Last updated: 01.00 BST

A strain of swine flu which is resistant to Tamiflu appears to have spread between patients at a hospital in Wales.

The Health Protection Agency (HPA) has confirmed that five patients at the unit, who all have serious underlying health problems and suppressed immune systems, are resistant to the antiviral drug.

The HPA said the risk to the general healthy population was low and there was no evidence that the new strain is more virulent than any other type of flu.

The resistant virus is still sensitive to the other frontline antiviral drug, Relenza.

Dr Tony Jewell, Chief Medical Officer for Wales, said: “We know that people with suppressed immune systems are more susceptible to the swine flu virus.
 
“We have stringent processes in place for monitoring for antiviral resistance in the UK.  Identifying these cases shows that our systems are working, so patients should be reassured.
 
“Treatment with Tamiflu is still appropriate for swine flu and people should continue to take Tamiflu when they are prescribed it.”

Two of the patients with Tamiflu-resistant swine flu have recovered and been sent home from the unit at the University of Wales Hospital, Cardiff. One other remains in critical care and two are being treated on the ward.

Earlier this week, Sir Liam Donaldson, the Chief Medical Officer, announced that young children would soon be offered the swine flu vaccine.

Children between the ages of six months and five years have been prioritised based on evidence that they are more likely than other groups to be hospitalised. There have also been high rates of admission to critical care in this age group.

Sir Liam made the announcement at the weekly update and urged everyone who is offered the vaccine to accept it:

“While the risks of serious complications from flu may be small, the impact on those affected can be devastating.

“Protecting those most at risk from the disease will reduce the levels of serious illness and deaths. That’s why we will shortly offer the vaccine to young children”.

Parents of children who are over six months and under five years old should wait to be contacted by their local GP surgery.

Until now, the vaccine has only been given to people with long-term health conditions, pregnant women, people who live with those whose immune systems are compromised, and health workers.

Also announced at this week’s update:

• UK swine flu cases have fallen for the second week in a row. There were an estimated 53,000 new infections in the past week, down from 64,000 the week before.
• Despite the fall in new infections, the number of people in hospital with the virus remains high, with 783 patients in hospital, 180 of whom are in critical care.
• There has been a substantial increase in the number of under-5s in hospital, including in critical care.
• There has been a further substantial increase in the number of deaths related to swine flu, with 32 deaths in the UK in the past week. To date, there have been 142 deaths in England, 38 in Scotland, 21 in Wales and 13 in Northern Ireland.
• GP consultation rates and use of the National Pandemic Flu Service have stayed roughly the same.
• GP consultation rates among school-aged children have risen following a decrease during half-term.
• The Department of Health has published a leaflet for pregnant women.

 

Vaccinations

Vaccination of people in clinical risk groups is well under way, with more than seven million doses of vaccine already distributed. NHS hospitals and GPs are now vaccinating patients facing the greatest risk of complications. Patients will be contacted by their GPs if they fall into one of the at-risk categories.

Healthcare staff dealing with the public are also being vaccinated to help keep medical services running smoothly and to prevent them from passing the virus to patients.

Recently, healthy children aged six months and over to under five years were added to the priority groups. Vaccination of this group will begin shortly. Parents of children of this age should wait to be contacted by their local surgery.

 

Who is a priority for vaccination?

People who are most at risk from swine flu need to be vaccinated first. These groups are, in order of priority:

• People aged between six months and 65 years in the seasonal flu vaccine at-risk groups.
• All pregnant women. The European Medicines Agency has indicated the vaccine can be given to pregnant women regardless of their stage of pregnancy.
• People who live with those whose immune systems are compromised, such as cancer patients or people with HIV/AIDS.
• People aged 65 and over in the seasonal flu vaccine at-risk groups.
• Healthy children aged six months and over to under five years.

Frontline health and social care workers will also be offered the vaccine at the same time as the first clinical at-risk groups. Health and social care workers are both at an increased risk of catching swine flu and of spreading it to other at-risk patients.

 

What are the seasonal flu vaccine at-risk groups?

These are people with:

• chronic respiratory disease, such as chronic obstructive pulmonary disease (COPD),
• chronic heart disease, such as heart failure,
• chronic kidney disease, such as kidney failure,
• chronic liver disease, such as chronic hepatitis,
• chronic neurological disease, such as Parkinson's disease,
• diabetes requiring insulin or oral hypoglycaemic drugs, and
• immunosuppression (a suppressed immune system), due to disease or treatment.

 

Planning assumptions

Revised guidance for planners was issued on October 22. The new guidance is based on the latest scientific understanding of the swine flu virus, drawing on our own experience to date and the southern hemisphere’s experience of winter.

This improved understanding means it is now anticipated that the impact of the virus on the UK is likely to be less severe than previously thought.

The additional information now available confirms earlier guidance that children under 16 are significantly more susceptible to the virus, and up to 30% may fall ill during this second wave.

The worst-case clinical attack rate is revised down from 30% to 12% between October 1 and the end of the normal flu season.  The worst-case hospitalisation rate is now considered to be 35,000 with up to 5,300 requiring critical care over the same period.  The worst case number of deaths is now assumed to be a further 1,000 spread across all age groups.

The threat that swine flu still poses should not, however, be underestimated.

Up to 1.5 million people could still become ill in the peak week. Children under 16 are particularly susceptible to the illness and unfortunately in rare cases healthy children have developed severe complications.

 

Who is at greatest risk of serious complications from swine flu?

Some people are more at risk of complications if they catch swine flu, and need to start taking antivirals as soon as it is confirmed that they have the illness. Doctors may advise some high-risk patients to take antivirals before they have symptoms, if someone close to them has swine flu.

It is already known that people are particularly vulnerable if they have:

• chronic (long-term) lung disease,
• chronic heart disease,
• chronic kidney disease,
• chronic liver disease,
• chronic neurological disease (neurological disorders include motor neurone disease, multiple sclerosis and Parkinson's disease),
• immunosuppression (whether caused by disease or treatment), or diabetes mellitus.

Also at risk are:

• patients who have had drug treatment for asthma in the past three years,
• pregnant women,
• people aged 65 and over, and
• children under five.

  National Pandemic Flu Service

The National Pandemic Flu Service was launched in July. This online service assesses patients for swine flu and, if required, gives them an authorisation number that can be used to collect antiviral medication.

The system, which can also be accessed by phone, will take the strain off GPs as swine flu spreads. For the moment, it is being used only in England.

“The National Pandemic Flu Service is a new self-care service which will give people with pandemic swine flu symptoms fast access to information and antivirals,” said a Department of Health spokesman.

“This new service will free up GPs, enabling them to deal with other illnesses that need their urgent attention.”

The launch of the system brought important changes to the official advice that is given to people who think they may have swine flu. That advice – and the new system – is supported by the Royal College of General Practitioners.

  Advice for antivirals

Several newspapers reported that the World Health Organization (WHO) had changed its advice regarding use of antivirals for swine flu. Its advice suggests that while antivirals should always be given in serious cases, they may not always be necessary for otherwise healthy people.

The papers pointed out that this appeared to differ from the approach taken in the UK, where Tamiflu is being widely used.

However, the Department of Health said:
"We believe a safety-first approach of offering antivirals, when required, to everyone remains a sensible and responsible way forward. However, we will keep this policy under review as we learn more about the virus and its effects.

"The WHO recommendations are in fact in line with UK policy on antivirals. We have consistently said that many people with swine flu only get mild symptoms, and they may find bed rest and over-the-counter flu remedies work for them.”

Research on a “brain-eating tribe” may hold the key to understanding and even treating mad cow disease, according to The Daily Telegraph.

A genetic study of the Fore tribe of Papua New Guinea has shown that certain members carry genetic mutations that protect them from a disease called kuru, which can be contracted by eating prion proteins in brain matter. The disease, which kills tribe members lacking the mutation, is similar to Creutzfeldt–Jakob disease (CJD), sometimes erroneously referred to as ‘mad cow disease’.

The findings further the understanding of the role that inherited genes play in the protection and susceptibility to prion diseases such as kuru and CJD. This was an informative study of the genetics of a unique population, but it does not directly improve our knowledge of the prevention or treatment of CJD in the UK.

 

Where did the story come from?

The research was carried out by Dr Simon Mead and colleagues from University College London Institute of Neurology, Medical Research Council Prion Unit and other medical and academic institutions in the UK, Papua New Guinea and Australia. The research was funded directly or indirectly by the Wellcome Trust, the Medical Research Council and the Department of Health’s National Institute for Health Research funding scheme.

The study was published in the peer-reviewed New England Journal of Medicine.

 

What kind of research was this?

This was a population genetics study on the Fore tribe of Papua New Guinea that included genealogy assessments and blood tests. Researchers were interested in this group because of their experiences of a fatal, progressive neurodegenerative disease called kuru. Kuru is one of a group of prion diseases that can affect humans and animals, apparently through abnormal versions of proteins damaging normal proteins in the brain.

Until ritual cannibalism was outlawed in the 1950s, the Fore tribe had traditionally participated in this practice, consuming tribe members when they died. During these “mortuary feasts”, members of the tribe, particularly women and children, would be exposed to the prions that cause kuru. Some members of the Fore tribe were resistant to kuru in spite of their prion exposure, and the researchers believed that investigating the reasons for this resistance might further our understanding of this and other prion diseases.

Other prion diseases include bovine spongiform encephalopathy (BSE or “mad cow disease”) in cows and variant Creutzfeldt–Jakob disease in humans (vCJD), which is sometimes incorrectly referred to as “mad cow disease”. People in the UK were exposed to prions of BSE through their diets, which increased their risk of getting vCJD. The authors of this study hoped their research could shed further light on prion diseases and what can be done to prevent and treat them.

 

What did the research involve?

The study is an expansion of a previous study, but included more samples. The earlier study found that a particular mutation was more prevalent in a small group of women from the Fore tribe who had participated in multiple mortuary feasts but had survived.

Researchers obtained information on genealogy and took blood samples (for genetic analysis) from members of the Fore tribe. These tribe members were sourced from regions exposed to the disease and regions with no recorded cases. The people who had been exposed to kuru disease were those who would have participated in multiple mortuary feasts in which deceased relatives were dismembered and consumed in ritual settings. The researchers wanted to further investigate the genetic variation that appeared to confer a survival advantage when the disease was rife.

The researchers used information on the participants’ family histories to determine what they called an “exposure index” for each of the villages in the community. This was an estimate of the relative intensity of disease in these communities in 1958. Using this, they were able to split the geographical regions of their samples into various zones: high exposure, mid-level exposure and low exposure, as well as two additional unexposed zones.

There were 557 exposed elderly survivors, 2,053 people who were currently healthy from exposed and unexposed areas, and 313 people from more distant regions in the country. The genes of these participants were analysed from their blood samples and researchers determined whether there was a link between particular genetic make-ups and degree of exposure to kuru disease.

The researchers performed several well-established genetic analyses to investigate how the protective genetic variation may have spread through the population, and when it might have arisen.

The study was approved by ethics committees in the UK and Papua New Guinea and had the full support and involvement of the members of the Fore tribe.

 

What were the basic results?

Investigation of the participants’ genes revealed that people who were exposed to kuru but were not infected were more likely to have one copy of a particular variant (called 129V) in one of the areas of the prion protein gene. This confirmed the findings of other studies. The study also identified a previously unknown mutation (called 127V) that was more common in women from high- and medium-exposure regions. None of the people suffering from the disease had this mutation.

Both of these genetic variations were more common in people from regions that had been exposed to kuru than in people from unexposed regions. This suggests that the presence of kuru provided “selection pressure”. This means that people who carried these variants were resistant to kuru, and therefore more likely to survive kuru and pass on their genes to future generations.

