“Sitting in a window seat during a long flight can increase the risk of deep vein thrombosis,” according to The Daily Telegraph. It has long been known that flying is associated with an increased risk of deep vein thrombosis (DVT), a type of serious blood clot in a major vein, but new US guidance has looked at a range of factors that could potentially raise the risk.

Those of you thinking of booking your summer holiday might be interested to know that flying in cramped budget seats, while often annoying, presented no greater risk than flying in business class. And while pricey booze available during a flight can prove wallet-damaging, the guidelines say there was no firm evidence that drinking it could bring on DVT. However, sitting by a window during a long-haul flight was associated with a greater risk because of the limited opportunities for walking around. People’s age, previous DVT and recent operations were among the other factors found to raise DVT risk.

The evidence-based guidelines were produced by the American College of Chest Physicians to address the risk of both DVT after long-haul flights and the potentially fatal lung clots (pulmonary embolisms) that can follow. The guidelines also include recommendations about the best ways for travellers to reduce their risk of DVT.

The guidelines seem to debunk the long-held assumption that a lack of legroom causes DVT. This much-debated phenomenon is often referred to as “economy-class syndrome”.

What is “economy-class syndrome”?

It is long established that inactivity is associated with DVT, and so some people believe that the lack of legroom when flying in economy class can increase the risk of developing a blood clot. This has led to the theoretical phenomenon being dubbed “economy-class syndrome”.

Some have also suggested that dehydration is more common during economy travel and may increase the risk of DVT. However, the existence of this so-called “economy-class syndrome” is controversial and has never been proven.

What is DVT?

Deep vein thrombosis or DVT is when blood clots form in a deep vein. A clot that develops in a vein is also known as ‘venous thrombosis’. DVT most commonly affects the leg veins or deep veins in the pelvis. It can cause pain and swelling in the leg but in some cases there may be no symptoms.

DVT can lead to the potentially life-threatening condition known as a pulmonary embolism. This occurs when a clot breaks off into the bloodstream and travels to the chest, where it blocks one of the blood vessels in the lungs.

Experiencing DVT and pulmonary embolism together is known as venous thromboembolism (VTE), which is a condition that can be life-threatening. Each year more than 25,000 people in England die from VTE contracted in hospital. This is approximately 25 times the number of people who die from MRSA. VTE occurs in hospitals as a result of patients lying sedentary in bed for extended periods following an operation. In recent years the NHS and Department of Health have run a major programme of measures to help reduce the rates of VTE developed in hospitals. For example, many patients are now given a VTE risk assessment when being booked into hospital.

Who is at risk of DVT?

In the UK each year about one person in every 1,000 is affected by DVT. Anyone can develop it but there are certain known risk factors that include:

• increasing age
• pregnancy
• previous venous thromboembolism
• family history of thrombosis
• medical conditions such as cancer and heart failure
• inactivity (for example after an operation or on a long-haul flight)
• being overweight or obese

Where has the advice come from?

The advice comes from new evidence-based guidelines produced by the American College of Chest Physicians (ACCP). The findings were published in the February issue of the medical journal CHEST.

The guidelines are extensive, running over hundreds of pages. They detail both the risk factors for DVT and measures to diagnose and prevent DVT.

What do these guidelines tell us?

The evidence review that informed the guidelines looked at a range of risk factors for the development of DVT in long-distance travellers. These included the use of oral contraceptives, sitting in a window seat, advanced age, dehydration, alcohol intake, pregnancy and sitting in an economy seat compared to business class.

The reviewers conclude that developing DVT or pulmonary embolism from a long-distance flight is generally unlikely, but that the following factors increased people’s risk:

• previous DVT or pulmonary embolism or known ‘thrombophilic disorder’
• cancer
• recent surgery or trauma
• immobility
• advanced age
• oestrogen use, including oral contraceptives
• pregnancy
• sitting in a window seat
• obesity

The finding relating to window seats was discussed further. The study authors suggest that long-distance travellers sitting in a window seat tend to have limited mobility, which is responsible for their increased risk of DVT.

However, the review did not find any definitive evidence to support the theory that dehydration, alcohol intake or sitting in an economy seat (compared with sitting in business class) increases the risk of DVT or pulmonary embolism during a long-distance flight. On this basis, they conclude that travelling in economy class does not increase the risk of developing a blood clot, even during long-distance travel. However, they believe that remaining immobile for long periods of time does.

Overall, the study authors say that “symptomatic DVT/PE [pulmonary embolism] is rare in passengers who have returned from long flights”, but that the association between air travel and DVT/PE is strongest for flights longer than 8-10 hours. Furthermore, most of the passengers who do end up developing a DVT/PE after long-distance travel have one or more risk factors.

What can be done to prevent DVT?

