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In 2004, Tim was diagnosed with diabetic retinopathy, a complication of diabetes that can lead to blindness. He describes how he was diagnosed and the treatment options available.

Victoria was raped in 2009. She describes what happened to her and how she has been affected. And an expert gives advice on where to find your nearest sexual assault referral centre.

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It is believed that one in five pregnancies end in miscarriage. An expert explains what defines a miscarriage, as well as possible causes and the effect it has on the parents. Mark and Lara describe how they dealt with the miscarriage of their first baby.

An expert discusses neonatal death - when a baby dies within 28 days of being born. David and Leigh's twins Kristina and Lucy were born prematurely at 25 weeks and died aged 17 and 21 days. They describe how they grieved and coped in their own way.

“Swings in blood pressure ‘could better predict stroke than average high readings’,” reported The Daily Telegraph. The paper reported that “variations in people’s blood pressure rather than the average level predicts stroke most powerfully”.

The news story was based on a collection of studies published in The Lancet. The authors have presented a compelling argument that fluctuations in blood pressure may help to predict the risk of vascular events such as stroke.

As mentioned in an accompanying editorial published in the same journal, it is important to point out that the authors are not questioning the validity of using average blood pressure to predict risk, but are suggesting that variable blood pressure could also be used as a supplementary indicator of increased risk.

At this stage, further evidence needs to be presented that fluctuating blood pressure can be used in this way before guidelines on identifying cardiac risk would be updated. Patients should not stop taking their blood pressure medication, but should consult their GP if they have any queries regarding it.

Where did the story come from?

The story is based on a collection of papers published in The Lancet and The Lancet Neurology, both peer-reviewed medical journals. The papers were written by Professor Peter Rothwell from the Stroke Prevention Research Unit at the John Radcliffe Hospital, Oxford, and colleagues from institutions in England, Ireland and Sweden. Funding was provided by several institutions and organisations, including the UK Medical Research Council, the National Institute for Health Research and Pfizer.

What kind of research was this?

The collection of papers includes a cohort study, a separate systematic review and meta analysis, and a narrative review in The Lancet, and an article in The Lancet Neurology. All papers looked at the relationship between blood pressure and the risk of vascular disease such as stroke.

Professor Rothwell says that high blood pressure is the most prevalent treatable risk factor for vascular events such as stroke, but how blood pressure causes the damage that leads to such vascular events is poorly understood. Most clinical guidelines base their advised courses of action on the risks of vascular events according to a person’s stable (usual) blood pressure. The stable blood pressure reading would be calculated as the average of measurements taken at the doctor’s surgery over a number of visits.

In this review, the professor puts forward the theory that fluctuations in blood pressure, rather than maintained high blood pressure readings, may be a more accurate prediction of the risk of vascular events.

What did the research involve?

The review covered the following areas:

• Whether there is likely to be variability in blood pressure measurements between an individual’s visits to the doctors. If there is high variability, an average measurement may not give a complete picture of the patient’s blood pressure status throughout time, and risk statistics for stroke calculated using average values may be affected.
• If drugs used to treat hypertension (high blood pressure) and the risk of vascular events also have an effect of reducing fluctuations in blood pressure.
• Particular attention was paid to the risk of stroke and its relationship to blood pressure. The author looked at studies where patients had their blood pressure monitored for 24 hours, and that had assessed the risk of stroke.

Professor Rothwell provides some background to these issues and discusses them in some detail. He mentions one study showing that 69% of people who had previously experienced a stroke had episodic (every now and again) hypertension, whereas 12% had stable hypertension as consistently demonstrated over a 24-hour period.

He reviews several epidemiological studies looking at how estimated stable blood pressure can predict the risk of vascular events. The author discusses how fluctuations in blood pressure may play a role in this. He notes that some epidemiological evidence appears to support this, including the fact that there appears to be an increase in strokes mid-morning, which matches the daily pattern of blood pressure variation, and that other reasons for increases in transient blood pressure are also risk factors for stroke.

The author says that risk calculations of stroke are based on the usual blood pressure measurement based on the average of measurements taken on multiple visits to the doctor. He argues that as there can be large variations in readings between visits, any risk predictions based on average readings alone may not reflect the whole picture.

In his review, Professor Rothwell also looks at trials examining the effect of calcium channel blockers (for reducing blood pressure variability) compared with other blood pressure lowering drugs such as angiotensin-converting enzyme inhibitors or beta-blockers, which have differing modes of action. He notes that all the drugs lowered patients’ blood pressure to the same extent, but the calcium channel blockers lowered the risk of stroke compared with the other drugs.

The cohort study by Professor Rothwell and his colleagues reappraised data from previous cohort studies to assess whether variations in blood pressure were a better predictor of stroke outcome than an averaged measurement of blood pressure. The first part of this review assessed the risk of stroke in relation to visit-to-visit variability in blood pressure in people who had experienced a previous stroke. For this, they used data from the UK-TIA aspirin trial and three similar cohort studies. The second part of the review used data from the Anglo-Scandinavian Cardiac Outcomes Trial Blood Pressure Lowering Arm (which involved 24-hour blood pressure monitoring) to assess the effect of blood pressure variability in people treated for hypertension. The researchers found that visit-to-visit variation in blood pressure was a strong predictor of subsequent stroke, and this was independent of the average of all of the patients’ measurements. They also found that the maximum blood pressure measure recorded was also a strong predictor of stroke. They found that in studies where patients’ blood pressure was measured continually over 24 hours, the variation measured in this short period was also a weak predictor of stroke, and was most predictive in younger patients.

A separate systematic review and meta analysis of trials looked at the effects of different classes of blood pressure lowering drugs in preventing stroke. Those trials included took multiple measures of blood pressure at baseline and during follow-up, rather than just quoting a single average measure. The meta analysis found that, compared with other drugs - such as angiotensin-converting enzyme (ACE) inhibitors - there was 19% lower variation in participants’ blood pressure measurements when patients were taking calcium channel blockers and 13% less variation in patients receiving non-loop diuretic drugs.

How did the researchers interpret the results?

Professor Rothwell concludes that increased mean blood pressure is an important cause of arterial disease, but variability and instability in blood pressure also have important roles in the progression of organ damage and the likelihood of vascular events such as stroke. He suggests that variability in blood pressure measurements should be routinely reported in trials looking at the role of high blood pressure on stroke, and that more research is needed to quantify variability and instability of blood pressure in routine practice.

Conclusion

Professor Rothwell has presented a compelling argument in support of his theory that fluctuations in blood pressure may help to predict the risk of vascular events such as stroke.

As mentioned in an accompanying editorial, it is important to point out that Professor Rothwell is not questioning the validity of using average blood pressure to predict risk, but is advocating also using variable blood pressure as a supplementary indicator of increased risk.

As with all narrative reviews the research methods that the author used to identify evidence to support his theories are not definitively laid out. It is therefore not possible to carry out a full appraisal of this evidence. However, the systematic appraisal of data on blood pressure and stroke is a robust and standardised way of appraising all of the available data in a research area.

At this stage, further evidence needs to be presented that fluctuating blood pressure can be used in this way before guidelines on identifying cardiac risk would be updated. This research does not affect patients who are currently taking blood pressure lowering medications. Patients should not stop taking their blood pressure medication, but should consult their GP if they have any queries regarding it.

Currently NICE recommendations on the treatment of hypertension should be followed and drug therapy offered to those who:

• have persistent (measurement on >2 occasions) high blood pressure of 160/100 mmHg or more
• are at raised cardiovascular risk (10-year risk of cardiovascular disease (CVD) of 20% or more, or existing CVD or target organ damage) with persistent blood pressure of more than 140/90 mmHg

Links To The Headlines

Blood pressure fluctuations 'warning sign for stroke'. BBC News, March 12 2010

Swings in blood pressure 'could better predict stroke than high average readings'. The Daily Telegraph, March 12 2010

Blood pressure variations key indicator of stroke risk, research says. The Guardian, March 12 2010

Links To Science

Rothwell PM, Howard SC, Dolan E, et al. Prognostic significance of visit-to-visit variability, maximum systolic blood pressure, and episodic hypertension. The Lancet 2010, 375: 895 - 905

Webb AJS, Fischer U, Mehta Z, Rothwell PM. Effects of antihypertensive-drug class on interindividual variation in blood pressure and risk of stroke: a systematic review and meta-analysis. The Lancet 2010, 375: 906 - 915

Rothwell PM. Limitations of the usual blood-pressure hypothesis and importance of variability, instability, and episodic hypertension. The Lancet 2010; 375: 938 - 948

Carlberg B, Hjalmar Lindholm L. Stroke and blood-pressure variation: new permutations on an old theme. The Lancet Neurology 2010; 375l: 867 – 869

Rothwell PM, Howard SC, et al. Effects of ß blockers and calcium-channel blockers on within-individual variability in blood pressure and risk of stroke. The Lancet Neurology 2010

“Women who use the Pill can expect to live longer,” according to The Times. The news is based on research looking at the long-term effects of taking the contraceptive pill.