 

How did the researchers interpret the results?

The researchers concluded that the new genetic variation they identified (127V) increased resistance to acquired prion disease. They say that the two genetic variations they examined demonstrate that there has been a population genetic response to an epidemic of prion disease, and that this “represents a powerful episode of recent selection in humans”.

 

Conclusion

This study has shown that variations in two particular regions of the gene that codes for the prion protein are more common in those people who were exposed to the kuru disease but who had not become infected.

The researchers note that they cannot rule out the possibility that one of the mutations is responsible for kuru disease, but discuss several reasons why this is highly unlikely.

The study demonstrates that the kuru disease resulted in a strong selection pressure in this population. This means that any individuals with characteristics that would make them less susceptible to the disease would be more likely to survive, and therefore to pass these genes on to successive generations. If this were true, then a kuru epidemic would be responsible for an inflated prevalence of mutations that conferred a survival advantage, and this appears to be what has happened in these groups of people.

Overall, the study adds to the understanding of how prion diseases can arise and what particular genetic factors might increase susceptibility or offer some protection. This novel study on a rare disease in a unique population does not currently have direct relevance to the prevention or treatment of CJD in the UK, but may eventually lead to research that does.

Links To The Headlines

Brain-eating tribe enriches understanding of mad cow disease. The Times, November 19 2009

Immune tribe 'indicates CJD hope'. BBC News, November 19 2009

Brain-eating tribe could help find treatment for mad cow disease. The Daily Telegraph, November 19 2009

Links To Science

Mead S, Whitfield J, Poulter M et al. A Novel Protective Prion Protein Variant that Colocalizes with Kuru Exposure. NEJM, Volume 361:2056-2065

The Norwegian Institute of Public Health has informed WHO of a mutation detected in three H1N1 viruses. The viruses were isolated from the first two fatal cases of pandemic influenza in the country and one patient with severe illness.

“Stem cells could create new skin to help burn victims,” BBC News reported. It said that French researchers have duplicated the biological steps that occur during skin formation in embryos. This could potentially provide an unlimited source of temporary skin replacements for burn victims while they wait for grafts from their own skin.

The study in mice behind this report used human embryonic stem cells to make keratinocytes (the most common cell types in the skin). These cultured cells were used to create skin equivalents, which grew successfully when they were grafted onto the backs of mice.

This well-conducted research has potentially developed a successful method of culturing tissue in the laboratory that resembles human skin. Only human trials of the technology will show whether such grafts will be accepted (i.e. not rejected by human patients) as permanent transplants or can provide a temporary skin replacement before grafting.

 

Where did the story come from?

The research was carried out by Dr Hind Guenou and colleagues from the Institute for Stem Cell Therapy and Exploration of Monogenic disease, and BIOalternatives SAS in France along with colleagues in Madrid. The research was funded by the Institut National de la Santé et de la Recherche Médicale, University Evry Val d’Essonne, Association Française contre les Myopathies, Fondation René Touraine, and Genopole. The authors declare that they have no conflicts of interest and say that the funders had no role in the study’s design, analysis or write-up.

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

BBC News has covered this research in a balanced way, pointing out that this is animal research and that human studies will follow.

 

What kind of research was this?

This well-conducted research involved laboratory and animal research which investigated whether epidermal stem cells could be cultured in the laboratory and used in skin grafts.

 

What did the research involve?

Burn patients are often treated using autologous skin grafts. These involve a section of healthy skin being removed from another part of the body to harvest the patient’s own skin cells for culture. A graft for the burn site is produced from this culture. There is a delay of about three weeks between the harvesting of the skin and the graft to allow the cells to grow. During this time, the patient is at risk of dehydration and infection.

Having a ready source of skin cells for temporary grafts while patients are waiting for their autologous grafts would improve the outcome of treatment. With this in mind, the researchers investigated whether keratinocytes (the major cell constituent of the outer layer of the skin, or epidermis) could be derived from human embryonic stem cells.

The researchers began by culturing embryonic stem cells in a specialised medium that encourages cell differentiation (the process whereby cells become specialised). Embryonic stem cells can renew themselves and also have the potential to develop into any type of specialised cell.

Cultures of human embryonic stem cells were then grown on a framework made of fibroblast cells and collagen (a fibrous protein that can form a mesh-like structure) made by fibroblasts. Fibroblasts are the cells that form the underlying structure of tissues and are involved in healing.

The stem cells were manipulated so that they developed into epidermal cells, and monitored throughout their specialisation process to make sure the cells were developing into skin cells. The researchers named the cells “keratinocytes derived from human embryonic stem cells” (K-hESCs).

After several rounds of subculturing and replication, the cells could be frozen and used in further experiments. “Bioengineered skin equivalents” were then created by growing the K-hESCs on an artificial matrix. These were then grafted onto the backs of five six-week-old immunodeficient female mice. After 10-12 weeks, samples were taken from the implants for analysis.

 

What were the basic results?

The researchers confirmed the embryonic stem cells differentiated into keratinocytes, which could be grown in culture medium and which replicated well. These derived skin cells were structurally and functionally similar to normal skin cells in that they could be grown on an artificial matrix using classic techniques.

After 12 weeks of growth on immunodeficient mice, the grafted epidermis had developed into a structure that was consistent with mature human skin.

 

How did the researchers interpret the results?

The researchers concluded that their findings build on previous research and show that K-hESCs can develop into a multi-layer epithelium. This epithelium resembles normal human skin both in cell cultures (in vitro) and following grafting onto live animals (in vivo).

They say that growing human skin from human embryonic stem cells could provide an unlimited resource for temporary skin replacement in patients with large burns who are waiting for autologous skin grafts.

 

Conclusion

If it can be demonstrated that it works in humans, this technology could improve outcomes for burns patients. The researchers report that the first human trial is currently underway.

At present, skin from deceased donors is used to treat burns patients while they wait for their own skin transplant, but there are often problems with rejection. The researchers highlight several potential benefits of an epidermis reconstructed using K-hESCs, including:

• The potential to make large quantities as it can be developed fully in the laboratory. The researchers say that industrialisation of the manufacturing process would reduce the risk of infection.
• Less chance of rejection by the host because K-hESCs are in an early developmental stage and therefore don’t produce much antigen (the substance which evokes an immune response).

It is important to note that, at present, the researchers are only investigating this technology for providing temporary grafts. They say that whether it can be used for permanent grafts for patients who can’t use their own cells needs further investigation. They say that for temporary use, the grafts would only be used for the three-week period while the patients’ permanent graft was grown.

This is a good study and the findings are exciting in this field, but only human research will tell whether it will have a wider application in the treatment of burns patients.

Links To The Headlines

Stem cells could create new skin to help burns victims. BBC News, November 20 2009
 
 

 

Links To Science Guenou H, Nissan X, Larcher F. et al. Human embryonic stem-cell derivatives for full reconstruction of the pluristratified epidermis: a preclinical study. The Lancet 2009; 374: 1745-1753

As of 15 November 2009, worldwide more than 206 countries and overseas territories or communities have reported laboratory confirmed cases of pandemic influenza H1N1 2009, including over 6770 deaths.

“Elderly people succumb to viruses 'because their immune systems work too hard',” The Daily Telegraph has reported. The newspaper says that new research into the immune system could also affect the way flu vaccination is planned.

This animal study tested immune responses and liver damage caused by a common virus, the herpes virus, in mice of different ages. When the researchers blocked part of the action of the immune system in older mice, they found that the mice survived with the virus for longer. This suggests that their immune systems where previously causing liver damage. However, whether the results of this animal study can be applied to humans is debateable and will need further careful research.

The Daily Telegraph reports one researcher’s suggestion that blocking some actions of the immune system may be better than immunisation for preventing human susceptibility to viral infections. The newspaper’s implication that this study might influence seasonal and swine flu vaccinations is not justified by this early research in mice.

 

Where did the story come from?

This research was carried out by Dr Heather W Stout-Delgado from the Department of Internal Medicine at the Yale University School of Medicine and other colleagues in the US. The work was supported by grants from the US National Institutes of Health and was published in the peer-reviewed science journal Cell Host & Microbe.

The Daily Telegraph’s coverage of this research was reasonable, but could imply that this study had more relevance to humans than is warranted.

 

What kind of research was this?

This animal study compared the immune system responses to a viral infection in aged mice and young mice. The study was well conducted and used a sound design to answer the researchers’ questions. They were specifically interested in understanding how ageing modifies the immune system’s inflammatory response to viral infection.

Early research such as this can suggest areas for future study in humans. Positive media coverage of early research could positively affect the funding of future research programmes.

 

What did the research involve?

The researchers explain that, as an individual ages, infection and cancer become more common, suggesting there is an impairment of immunity. The exact mechanism underlying this is unclear, but one theory is that ageing leads to reduced ability to overcome viral infections.

Substances called inflammatory mediators, or cytokines, are released by specific white blood cells of the immune system. These mediators are used by the body to carry signals between cells. One group of these mediators is called the interleukin 17 (IL17) family, and these are collectively responsible for many early inflammatory and allergic responses. Some members of the IL17 family trigger the production of further chemical messengers. It was this complex cascade of immune pathways in mice that the researchers were interested in investigating further. They focussed on one particular mediator called IL-17A.

The researchers used a herpes virus (HSV-2) to infect groups of young mice (2-4 months old), middle-aged mice (8-10 months) and aged mice (18-20 months). They then examined their blood for inflammatory substances, timed how long it took the mice to die and examined the livers of the mice after death.

They then tried blocking the action of IL-17A by introducing an anti-IL-17A antibody to further sets of mice, either before or after they were infected with the virus. The researchers measured the inflammatory responses in the three age groups of mice.

The results of this study have been well reported and analysed. The detailed description of the methods will allow other groups of scientists to perform similar tests to see if the results can be repeated and to explore related biological pathways.

 

What were the basic results?

The researchers observed a large difference in outcomes, which depended on the age of the mice. For example, almost none of the 16 young mice succumbed to the effects of HSV infection, even after 50 days. All 20 of the aged mice died within about eight days of being infected. After infection, levels of IL-17A rose dramatically in the aged mice compared to the young mice. Liver damage was responsible for the deaths of the mice.

When the researchers gave the mice the anti-IL-17A antibody, this protected them from the harmful effects of the virus. Even the six aged mice tested now survived for about as long as the younger mice that did not have the antibody’s protection.

 

How did the researchers interpret the results?

The researchers say that aged mice had defective immune responses, but instead of trying to boost their immune response, they tried to "inhibit certain inflammatory pathways to prevent susceptibility to viral infections”.

Their research also showed that the process of liver damage was dependent on the presence of cytokine IL-17A. They say that the findings show that unusual IL-17A responses to viral infection contribute to the death of the mice through a process that is dependent on the white cells (neutrophils).

In their paper, the researchers cautiously put forward the theory that, if the cells that produce IL-17 are increased in aged humans with viral infections, then age-dependent increases in IL-17 responses may have a role in human viral infections. They say this could explain why older people are more susceptible to infection from the seasonal flu virus.

In their press release, the researchers conclude more strongly that, "Our study could also explain why other susceptible populations succumb to viruses, such as the H1N1 pandemic virus, since it is possible that heightened immune responses – rather than defective immunity – attack the body and lead to disease in these individuals."

 

Conclusion

This well-conducted scientific study looked at complex immune pathways in mice and appears to have been over-interpreted in the study’s press release and lay media reports, which suggest that these findings have important implications for seasonal flu and H1N1 vaccination.

It is important that scientists study the complex mechanisms in animal and human immunity, and this early research warrants further exploration. However, given the experimental nature of this animal study, it is premature to conclude that this study is relevant to flu vaccination programmes.