For travellers on flights longer than six hours who have an increased risk of DVT the new guidelines recommend:

• Frequent walking about during the flight.
• Calf muscle stretching.
• Sitting in an aisle seat if possible (as you are more likely to get up and move around during the flight).
• Wearing below-the-knee compression stockings that are ‘graduated’, meaning they apply greater pressure lower down the leg. They are designed to put pressure on the lower legs, feet and ankles to increase bloodflow, thereby making it harder for a clot to form.

The guidelines do not recommend compression stockings for long-distance travellers who are not at increased risk of DVT.

The guidelines advise against using blood-thinning aspirin or anticoagulant therapy to prevent DVT or pulmonary embolism for most people. They suggest that anti-clotting medications should be considered on an individual basis only for those at particularly high risk of DVT, as in some cases the risks may outweigh the benefits.

Links To The Headlines

DVT risk raised by sitting in the window seat. The Daily Telegraph, February 7 2012

Dangers of DVT: Why you should avoid the window seat on the plane (even in First Class). Daily Mail, February 7 2012

Links To Science

Bates SM, Jaeschke R, Stevens SM, et al. Diagnosis of DVT : Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012;141;e351S-e418S. Published online February 7 2012

Press release

American College of Chest Physicians: New DVT Guidelines: No Evidence to Support "Economy Class Syndrome": Oral Contraceptives, Sitting in a Window Seat, Advanced Age, and Pregnancy Increase DVT Risk in Long-distance Travelers. February 7 2012

Women concerned about French-made PIP breast implants can find all the latest NHS information about the issue on this page.

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

It is thought that around 40,000 women in the UK have the implants, with about 95% of them having been provided privately for purely cosmetic reasons.

What’s the problem?

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

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

What type of implants are involved?

The implants involved are called Poly Implant Prosthèse (PIP) and were made, starting in 2001, by a French company of the same name. Implants made earlier by the firm are not thought to be affected.

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

It is reported that the company had started using a cheap type of silicone gel intended for making mattresses. The marketing, distribution and use of the PIP implants was suspended in March 2010.

Do the implants have to be removed early?

Most breast implants need to be removed or replaced after 10-15 years.

An expert committee was set up recently to examine the specific risks associated with PIP implants. It concluded that as yet there was not enough evidence to recommend their early removal. For more details of its findings read the expert review group's report [PDF 159Kb, opens in new window].

Links To The Headlines

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

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

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

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

“We don’t know what causes deadly hospital superbug to spread, admit scientists,” the Daily Mail has reported. “Hospitals may be adopting the wrong strategy for combating a notorious bug on the wards,” it goes on to say. This story is based on new research investigating the transmission of Clostridium difficile (C. difficile), a hospital-acquired infection that can be fatal.

C. difficile is thought to be spread in hospital through contact with infected patients, but new UK research has found that this may not be the case. The research found that two-thirds of new cases in hospital were not linked to any cases of patients known to be infected. Less than a quarter of the newly infected patients had the same type of C. difficile infection as a patient on their ward who was known to be infected.

This research challenges the assumption that C. difficile is spread on wards through contact with infected patients. It means that current strategies focusing on preventing person-to-person spread may not stop C. difficile transmission.

This research cannot tell us how good hospital prevention strategies are at stopping C. difficile from spreading. People visiting and being admitted to hospital should continue to follow their hospital’s hygiene advice, particularly regarding hand washing and the use of alcohol hand gels.

Where did the story come from?

The study was carried out by researchers from John Radcliffe Hospital Oxford, the Medical Research Council, the University of Oxford, Leeds General Infirmary and the University of Leeds. It was funded by several academic institutions including the Oxford NIHR BioMedical Research Centre and the UK CRC Modernising Medical Microbiology Consortium.

The study was published in the peer-reviewed journal Public Library of Science: Medicine.

While the Mail accurately reported the study’s findings, it’s headline and introduction may suggest that current infection-control studies are wrong. In fact, infection control studies are useful for combating most bacterial menaces, and may still have a role in halting C. difficile. The headline may also give the impression that scientists have been withholding information and have had to admit that they were wrong. In reality, this is newly published and impressively comprehensive research.

What kind of research was this?

The researchers point out that C. difficile is a leading hospital-acquired infection that can result from antibiotic treatment. This is because antibiotics can disrupt normal healthy gut bacteria allowing C. difficile to multiply rapidly and produce toxins that cause illness. C. difficile causes gastrointestinal problems including diarrhoea, leading to severe illness and even death, especially in older patients and those who are seriously ill.

Following hospital outbreaks of C. difficile worldwide, greater effort has been put into preventing and controlling infection with the bacteria, and this is thought to have reduced incidence. Yet, to date, say the authors, there have been no robust evaluations of whether such strategies are reducing the spread of infection between individuals. The authors argue that a better understanding of person-to-person spread of C. difficile is crucial to reducing the incidence further.