From 1968 to 2007 the study followed 46,000 women that had either used or never used oral contraceptives, comparing their mortality rates. The four decades of data showed that there was a small decrease in the mortality rates of women who had taken the Pill, as well as a small decrease in the overall risk of developing cancer.

This study has shown that the Pill is not associated with long-term health risks and also presents some associations between taking the Pill and decreased cancer risk. However, the study has some limitations in that it did not look at other lifestyle factors, such as diet and exercise, that can affect health. It also failed to adjust for some medical factors that may have a bearing on using the Pill and mortality risk.

This study followed women who had taken the earliest forms of the Pill. Its results are not directly applicable to modern forms of the Pill, which differ in hormone composition.

Where did the story come from?

Professor Philip Hannaford and colleagues from the University of Aberdeen carried out this research. The study was funded by the Royal College of General Practitioners, the Medical Research Council, the British Heart Foundation, the Cruden Foundatio, and several pharmaceutical companies including Schering Healthcare, Wyeth Ayerst International, Ortho Cilag and Searle. The study was published in the peer-reviewed British Medical Journal.

Many media outlets correctly highlighted that the women in this study had taken the Pill approximately 20 to 40 years ago and that the composition of contraceptive pills available then may differ from those used today. They also highlighted that the decreased relative mortality rates were quite small and that the important message from this research was that there was not a long-term increase in death rates following the use of contraceptive pills.

The Times quoted from the study that younger women were at slightly higher risk of suffering heart attack, stroke or breast cancers while taking the Pill. This research study did not provide evidence for risk of these particular diseases, although its sub-analyses did reveal there to be a greater risk of overall mortality in Pill users recruited to the study at a young age (below 30). The reasons for these differences are unclear and need to be investigated further.

What kind of research was this?

This was a cohort study that looked at whether taking the contraceptive pill had any effect on mortality risk.

The Royal College of General Practitioners Oral Contraception Study is a continuing investigation into the health effects of contraceptive pills. The study has been following women who have used the Pill since 1968. In its early days, the Pill was reported to be associated with increased risks of mortality; however, the researchers note that further studies suggest that oral-contraceptive use is associated with a reduced overall risk of cancer. This study aimed to assess the risks over a period of several decades, and to see how these risks altered if women stopped taking the Pill.

What did the research involve?

In 1968 approximately 23,000 women who were using the oral contraceptive pill were recruited through 1,400 GP surgeries. These women were termed the “ever users”. The researchers recruited a similar number of women who had never taken the Pill, classed as the “never users”. All of the women were married or living as married. Most were white and their average age at recruitment was 29.

At this time, information about whether they had children, whether they smoked, their medical history and their social class (based on their husband’s occupation) were recorded. Every six months the women’s GPs supplied information about any prescriptions for the Pill, any pregnancies and any illnesses or deaths that had occurred.

The women were monitored until one of the following occurred:

• They left the area of the recruiting doctor.
• Their doctor left the study.
• They obtained the Pill from a source other than their GP.
• Follow-up by GP practices ended, which eventually happened in 1996.

Medical records were also flagged so that data on cancer or death would be gathered on women who dropped out of the study and after GP follow-up had ended. These flagged records were examined up until 2007.

The researchers analysed two different datasets. The first contained all of the information up until 1996 (when the GP follow-up ended), while the second also included data from the flagged records followed until 2007.

In total, 46,112 women were followed up. As women were followed for different lengths of time, the researchers analysed the data in terms of a measure called “women years”: the number of women in a group multiplied by the number of years that they each participated in the study. The full study up to 2007 contained more than 819,000 women years for women who had ever used the Pill, and 378,000 women years for women who had never taken the Pill. The GP follow-up only study had 343,000 women years for “ever” users, and 237,000 for “never” users.

What were the basic results?

In the full study up to 2007, the risk of death due to any cause was lower in the women who had ever taken the Pill compared with women who had never used it. The relative risks were adjusted to account for the influence of age, smoking, social class and whether the women had had children.

The researchers found a 15% lowered risk of any cancer in ever users than in never users (Relative Risk 0.85, 95% Confidence Interval 0.78 to 0.93). Ever users also had a decreased risk of cancers of the large bowel and rectum, uterus and ovaries. Ever users were also found to have a higher rate of accidental violent death (Relative Risk 1.49 95% Confidence Interval 1.09 to 2.05).

Age seemed to play a large role in the risk of death due to any cause. In women who were under 30 at the time of recruitment, the relative risk of death was three times greater in ever users compared with never users. However, if the women were over 50 at the time of recruitment, the rate of death was lower in ever compared to never users.

Analysis of the smaller dataset of GP follow-up data showed no difference between never or ever users of the Pill in terms of overall mortality or cancer.

The average length of time that women took the Pill in this study was 44 months. The length of time taking the Pill did not affect the risk of death.

How did the researchers interpret the results?

The researchers concluded that “oral contraception was not associated with an increased long-term risk of death in this large UK cohort; indeed, a net benefit was apparent. The balance of risks and benefits, however, may vary globally, depending on patterns of oral-contraception usage and background risk of disease”.

Conclusion

This study followed a large number of women who had taken the contraceptive pill over 39 years. It showed that there was a small decrease in mortality rates for women who had ever used the Pill compared to those who had never used it.

However, there are several things to consider when interpreting these results, many of which the researchers highlight:

• Medical diseases and risk factors may have differed between the two groups of women but were not adjusted for in the analyses.
• A lack of adjustment for medical history may have influenced the results as the oral contraceptive pill is not suitable for all women as a number of medical factors make taking the Pill undesirable or unsafe, including a history of vascular disease (e.g. deep vein thrombosis, DVT), past strokes or mini-strokes, heart disease and liver disease. Other women with risk factors for these diseases may only be cautiously considered for the Pill. On this basis, medical reasons may potentially have confounded any increase in mortality in the “never used” group.
• Equally, “ever use” of the Pill in this cohort was associated with an overall decreased risk of death from any circulatory diseases. However, it is unclear whether differences in cardiovascular diseases or disease risk were already present at the time decisions were being made to prescribe the Pill.

There are a number of other points to consider when interpreting this research:

• Although the analysis adjusted for whether the women smoked, the smoking data was not routinely updated throughout the study. Using only the information about smoking collected at the start of the study may have underestimated the effects of smoking.
• Other lifestyle factors such as diet and exercise were not measured. This may have affected the outcome of the study.
• There are many different formulations available, but the study did not assess whether the risk of death differed according to hormonal content of the contraceptive pill used. In the early 1970s there were few oral contraceptive pills available compared to the numerous brands there are today. The hormone content of the early contraceptive pills is likely to differ from those taken today, principally in that the oestrogen concentration in today’s tablets is often lower, and today’s combined pills contains the hormones oestrogen and progestegen rather than oestrogen alone.
• The women in the cohort were all married and mostly white, so these results may not be applicable to other ethnicities and society as a whole.
• The researchers’ subanalyses did reveal there to be a greater risk of overall mortality in pill-users recruited to the study at a young age (below 30). The reasons for these apparent differences in risk according to age need to be further investigated.
• Although the overall risk of cancer was less in ever users, the specific cancers that did demonstrate an association with Pill use had relatively small case numbers (e.g. 19 cases of uterine cancer in the Pill group compared to 13 in the never used group). There is a high possibility that calculated differences between such small numbers have occurred by chance. Further research is needed to see whether there is a direct causal link between hormone treatments such as the Pill and cancer risk and the mechanism behind it.
• As the authors say, there has been a substantial loss of subjects during follow-up, and their full dataset represents only two-thirds of their potential cohort.

Overall, this study demonstrates that use of the contraceptive pill is not associated with increased long-term mortality rates, as early research may have suggested. 