Links To The Headlines

Elderly people succumb to viruses 'because their immune systems work too hard'. The Daily Telegraph, November 19 2009 

Links To Science

Stout-Delgado HW, Du W, Shirali AC et al. Aging Promotes Neutrophil-Induced Mortality by Augmenting IL-17 Production during Viral Infection.Cell Host & Microbe, Volume 6, Issue 5, 446-456, November 19 2009

Several newspapers reported that drinking excessive alcohol is good for the heart. The Independent estimated that “half a dozen beers every day” could cut the risk of heart disease while The Daily Express claimed that a bottle of wine a night can halve the odds.

These reports are based on a large population study that found a link between higher alcohol intake and reduced risk of coronary heart disease. The study has several limitations, including the fact that the participants were not clinically assessed for heart disease before the study began.

The most important limitation, however, is that it did not consider the many other known dangers of excess drinking, including the increased risk of liver disease, obesity, pancreatic diseases and certain cancers.

This research provides no reason for exceeding the recommended alcohol limits of 2-3 units a day for women and 3-4 units a day for men.

 

Where did the story come from?

This research was carried out by L Arriola and colleagues from a number of health and research institutions in Spain, including the Basque government’s Public Health Department of Gipuzkoa. The study received funding grants from a number of organisations, including the Spanish Ministry of Health, the European Commission and the International Agency for Research on Cancer. The study was published in the peer-reviewed medical journal Heart.

This research has been widely reported in the media, with most news stories highlighting the study’s “positive” finding: that greater alcohol consumption was associated with reduced risk of heart disease. However, while the Daily Mirror and Daily Express predominantly focused on this finding, other news sources have rightly treated the study’s results with caution. Both The Daily Telegraph and The Times warned of the other health risks of excess drinking and featured expert opinions on the flaws of this study.

The Independent noted that Spain is the world's third-largest wine producer and ninth-largest beer producer.

 

What kind of research was this?

This was a cohort study which investigated the association between alcohol intake and risk of coronary heart disease (CHD). Many previous studies have suggested that moderate alcohol intake reduces the risk of CHD, and this study was designed to examine this theory in more depth.

A cohort study is the best way to investigate the relationship between an exposure and later disease risk. A randomised trial in which people are assigned to drink different amounts of alcohol is clearly not feasible or ethical. Studies examining the link between alcohol and CHD would need to ensure that people did not have CHD at the start of the study, to see whether disease later developed as a consequence.

A drawback of the study is that it is difficult to establish an accurate measure of a person’s alcohol consumption and for researchers to know that this did not change over time. Also, most people underestimate how much they drink when filling in questionnaires for research studies.

 

What did the research involve?

The study involved participants of the European Prospective Investigation into Cancer (EPIC). Participants (15,630 men and 25,808 women) were recruited from 10 European countries between 1992 and 2000. When they were recruited, participants completed dietary and lifestyle questionnaires and had their weight and height measured.

The researchers asked participants if a doctor had ever told them that they had suffered from a heart attack, angina, blood clot, stroke or bleed in the brain, high blood pressure, high cholesterol or diabetes. Women were also asked if they used hormone replacement therapy. Three years later, the researchers were able to contact 98% of the participants to ask whether they had had any coronary events or diagnoses since recruitment. Their responses were verified against hospital discharge data and mortality registers.

The researchers' analysis estimated participants’ diet and lifestyle habits using data from their earlier questionnaire responses. This can lead to potential limitations:

• Estimates of the size and strength of drinks are likely to vary between participants.
• Information on alcohol consumption was given at a single point in time, but drinking habits are likely to change over time.
• Although the participants were asked to estimate how their intake differed at 20, 30, 40 and 50 years of age, it may be difficult to recall this accurately.
• Cardiovascular diagnoses at recruitment to the study relied on the participants’ self-reports. This is not as accurate as verifying diagnoses using medical records or examinations. It is likely that some participants had unreported or undiagnosed cardiovascular disease at the start of the study.

The analyses of the data can be expected to involve some degree of inaccuracy as relatively few people developed CHD, both overall and in each alcohol category. This decreases the reliability of the risk estimate.

This research also used participants and data from the EPIC cancer cohort, which was not designed to investigate how alcohol intake affects cardiovascular risk. Analysing data from another study and applying it to a different analysis is a potential limitation of the study.

 

What were the basic results?

At the end of the follow-up period, 481 coronary events had occurred in men and 128 in women (incidence rate of 300.6 per 100,000 person years for men and 47.9 per 100,000 person years for women). The researchers adjusted their results to account for physical activity, waist/hip ratio, energy intake and use of certain medications.

No relationship between alcohol intake and CHD was seen in women.

In men, the researchers found that there was no affect on risk of CHD for former and low-alcohol drinkers. Compared to never-drinkers, moderate alcohol consumption was associated with a 51% decrease in risk of CHD, high intake with a 54% decrease in risk and very high alcohol consumption with a 50% decrease in risk.

Further adjustment for diabetes, blood pressure and cholesterol did not affect the significance of the relationships.

 

How did the researchers interpret the results?

The researchers concluded that drinking alcohol was associated with a more than 30% lower CHD incidence.

 

Conclusion

Although this study demonstrated a link between higher alcohol intake and reduced CHD risk, it is has several limitations. Therefore, it cannot be assumed that high levels of alcohol consumption lower the risk of CHD. People are advised not to exceed the recommended daily limits of 2-3 units a day for women and 3-4 units a day for men.

Importantly, the study did not take into account any other adverse effects of alcohol, such as the increased risk of liver disease, obesity, pancreatic diseases, certain cancers, possible addiction, depression, accidental injury or reduced judgement in social situations.

Further limitations to this research include the following:

• Asking someone to recall daily or weekly alcohol intake in the previous 12 months is likely to involve a high degree of estimation, inaccuracy and variability in response.
• Trying to remember alcohol intake from several decades ago is also likely to lead to inaccurate results.
• Most people underestimate how much they drink when filling in questionnaires for research studies. This study used participants’ estimates to assess drinking habits.
• Although this was a large cohort, relatively few people had coronary events during follow-up, and the numbers were even smaller in each of the alcohol categories. This reduces the accuracy of any risk calculations.
• It cannot be accurately established that none of the participants had cardiovascular disease at start of the start of the study as this was not assessed using clinical methods.

Links To The Headlines

Drink half a dozen beers every day and have a healthier heart. The Independent, November 19 2009

Controversial study suggests heavy drinking in men ‘good for heart’. The Times, November 19 2009

Alcohol 'protects men's hearts'. BBC News, November 19 2009

Drinking up to bottle of wine a day can cut heart disease risk. The Daily Telegraph, November 19 2009

Men are ale and hearty. Daily Mirror, November 19 2009

Heart disease: a bottle of wine a night can halve risk. Daily Express, November 19 2009

Links To Science

Arriola L, Martinez-Camblor P, Larranaga N et al. Alcohol intake and the risk of coronary heart disease in the Spanish EPIC cohort study. Heart 2009

To date, WHO has received vaccination information from 16 of around 40 countries conducting national H1N1 pandemic vaccine campaigns. Based on information in these 16 countries, WHO estimates that around 80 million doses of pandemic vaccine have been distributed and around 65 million people have been vaccinated. National immunization campaigns began in Australia and the People’s Republic of China in late September.

Several newspapers have reported that pregnant women and other vulnerable people are refusing to have the swine flu vaccine. The Times reported that a poll of GPs found that only 46% of people who were offered the vaccine have accepted it, and one doctor estimated that only 5% of pregnant women have had it.

The news reports are based on a “snapshot” survey of 107 GPs. The survey asked how likely they were to hit the government’s target of vaccinating at least half of their patients who are under 65 and in high-risk groups this winter. GPs were also asked to estimate how many of the people who were offered the vaccine in their practice had agreed to have it (the uptake).

It is not clear if the experiences of this relatively small sample of GPs is representative of the 30,000 GPs in the UK. This picture of overall uptake is based purely on these 107 GPs’ estimates. It is possible that these GPs chose to take part in the survey themselves, and that GPs who chose not to take part may have a different experience of vaccine uptake.

Based on this survey, it can’t be assumed that there is similar vaccine uptake nationwide, or that particular groups, such as pregnant women, are more likely to reject the vaccine.

 

What are the news reports based on?

These news reports are based on two articles in Pulse, a magazine for GPs. Both articles are on the swine flu vaccination programme, which has been in progress since late October. One article, on overall uptake of the vaccine, was based on a “snapshot” survey of GPs that was recently carried out by the magazine. The other article, on uptake in pregnant women, may be from the same survey, but this was not made clear.

One of the articles reports that GPs are “braced” to miss a target that was set by the government to vaccinate at least half of all people in high-risk groups aged under 65 against swine flu during this winter’s campaign. The other article reports that pregnant women are rejecting the vaccine because of fears over its safety.

Pulse surveyed 107 GPs, asking them whether they felt they would achieve this target in their practice and to estimate how many of the people who were offered the vaccine in their practice had accepted so far. The GPs could also make any other relevant comments.

 

What did the survey find?

The survey found that only 37% of GPs believed that their practice could achieve the government’s target, based on their experience so far. Just over half (53%) said they would not hit the target, and 10% said it was too early for them to say. The reasons given by GPs for not hitting the target are a low uptake of the vaccine by those who were offered it and delays in receiving vaccine supplies. Just over half the practices had started the vaccination campaign, and these practices estimated that less than half the people offered the vaccine had accepted it.

In the article on vaccine uptake in pregnant women, one GP estimated that only 5% of pregnant women in their practice had agreed to be vaccinated, while another GP estimated that the figure in their practice was less than 25%. Other GPs stated that there was scepticism about the vaccine among their pregnant patients.

 

Do these findings represent all GPs? 

This survey cannot answer that question. It was a relatively small survey which asked GPs’ opinions on the likelihood of reaching vaccination targets and their estimates of vaccine uptake in their practices. It is not clear how these GPs were selected to take part in the survey, how many of those who were asked agreed to take part, or which areas of the country were covered. The figures on overall uptake were based on the GPs’ estimates.

The only figures that estimated uptake in pregnant women came from two GPs, but one estimate was five times higher than the other (one in 20, and less than one in four). It is difficult to gauge uptake based on this limited survey, and it is not possible to say whether these results are representative of the entire country.

Regarding reasons for low uptake, the GPs could only state the concerns that their patients had reported to them. It is not possible to say how representative these reports were of people’s reasons for not having the vaccine. It is also not clear whether certain at-risk groups are more likely to reject the vaccine than others.

 

What are the problems with supply?

Pulse reported that each practice in England and Wales, regardless of size, was due to receive an initial delivery of 500 doses of the vaccine, and GPs should be able to order further deliveries from mid-November. However, the magazine says that larger practices reported not having enough doses of the vaccine to go round, which has led some of them to delay their vaccination campaigns.

 

What reasons were given for rejecting the vaccine?

The GPs surveyed said that people who rejected the vaccine did so because of concerns about its safety and the risk of side effects, which were reported as headaches, sleeplessness and stomach cramps. Some GPs also reported that patients were concerned over an ingredient in the vaccine called thiomersal.

Pandemrix is one of the two swine flu vaccines being used in the UK. It contains a very small amount of thiomersal as a preservative. It is added to prevent bacterial or fungal contamination occurring during the preparation, storage and use of the vaccine.

In the 1990s, some people raised concerns about the use of thiomersal in vaccines, which lead the WHO Global Advisory Committee on Vaccine Safety to review the scientific evidence about its safety, which it did most recently in 2006. It concluded that "there is no evidence of toxicity in infants, children or adults exposed to thiomersal in vaccines."