This population-based study was set up to examine in detail transmission in hospital wards, to give better insight into the nature of person-to-person spread and to improve infection-control measures. In particular, it investigated the proportion of new cases of infection arising from ward-based transmission from infected patients.

What did the research involve?

From September 2007 to March 2010, all patients admitted to Oxfordshire hospitals with persistent diarrhoea, and all patients of 65 or older with any diarrhoea, had stool samples taken for C. difficile testing. The researchers tested the samples using specialised laboratory techniques (enzyme immunoassay and culture). Where C. difficile was identified, they used further tests (called multi-locus sequence typing) to identify the particular strains of C. difficile infection.

Based on the similarities and differences in the strains, the researchers used this “genetic fingerprint” of the bug to investigate how it had spread. This approach was based on the assumption that the same strain found in two people was evidence of direct contact between patients on the ward. They constructed potential “networks” of cases and potential routes of transmission for up to 26 weeks, for each strain of C. difficile they had identified. Their analysis was based on infected patients spending time on the same ward.

In order to show how far C. difficile was spread in a ward from person to person, the researchers traced ward contacts between all pairs of cases with the same strain. To reduce the possible bias caused by the same infection occurring spontaneously in a shared ward without contact, the researchers used patients whose stools had tested negative for C. difficile as controls. They analysed the data using standard statistical methods.

What were the basic results?

The researchers tested 29,299 stool samples for C.difficile from 14,858 patients.

• 1,282 (4.4%) samples tested positive for C. difficile 
• 69 different types of C. difficile were identified
• most (66%) C. difficile infections were not linked to other known cases with the same strain
• only 23% of cases sharing the same ward shared the same type of C.difficile

How did the researchers interpret the results?

The researchers found that most new cases of C. difficile infection could not be accounted for by contact with other people with C. difficile on the same ward. They say that this means that they cannot be sure that the infection can be controlled by current strategies based on preventing person-to-person spread. Greater understanding of other routes of transmission is needed to determine what type of interventions will prevent the spread of the infection, they argue.

Conclusion

This research is important because it suggests that the previous assumption that all C.difficile is spread on wards through contact with infected patients may not be entirely correct. As the authors point out, this means that transmission may not be adequately controlled by current strategies, which focus on preventing person-to-person spread. Further study is required to look at how the infection is transmitted.

It’s worth noting that the research concentrated on established cases of Clostridium difficile and the potential transmission between infected patients. As such, it did not look at how far C. difficile may have been stopped from spreading in the wards by current hospital prevention strategies.

Infection control measures in the NHS and private hospitals remain valid because they are largely effective at preventing many forms of infection. People going into hospital should continue to follow the stated hygiene procedures, particularly hand washing.

Links To The Headlines

We don’t know what causes deadly hospital superbug to spread, admit scientists. Daily Mail, February 8 2012

Links To Science

Walker AS, Eyre DW, Wyllie DH, et al. (2012) Characterisation of Clostridium difficile Hospital Ward–Based Transmission Using Extensive Epidemiological Data and Molecular Typing. Public Library of Science Medicine 9: e1001172. Pulished online February 7 2012.

“Spoon feeding makes babies fatter,” the BBC reported today. According to the broadcaster, babies weaned on pureed food tend to end up fatter than infants whose first tastes are finger foods.

This high-profile news is sure to be of interest to parents. However, the research behind the coverage is not strong enough to support such claims. The study compared information gathered on the diet and BMI of 92 child weaned on finger foods (“baby-led” weaning) and 63 children weaned using spoon-feeding. In total, 10 spoon-fed children were above a healthy weight compared to nine in the baby-led weaning group. However, the reliability of the research is undermined by a number of shortcomings, such as the small number of children studied (just 155), the fact that most children in each group had a normal weight and because the study looked at eating habits at a single point in time, rather than recording them over time.

Overall, the study does not support the various claims in the media that spoon-feeding makes babies fatter or encourages a sweet tooth, or that baby-led weaning makes children healthier. It is possible, for example, that a child’s food preferences might influence how they end up being weaned, or even that the results are due to chance. Examining the issue will require larger studies which look at children’s eating and weight over time.

Where did the story come from?

The study was carried out by researchers from the University of Nottingham, which also funded the research. The study was published in the peer-reviewed medical journal BMJ Open.

The study was reported uncritically in most papers, with quotes from independent experts who reportedly supported its findings.

What kind of research was this?

This small cross-sectional study examined the association between weaning method, food preferences and frequency of food consumption. The researchers were also interested in how heavy the children were for their height (body mass index or BMI) and whether they were “picky eaters”. The researchers say that at present, little evidence is available on the possible impact of different weaning methods on food preferences and health, but that baby-led weaning is associated with “reduced maternal anxiety” about feeding and “a maternal feeding style that is low in control”.