Links To The Headlines

Women on pill 'may live longer'. BBC News, March 11 2010

Girls who take pill live longer. The Mirror, March 11 2010

Is the Pill saving lives? Women who use it 'cut their chances of dying of cancer and heart disease'. Daily Mail, March 11 2010

The pill is given health all-clear. The Independent, March 11 2010

Women who use the Pill can expect to live longer, Royal College of GPs finds. The Times, March 11 2010

Taking the pill can prolong women's lives. Metro, March 11 2010

The pill cuts risk of serious illness. Daily Express, March 11 2010

Taking the Pill 'could help women live longer'. The Daily Telegraph, March 11 2010

Links To Science

Hannaford PC, Iversen L, Macfarlane TV, et al. Mortality among contraceptive pill users: cohort evidence from Royal College of General Practitioners’ Oral Contraception Study. BMJ 2010; 340: c927

“Having a massage is no better at beating stress than home relaxation techniques like breathing deeply and listening to soothing music,” reports The Daily Telegraph. It said that while all methods can ease anxiety, simple relaxation at home costs nothing and can be just as effect an expensive massage or thermotherapy (using a heat-based treatment) session.

This news is based on a trial on the effectiveness of therapeutic massage in treating generalised anxiety disorder (GAD), compared to thermotherapy or relaxation room therapy. After 12 weeks, anxiety scores improved in all three groups.

But this was a very small trial with limitations. So it is likely that the findings are due to chance only. There is no suggestion that these treatments are alternatives to medical drugs or psychotherapies. Nor can it be inferred that similar results would be seen in people without GAD or that the treatments would get similar scores on other scales of mental wellbeing.

Overall, the findings of this small trial indicate that any of these three therapies may help people with GAD, but not in place of prescribed drug treatments or psychotherapies.

Where did the story come from?

The research was carried out by Dr Karen J. Sherman and colleagues from the University of Washington. The study was funded by the National Center for Complementary and Alternative Medicine. The paper was published in the (peer-reviewed) medical journal Depression and Anxiety.

Generally, the newspaper accurately reflected the findings of the study, but it did not discuss its limitations, including the fact that the results are only directly applicable to people with diagnosed generalised anxiety disorder.

What kind of research was this?

This randomised controlled trial investigated the effectiveness of therapeutic massage for treating generalised anxiety disorder (GAD) and compared it to other forms of relaxation.

This kind of trial is the best way of assessing the efficacy of a treatment. There needs to be adequate numbers of people in each of the treatment arms to detect differences between the groups, and the trial should preferably follow people for an adequate amount of time to determine the short and longer-term effects of treatment.

What did the research involve?

This was a three arm, randomised trial conducted at Group Health, an integrated healthcare system with about 600,000 members from the Washington and Idaho states in the US. From these members, the researchers identified people who met recognised diagnostic criteria for GAD. Participants were identified through telephone canvassing, electronic records, mailed questionnaires and face-to-face interviews.

The researchers excluded anyone with other mental health disorders or medical disorders that may have affected their participation in the trial. This left 68 people who met recognised diagnostic criteria for GAD. Some participants were taking antidepressant or anti-anxiety medications, and some were seeing mental health professionals.

Participants were randomised to therapeutic massage (23 people), thermotherapy (22), or relaxing room therapy (23) for 10 one-hour sessions over 12 weeks. All treatments were performed by licensed therapists in a softly lit room with nature sounds or relaxing music being played at a low volume. Therapeutic massage involved ‘releases’ of specific body regions or muscle groups, Swedish massage techniques and deep breathing instruction. Thermotherapy involved the use of customised warm and cool contrast treatments, while the control group simply relaxed comfortably in the same relaxation room and had no therapist interaction.

The main outcome was a reduction in anxiety on a recognised clinical scale (Hamilton Anxiety Rating Scale, HARS), measured immediately after treatment and six weeks later.

What were the basic results?

Follow-up rates were 94% at six weeks and 85% at 12 weeks, with similar numbers of people across groups. All groups had improved anxiety scores at the end of treatment (an average 10-13 point improvement on HARS), and these improvements were maintained at six weeks. All three groups had the same success rate in reducing anxiety. There were also improvements on the secondary outcome of symptom reduction.

How did the researchers interpret the results?

The researchers conclude that massage was not superior to thermotherapy or relaxation room therapy, and all gave clinically important improvements for people with generalized anxiety disorder. They say that as simple relaxation room therapy is substantially less expensive than the other treatments, a similar treatment package may be the most cost-effective option for people with GAD who wish to try relaxation-orientated therapy.

Conclusion

This trial carefully recruited people with diagnosed GAD with the aim of comparing three different relaxation techniques over a period of 12 weeks. However, it has a number of important limitations:

• There were relatively few participants in each of the three groups. With such small numbers, there is a stronger chance that the findings are due to chance only.
• Participants could not be blinded to the fact that they were receiving relaxation treatment. Simply by receiving some form of relaxation therapy over 12 weeks may have helped people to feel less anxious. As the researchers admit, a ‘no treatment’ group who received no form of therapy of at all would have addressed some of this uncertainty.
• This was a specific group of people with diagnosed GAD, a considerable number of whom were taking medications for their anxiety. The effect of the treatments were measured using a clinical score for rating anxiety. As such, it cannot be inferred that similar results would be seen in people without GAD or that the treatments would get similar scores on other scales of mental wellbeing.
• Massage and thermotherapy were both carried out by qualified professionals. The effects of the techniques used here may not be directly transferable to other forms of these therapies. Additionally, the control of simple relaxation was performed in a controlled environment in the therapy centre, which may give slightly different results compared to the person trying to relax at home. The participant is entering an environment geared towards their comfort and relaxation, free of the many distractions of home.
• This finding does not suggest that these therapies are an alternative to formal treatments such as medication or psychotherapies.

As the researchers conclude, the findings of this small trial indicate that these three therapies may help people with GAD, but would not replace prescribed drug treatment or psychotherapies. Further research needs to establish whether the relaxation therapies are as effective as each other.

Links To The Headlines

Massage no better at beating stress than deep breathing and soft music. The Daily Telegraph, March 11 2010

Links To Science

Sherman KJ, Ludman EJ, Cook AJ, et al. Effectiveness of therapeutic massage for generalized anxiety disorder: a randomized controlled trial. Depression and anxiety 2010

A new drug “cuts heart attack and stroke risk without side effects”, according to the Daily Mail. The newspaper says that the eprotirome tablets could rapidly lower cholesterol in people that do not respond to conventional statin drugs.

This is an important and well-conducted trial that gave participants either eprotirome or a placebo alongside their prescribed statin drugs. After 12 weeks of treatment with eprotirome, which is designed to mimic a thyroid hormone, there was a significant reduction in LDL cholesterol. Greater reductions were seen with increasing doses of eprotirome.

While the trial produced good results, newspapers have been premature in predicting the action of the eprotirome - all people in the study still took their prescribed statins so it is unclear how the drug works in isolation. The trial was also limited by size and duration, with only 189 participants and just 12 weeks of treatment.

Overall, the findings of this early trial are promising, but further testing will be needed to establish the drug’s actions in isolation, long-term safety and to see whether it actually cuts heart attack and stroke risk, as newspapers have claimed.

Where did the story come from?

This research was conducted by Dr Paul Ladenson and colleagues from Johns Hopkins University School of Medicine, Baltimore, and other institutions in the US and Sweden. The study was funded by grants from the Swedish Research Council, the Swedish Heart-Lung Foundation, Karolinska Institutet and Stockholm City Council. The study was published in the peer-reviewed The New England Journal of Medicine.

The news reports in the Daily Mail and Daily Express are premature in hailing a ‘new statin’ that cuts cholesterol and disease risk without side effects. All study participants were also taking prescribed courses of statins, but the newspapers have not considered the key fact that this trial has only looked at this drug as an addition to conventional statin treatment, and not as a replacement for it.

There is also a need for longer-term follow-up trials in much larger numbers of people before any firm conclusions can be made on the drug’s safety and efficacy. In particular, no conclusions can be made from this trial about the effect eprotirome has on cardiovascular health or disease risk, as the trial only looked at immediate changes in cholesterol levels.

What kind of research was this?

This was a double-blind randomised controlled trial investigating the cholesterol-lowering effects of a new compound called eprotirome. The drug acts in a similar way to a thyroid hormone, which has been demonstrated to lower levels of low density lipoprotein (LDL), often referred to as ‘bad’ cholesterol. In this trial, people who were already taking a statin were randomised to take either eprotirome or a placebo alongside their existing statin treatment.

Randomised controlled trials are the best way of investigating the safety and efficacy of a new treatment. With this particular ‘thyroid-mimicking’ drug, there is a particular need to ensure that the treatment does not cause adverse effects similar to what would be seen in a person with thyroid disease (either underactive or overactive). Given this potential risk, the safety findings of this small trial would need to be replicated in larger numbers of people using the treatment for a longer duration than 12 weeks.

Importantly, all the people in the trial were already receiving statins and the eprotirome or placebo was added to see whether there was any incremental effect of the new drug. The fact that nobody used eprotirome alone means that at this stage no comparison can be made between eprotirome alone and existing statins with regard to cholesterol-lowering effects, adverse effects, or effects upon risk of cardiovascular disease.