 

Are the vaccines safe?

Both swine flu vaccines (Pandemrix and Celvapan) have been authorised for use by the European Medicines Agency (EMEA). Vaccines would not be licensed if they were considered unsafe.

What is known about the safety of these vaccines is based on clinical trials of prototype bird flu vaccines and trials using the swine flu vaccine itself. Based on these studies, the swine flu vaccine has been judged to be acceptably safe for use.

People who are offered the vaccine and are concerned about its safety should discuss this with their doctor.

 

Does the vaccine have any side effects?

The Medicines and Healthcare products Regulatory Agency (MHRA) reports that “as with any vaccine, the swine flu vaccines will cause side effects in some people, although not everybody will have a side effect. The most common side effects will be injection site reactions (pain, swelling and/or redness), headaches, dizziness, muscle aches, mild fever and fatigue. These side effects are mainly mild and last only two to three days. Some of these symptoms may be similar to a mild flu-like illness, although it should be stressed that the vaccines cannot cause swine flu itself.”

Because clinical trials are relatively small, they may not identify very rare side effects. To identify these, the side effects of the swine flu vaccine will be monitored as it is used. It is important to note that the same is done for all new medicines and vaccines, not just the swine flu vaccine.

  

Who should be vaccinated and why?

Although swine flu is mild in most people, some people who get swine flu have serious complications, which can be fatal. To reduce the risk of these complications, the vaccination programme prioritises people who are most at risk of having complications from swine flu. These priority groups are:

• People aged between six months and 65 years who belong to at-risk groups that would usually be offered the seasonal flu vaccine (see below).
• Frontline health and social care workers.
• Pregnant women.
• People who live with those whose immune systems are compromised, such as cancer patients or people with HIV/AIDS.
• People aged 65 and over who would usually be offered the seasonal flu vaccine.

Frontline health and social care workers are prioritised because they deal with at-risk groups, so are more likely to catch and spread swine flu to at-risk patients. Prioritising them also aims to ensure that the health service will continue to run smoothly during the pandemic.

People who would usually receive the seasonal flu vaccination include those who have:

• Chronic respiratory disease, such as chronic obstructive pulmonary disease (COPD).
• Chronic heart disease, such as heart failure.
• Chronic kidney disease.
• Chronic liver disease, such as chronic hepatitis.
• Chronic neurological disease, such as Parkinson's disease.
• Diabetes requiring insulin or oral diabetic medications.
• Immunosuppression (a suppressed immune system) due to disease or treatment.

 

Why is it important for pregnant women to be vaccinated?

Pregnant women are one of the groups that are more likely to have serious complications if they get swine flu, which could result in miscarriage and premature labour.

There is evidence that pregnant women are at increased risk of severe disease and of being admitted to hospital with flu-related problems. The risk increases as the pregnancy progresses, and women in the third trimester of pregnancy are particularly at risk (WHO 2009; Jain et al, 2009; Jamieson et al, 2009).

The World Health Organization has stated that 7–10% of all hospitalised patients with swine flu are pregnant women in their second or third trimester. Pregnant women are 10 times more likely to need care in an intensive care unit than the general population (WHO, 2009).

Complications in pregnant women, based on information on seasonal flu, may include pneumonia and cardiorespiratory complications (Kort BA et al, 1986; Neuzil KM et al, 1998).

Both swine flu vaccines have been licensed for use in pregnant women, but it is recommended that pregnant women are given Pandemrix. This is because it appears to give adequate levels of antibodies after a single dose, protecting the recipient more quickly than Celvapan, which requires two doses given three weeks apart.

Links To The Headlines

Vulnerable patients shunning swine flu vaccine, GPs warn. The Daily Telegraph, November 18 2009

Pregnant women 'sceptical' about swine flu vaccination. The Independent, November 18 2009

Pregnant women refusing to take swine flu vaccination, say doctors. The Times, November 18 2009

Mothers-to-be 'are refusing swine flu jab' over safety fears. Daily Mail, November 18 2009

Links To Science

GPs braced to miss swine flu target. Pulse, November 16 2009

Pregnant women rejecting swine flu vaccine over safety fears. Pulse, November 16 2009

BBC News reported that pregnant women who have pre-eclampsia are more likely to suffer from thyroid problems.

This news comes from well-conducted research that used two separate studies to explore whether pre-eclampsia during pregnancy affects thyroid function. Both studies found a clear link between pre-eclampsia and blood test results that indicated underactive thyroid function, but many questions remain unanswered. Principally, it is unclear whether these blood test results were associated with any noticeable health problems or later thyroid disease, and whether any thyroid problems persisted after the birth.

From this study, it is not possible to say whether pre-eclampsia raises the risk of thyroid problems or if thyroid problems contribute to pre-eclampsia. There is a need for further research into this association.

 

Where did the story come from?

This research was conducted by Richard Levine from the National Institute of Child Health and Human Development, Bethesda, USA, and colleagues from other institutions in the US and Norway. The study received funding from various sources, including the Eunice Kennedy Shriver National Institute of Child Health and Human Development, and through salary support from the National Institutes of Health in the US. The study was published in the peer-reviewed British Medical Journal.

Coverage by BBC News accurately reflected the study report, without going into great clinical detail.

 

What kind of research was this?

This research featured two different studies which explored the association between problems of the thyroid gland and pre-eclampsia. Pre-eclampsia is a condition in which a pregnant woman develops high blood pressure, fluid retention and protein in her urine. It raises the risk of further complications for both the mother and baby.

The first phase of the research was a case control study that compared women who had experienced pre-eclampsia during pregnancy with women that had not. The second phase looked at the results of a large cohort study in 7,121 women, which measured their thyroid function following their first pregnancy.
 
This well-conducted research used two study designs to investigate whether pre-eclampsia is associated with thyroid problems. It should be noted that the data for the first study phase was gathered from members of a previous trial that investigated a treatment to prevent pre-eclampsia (the Calcium for Pre-eclampsia Prevention trial). This study was not specifically designed to investigate the link between pre-eclampsia and thyroid problems, which adds a limitation to the case control part of this subsequent study. Also, the women who were selected for the study may have had specific characteristics which mean the observed associations may not apply to all pregnant women.

 

What did the research involve?

The calcium trial was conducted in the US between 1992 and 1995. It found that calcium supplementation did not have an effect on the risk of pre-eclampsia. The subsequent case control study matched 141 of the participants with pre-eclampsia (cases) with 141 women without the condition (controls). All had given blood samples before they developed pre-eclampsia, at around 21 weeks of pregnancy. Blood samples were also taken after pre-eclampsia started (just before delivery).

The researchers then looked for associations between underactive thyroid and levels of a blood enzyme that has been associated with pre-eclampsia (called soluble fms-like tyrosine kinase 1).

This case control study was limited by the fact that thyroid function was not measured after the birth. While the study measured levels of markers of thyroid function in the blood, it does not report whether the women experienced clinical signs and symptoms of an underactive thyroid during pregnancy or if symptoms persisted after the birth. This means that it is not possible to tell if the thyroid problems were harmful to the women or if any problems resolved themselves.

The cohort study phase was conducted in Norway between 1995 and 1997. It involved 7,121 women who had first given birth after 1967 and had subsequently had their thyroid function measured. The researchers used these records to calculate the risk of having an underactive thyroid in relation to having pre-eclampsia.

 

What were the basic results?

In the calcium trial, women who developed pre-eclampsia experienced a significant increase in levels of thyroid stimulating hormone (TSH) compared to control participants. They also experienced a decrease in their thyroid hormone levels. Together, these indicate an underactive thyroid in the women who developed pre-eclampsia.

Across both groups, increases in TSH concentration were significantly associated with increased levels of the kinase enzyme associated with pre-eclampsia.

In the cohort study phase, women with a history of pre-eclampsia in their first pregnancy had a significantly increased risk of having TSH levels that exceeded the normal range. In most of these cases, there was an absence of thyroid antibodies, which suggests that these levels were not due to autoimmune thyroiditis. This is the most common cause of an underactive thyroid and happens when the body’s immune system attacks its own thyroid cells.

It is unclear at what point following pregnancy the women had their thyroid function assessed and, therefore, how long the situation persisted. There is also no indication that thyroid function was associated with any disease symptoms, although the researchers’ indication that underactive thyroid was “subclinical” (without apparent symptoms) suggests that it was not.

 

How did the researchers interpret the results?

The researchers conclude that increased enzyme concentration in the blood during pre-eclampsia is associated with subclinical hypothyroidism (underactive thyroid) during pregnancy. They say that pre-eclampsia may also predispose women to having reduced thyroid function in later years.

 

Conclusion

This well-conducted research used two separate studies to examine whether pre-eclampsia during pregnancy affects thyroid function. Although both studies found a clear link between pre-eclampsia and blood tests that indicated an underactive thyroid, many questions remain unanswered.

• Principally, it is unclear whether blood test results that indicated an underactive thyroid were associated with any signs or symptoms of disease. While women had altered levels of one of the thyroid hormones tested, few women were found to have abnormal levels of both. Abnormal levels of just one hormone does not necessarily suggest clinical hypothyroidism.
• It is not known whether thyroid function went back to normal following birth, whether it persisted and for how long, or whether any hypothyroidism seen was severe enough to require treatment.
• The first case control study was not originally designed to investigate the association between pre-eclampsia and thyroid function. It was a trial to investigate the use of calcium during pregnancy, and the women selected for the study may not be representative of pregnant women in general.
• The cohort study phase only measured thyroid function following birth. It is not known how this compared to pre-pregnancy levels.
• It is not clear whether the health of the children in these studies was in any way affected.

The causes of pre-eclampsia are not known, although there may be a genetic link. There are various causes of an underactive thyroid, including problems of the immune system attacking the body’s thyroid tissue. Other causes include surgical treatment affecting the thyroid, iodine deficiency and side effects of some medications.

From this study, it is not possible to say whether pre-eclampsia contributes to underactive thyroid or if thyroid problems contribute to pre-eclampsia. It is also possible that a person with certain physiology would be more likely to develop both conditions. There is currently limited available evidence on the link between thyroid function and pre-eclampsia, and further research into this subject is needed.

Links To The Headlines

Thyroid 'risk from pre-eclampsia'. BBC news, November 17 2009

Links To Science

Levine RH, Vatten LJ, Horowitz GL et al. Pre-eclampsia, soluble fms-like tyrosine kinase 1, and the risk of reduced thyroid function: nested case-control and population based study. BMJ, November 17 2009 (published online)

"Chemicals used in plastics feminise the brains of little boys", according to the Daily Mail. The newspaper claimed that boys who are exposed to high doses of phthalate chemicals in the womb are less likely to play with male toys or join in with rough games. Phthalates are a family of chemicals found in PVC shower curtains and vinyl flooring.

The research behind this news compared phthalate concentration in pregnant women’s urine to whether their children’s play habits were typically masculine or feminine at the ages of four to seven. However, the study only looked at a small number of children, and of those invited to take part, only half responded. In addition, phthalate concentration was only measured once during pregnancy. These limitations mean that the evidence from this study alone is too weak to form any definite conclusions.

Parents should not be concerned about reports of “gender-bending” phthalates affecting their children’s brains or habits.
 

Where did the story come from?

This research was conducted by Shanna H Swan and colleagues from the University of Rochester, New York, and other institutions in the US and UK. The study was funded by grants from the US Environmental Protection Agency, the National Institutes of Health in the US, and the State of Iowa. The study was published in the peer-reviewed International Journal of Andrology.