This study compared two groups of parents who used different weaning methods for their children and looked at their children’s food preferences and BMI. However, it cannot prove cause and effect, nor can it show that baby-led weaning results in healthier food choices and healthier weight. A more reliable method of assessing this question would be a randomised controlled trial in which parents were randomly allocated one of the two weaning methods to use, and their babies followed over a period of time to see whether weaning method led to differences in dietary preference or BMI. However, such as trial may have ethical and feasibility issues.

Alternatively, a prospective study that followed children weaned by the two methods over a period of time would also be preferable to a cross-sectional study, which only looks at weaning methods, children’s food preferences and other factors at one point in time.

What did the research involve?

The researchers recruited the parents of 155 children aged 20-78 months between June 2006 and January 2009. The group that used baby-led weaning were recruited by advertising on the internet while those who used spoon-feeding were recruited from the researchers’ own laboratory database.

All the parents completed a standard questionnaire which asked about:

• their infants’ feeding and weaning style
• their infants’ preferences for 151 foods (with ratings from 1 “loves it” to 5 “hates it”) – the preferences were then analysed by standard food categories, such as carbohydrates, proteins and dairy, and there was also a category for whole meals, such as lasagne
• their frequency of consuming particular foods (with ratings from 1 “more than once a day” to 7 “less than once a month”)
• whether they would classify their children as picky eaters
• the children’s height and weight

The parents’ socioeconomic status was also assessed using validated measures.

The researchers pointed out that because no formal definition of weaning exists, they used the parents’ own reports of weaning styles to divide parents into two groups. To try to verify these self-reported methods, they also questioned some parents in more detail about weaning.

As the baby-led weaning group tended to be younger than the spoon-fed group, the researchers carried out their analyses on food preferences and weaning method using a sub-sample of 74 infants – 37 from the spoon-fed group matched by age to 37 from the baby-led weaning group. They used the whole sample for all other analyses.

What were the basic results?

The general trend in results was as follows:

• Carbohydrates were the most popular food category for the baby-led weaning group, who liked carbohydrates more than the spoon-fed group.
• Sweet foods were most liked by the spoon-fed group.
• Preference and frequency of consumption were not influenced by socioeconomic status, although an increased liking for vegetables was associated with a higher social class.
• Using NHS BMI guidelines, eight children in the spoon-fed group were obese (12.7%) compared to none in the baby-led group. However, nine children in the baby-led weaning group (14.3%) were overweight compared to two in the spoon-fed group (3.2%).
• Three children in the baby-led weaning group were classed as underweight (4.7%) compared to none in the spoon-fed group.
• No difference in picky eating was found between the two groups.

How did the researchers interpret the results?

The researchers concluded that “weaning style impacts on food preferences and health in early childhood.” They say their results suggest that the baby-led approach to weaning helps infants learn to regulate their food intake in a way that leads to healthier weight and a preference for healthy foods, such as carbohydrates.

Conclusion

While it was widely reported, this small cross-sectional study proves very little about the possible impact of different weaning methods on children’s food preferences, BMI or other health outcomes. Instead, because of its cross-sectional design, it can provide only a snapshot of all these factors (as reported by parents) at one point in time. It cannot show, for example, that babies who prefer carbohydrates do so because they were weaned on finger foods, as some news sources have reported.

Many factors can affect a child’s food preferences and BMI, including genetic factors, exercise and social and demographic background (which was indicated to a degree by the fact that higher socioeconomic status was associated with higher vegetable intake). Though the study found differences in the BMI status of the children, the small sample size makes it difficult to draw reliable comparisons between the groups. For example, though eight children were obese in the spoon-fed group and none in the baby-led group, this finding could be due to chance. Also, when overweight and obese children were combined, ten children in the spoon-fed and nine in the baby-led groups were overweight or obese. This raises the strong possibility that there would be no real difference in BMI if a much larger group of children were looked at.

With rising rates of childhood obesity, the issue of how best to wean and how this might affect children’s attitudes to food and their long-term health is of concern to parents. However, a large-scale prospective study that follows babies for several years would be a much better way to shed light on the issue.

Links To The Headlines

Giving babies finger food could stop obesity. Sky News, February 7 2012

How giving babies finger food during weaning can stop them growing up fat. Daily Mail, February 7 2012

Spoon feeding 'makes babies fatter'. BBC News, February 7 2012

Baby weight: finger foods better than spoon-feeding, study suggests. The Guardian, February 7 2012

Links To Science

Townsend E, Pitchford NJ. Baby knows best? The impact of weaning style on food preferences and body mass index in early childhood in a case–controlled sample. BMJ Open 2012;2:e000298 (published online)

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 an experimental medical technique, scientists are 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 from 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 on. 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 claimed as a first. 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