What did the research involve?

People were enrolled in this trial between November 2007 and January 2008. All subjects had to have been stable on statin treatment (atorvastatin or simvastatin) for at least three months, but still have elevated cholesterol (=116mg per decilitre, equivalent to =3.0mmol per litre). The researchers excluded those who had a history of thyroid disease, heart failure, recent heart attack or cardiac surgery, stroke, liver disease, uncontrolled diabetes, severe high blood pressure or drug or alcohol misuse problems.

Those that were eligible and agreed to participate (189 people) then received a four-week dietary education programme before being randomised to receive either eprotirome or placebo for 12 weeks in addition to their prescribed statin. Three different doses of eprotirome were used: 25, 50 or 100 micrograms.

After the 12 weeks the participants discontinued the trial drugs but continued their statin use. They were then reassessed four weeks later, with the main outcome being change in LDL cholesterol from the start of the trial to week 12. Safety assessments documented details of heart rate, blood pressure, body weight, electrocardiogram readings, blood tests (specifically effects on thyroid function) and any adverse effects.

What were the basic results?

Of the 189 participants randomised into the study, 168 (89%) completed the trial, 184 (97.4%) were included in the efficacy analyses and all 189 were included in the safety analysis.

The average LDL cholesterol level was 141mg per decilitre at study start. Supplementing prescribed statin treatment with trial treatments reduced levels to:

• 127mg per decilitre with placebo (7% reduction)
• 113mg per decilitre with the 25 microgram dose eprotirome (22% reduction)
• 99mg per decilitre with the 50 microgram dose eprotirome (28% reduction)
• 94mg per decilitre with the 100 microgram dose eprotirome (32% reduction)

The proportions of patients who had an LDL cholesterol level of less than 100mg per decilitre (<2.6mmol per litre) at week 12 were:

• 6% of the group who received placebo
• 36% of those who received 25 microgram eprotirome
• 50% of those who received 50 microgram eprotirome
• 57% of those who received 100 microgram eprotirome

The improvement in LDL cholesterol levels was significantly greater in the eprotirome groups than in the placebo group. Other blood cholesterol and fat levels were also reduced with eprotirome compared with placebo. The four groups showed similar rates of adverse effects, with most effects being of mild or moderate severity.

While eprotirome had no effect upon one of the thyroid hormones measured (triiodothyronine), levels of the other (thyroxine) decreased. However, levels of both hormones remained within the normal range and there were no symptoms of thyroid disease. These effects were reversed on discontinuation of the drug.

How did the researchers interpret the results?

The researchers concluded that 12 weeks of treatment with the thyroid hormone eprotirome, in addition to continued statin treatment, decreased blood cholesterol levels.

Conclusion

This is an important and well-conducted trial, which has demonstrated the potential of a drug, eprotirome, to lower cholesterol levels. However, conclusions about the effects of this drug should not be made too prematurely and much further research is needed:

• So far, use of the drug alone has not been compared to statin treatment. In this trial eprotirome or inactive placebo was only ever given in addition to people’s long-term statins. Therefore no comparison of cholesterol-lowering effect of each of the treatments alone can be made.
• Only a small number of people were included in the trial: 47 on the 25microgram dose, 46 on 50micrograms, and 44 on the 100microgram dose of eprotirome. These groups of participants are too small to draw any conclusions on the safety or efficacy of eprotirome. The trial will need replication in much larger groups of participants, particularly when trying to determine the dose of eprotirome that provides the optimal balance between benefits and risks.
• With both the short, 12-week duration of this trial and the small number of participants, it is not possible to draw firm conclusions about the safety of eprotirome and it is too early to say that this drug is ‘without side effects’ as headlined by the Daily Mail. In particular, the longer-term effects of this drug upon the body’s thyroid function and liver enzymes need to be assessed.
• As this was only a 12-week trial, it is not possible to tell the longer-term effects that eprotirome could have upon cardiovascular health and mortality risk. Therefore, newspaper claims that eprotirome ‘cuts heart attack and stroke risk’ are currently unfounded.

The findings of this early trial into the use of eprotirome to lower cholesterol in addition to statins are promising, and further research is awaited.

Links To The Headlines

New 'statin' which cuts heart attack and stroke risk without side effects developed by scientists. Daily Mail, March 11 2010

New drug to help beat menace of cholesterol. Daily Express, March 11 2010

Links To Science

Ladenson PW, Kristensen JD, Chester Ridgway E. Use of the Thyroid Hormone Analogue Eprotirome in Statin-Treated Dyslipidemia. The New England Journal of Medicine, volume 362:906-916, March 11 2010 Number 10

“If you want good sex, you better get down the gym and tuck into your fruit and veg,” says the Daily Mirror. The newspaper reports that a “big-bang theory” has found a link between sexual activity and general health.

The news is based on two US surveys that looked at more than 6,000 people aged 25 to 85. It found that a satisfactory sex life is positively associated with health in middle age and later life. It also noted that between the ages of 75 to 85, 39% of men were sexually active compared to just 17% of women.

The study has also introduced the idea of a new health measure, called "sexually active life expectancy", which can denote the average remaining years of sexually active life. The research showed that men aged 55 could expect another 15 years of sexual activity, but despite their longer life spans, women the same age could expect fewer than 11 years.

While the accuracy of self-reported sexual activity is often questioned in this type of sexuality research, it seems likely that the sexually active life expectancies estimated in this study are accurate.

Where did the story come from?

The research was conducted by Professor Stacy Tessler Lindau and Natalia Gavrilova from the University of Chicago in the US. The study was funded by the Center on Demography and Economics of Aging in Chicago and a grant from the US National Institutes of Health/National Institute on Aging. The study was published in the peer-reviewed British Medical Journal.

Other newspapers, including The Times, report this study. The coverage is accurate, commenting on other issues for older people, including use of drugs such as Viagra, sexual problems and the use of condoms.

What kind of research was this?

This research set out to examine the links between health and sexuality in a cross-sectional analysis. The researchers also wanted to estimate the number of sexually active years that middle-aged and older adults had remaining, and how this varied in groups people of different gender and health status.

The research provides a snapshot of sexual activity in the US through data from two surveys conducted in 1995-96 and 2005-06. These surveys asked members of the public about their sexual activity, quality of sexual life and interest in sex. They calculated a new measure for various ages: the average remaining years of sexually active life, referred to as “sexually active life expectancy”.

This was observational research that relied on self-reported health measures and responses to personal questions asked by questionnaire. Rates of non-response to questions on sexuality was higher among women and older people, although 84% of all respondents returned the questionnaires. The accuracy of responses is a problem for sexuality research, but good response rates and study design suggest that inaccuracy is unlikely to account for the large differences seen in the elderly groups.

What did the research involve?

The researchers had data from two large, nationally representative, population surveys: the National Survey of Midlife Development in the US (MIDUS, or midlife cohort) and the National Social Life, Health and Aging Project (NSHAP). The two surveys asked similar questions on sexuality and had sufficient numbers of older people to allow for assessments of sexuality in age groups of up to 85 years old.

In the 1995-96 MIDUS survey, telephone numbers were used to randomly select adults aged 25 to 74 from the English-speaking population of 48 US states. The participants completed both a telephone interview and a postal questionnaire. The response rate was 60.8%, with 3,032 respondents (1,561 women, 1,471 men) providing responses to both parts of the survey.

For the 2005-06 NSHAP survey, the process was slightly different. In this survey, the age range followed was marginally older (57 to 85) and the sample was generated from households previously screened in 2004. In order to closely analyse certain populations the researchers recruited disproportionately large numbers of people from some ethnicities minorities (such as African-Americans, Latinos) and from other subgroups including males and very old people. Participant interviews were conducted at home by professional English and Spanish-speaking interviewers. For this survey there were 3,005 respondents, equating to a response rate of 75.5%.

The two studies featured several similar questions and recorded comparable datasets on factors such as age, partnership/relationship status (married, co-habiting, single with partner or without), sexual activity (defined as sexual activity within six months in one survey and within 12 months in the other) and frequency of sex. Quality of sex and interest in sex was rated on a scale from 1 to 10 for the MIDUS study.

The researchers used standard mathematical modelling techniques to report the likelihood of being sexually active, having a good quality sex life and being interested in sex among those of a particular age or health status when compared with those in a baseline category.

They calculated sexually active life expectancy using publicly available data on life expectancy for various ages and matched these to the people in the same age groups in their study. They also adjusted for the fact that a substantial proportion of the older population live in institutions.

What were the basic results?