Although the BBC, Daily Telegraph and Daily Mail have accurately reported the sample size and main findings of the study, none of them mentions the most important limitation: that extremely few of the initial sample participated in the follow-up research sessions. When considered in isolation, the evidence gathered from this small number is unlikely to be representative of the whole sample.

 

What kind of research was this?

This was a small cohort study which investigated how boys’ brain function and development are affected by foetal exposure to phthalate chemicals. Animal studies have previously demonstrated that foetal exposure to such ‘antiandrogens’ in rats leads to less male-type behaviour.

A cohort study is usually a reliable form of study for assessing the relationship between cause and effect. However, this particular cohort study has several limitations, principally its small size. Only 74 boys and 71 girls were assessed, which represents 45% of those who were invited to participate. There is also some difficulty in attributing phthalate exposure to the cause of the children’s gender-type behaviour due to numerous possible confounding factors that were not taken into account.

 

What did the research involve?

The researchers contacted couples who took part in the earlier Study for Future Families, which recruited expectant mothers and their partners between 2002 and 2005. At the time, they completed a questionnaire and gave a urine sample, which was used in this latest study to measure phthalate concentration. For the purposes of this study, the women were contacted when their child was four to seven years old.

The researchers looked at how the mother’s phthalate concentration in mid-pregnancy related to the child’s gender-type behaviour. Child behaviour was reported by parents using a list of 24 activities, child characteristics and items (e.g. type of toys). Half of the listed entries were considered to be feminine and half masculine. A Parental Attitude Scale was also used to take into account factors that may have affected the children’s choice of play, such as the type of toys available in their household and parents’ attitude towards boys playing with “girls’” toys.

The study design had strengths in that it used a validated scale for assessing child gender-type behaviour and also took into account how parental attitudes may have influenced this. When assessing the relationship between gender-behaviour and phthalate concentration in the mother’s urine in pregnancy, the researchers considered various possible confounding factors, including mother’s kidney function, sex and age of child, parental education, number and sex of siblings, ethnicity and parental attitudes.

However, little is known about the effects of phthalates in humans, and as children’s play behaviour is likely to be complex and affected by many factors, there are probably numerous other confounding factors that were not accounted for. Also, measuring phthalates in the urine at a single point during pregnancy is not a reliable indication of exposure levels over time, which may be highly variable. 

Importantly, the researchers only received completed questionnaires from 45% of families who were sent them (150/334). This is a low follow-up rate and limits the findings of a cohort study which had a small sample size to begin with. It is also unclear exactly what proportion of the original Study for Future Families this represents.

 

What were the basic results?

The research found that higher concentrations of certain phthalate chemicals in expectant mothers’ urine were associated with a less masculine behavioural score in sons. No relationship was seen between concentrations of other phthalate chemicals and boys’ behaviours, or between any phthalate chemicals and girls’ behaviour.

 

How did the researchers interpret the results?

The researchers conclude that their data, “although based on a small sample”, suggests that exposure to phthalates in the uterus may be associated with less male-typical play behaviour in boys.

 

Conclusion

This research has attempted to address the question of how phthalate exposure may affect gender-type play behaviour. However, there are important limitations to the study and the evidence is too weak to form any definite conclusions about the relationship.

• The cohort study was very small and represents less than half of the eligible families. As such, results should be interpreted with caution and are unlikely to be representative of the whole sample. If the whole cohort had been included, the results may have been different.
• Little is certain about the effects of phthalates on humans, and children’s play is a complex behaviour that is likely to be affected by a wide variety of factors. Given their complexity, both areas of interest are likely to be confounded by factors that have not been accounted for.
• A one-off measurement of the mother’s phthalate exposure gives no indication of her exposure over a longer period of time, which may be variable, or of the child’s direct exposure during their own lifetime.
• The significant association in boys was seen for only some phthalate chemicals and not others.
• The study carried out multiple statistical tests, which increases the possibility that significant findings will be found by chance.

The implications of this research are currently limited. Without much further research, there is no definite evidence of the influence that phthalates might have on gender play and behaviour, or which types of plastics are likely to give the highest exposure.

Links To The Headlines

Chemicals used in plastics feminise the brains of little boys 'so that they avoid rough and tumble games'. Daily Mail, November 16 2009

Chemicals in plastics ‘feminising’ baby boys, says study. The Daily Telegraph, November 16 2009

Plastic chemicals 'feminise boys'. BBC News, November 16 2009

Links To Science

Swan SH, Liu F, Hines M et al. Prenatal phthalate exposure and reduced masculine play in boys. International Journal of Andrology, November 16 2009

The quality of dementia care in hospitals has featured in many newspapers. The Times reported that campaigners have said, “Patients with dementia are staying too long in hospital and receiving ‘disgraceful’ care that worsens their condition.” The Daily Telegraph said that “one in three never go back to their own homes and are discharged to a nursing home instead.”

The news stories are based on a report from the Alzheimer’s Society, which surveyed a large number of carers, nursing staff and nurse/ward managers on the quality of care given to people with dementia. Although the report gives the current opinion of a broad cross section of these groups of people, it cannot be considered a consensus. The figures that have been quoted by the newspapers should also be considered as the collective opinion of those surveyed.

However, the people who were surveyed are among the most experienced in the care of people with Alzheimer’s, and their overwhelming opinion is that hospital care needs to be improved. The society has made several objectives to achieve this aim.
 

What is the basis for these news reports?

The news stories are based on a report called Counting the Cost, which was commissioned by the Alzheimer’s Society. The charity reports that there are 700,000 people with dementia in the UK and that their care varies considerably. This report is part of the charity’s 'Putting Care Right' campaign, which aims to improve the quality of care for people with dementia.

The Counting the Cost report surveyed 1,291 carers, 657 nursing staff and 479 nurse/ward managers from general wards in hospitals across England, Wales and Northern Ireland. All members of the Alzheimer’s Society (about 21,000 people) were also asked to participate. The ward manager/nurse survey was sent to all ward managers and nurse managers who were identified from two databases.

People who agreed to take part completed questionnaires on the quality of care given to people with dementia. The majority of respondents were from England (91% of carers, 89% of nursing staff and 86% of the nurse managers).

The report also used evidence from national reports, a systematic review of dementia care in hospital general wards, and other published research.

 

What did the report conclude?

The report is extensive and only a summary of its main findings are presented here:

• At any one time, a quarter of hospital beds are taken by people over the age of 65 with dementia, and 97% of nursing staff report that they always or sometimes care for a person with dementia.
• Across England, Wales and Northern Ireland, there is considerable variation in the quality of dementia care on general wards, with some being excellent and some demonstrating neglectful care.
• 86% of nurse managers said that people with dementia are hospitalised for longer periods than those admitted for similar medical conditions without dementia, and 49% of carers said that the duration of care was longer than expected.
• 47% of carers reported deterioration in the person’s physical health and 54% reported deterioration in dementia symptoms while they were in hospital.
• Over a third of people with dementia who were previously living in their own homes are discharged to a care home.
• 77% of nurse managers and nursing staff said that antipsychotic drugs were always or sometimes used to treat people with dementia in hospital. However, up to 25% of them thought that the drugs had not been appropriately prescribed.
• 77% of carers said they were dissatisfied with the overall quality of dementia care provided. Key areas of their dissatisfaction were:
  − Nurses not recognising or understanding dementia.
  − Lack of personal care.
  − Patients not being helped to eat and drink.
  − Lack of opportunity for social interaction.
  − Patients and carers not having as much involvement in decision-making as they would like.
  − The person with dementia not being treated with due dignity and respect.
• Nursing staff had concerns about:
  − Managing patients with challenging or difficult behaviour.
  − Communication difficulties.
  − Not having enough time to spend with patients and provide one-to-one care.
  − Problems with patients wandering around, and not being able to ensure patient safety.
• The report predicts that supporting people with dementia to leave hospital one week earlier than they currently do could result in savings of at least £80million a year.

 

Are these opinions widespread?

This report offers a broad cross section of the current opinion of carers and healthcare providers on the state of hospital care for patients with dementia. However, it cannot be considered a consensus as it is not clear exactly what proportion of those professional staff who were asked to participate did so, although the report says that the response level was high.

The report also notes that carers who responded to the questionnaire may have been more likely to have had a bad experience and, therefore, may not represent all carers’ views. Because of these factors, it is difficult to say exactly how representative these figures are of dementia care as a whole in England, Wales and Northern Ireland. Despite this, the report has identified key areas where improvements in care for people with dementia are needed.

 

Does this mean that hospital care for people with dementia is bad?

Although the survey looks at hospital care, it doesn’t take into account each individual’s situation. For example, various medical and social situations may influence decisions of whether to discharge a person from hospital to their own home or to another place of care. In many cases, it is not until a person with dementia is admitted to hospital that medical and social services become aware of their situation and recognise that they may need additional care. Admission to a care home should not always be assumed to be a bad thing. In some cases, it may lead to an improvement in the care of the person and give them opportunities for increased social interaction and a better quality of life.

In many cases, the medical reason for the person’s admission to hospital (e.g. infection or fall) and the unfamiliar environment may lead to some deterioration in both their physical and mental state. Although the carers’ survey identified many areas of dissatisfaction in the quality of nursing care provided, this should not be assumed to be intentional neglect by the healthcare professionals. Survey responses by nursing staff identify many of the challenges that they face in providing care. Recognition of these challenges provides an opportunity to address these issues.

 

What does the Alzheimer’s Society aim to do next?

The charity states that it aims to:

• Gain NHS recognition that dementia is a significant issue and that certain areas of care need to be improved.
• Reduce the number of people with dementia in the acute hospital setting.
• Get each hospital to identify a senior clinician to take the lead for quality improvement in dementia.
• Suggest the formation of specialist older people’s mental health teams to liaise with hospital management.
• Reduce the use of antipsychotics in people with dementia.
• Ensure that all patients are assisted in eating and drinking where necessary.
• Ensure that carers are informed and effective in the care of people with dementia.
• Involve people with dementia and their carers, family and friends in their care to improve personal care.
• Start to change the approach to care for people with dementia to one of dignity and respect.

Links To The Headlines

'Disgraceful' care leaves dementia patients in worse condition. The Times, November 17 2009

Hospital ‘makes dementia worse’. Daily Mail, November 17 2009

Half of Alzheimer’s patients come out of hospital 'worse than when they went in'. The Daily Telegraph, November 17 2009

Dementia gets worse in hospital. Daily Mirror, November 17 2009

Dementia patient care criticised. BBC News, November 17 2009

Links To Science

Counting the cost: caring for people with dementia on hostital wards. Alzheimers Society 2009

 

 

Preliminary tests reveal no significant changes in the pandemic (H1N1) 2009 virus based on investigations of samples taken from patients in Ukraine. Analyses are being performed by two WHO influenza collaborating centres as part of the global influenza surveillance network.

Several newspapers have reported the dangers associated with cosmetic surgery, including a lack of regulation in some areas of the industry. The reports also feature warnings from Nigel Mercer, the president of the British Association of Aesthetic Plastic Surgeons, who voiced his views as part of a series of medical articles on cosmetic surgery. Mr Mercer called for tighter regulation and testing of drugs, procedures and implants to offer more protection to patients.

The Times reported that the number of cosmetic surgical operations conducted by “audited members of the profession” has more than tripled to 34,000 since 2003, but that many additional procedures are being carried out illegally on the black market. The newspaper says that these are “fuelled by internet promotions, magazine advertising and aggressive discounting”.

 

What is the basis for these news reports?

The reports were based on a special edition of the journal Clinical Risk, which featured several articles on the issues surrounding cosmetic surgery. These issues include the potential for physical and psychological harm, and the need for tighter regulation of the industry, better training programmes for surgeons and measures to improve patient experience.

