Mail has reported today. Milk is being hailed as a memory aid, the newspaper says, with a study showing that dairy products could “help stave off mental decline”.

The study on which the story is based found that adults with higher intakes of milk and other dairy products did better in memory and other brain function tests than those who drank little or no milk.

However, the Mail’s excitement is misplaced – the study did not show that milk was responsible for better mental performance. The type of study reported cannot show cause and effect. All it showed was that, at one point in time, people who drank more milk performed better in mental tests than those who drank less. It is possible that many other things influenced people’s performance in mental function tests, including occupation, stress levels, even how well they were feeling at the time they took the tests.

Milk may be good for your bones but so far there is no good evidence that it improves mental performance.

 

Where did the story come from?

The study was carried out by researchers from the University of Maine in the US and the University of South Australia. It was published in the peer-reviewed International Dairy Journal. It was partly funded by the Maurice de Rohan International Scholarship, the University of South Australia and the National Heart, Lung and Blood Institute, the National Institute on Aging and the National Institutes of Health, all in the US.

The Mail reported the study uncritically. Its suggestion that milk could help stave off mental decline is not supported by this research. It’s worth noting that the study was released to the press by a US PR company on behalf of the National Fluid Milk Processor Promotion Board, which is an industry-funded organisation set up by the US government to promote milk. This may explain how it found its way into the Daily Mail.

 

What kind of research was this?

This was a cross-sectional analysis of nearly 1,000 participants that aimed to investigate whether dairy food intake was associated with mental functioning. This type of study can provide a “snapshot” of various lifestyle factors and people’s health at one point in time, but it cannot establish cause and effect. A cohort study that recorded people’s dairy consumption over time and then tested their mental function more than once would provide more reliable results although even this type of study cannot establish cause and effect.

The researchers say that as the whole population ages, cognitive decline and dementia place a severe strain on both families and healthcare systems. Change in diet may have a role in preventing cognitive decline, but they say little attention has so far been paid to the relationship between dairy foods and mental performance.

The researchers say there is growing evidence that dairy products may be of benefit to cardiovascular health. Many experts would dispute this. Some dairy foods are high in saturated fat, which is associated with obesity and heart disease. Most dietitians advise a restricted intake of dairy products or consumption of low-fat varieties.

 

What did the research involve?

Researchers recruited 1,049 adults of all ages who were taking part in research looking at cardiovascular health and mental functioning. They collected health and lifestyle data from the participants by various methods including self-reports, medical examination, diagnostic interviews, health records and neuropsychological testing.

After excluding those who did not fulfil eligibility criteria (for example, because dietary or cognitive data were missing or because they had suffered a stroke), they were left with 972 participants.

To measure mental functioning of the participants, the researchers used a validated series of tests measuring memory, verbal recall, visual–spatial perception, organisational and verbal skills, and abstract reasoning ability. For dietary intake, they used a recognised questionnaire that included questions about nutrition and lifestyle.

The dietary component of this questionnaire included questions about dairy products. Milk was considered separately from total dairy foods. Total dairy foods were grouped as followed:

• cheese
• yoghurt and dairy desserts
• cream and ice-cream

Participants were asked how frequently they consumed such foods, with six possible responses:

• never
• seldom
• once a week
• 2-3 times a week
• 5-6 times a week
• once or more a day

Participants were also asked which type of milk they consumed – full fat, reduced fat or skimmed.

The researchers used validated statistical methods to analyse the relationship between mental performance scores and dairy intake. They adjusted their results for other factors that might affect the results, including age, education, smoking and alcohol.

 

What were the basic results?

The researchers report that participants who consumed dairy products at least once a day had “significantly higher scores on multiple domains of cognitive function” compared with those who never or rarely consumed dairy foods. In addition, those who reported eating dairy foods between two and four times a week performed significantly better on some of the tests than those who ate dairy foods once a week. The association between greater dairy food consumption and mental performance remained significant after adjusting for a number of risk factors. There was no significant association, however, between intake of specific categories of dairy foods (such as milk, cheese or yoghurt) and results of the tests.

 

How did the researchers interpret the results?

The researchers say their results support an association between high dairy food consumption and cognitive function. Although little is known about how dairy foods might influence mental functioning, they say that one possibility is that dairy food consumption may be beneficial for mental functioning through its “favourable effect” on cardiovascular risk factors such as obesity.

 

Conclusion

Contrary to the headlines, this study does not show that dairy food consumption has benefits for mental functioning. All it can do is provide a “snapshot” of a group of people’s dairy consumption and their mental functioning at one point in time. Some limitations are that:

• It relied on people self-reporting their dairy intake, which introduces the possibility of error.
• It is possible that many other factors (known as confounders) might have affected the results, including exercise habits, alcohol and stress levels, although researchers tried to adjust their findings for some of these.
• As the authors acknowledge, the dietary questionnaire did not specify size of portions or servings, which undermines the accuracy of estimated intakes.

Dairy products contain many nutrients that are needed for good health, in particular for the development of healthy bones and teeth. However, they are also high in saturated fat, which is associated with heart disease and obesity. At present there is no good evidence that dairy foods are especially beneficial for brain functioning.

Find out how dairy fits into a healthy diet using the Eatwell Plate.

Links To The Headlines

The white stuff: Drinking just one glass of milk a day could boost your brain power. Daily Mail, January 31 2012

Links To Science

Crichton GE, Elias MF, Doreb GA, Robbins MA. Relation between dairy food intake and cognitive function: The Maine-Syracuse Longitudinal Study. International Dairy Journal 2012:22;15-23