Men were more likely than women to be sexually active, report a good quality sex life, and be interested in sex. Among the 75 to 85-year-olds, 38.9% of men and 16.8% of women were sexually active.

Men and women reporting very good or excellent health were about twice as likely to be sexually active compared with similarly aged people in poor or fair health. When broken down by gender and study:

• Men with good/excellent health were around 2.2 times more likely than less healthy men to be sexually active in the MIDUS mid-life study.
• Women with good/excellent health were around 1.6 times more likely than less healthy women to be sexually active in the MIDUS mid-life study.
• Men with good/excellent health were around 4.6 times more likely than less healthy men to be sexually active in the NSHAP older-life study.
• Women with good/excellent health were around 2.8 times more likely than less healthy women to be sexually active in the NSHAP older-life study.

At the age of 30, sexually active life expectancy (active years remaining) was 34.7 years for men and 30.7 years for women, compared with about 15 years for men and 10.6 years for women at age 55. This difference in sexually active life expectancy was smaller for people with a spouse or other intimate partner.

How did the researchers interpret the results?

Researchers say that sexual partnership, frequency of sexual activity, a good quality sex life, and interest in sex are positively associated with health among middle-aged and older adults in the US. Since 2000 they say, interest in sex among middle-aged and older men in the US has increased.

The researchers say that men lose more years of sexually active life as a result of poor health than women. They claim that the estimation of ‘sexually active life expectancy’ is a new life expectancy tool that can be used in the arena of sexual health planning and treatment.

Conclusion

This observational cross-sectional study has provided a detailed and interesting body of new information on the sexual life of different age groups in America. It has the following strengths:

• The data was collected by large population surveys using broadly similar measures of sexuality. The size of the sample increases confidence in the results.
• The numbers of people in the groups for partnership, sexual activity, sexual frequency and good quality sex life were similar in both surveys and similar rates of activity have been reported in other international reports, suggesting that the sampling was representative.
• There was a low non-response rate to items in both surveys, although older respondents and women were more likely than others to refuse to answer questions on sexuality. It is not clear how these refusals would affect the results.

The authors note that as this data was not collected over time, it is not possible to say if regular good health facilitates a good sex life or if the opposite may be true, that being sexually active contributes to good health. The researchers also say that because of the study population, their findings may not be relevant to non-Western cultures or for people who are lesbian, gay or who do not identify as heterosexual.

Overall, despite the fact that self-reported sexual activity might be inaccurately reported, it seems likely that the large differences in sexually active life expectancy shown between the sexes in this study are genuine.

Links To The Headlines

Experts' big bang theory on keep-fit. Daily Mirror, March 10 2010

Healthy people can enjoy sex into their 60s, say Chicago studies. The Times, March 10 2010

Links To Science

Tessler Lindau S and Gavrilova N. Sex, health, and years of sexually active life gained due to good health: evidence from two US population based cross sectional surveys of ageing. British Medical Journal 2010;340:c810

The discovery of a “virus that 'kills off' prostate cancer cells” has been described in the Daily Mail. It reported that scientists injected six prostate cancer patients with a ‘tame’ virus and found it killed cancer cells while sparing healthy tissue.

The research article reports both pre-clinical studies on cancer cells and mice in the laboratory as well as an early clinical trial in six patients with advanced prostate cancer. The virus was injected into their cancers three weeks before their prostates were due to be removed. The infected cancer cells showed evidence of cell death and there were signs of an immune system response and cell changes, suggesting that the virus could be an effective cancer treatment.

This is an early report of a new type of treatment for prostate cancer. Based on these results, the researchers hope to go on to the first stage of full trials of the viral treatment in more people with advanced prostate cancer. These trials will go some way to indicating how useful this treatment might be, compared with existing treatments for prostate cancer.

Where did the story come from?

The research was carried out by Dr Chandini M. Thirukkumaran and colleagues from the University of Calgary and other institutions in Canada. The study was supported by grants from the Prostate Cancer Research Foundation of Canada, the National Cancer Institute of Canada, the Canadian Cancer Society and Oncolytics Biotech, Inc. (the Canadian company developing the treatment). The paper was published in the peer-reviewed medical journal Cancer Research.

The Daily Mail correctly highlights that these are early days for the treatment and that “much larger trials are needed to make sure it works, and even then it would take a decade for the treatment to be widely available”.

What kind of research was this?

The journal article reports on several studies in cells, animals and humans that all focussed on a new viral treatment for cancer. The treatment is based on a ‘reovirus’ (short for respiratory, enteric, orphan virus). This virus is common and usually causes very minor flu symptoms, and often no symptoms at all, in humans. The virus appears to kill cancerous cells over healthy cells. It has already been shown to have potential for treating other cancers such as bowel, colon, ovarian, breast, and bladder cancer.

What did the research involve?

The aim of this research was to provide the necessary preclinical data for a full phase I clinical trial of a treatment utilising the virus in men with advanced prostate cancer.

The researchers report on three studies, each at a different stage of the process towards developing a treatment. In the first study, normal human prostate cells and prostate cancer cells grown in the laboratory were exposed to either dead or live reovirus, to see what effect it had. The researchers also tested how much virus the infected cells were producing up to 72 hours after infection. The second study involved injecting human prostate cancer cells into the hind legs of mice. The researchers then measured the growth of any tumours that developed and took various cellular measures of cancer behaviour, both with and without the injection of the virus.

For the clinical parts of the study, six patients were recruited from local prostate cancer referral clinics in Calgary, Canada. All six had advanced cancer confined to the prostate gland, which means that the study was not testing the treatment for prostate cancer that had spread beyond the prostate gland. The patients had been given a biopsy confirming prostate cancer, and were booked for surgery called radical prostatectomy, in which the whole of their prostate would be removed. They were otherwise healthy and not taking any drugs to suppress their immune system.

Patients were then treated with the reovirus by injection. The methods were said to have been developed in a previous phase I study. Guided by an ultrasound probe, 1 mL of the virus solution was injected directly into an identified cancerous region and a metal marker left at the injection site so that the cells nearest to the injection could later be identified for analysis after the prostatectomy.

Patients were then tested weekly for three weeks for signs of toxicity and evidence of viral shedding (or spread) in the urine, faeces and blood, and monitoring of prostate-specific antigen levels (a marker of cancer activity) before their prostatectomy. The prostatectomy went ahead as planned, and the entire prostate was removed.

After the planned surgical removal of the prostate gland, the tissue was examined for signs of inflammation and cell death.

What were the basic results?

In the preclinical part of the study, the researchers found that the live reovirus was able to infect human prostate cancer cells and kill them. Human prostate cancer tumours grown in mice shrank when injected with the virus.

In the clinical part, the researchers found that the treatment was well tolerated, except for a mild flu–like illness seen in four of the six patients. Patients recovered from these symptoms within 24 hours without needing treatment.

Cancer activity, as indicated by prostate-specific antigen values, did not change greatly over the course of the study. Three patients showed signs of the virus in their urine at week one, but had negative blood tests for the virus.

There was a rise in antibodies to the virus within one week of the injection, suggesting that there had been an immune response to the new virus and that this may have limited the viruses spread to other areas of cancer in the gland.

Analysis of the prostate tissue also suggested that the reovirus did not infect healthy noncancerous tissue, possibly also inhibiting its spread to other cancerous areas. There were signs that cells near to the injection site were dying, and that immune system cells were infiltrating the area.

How did the researchers interpret the results?

The researchers say that this is the first study to provide evidence of an effect of the new reovirus
treatment for prostate cancer in both preclinical and clinical settings.

They suggest the potential value of their finding is that patients may be able to avoid some of the problems of current treatments for localised prostate carcinoma, such as erectile dysfunction,
bowel and bladder problems.

In addition, they say, “Those patients in which radical radiotherapy or radical prostatectomy are contraindicated may well be candidates for reovirus therapy.”

Conclusion

This is early research on a new treatment for prostate cancer. It is worth noting that:

• The virus has already been tested, and shown some success, in treatment for other cancers. This means that the route to clinical use may be shorter for this treatment indication but it will not get around the fact that many more patients will need to be tested in rigorous trials to see if the treatment is better than current alternatives.
• The treatment seemed to have very few side effects, which is a positive sign for a cancer treatment.
• The researchers acknowledge that it is unfortunate that the reovirus did not seem to infect non-cancerous tissue after the injection as this means that it is unlikely that the virus could spread to other areas of the prostate cancer and kill these, in the same patient.

Overall, this report shows another type of cancer that may respond to the reovirus treatment. More studies in many more patients will be needed to decide if the new treatment has a place and where that place might be among existing treatments for prostate cancer.