Nigel Mercer, president of the British Association of Aesthetic Plastic Surgery, wrote an accompanying editorial arguing that the availability of consumer credit and a change in public attitudes has led to an explosion in cosmetic surgery in recent years. According to Mercer, this growth, combined with increasing public expectation and media hype, has resulted in “the perfect storm in the cosmetic surgical market”.

 

What is cosmetic surgery?

Cosmetic surgery, sometimes called aesthetic surgery, was described by a doctor in the journal Clinical Risk as being “purely elective, a lifestyle choice undertaken to enhance physical appearance, improve self-esteem and boost confidence”. Another doctor says that it differs from all other forms of surgery in that it is a treatment for “want” rather than for “need”.

In the 2005 Regulation of Cosmetic Surgery report, published by the Department of Health, cosmetic surgeries are defined as “operations and other procedures that revise or change the appearance, colour, texture, structure or position of bodily features, which most would consider otherwise to be within the broad range of ‘normal’ for that person”.

Cosmetic surgery differs from plastic surgery, which is generally surgery to repair or reconstruct tissue or skin damaged by congenital (inherited) disease, injuries or burns. The primary role of plastic surgery is to restore function, and aesthetic improvement is secondary.

 

How is cosmetic surgery currently regulated in the UK?

At present, there are measures and standards to help regulate the industry, but some cosmetic surgeons operate outside these regulations. Some treatments and procedures are unlicensed for cosmetic use but can be given at the discretion of doctors, or “off licence”, in some clinics.

Surgical practice in the UK is regulated by the General Medical Council (GMC) and practising surgeons should be enrolled on its specialist register. However, some concessions are made for private cosmetic surgeons who have been practising since before April 2002. By satisfying certain criteria, these doctors can practise without the need to be on the specialist register.

Invasive cosmetic surgery and laser treatments are also regulated under the Care Standards Act 2000. The Healthcare Commission inspects all registered establishments that carry out invasive procedures and laser surgery in the UK, and has the power to revoke practice licenses and to take enforcement action.

Some cosmetic surgical procedures are not covered by current regulations, such as botox injections and injections of aesthetic fillers. Botox is not licensed for cosmetic use, but it can be prescribed “off license”, in which circumstances the doctor assumes liability for its use. Most fillers are tested in the UK as “devices” rather than as drugs. This means that they are regulated based on the standard of their production and not on whether the treatment works.

The Department of Health report concluded that the regulatory situation for cosmetic surgery was not satisfactory because of the group of doctors who can practise without being on the GMC specialist register and the lack of clarity around the definition of “fillers”. Although practitioners of cosmetic surgery must demonstrate certain competencies, these may not be the equivalent standard of NHS consultants.

 

What do these journal articles say about cosmetic surgery?

The authors of these articles have argued several opinions, including that:

• Patient psychology should be considered by clinical staff as issues of mental health and body image may be behind the desire for cosmetic changes. These could also arise in people who feel disappointed or upset by the results of their surgery.
• Surgeons should keep records that detail their patients’ expectations and provide them with guidance on whether these are realistic.
• There are risks associated with any type of surgery and patients should be informed of these and their surgeon’s success rates when considering procedures.
• It is important that patients are given time to consider their options. Doctors should also inform patients about alternative treatments that may be available.
• Before procedures are carried out, it should be clear who will be financially liable for the correction of any complications.
• There may be some merits to adopting a regulation system similar to that in France. Under this system, patients must be given information on costs, risks and the surgeon’s qualifications to perform their selected procedures.
• The way that cosmetic surgery is marketed should also be regulated.

What is the problem with cosmetic surgery marketing?

Mercer says that cosmetic procedures are often marketed using special offers, including vouchers, two-for-one deals and surgery holidays, and that these practices contribute to an “unregulated mess”. 

The articles also feature a call to ban advertising of cosmetic procedures, stating that, like tobacco, there should perhaps be a Europe-wide ban on advertising all cosmetic surgical procedures, including on internet search engines. While advertising can be powerful, says Mercer, it is often misused by the cosmetic surgery industry and misinterpreted by those it is aimed at.

 

Where can I find more information on reputable cosmetic surgeons?

The British Association of Aesthetic Plastic Surgery is a not-for-profit organisation based at the Royal College of Surgeons. It was established to advance the education and practice of cosmetic surgery for public benefit. While it is not a regulatory body, it has long been involved in giving the public information on the safety of cosmetic surgery.

Its research into cosmetic surgery tourism was discussed at a recent conference and its press releases highlight a number of dangers associated with unregulated procedures, including DIY injectable treatments available over the internet.

Links To The Headlines

Royal Society warns of dangers at hands of 'greedy' cowboy cosmetic surgeons. Daily Mail, November 16 2009

Leading article: Face the facts on plastic surgery. The Independent, November 16 2009

Warning over 'cosmetic ops risk'. BBC News, November 16 2009

British cosmetic surgery an unregulated mess, leading doctors warn. The Times, November 16 2009

Links To Science

Mercer N. Clinical risk in aesthetic surgery. Clin Risk 15(6): 215-217

Slack R. Aesthetic surgery and regulatory risk for doctors. Clin Risk 15(6): 218-220

Boyd M. Managing risk to reputation. Clin Risk 15(6): 221-223

Fogli A. France sets standards for practice of aesthetic surgery. Clin Risk 15(6): 224-226

Bradbury E. Clinical risk in cosmetic surgery. Clin Risk 15(6): 227-231

Nahai F. Minimizing risk in aesthetic surgery. Clin Risk 15(6): 232-236

Khoo C. Risk reduction in cosmetic surgery. Clin Risk 15(6): 237-240

Grover R. Improving the safety of aesthetic surgery: Recommendations following a 14-year review of cases referred to the Medical Defence Union from across the United Kingdom (1990–2004). Clin Risk 15(6): 241-243

“You can eat an extra cheeseburger a day,” according to the Daily Mail, which reported that the official guidelines on recommended calorie intakes have been lower than they should have been for the past two decades. The newspaper said that the average adult could “happily squeeze in an extra 400 calories a day”.

The news is based on a draft report by an advisory committee to the government. It found that the original recommendations for daily energy (calorie) intakes, which were made in 1991, underestimated the average requirement by up to 16%. This discovery came about through a re-evaluation of the amount of energy needed by the average person based on what the authors consider a more accurate interpretation of average physical activity levels.

This news does not mean that everyone can, or should, now eat an extra cheeseburger or its equivalent in calories a day. The advisory committee makes it clear that the revised energy intake recommendations do not mean that people should increase the amount they eat and that, if people do eat more, they will need to do more exercise to avoid being overweight or obese.

 

What is the basis for the news reports?

The news is based on a draft report from the Scientific Advisory Committee on Nutrition (SACN), a committee of independent experts that advises the Food Standards Agency and Department of Health, as well as other government agencies and departments.

The main point of the SACN report is that the existing recommended calorie intake appears to be too low for adults, and may be increased by up to 16%.

 

What did the report conclude?

The 250-page report highlights the findings and recommendations of the SACN Energy Requirements Working Group. Its purpose was to review and agree the methods and assumptions that are used to define energy requirements, to decide how to determine requirements for the UK population, and to agree dietary reference values (recommended intakes) that take into account age, body size, activity levels, gender and physiological state (pregnancy, growth etc).

The report discusses the theory behind dietary intakes of energy, physical activity and energy expenditure levels, population energy requirements, the effect of diet on the risk of weight gain and the effects of physical activity.

The draft report's main conclusions are:

• SACN has determined new estimated average requirements (EARs) for energy for children, adolescents and adults. This is based on an improved understanding of physical activity levels. For teenage boys from 15, girls from 11 and for all adults, EAR values should be increased by up to 16% (based on an increased average physical activity level, or PAL, of 1.63, see below). Values have been established for three physical activity levels (average, less active and more active) in each age group and gender. The report says that for those people judged to be either less or more active than average, PAL values of 1.49 and 1.78 are appropriate. They say that energy requirements may be slightly lower for less active individuals and active individuals may have higher energy requirements.
• Revised reference values do not mean that individuals or groups should increase their energy intake. Energy expenditure (the amount of energy that people use up) needs to increase in relation to energy intake from food to reduce the number of overweight and obese people.
• SACN fully endorses the current recommendations on physical activity, which state that adults should do at least 30 minutes of moderate-intensity activity five or more days a week, while children and teenagers should aim for 60 minutes a day.

 

What are the existing calorie intake guidelines?

Current guidance is based on the recommendations of the UK Committee on Medical Aspects of Food Policy (COMA), which were made in 1991. This guidance has since been adapted to include recommendations for fibre intake by the Food Standards Agency and for salt intake by SACN.

The current UK guideline daily amounts are 2,000 calories for women, 2,500 calories for men and 1,800 calories for children aged five to 10.

 

Why is the original guidance thought to be wrong?

The researchers say that the recommendations made by COMA in 1991 were based on a potentially less accurate methodology, which included assumptions that individuals’ physical activity levels could be predicted from activity diaries and lifestyle questionnaires. They say that this method underestimated the influence of routine activities of daily living on energy expenditure.

For their estimates of physical activity levels, the researchers carried out a search of the literature for studies that assessed total energy expenditure in a particular way. They looked at a range of basal metabolic rates (the energy a person expends when resting), total energy expenditures and other measurements (e.g. growth), which they used to determine the physical activity levels of the UK population for a range of ages. The calculations are complex, but the authors say that while there are limitations to the way they derived physical activity levels for the different age groups, their approach is evidence based and more accurate than the one previously used.

Much of the report is dedicated to justifying the need for improved methodology to determine energy recommendations for adults and children in the UK.

The authors say that the COMA group estimated the average physical activity level in the UK to be 1.4. The measure of physical activity (PAL) is described as being an index of 24 hour total energy expenditure (TEE), adjusted for the basal metabolic rate (BMR), i.e. it is a ratio of TEE to BMR. The authors say that this is a relatively low value but, at the time, was “seen to be in keeping with the sedentary lifestyle of the UK population”. However, according to their own calculations, this estimate is likely to be lower than the true average physical activity of the UK population (90% of the subjects considered relevant for this report had physical activity levels greater than this value). Their estimate for the average physical activity level for adults is 1.63.

Using this value, the researchers estimated the average energy requirements for adults to be up to 16% higher than the original recommendations.

 

Can you really eat an extra cheeseburger a day?

This news does not mean that everyone can, or should, now eat an extra cheeseburger or its equivalent in calories a day. The conclusions of this report should not be oversimplified. People who are overweight are still likely to be consuming more energy (i.e. food) than they are burning (using up). The researchers state in their report:

“The high prevalence of overweight and obesity in the UK population shows that, for the majority of people, energy intakes are in excess of energy requirements. It is important that the proposed EAR values are not used to signal or encourage an increase in energy intake of the population as a whole; this would increase the prevalence and magnitude of overweight and obesity in the absence of a corresponding increase in energy expenditure.”

 

What happens now?

This draft report by SACN has now entered a consultation period. Its findings and recommendations will need peer review and further consideration by experts before they are incorporated into national guidance. The consultation period will run until February 11 2010, after which time the feedback and subsequent review will be made available to the public.

An announcement on the SACN website says that estimating energy requirements is complex and the new draft recommendations are themselves based on assumptions.

If the government adopts the new recommendations, they will have implications for the health and food industries. For example, food labelling is based on the current recommended daily allowances.