Links To The Headlines

Virus that 'kills off' prostate cancer cells: Volunteer patients injected with 'tame' bug. Daily Mail, March 10 2010

Links To Science

Thirukkumaran CM, Nodwell MJ, Hirasawa L. Oncolytic Viral Therapy for Prostate Cancer: Efficacy of Reovirus as a Biological Therapeutic. Cancer Research 2010; Published online first March 9 2010

“A technique that ‘washes out’ the brains of severely ill premature babies may aid survival,” says the BBC. The article says that the treatment, called DRIFT (drainage, irrigation and fibrinolytic therapy), could help around 100 babies per year.

The research behind the news looked at whether DRIFT could reduce the risk of death and disability in premature infants that had a type of bleeding that enlarged the fluid-filled spaces in the centre of the brain. This condition is very serious and can lead to death or severe disabilities such as cerebral palsy. Although DRIFT was associated with more secondary bleeding than standard care, subsequent follow-up showed that DRIFT reduced the proportion of infants that died or had severe disabilities by the age of two. The researchers suggest that modifications to the DRIFT process used in the trial could reduce the risk of second bleeds.

Overall, this study suggests that the DRIFT technique could help premature babies with this very serious condition. Further studies should look at whether modifications to the technique can, as claimed, reduce the risk of second bleeds while maintaining the benefits seen in this study.

Where did the story come from?

Dr Andrew Whitelaw and colleagues from the University of Bristol, Frenchay Hospital in Bristol, and research centres in Poland carried out this research. The study was funded by the Cerebra charity and the James and Grace Anderson Trust. The study was published in the peer-reviewed journal Pediatrics.

The Daily Mail, Daily Express and BBC News have covered this study. The BBC provides the most detailed coverage of the study, and reports the findings accurately. The Mail and Express concentrate on the story of one boy who took part in the trial.

What kind of research was this?

This was a randomised controlled trial comparing DRIFT (drainage, irrigation and fibrinolytic therapy) with the standard care for premature infants with a dangerous condition called posthemorrhagic ventricular dilatation (PHVD).

PHVD is caused by bleeding into the fluid-filled spaces in the centre of the brain (ventricles) that causes them to expand, putting pressure on the brain. Bleeding occurs due to the fragile, immature blood capillaries in the premature baby’s brain being unable to withstand changes in blood flow and pressure in the brain following birth. Babies at the greatest risk of PHVD are those who are more severely premature (born at less than 32 weeks) or of very low birth weight.

Developing PHVD as a baby can lead to serious cognitive, motor, and sensory disability, for example the development of cerebral palsy. The DRIFT technique is designed to reduce the excess pressure and build-up of leaked blood in the ventricles soon after bleeding, and aims to reduce the chances of brain damage and death from PHVD. The technique involves draining excess fluid and replacing it with artificial cerebrospinal fluid containing antibiotics while maintaining a steady, normal pressure in the ventricles.

This was a randomised controlled trial, the best way of comparing the effects of two treatments. Randomly assigning individuals into groups (randomisation) is the best way to ensure that the groups are well balanced for factors that could affect results. However, when the numbers of individuals randomised is small, such as in this study, randomisation may not work that well. In these situations researchers should check key factors to make sure that they are balanced, a step that was performed in this study.

What did the research involve?

The researchers recruited 77 preterm infants with bleeding into their ventricles: 54 from Bristol, 20 from Katowice in Poland, two from Glasgow and one from Bergen in Norway. Eligible infants whose parents agreed to participate were randomly assigned to receive either DRIFT or standard care (39 in DRIFT group, 38 in standard care). The infants were then followed up for two years to determine if they survived and whether they had any cognitive, motor or sensory disabilities.

Infants were eligible if they were no more than 28 days old, had been diagnosed with bleeding into their ventricles with ultrasound and showed progressive enlargement of the ventricles in both hemispheres of the brain.

Standard care was to not offer any intervention unless the infant showed signs of having raised pressure within the brain (such as irritability, persistent vomiting or reduced consciousness), or if the infant showed excessive head enlargement (over 2mm expansion in a day). If infants showed these signs, they were given a lumbar puncture to release cerebrospinal fluid and reduce pressure in the brain. The process was repeated as needed.

Treatment with DRIFT involved inserting tubes (catheters) into the ventricles and injecting an anticlotting agent to prevent blockage of the catheters with blood clots. The catheters were used to drain bloody fluid from ventricles and replace it with artificial cerebrospinal fluid containing antibiotics, while maintaining a steady normal pressure in the ventricles. Treatment with DRIFT was administered until the fluid being drained became clear, indicating that all leaked blood had been removed. Treatment with DRIFT continued for an average (median) of three days. If enlargement of the ventricles and excessive head growth did not stop in infants who had received DRIFT, they also received lumbar puncture.

In clinical trials such as this, there is often an external safety monitoring group that looks at the ongoing results of the trial to determine if the treatments being administered are safe. If they judge that the treatments are not safe, they can stop the trial. The safety monitoring group stopped the DRIFT trial because there was an increase in secondary bleeding into the ventricles in the DRIFT group. While DRIFT treatment was discontinued, the children in the study were still followed up to see what their outcomes were.

The children were assessed at an average of 25 months after their expected delivery date. The researcher assessing them did not know whether they had received DRIFT or standard care. The assessment used a standard scale to assess cognitive ability and development. Severe sensory and motor disabilities were defined as:

• inability to walk
• inability to walk unaided
• inability to sit without support
• inability to control head without support
• inability to use hands to feed self
• blindness or only light perception
• hearing loss uncorrected by hearing aid
• inability to communicate by speech

The researchers then compared the overall rate of death or severe disability between the group that received DRIFT and the group that received standard care. They carried out unadjusted analyses, as well as analyses that took into account how child gender, birth weight and severity of bleeding may have affected the results.

What were the basic results?

The researchers found that the DRIFT group and standard care group were similar, except that:

• there were more boys in the DRIFT group than the standard care group (29% vs. 24%)
• the DRIFT group had slightly lower birth weight (1050g vs. 1130g)
• babies in the drift group were born slightly earlier (27 weeks vs. 28 weeks)
• the DRIFT group had a greater proportion with the most severe bleeds, which have a very high mortality and complication rate (grade IV bleeds: 20% vs. 18%)

The researchers were able to assess what happened to all 77 children enrolled in the trial.

• Three children in the DRIFT group and five children in the standard care group had died before the age of two.
• Eighteen of the DRIFT group and 22 children in the standard care group had severe disabilities (cognitive, motor or sensory) by the age of two.
• This equated to 51% of the DRIFT group and 71% of the standard care group either dying or becoming severely disabled by the age of two. This difference was statistically significant once gender, birth weight and severity of bleeding into their ventricles were taken into account (odds ratio 0.25, 95% confidence interval 0.08 to 0.82).

Survivors in the DRIFT group were less likely than those in the standard care group to have severe cognitive disabilities at the age of two (31% vs. 59%). There was a trend for lower rates of individual sensory/motor disabilities in the DRIFT group, but this difference did not reach statistical significance.

How did the researchers interpret the results?

The researchers concluded that, “despite an increase in secondary intraventricular bleeding, DRIFT reduced severe cognitive disability in survivors and overall death or severe disability”.

Conclusion

This small study suggests that, compared to standard care, DRIFT reduces the risk of the combined outcome of death or severe disability in premature infants with enlargement of the ventricles in the brain due to bleeding. There are a number of points to note:

• The study was relatively small, with 39 children in the DRIFT group and 38 in the standard care group. The trial was also stopped early due to safety concerns. The researchers note that these factors mean the results should therefore be interpreted cautiously.
• While larger studies are preferable, the severity of the condition, its relatively uncommon nature and the difficulties associated with carrying out trials in infants mean that larger studies may not be feasible.
• There were some differences between the groups at the start of the study, but the researchers took these into account in their analyses. However, there could be other unmeasured differences between the groups that could have affected the results.
• The researchers believe that the increase in secondary bleeds into the ventricles with DRIFT treatment was likely to be caused by the use of an anticlotting agent called tPA. They say that if DRIFT is used in future that they would not recommend using this anticlotting agent routinely, but would only use it if there was a need to clear a clot blocking the drainage tubes.

Links To The Headlines

Brain 'wash out' may help premature babies. BBC News, March 7 2010

'Brain washing' technique cuts risk of premature babies suffering severe disabilities. Daily Mail, March 7 2010

Miracle of ‘brainwash’ boy. Daily Express, March 8 2010

Links To Science

Whitelaw A, Jary S, Kmita G et al. Randomized Trial of Drainage, Irrigation and Fibrinolytic Therapy for Premature Infants with Posthemorrhagic Ventricular Filatation: Developmental Outcome at 2 years. Pediatrics; published online March 8 2010

“What women eat while they are in the early stages of pregnancy influences the sex and health of their unborn baby,” The Daily Telegraph reported. It said that eating breakfast and a high-fat diet around the time of conception made it more likely the offspring would be a boy.

The newspaper article is actually reporting two different studies. The findings about the effect of a high-fat diet and breakfast on a child’s gender are from a study in humans that the newspaper says was published two years ago.

The new study that has prompted this report was in mice, and it did not aim to look at whether a high fat diet during pregnancy affects the sex of offspring. The researchers’ main aim was actually to investigate whether the amount of fat in the diet of pregnant female mice affected gene activity in the placenta, and whether this varied depending on the gender of the foetus. Such research could potentially help to explain how maternal diet in pregnancy has an effect on offspring health.

There are many differences between mice and humans and these findings may not be representative of what happens in people. Further study in humans would be needed to establish if this were the case. Pregnant women should aim to have a healthy balanced diet to maintain good health in themselves and their offspring.

Where did the story come from?

Dr Jiude Mao and colleagues from the University of Missouri and GenUs BioSystems, Inc carried out this research. The study was funded by the National Institutes of Health. The study was published in the peer-reviewed medical journal Proceedings of the National Academy of Sciences of the USA.

The Daily Telegraph reported this study. The article presents the study’s findings and does say that the current research is in mice. It also refers to a previous study looking at the effect of diet on baby gender in humans, but this study is not assessed here. The reporting of the findings of this previous study, which had different aims to the current research, could lead to confusion about what the new research has found.

What kind of research was this?

This research in pregnant female mice examined how maternal diet affected the activity of genes in the cells of the placenta that was supporting each male or female foetus. The researchers say that diet during pregnancy affects the future health of offspring, and that the effects differ for foetuses of different genders. Therefore, they wanted to look at whether they could find differences in gene expression in the placenta that could potentially account for these effects.

Studies such as this are useful in that they help scientists to understand how certain environmental conditions might affect health. However, differences between the species may mean that results obtained in mice may not be representative of what happens in humans.

What did the research involve?

The researchers fed female mice one of three diets from the age of five weeks: a very high-fat diet, a low-fat high in carbohydrate diet, or a chow diet with a level of fat between these two extremes. These mice were mated at 35 to 40 weeks of age and the pregnant mice studied further. The researchers then looked at the activity of a large panel of genes in the placentas of the mice at 12.5 days of pregnancy. They looked at whether the pattern of activity was affected by diet and by the gender of the foetus.

What were the basic results?

The three maternal diets affected the activity of 1,972 genes in the placentas, with the differences in activity at least double between at least one pair of diets. The differences were more pronounced in female foetuses than in males. Each diet showed a distinct pattern of gene activity depending on the gender of the foetus.

The genes that were affected by diet are usually involved in kidney function and in sensing odours.

The researchers report that there was a tendency for more female offspring in the low-fat, high-carbohydrate diet group, but that there were too few offspring in the very high-fat diet group to determine the statistical significance of this.

How did the researchers interpret the results?

The researchers conclude that gene activity in the placenta of mice is affected by maternal diet and foetal gender. The placentas of female foetuses are more sensitive to maternal diet than the placentas of male foetuses.

Conclusion

This study investigated how the mother’s diet in pregnancy might have an effect on the developing foetus. The researchers aimed to identify alterations in the activity of genes in the placenta that could potentially contribute to this effect. They found a number of changes in gene activity as a result of different maternal diets in mice, and that these changes were also affected by the gender of the foetus. However, differences between the species may mean that results obtained in mice may not be representative of what happens in humans.

This study did not aim to investigate whether maternal diet in pregnant mice affects the gender of their offspring.

The developing foetus obtains nutrition and oxygen, and also eliminates waste, via the placenta. Therefore changes in the placenta, such as changes in placental gene activity due to diet and foetus gender, could potentially influence foetus health and possibly survival. However, as the authors themselves acknowledge: “The reason why a maternal high-fat (low-carbohydrate) diet favours survival of sons while a maternal low-fat (high-carbohydrate) diet results in more daughters continues to elude us.”

Links To The Headlines

Eating breakfast and fatty diet during early pregnancy increases chances of having a boy. The Daily Telegraph, March 9 2010

Links To Science

Mao J, Zhang X, Sieli PT, et al. Contrasting effects of different maternal diets on sexually dimorphic gene expression in the murine placenta. PNAS 2010; Published online before print

“Women who like a glass of wine after work are less likely to gain weight than those who stick to mineral water,” according to The Times, which claims that moderate female drinkers have a lower risk of obesity than teetotallers.

The research behind these claims asked a group of middle-aged American women of a healthy weight about their alcohol consumption. The women were sent follow-up questionnaires over the next 13 years to track how their weight changed. Over the course of the study most of the women gained weight, but on average those who originally consumed at least four units per day gained around 2kg less than their non-drinking counterparts.

While this study has found that higher alcohol consumption was associated with slightly lower weight gain over time, there are a number of limitations to the research. Equally, the study did not look at potential mechanisms by which alcohol could have an effect on weight, although it suggests that drinkers may have replaced dietary calories with calories from alcohol. However, the negative health effects of regular alcohol consumption are well-known, and women are advised to limit alcohol consumption to two to three units per day.

Where did the story come from?

This research was conducted by Dr Lu Wang and colleagues from Brigham and Women’s Hospital and Harvard University. The study was funded by the US National Institute of Health and published in the peer-reviewed medical journal Archives of Internal Medicine.

Several newspapers have reported on this research, with some suggesting that alcohol may aid weight loss. However, the research did not directly prove that alcohol consumption prevents weight gain, instead showing that the dietary and exercise habits of drinkers versus non-drinkers differed. Some news sources also reported on a theory that alcohol may be broken down in the liver to create heat rather than fat. That theory was not tested by this research.

What kind of research was this?

This was a prospective cohort study following a group of American women of normal weight to look at how their drinking habits affected the likelihood of them becoming overweight or obese over time.

The researchers say that alcohol contains 7.1 calories per gram and that the extra calories it contributes to the daily diet may increase weight gain. They add that studies have not provided consistent evidence that alcohol consumption is a risk factor for obesity. The researchers therefore used data from a large prospective cohort study in women to see whether there was any association between alcohol consumption and obesity in women.

What did the research involve?

The researchers drew participants and data from the Women’s Health Study, a randomised clinical trial that evaluated the effects of low-dose aspirin and vitamin E in the prevention of cancer and cardiovascular disease. The trial involved 39,876 female healthcare professionals aged 39 to 89 who were free of cancer and cardiovascular disease. For this subsequent alcohol study the researchers included 19,220 women with a body mass index (BMI) ranging from 18.5 up to 25, which is considered to be within the healthy range.

At the start of the study the participants were given a questionnaire asking how many alcoholic drinks they consumed. The frequency was graded in nine possible responses that ranged from “never or less than once per month” to “more than six times a day”. Their alcohol consumption was calculated according to the alcohol content in each type of beverage. The researchers defined one alcoholic unit as containing 8g of pure alcohol.

At the start of the study the researchers also collected baseline information on each participant’s age, smoking status, physical activity level, menopausal status, postmenopausal hormone use, multivitamin use, history of diabetes, hypertension (high blood pressure) and high cholesterol levels. The participants also completed a food frequency questionnaire that assigned a portion size for each specified food item. These were used to calculate an estimate of each participant’s calorie intake.

Information on the participants’ body weights was updated using follow-up questionnaires given 2, 3, 5, 6 and 9 years after the first questionnaire. In addition 16,322 of the women agreed to be followed up for a further four years, providing a dataset spanning 13 years from the initial questionnaire.

The women had their BMI calculated and categorised as normal (18.5-25), overweight (25-30) or obese (over 30). If a participant became overweight or obese while being followed up, the year in which this event occurred was recorded. If a woman developed diabetes, the date of the diagnosis was also recorded.

When the researchers performed their initial analysis they only adjusted their data to account for the women’s ages. As additional factors may have affected the women’s weight, the researchers made further adjustment to account for BMI at baseline, non-alcoholic energy intake and the type of food they ate (such as fruit and vegetables, meat, refined or whole grains, fibre and dairy produce). They also adjusted for the amount of exercise they did, their smoking status, hormone status, and any history of high cholesterol or high blood pressure.

What were the basic results?

The women’s baseline characteristics at the time of the first questionnaire showed that those who drank greater amounts of alcohol were more likely to be older, white, current smokers, postmenopausal, have high blood pressure and have a lower baseline BMI. They also found that although the total energy intake was greater in women who drank lots of alcoholic beverages, these women took in fewer calories from food than the non-drinkers.