Links To The Headlines

Rethink for calorie eating levels. BBC News, November 16 2009

Calorie count guidance may rise by a cheeseburger. The Guardian, November 16 2009

'You can eat an extra cheeseburger a day' - say diet experts. Daily Mail, November 16 2009

Calorie guidelines could be wrong. The Daily Telegraph, November 16 2009

Diet guidelines are all wrong. Daily Express, November 16 2009

Links To Science

Draft Energy Requirements report 'scientific consultation'. SACN, November 2009

 

 

Dark chocolate cuts levels of stress hormones and rebalances other body chemicals, according to the Daily Mail. The Daily Express also featured the claim that chocolate reduces the risk of heart disease and high blood pressure and improves brain function.

The research behind these reports was commissioned by Nestlé. Researchers gave 30 healthy people 40g of dark chocolate a day for 14 days. They examined changes in metabolism and chemicals that are reportedly related to stress. The study’s methods have numerous limitations, including its small number of participants, short study period and selection of only young, healthy people to take part. Also, while the researchers measured levels of the “stress” hormones in urine, they did not directly look at changes in the participants’ stress levels.

By itself, the study is insufficient to provide evidence that dark chocolate has any benefits or effects on stress, psychological or mental health, or cardiovascular health.

 

Where did the story come from?

This research was conducted by Francois-Pierre J Martin and colleagues from Nestlé Research Center in Switzerland, and Metanomics GmbH in Germany. No external sources of funding were reported for this study. The study was published in the peer-reviewed Journal of Proteome Research.

Newspaper reports have mostly focussed on details from the presentation and conclusion of the study. However, the articles did not discuss the numerous limitations of this research. For example, while the Daily Mail mentions that the researchers work for Nestlé, it does not mention the small number of participants or the fact that effects were only measured over 14 days.

 

What kind of research was this?

This was a non-randomised experimental study in 30 individuals, which looked at the metabolic response to consuming 40g of dark chocolate a day for up to 14 days. The researchers particularly looked at how participants’ initial anxiety levels may affect changes in chemical measures related to stress.

This research model had a number of methodological flaws, including the small number of participants, the very short follow-up period and the lack of randomised groups. As such, only limited conclusions can be made from its results.

The trial could have been improved by randomising a larger number of people with equivalent anxiety levels to consume either dark chocolate or a placebo (if possible) and considering longer-term clinical effects (such as stress levels, weight gain and changes in cardiovascular health) over a longer follow-up period. The effects should also have been assessed by a researcher who was blinded to which group each participant had been assigned to.

 

What did the research involve?

The study recruited 30 ‘healthy and free living’ young adults: 19 women and 11 men, aged 18 to 34. The researchers excluded people who smoked, drank excessively, were overweight or obese, were on a diet or had medical disorders (including metabolic or eating disorders).

A validated psychological questionnaire was used to classify participants as having either low or high anxiety traits. According to the questionnaire, there were nine high-anxiety women, 10 low-anxiety women, four high-anxiety men and seven low-anxiety men.

Participants did not eat any chocolate in the eight days before the trial. They then received 40g of dark (74% cocoa) Nestlé chocolate a day for 14 days. They ate 20g mid-morning and 20g in the afternoon. On days one, eight and 15, the researchers took blood and urine samples. Metabolic changes following chocolate consumption were assessed using a number of different laboratory tests.

The study only analysed blood and urine samples, and did not provide any indication of the effects of chocolate consumption on the participant’s health, psychological status or wellbeing. This was another of the study’s limitations. It is also not known what other factors may have differed between the study participants, for example intake of other food and drinks or activity levels during the study period. In any case, the study’s duration was too short for questions about longer-term effects, such as cardiovascular disease or psychological changes, to be answered.

Stress hormones and energy levels in those who had higher anxiety at the start of the study were perceived to approach normal levels following chocolate consumption. However, as a psychological assessment was not performed at the end of the study, it is not clear whether these metabolic changes produced meaningful clinical differences.

 

What were the basic results?

The researchers noted that those who had higher anxiety traits initially demonstrated differences in energy metabolism in the body, hormone metabolism and microbe activity in the gut. Following dark chocolate consumption, there was a reduction in stress hormones excreted in the urine (cortisol and catecholamines) and reduced difference in energy metabolism and gut microbial activities in all participants.

 

How did the researchers interpret the results?

The researchers say that their study provides “strong evidence that a daily consumption of 40g of dark chocolate during a period of two weeks is sufficient to modify the metabolism of free living and healthy human subjects”. They say that these changes, seen after only two weeks, had “potential long-term consequences on human health”.

 

Conclusion

This study has numerous methodological flaws, and when considered in isolation does not provide any evidence that dark chocolate has benefits or effects on stress, psychological or mental health, or cardiovascular health.

• Although the researchers refer to their study as “randomised” in their report, there does not appear to be any control group, so it is unclear exactly what they mean by this term.
• The trial involved a small sample of 30 people. The effects of chocolate were assessed in even smaller subgroups of people with different anxiety traits.
• All the people in this study were healthy young adults who were not overweight or obese, did not drink excessively or smoke, and did not have conditions such as diabetes. These results cannot be applied to people who are older, unwell or have less healthy lifestyles.
• While the researchers observed changes in metabolism or stress hormones, it is not definite that chocolate consumption was responsible for this. For example, being part of a trial situation and removing participants from everyday life may have caused this effect. Additionally, other measures that may have played a role in the metabolic changes, such as diet and physical activity, were not reported.
• A follow-up period of 14 days is far too short to make any conclusions about how long-term daily consumption may affect stress, mental health, cardiovascular health or weight gain. The researchers themselves do not state that dark chocolate has any of these effects.
• As the trial was conducted by the food manufacturer and confectioner Nestlé, the researchers may have had a vested interest in promoting the positive results of their trial.

Although this study provides little evidence to show that daily consumption of chocolate promotes mental or cardiovascular health, chocolate may still be enjoyed as part of a balanced diet. However, chocolate (including dark chocolate) is high in fat and calories and should be eaten only in moderate amounts.

Links To The Headlines

How a daily dose of dark chocolate can cure stress. Daily Express, November 13 2009

How a bar of dark chocolate a day could cut your stress levels. Daily Mail, November 13 2009

Links To Science

Martin F-PJ, Rezzi S, Pere-Trepat E, et al. Metabolic effects of dark chocolate consumption on energy, gut microbiota, and stress-related metabolism in free-living subjects. J. Proteome Res 2009; October 7

“About 145,000 people with dementia are wrongly being prescribed powerful anti-psychotic medication which causes around 1,800 deaths a year,” The Times reported. Many newspapers have reported this finding from a government-commissioned review. The government has responded to the report and agrees with its main findings.

The report makes several recommendations, mainly that people with dementia should receive antipsychotics only when they really need them, and that reducing their use in this group should be a priority for the NHS. It suggests this can be achieved by various means including training carers and medical staff to use alternatives to antipsychotics, providing psychological therapies for people with dementia and their carers, carrying out further research into alternative treatments, and audits.

The report estimated that antipsychotic use could be safely reduced to a third of its current usage over a period of three years.

 

Why are antipsychotics used in dementia?

Antipsychotics are used to manage the psychological and behavioural symptoms of dementia. These include aggression, agitation, shouting and sleep disturbance. It is important to find ways to deal with these symptoms as they can cause major problems for the person with dementia and their carers.

 

What is the basis for the news reports?

In 2008, the government asked Professor Sube Banerjee to carry out an independent report about the use of antipsychotic medication for people with dementia in the NHS in England. Professor Banerjee is a professor of mental health and ageing at the Institute of Psychiatry, part of King’s College London.

The review was commissioned as there have been “increasing concerns over the past years about the use of these drugs in dementia”. This report has now been published, along with the government’s response.

 

What did the report find?

The report found that the current approach to treating the psychological and behavioural symptoms of dementia appears to be largely based on the use of antipsychotics. It also found that the evidence regarding the use of antipsychotics in people with dementia is complex, sometimes contradictory and contains gaps. Due to the gaps in the evidence, any conclusions need to be drawn cautiously.

The report concluded that, overall, the evidence suggests that antipsychotics appear to have only a limited positive effect in treating these symptoms and cause significant harm to people with dementia.

However, it also said that some people with dementia do benefit from antipsychotics and there are likely to be specific subgroups of people with dementia who benefit, such as those with severe symptoms. It said this has not yet been tested in rigorous trials.

Based on the best evidence available, Professor Banerjee estimated that:

• Each year, 180,000 people with dementia receive antipsychotics in England.
• Up to 36,000 of these people benefit to some degree from the treatment.
• Around 1,620 additional cerebrovascular adverse events (such as stroke) will result from the treatment. About half of these will be severe.
• Each year, about 1,800 additional deaths will be caused by the treatment in this frail population.

 

What did the report conclude?

Professor Banerjee concluded, “The current level of use of antipsychotics for people with dementia presents a significant issue in terms of quality of care, with negative impacts in patient safety, clinical effectiveness and the patient experience.”

He says that antipsychotic drugs appear to be used too frequently in dementia and that the potential benefits are likely to be outweighed by the risks. He suggests that this is a worldwide problem, but that actions can be taken to address it.

 

What recommendations does the review make?

The report makes 11 recommendations that aim to reduce the use of antipsychotics to a level where the benefits outweigh the risks. Professor Banerjee estimated that antipsychotic use could be reduced to a third of its current level, and that this could be done safely over 36 months.

Broadly, the report recommends that:

• People with dementia should receive antipsychotics only when they really need them.
• Reducing the use of antipsychotics in people with dementia should be a priority for the NHS.
• Care home staff are given a curriculum to develop skills in non-pharmacological treatment of behavioural disorder in dementia.
• Care homes could be assessed based on their use of antipsychotic medications and the availability of staff who are skilled in non-pharmacological management of behavioural and psychological symptoms in dementia.
• Psychological therapy resources should be made available for people with dementia and their carers.
• Further research should be carried out, including studies of non-pharmacological methods of treating behavioural problems in dementia and of alternative pharmacological treatments.

 

What was the government’s response?

The government welcomed the report and accepted its conclusions. It said that the level of additional deaths due to antipsychotic use in people with dementia was “totally unacceptable”.

It also agreed that “there should not be a ban on the prescribing of anti-psychotic medication to people with dementia, as there will undoubtedly be occasions when the use of drugs will be necessary and in the best interests of the person involved.” The Alzheimer’s Society has also given its support to the report.

 

Are there any other important points to note?

This report only looks at the use of antipsychotics in people with dementia. It does not apply to people who are prescribed antipsychotics for other conditions, such as schizophrenia. It is important that people with dementia do not stop taking any prescription medications without first consulting their doctor.

NICE recommendations on the use of antipsychotics in dementia include:

• People with dementia who develop non-cognitive symptoms (psychosis and/or agitated behaviour causing significant distress) or challenging behaviour should be offered a pharmacological treatment in the first instance only if they are severely distressed or there is an immediate risk of harm to the person or others. An assessment to establish likely factors that may cause, aggravate or improve such behaviour should be carried out at the earliest possible opportunity and a care plan drawn up.
• People with Alzheimer’s disease, vascular dementia, mixed dementias or dementia with Lewy Bodies (DLB) with mild-to-moderate non-cognitive symptoms should not be prescribed antipsychotic drugs because of the possible increased risk of cerebrovascular adverse events (e.g. stroke) and death. Those with DLB are at particular risk of severe adverse reactions.
• People with Alzheimer’s disease, vascular dementia, mixed dementias or DLB with severe non-cognitive symptoms may be offered treatment with an antipsychotic drug provided there is a full discussion with the person and their carers of the risks of adverse effects, there are specific treatment aims and goals and treatment effects which are regularly assessed and recorded. The drug should be selected on an individual basis, started at low dose, monitored regularly and changed or withdrawn as indicated.

 

How was the report produced?