Alcohol intake was associated with a greater intake of red meats, poultry and high-fat dairy products but a lower intake of whole grains, refined grains, low-fat dairy products, fats, carbohydrates and fibre. Women who consumed an intermediate amount of alcohol did more exercise than those who did not drink, or those who drank greater amounts. On average, all women put on weight over the follow-up period. However, the greatest average weight gain was in the women who did not drink alcohol.

The drinking and non-drinking groups had varied in a number of dietary and lifestyle factors at the start of the study, leading the researchers to perform a set of analyses that were adjusted to account for the influence of these variations. After these adjustments, they found that the relationship between weight gain and low alcohol consumption was stronger.

The researchers also found that 41.3% of the women had become overweight or obese during the follow-up period. When using a BMI of 30 as a cut-off, 3.8% of the women had become obese. The mean weight gain during 12.9 years of follow-up was 3.63kg for women who did not consume alcohol, compared to 1.55kg for those who consumed 30g per day or more. (95% confidence interval [CI], was 3.45-3.80kg vs 0.93-2.18KG).

How did the researchers interpret the results?

The researchers concluded that light-to-moderate alcohol consumption was associated with less weight gain and a lower risk of becoming overweight and/or obese over 12.9 years of follow-up in middle-aged women.

They suggested that other studies have shown that in British men, an equivalent increase in alcohol consumption was associated with increased BMI. They suggest that “male drinkers tend to add alcohol to their daily dietary intake, whereas female drinkers usually substitute alcohol for other foods without increasing total energy intake”.

Conclusion

This large cohort study that followed middle-aged women for almost 13 years found that there was an association between greater alcohol consumption and slightly slower weight gain over this period.

Despite the tone of press coverage, it should be remembered that this type of study can only show associations between factors, and cannot say how or whether alcohol directly causes the slower weight gain. There are also a number of limitations to this research, some of which the researchers have highlighted:

• The participants self-reported their weights and alcohol consumption, which may have resulted in a misclassification or underestimation of these values.
• The study used a single measurement of alcohol consumption taken at the start of the study. It is likely that the participants’ drinking habits changed over the 13-year study period.
• The questionnaire used in the study did not collect sufficient detail on some aspects of the women’s drinking habits. For example, it did not differentiate between women who drank a small amount on most days of the week and those who drank multiple drinks on one day of the week. These drinking patterns may have different effects on the body’s metabolism.
• The women in this study were predominantly white, female healthcare professionals who may differ in their socioeconomic status from other women, so these findings may not apply to the population as a whole or to men.
• The women included in this study were all originally in the healthy BMI range. This means the study has not looked at how the weight of women outside this range changes in relation to alcohol intake or whether alcohol may have contributed to existing weight problems.
• The average difference in weight gain between the groups was relatively small, at just over 2kg.

Given the limitations of this research, it is not possible to say whether alcohol consumption directly reduces the chances of weight gain. However, the data from this study contributes to our understanding of how related lifestyle factors such as alcohol consumption and eating habits can contribute to weight gain.

Excessive alcohol consumption is known to be bad for our health in several ways. For example, it can increase the risk of cancer and depression. Women are recommended to drink no more than two to three units a day. The daily limit for men is three to four units.

Links To The Headlines

Wine doesn't make women fat, report claims. The Daily Telegraph, March 8 2010

Drink up girls: wine isn't fattening. The Times, March 8 2010

Cheers, girls! The odd glass of wine is less fattening than water. Daily Express, March 8 2010

Links To Science

Wang L, Lee IM, Manson JAE et al. Alcohol Consumption, Weight Gain, and Risk of Becoming Overweight in Middle-aged and Older Women. Archives of Internal Medicine 2010;170(5):453-461 [Awaiting publication]

The Daily Telegraph has reported that “vitamin D 'triggers and arms' the immune system”. It said that researchers believe that vitamin D plays a key role in boosting the immune system.

The study looked at human T cells in the laboratory, and found that vitamin D was part of a complex process in which T cells become 'primed' and help to fight infection. While these findings suggest that people with vitamin D deficiency are more susceptible to infection or that vitamin D supplements might boost immunity, such theories need to be tested further before drawing any firm conclusions.

It is important to have enough vitamin D to maintain a healthy body. Vitamin D forms in our skin in response to sunlight. However, care should be taken to avoid burning or over-exposure. Vitamin D is also found in foods such as oily fish, eggs, fortified margarines, some breakfast cereals and vitamin supplements.

Where did the story come from?

Dr Marina Rode von Essen and colleagues from the University of Copenhagen and Bispebjerg Hospital in Denmark carried out this research. The study was funded by the Danish Medical Research Council, the Lundbeck Foundation, the Novo Nordisk Foundation, the King Christian the 10th Foundation and the A.P. Møller Foundation for the Advancement of Medical Sciences. Some of the chemicals used in the study were provided by the manufacturer Bayer Schering Pharma AG. The paper was published in the peer-reviewed scientific journal Nature Immunology.

The study was reported in The Daily Telegraph, Daily Mail, and Metro. The newspapers give reasonable coverage of this complex research. Metro includes the study’s sensible warning that sunburn should be avoided.

What kind of research was this?

This laboratory research investigated what happens to human T cells when they respond to foreign molecules (called antigens). T cells are immune-system cells that recognise antigens (for example molecules on the surfaces of viruses) and kill infected cells. In particular, the researchers looked at the 'priming' of the T cells, a process by which T cells prepare to respond to antigens. When exposed to an antigen, primed T cells are able to multiply in number faster and produce more chemicals to help promote further immune response than naive T cells. They looked at the role of a protein called phospholipase C, which is involved in sending signals within cells. They also looked at how vitamin D and the vitamin D receptor are involved in this process.

This type of laboratory study helps researchers to unravel the complex events that occur in individual cells in the immune system. A better understanding of how the immune system works could suggest ways of boosting immune responses. In this case, if vitamin D was found to play a role in the immune system, this would suggest that people with vitamin D deficiency might be more susceptible to infection or that vitamin D supplements might boost immunity. Such theories would have to be tested in human research before any firm conclusions could be drawn.

What did the research involve?

The researchers took 'naive' (unprimed by exposure to antigens) human T cells from freshly drawn blood and grew them in the laboratory. They grew some in solutions containing immune system molecules: conditions that 'primed' them for activation.

The characteristics and behaviour of the 'primed' T cells were then compared with the 'naive' T cells. This included the cells’ response to being 'restimulated' through re-exposure to the immune system molecules that originally primed their activation.

The researchers were especially interested in how much the cells produced a particular form of phospholipase C, called phospholipase C-?1, and how this was linked to the presence of the vitamin D receptor. They also looked at what happened if they blocked the cells from responding to vitamin D. They carried out experiments to investigate how the cells switched on the production of the vitamin D receptor.

What were the basic results?

The researchers found that 'naive' T cells that had not been primed produced only a small amount of phospholipase C-?1. However, following priming by exposure to the activator immune system molecules, the T cells began to produce far more phospholipase C-?1. For this to occur, the T cells needed to be in the presence of vitamin D and the vitamin D receptor.

They also found that naive T cells did not produce the vitamin D receptors, and that these receptors were only produced when the T cells were primed.

How did the researchers interpret the results?

The researchers conclude that T cells produce vitamin D receptors when they are primed to respond to antigens. Vitamin D then acts via the receptor to stimulate production of phospholipase C-?1. These changes are necessary for the T cells to be activated.

Conclusion

This research indicates that vitamin D is involved in the activation of the T cells of the immune system. It is important to note that this is a laboratory study, and it is useful in helping researchers to understand what happens in specific immune system cells when exposed to foreign entities such as bacteria or viruses. It does not tell us how variations in vitamin D levels might affect people’s susceptibility to infection, or what the ideal level of vitamin D is for supporting immune system responses to infection.

Other studies will no doubt look into these questions. However, as with other vitamins, it is clearly important to have sufficient vitamin D to maintain a healthy body. Vitamin D forms in our skin in response to sunlight, but care should still be taken to avoid burning or over-exposure. Vitamin D is also found in foods such as oily fish, eggs, fortified margarines, some breakfast cereals and vitamin supplements.

Links To The Headlines

How sunshine can help your body fight disease. Daily Mail, March 8 2010

Vitamin D 'triggers and arms' the immune system. The Daily Telegraph, March 8 2010

Sunshine linked to immune system boost. Metro, March 8 2010

Links To Science

Rode von Essen M, Kongsbak M, Schjerling P, et al. Vitamin D controls T cell antigen receptor signaling and activation of human T cells. Nature Immunology 2010; published online March 7 2010