Professor Banerjee looked at the available research evidence, legal issues and how antipsychotics are used in practice in dementia, both by the NHS and in other countries. He also asked for the views of people who have a professional or personal interest in the issue, including members of the public, people with dementia, carers, doctors, NHS managers and the pharmaceutical industry. These investigations were part of the development of the National Dementia Strategy.

Links To The Headlines

Chemical cosh’ for dementia kills 1,800 a year. The Times, November 13 2009

1,800 a year die from dementia ‘cosh’ pills. The Sun, November 13 2009

1,800 OAPS killed by dementia sedatives. The Mirror, November 13 2009

Chemical restraints killing dementia patients. The Guardian, November 13 2009

Dementia drug use 'killing many'. BBC News, November 13 2009

'Chemical cosh’ drugs 'killing thousands a year'. The Daily Telegraph, November 13 2009

Links To Science

The use of antipsychotic medication for people with dementia: Time for action. A report for the Minister of State for Care Services by Professor Sube Banerjee. Department of Health 2009 (PDF)

Government response to the report: November 12 2009 (PDF)

Alzheimer’s Society response: Review calls for action on dangerous use of antipsychotic drugs for dementia, 12 November 2009

As of 8 November 2009, worldwide more than 206 countries and overseas territories or communities have reported laboratory confirmed cases of pandemic influenza H1N1 2009, including over 6250 deaths.

“Scientists have found a way to disarm a protein thought to play a key role in leukaemia and other cancers,” the BBC has reported. It said that the protein in question, called Notch, is often damaged or mutated in patients with a certain form of leukaemia.

The researchers used an experimental technique called hydrocarbon stapling. This uses a chemical ‘scaffold’ to mould short sections of protein (called peptides) into specific three-dimensional shapes. The researchers hoped that these 'stapled peptides' would interact with the Notch protein and block its actions. The researchers found that one of their peptides was able to stop Notch from working and to reduce the growth of leukaemia cells in mice.

This research has identified a way to target the Notch protein, which has previously been an elusive target. The technique may lead to the development of new drugs to treat this type of leukaemia (called T-ALL), and to potential ways of using stapled peptides in other areas of research.

 

Where did the story come from?

Dr Raymond Moellering and colleagues from Harvard University carried out this research. The study was funded by several organisations, including the Leukaemia & Lymphoma Society and the National Institutes of Health in the US.

One of the researchers declared that they were a paid consultant and shareholder of Aileron Therapeutics, a company which has been granted a license to develop stapled peptide technology by Harvard University and the Dana Farber Cancer Institute. The study was published in the peer-reviewed journal Nature.

The BBC has covered this complex study in a balanced way.

 

What kind of research was this?

This was a laboratory study that included both biochemical and animal experiments. The researchers wanted to see if they could develop a method to block the action of transcription factors (a type of protein) in cells. Transcription factors switch on genes and, as such, they control the processes that occur within cells. While transcription factors play a role in normal cell function, they are also involved in the development of cancer. This means that they may be a good target for new cancer drugs, but their chemical characteristics have so far made it difficult to design drugs that block their function.

This study describes the early development of a new type of molecule that could be used in future drugs. This work will be followed by further research in animals to investigate the molecule’s effectiveness and safety. If this research proves promising, it may be followed by research in humans.

 

What did the research involve?

The researchers were interested in developing a drug that could block the action of a transcription factor called NOTCH1. Mutations can cause this transcription factor to be active when it shouldn’t be, which can lead to a form of leukaemia called T-cell acute lymphoblastic leukaemia (T-ALL).

Inside the cell, a protein called MAML1 binds to a complex of proteins that contains the NOTCH1 transcription factor. Laboratory tests have shown that a fragment of the MAML1 protein (called dnMAML1) can block the action of NOTCH1 in T-ALL leukaemia cells, stopping them from dividing.

However, protein fragments (peptides) may not be structurally robust, and may be susceptible to changing shape or being broken down. Research has suggested that peptides can last longer in the body and bind to other proteins more effectively if they are bonded to a chemically altered amino acid (the building blocks of proteins). This technique is called hydrocarbon stapling.

The researchers investigated whether a hydrocarbon-stapled form of dnMAML1 would still be able to block the action of NOTCH1. They designed six shorter hydrocarbon-stapled pieces of protein similar to dnMAML1, referred to as SAHM1, SAHM2 etc.

They examined how long these SAHMs took to get into the cell and selected those that looked most promising for further testing. They observed how well SAHMs bound to the complex of proteins that contained NOTCH1. They also looked at the effect of SAHMs on genes that are normally switched on by NOTCH1, and their effects on T-ALL cells in the laboratory. Finally, they looked at what effect the most promising SAHM had on a genetically engineered mouse model of T-ALL.

 

What were the basic results?

Laboratory tests on cells
The researchers found that some of the SAHMs, including SAHM1, were able to enter cells. SAHM1 could bind to the complex of proteins containing NOTCH1. SAHM1 also reduced the activity of genes in T-ALL leukaemia cells that would normally be switched on by NOTCH1. Treating T-ALL cells in the laboratory with SAHM1 stopped the cells from dividing as often as they normally would.

Animal testing
The researchers found that mice with progressive T-ALL that were given twice-daily SAHM1 injections experienced a reduction in the number of cancerous cells. Once-daily SAHM1 injections had a lesser effect, and T-ALL leukaemia progressed in untreated mice.

 

How did the researchers interpret the results?

The researchers concluded that the hydrocarbon-stapled peptide SAHM1 caused “potent, NOTCH-specific anti-proliferative effects” in both cells grown in the lab and the mouse model of T-ALL leukaemia. They say that their SAHM1 molecule should be useful in working out the role of NOTCH1 in normal and diseased tissues. It also provides a starting point for developing targeted drugs to treat NOTCH-related cancers and other conditions.

 

Conclusion

This study has developed a new method for targeting the NOTCH1 transcription factor. The technique may eventually lead to the development of new drugs for T-ALL and other Notch-related conditions. However, this will be a long-term goal as much more animal and human research will be needed to determine the effectiveness and safety of this new approach.

Links To The Headlines

Cancer protein 'can be disarmed'. BBC News, November 12 2009

Links To Science

Moellering RE, Cornejo M, Davis TN. Direct inhibition of the NOTCH transcription factor complex. Nature 2009; 462: 182-188

A headline in today’s Daily Mail stated: “Yoghurt drinks could beat bugs that pile the weight on.” It said scientists have shown that “bugs that live in our stomachs could be causing us to get fat.” The newspaper said the research could lead to probiotic yoghurts that can combat weight gain.

The newspaper’s claim about probiotic yoghurts is misleading. In fact, the study examined the effect of a change in diet on gut flora (microorganisms found in the gut) and weight in mice. The research was well conducted and should help advance investigations into gut flora. However, probiotic drinks such as Yakult, which was mentioned in the Daily Mail, did not feature in the study. While it is easy to see how the newspaper reached its interpretation, it is too great a leap, and the study's relevance to human diet needs more investigation.

While Yakult has had some more publicity because of this study, the research had nothing to do with probiotic yoghurts.

 

Where did the story come from?

The research was carried out by Dr Peter Turnbaugh and colleagues from Washington University School of Medicine and the University of Colorado. It was funded by the National Institutes of Health and the Crohn’s and Colitis Foundation of America. The authors declare that they have no competing financial interests. The study was published in the peer-reviewed medical journal Science Translational Medicine.

The Daily Mail and The Times reported this research, and both papers made confident statements that the findings show that diets high in fat and sugar are causing obesity. Both papers highlight that this study was in mice. The Daily Mail’s headline about probiotic yoghurts, such as Yakult, could be misleading as this research did not test probiotics (yoghurts or otherwise) and the researchers do not mention them.

 

What kind of research was this?

This study had several aspects, one of which was to examine the effect of modifying diet on gut flora and weight in mice. The researchers say that it is difficult to determine the relationships between diet, the behaviour of gut microbes and energy from food because of the effects of genes and environmental factors. By developing an ‘animal model’ of the complex ecosystem in the human gut, the researchers have provided a way forward for further studies.

 

What did the research involve?

This research involved several different experiments, all of which used ‘gnotobiotic mice’. These are animals which are raised in germ-free environments and deliberately colonised with specific microbes at particular times in their life. Mice such as these are useful in experiments about digestion as they can show how particular microbes and previously germ-free environments affect each other.

In the initial experiments, the researchers attempted to establish a mouse model of the human gut so that they could investigate the effect that diet had on it.

To make the mouse model, the researchers put microbes from human faecal matter into the guts of gnotobiotic mice to establish a human-like gut colony. The mice were fed a standard low-fat diet that was rich in plant matter. Researchers collected faeces from the mice one day, one week and one month after the mice were colonised with the human microbes. After a month, half of the mice were switched to a high-fat, high-sugar Western diet. The two groups remained on these diets for an extra two months, with weekly faecal sampling. The mice were then killed and the components of their guts compared.

In other experiments, the researchers assessed whether the human-like gut flora could be transferred between animals and whether this could be done using frozen faecal samples. In the experiment that the media has picked up on, the researchers examined whether diet-induced obesity could be caused in healthy mice by transplanting into them the gut flora from mice that were fed a Western diet.

 

What were the basic results?

The researchers developed a mouse model of the human gut using human faecal matter. These microbial colonies could be transplanted into other mice even through frozen faecal samples. This establishes this mouse model as useful for further research.

A Western diet caused mice to gain weight and changed the microbes in their gut. Transplanting the gut flora from these mice to healthy mice led to significant weight gain compared with mice that received gut flora from mice on a non-Western diet, even though there was no increase in food consumption.

The researchers identified the particular bacteria that were predominant in diet-related obesity, having found a bloom in bacteria called Erysipelotrichi and Firmicutes along the length of the gut.

 

How did the researchers interpret the results?

The researchers say that while human gut communities have been transplanted into germ-free animals many times in previous experiments, they used these methods to show that the human gut colony can be transferred to mice even if the starting material is frozen faeces.

They have also shown that this can be passed between mice and that the complement of microbes changes quickly and dramatically when the diet is switched from a low-fat diet to a high-fat, high-sugar Western diet. This diet-altered gut flora can be transplanted into other animals. Overall, the findings show that this is a potentially useful animal model for further study of the environment of the gut.

 

Conclusion

This animal study was well conducted. The purpose of the experiment, which is well described, was to establish an animal model for further studies of human diet and of the complex ecosystems that exist in the digestive system.

The study did not examine the effects of yoghurt or other probiotics on weight, as some news reports imply. Nor does it suggest that a probiotic yoghurt will soon be available that can aid weight loss. This extrapolation of the results is likely to have been based on the finding that a Western diet alters the microbial constituents of the gut. Researchers found that when the mice’s diet was changed from a low-fat diet to a Western-style high-fat, high-sugar diet, the component bacteria in their gut changed quickly and considerably. Stating that a probiotic yoghurt could “combat weight gain”, and including a picture of a normal yoghurt drink next to the article, could mislead people.

The results from this study will undoubtedly inform further research and the study has developed an important animal model for this type of research. Probiotics should not be seen as a ‘treatment’ for a poor diet, and eating a healthy, balanced diet and doing regular exercise remain the best ways to prevent overweight and obesity.

Links To The Headlines

Yoghurt drinks could beat bugs that pile the weight on. Daily Mail, November 12 2009

Sugar and fat-rich diets cause obesity by altering gut bacteria. The Times, November 12 2009

Links To Science

Turnbaugh PJ, Ridaura VK, Faith JJ et al. The effect of diet on the human gut microbiome: a metagenomic analysis in humanized gnotobiotic mice. Sci Transl Med 11 November 2009: 1; 6ra14