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“Scientists have discovered a dye that could slow down the ageing process in humans,” the Daily Express has reported. According to the newspaper, the yellow dye is a compound currently used in neuroscience laboratories to detect damaged proteins seen in the brains of patients with Alzheimer’s disease.

The laboratory study behind this report found that worms lived up to 70% longer when they were exposed to Thioflavin T (ThT), a dye commonly used in the laboratory to stain protein in cells. The dye also reversed paralysis caused by their muscle cells accumulating amyloid proteins, which are implicated in Alzheimer’s disease.

While the findings will be of interest to scientists, these are preliminary results and the effects of this dye on human health are unclear. Potential new treatments for humans face a long timeline of testing and review to determine whether they are safe and effective. It is unlikely the systems in the worms are comparable with what might happen in the human body, and it remains to be seen whether ThT can be used to extend life.

 

Where did the story come from?

The study was carried out by researchers from the Buck Institute for Research on Aging, the Dominican University in California and the Karolinska Institute in Sweden. The work was supported by the Larry L Hillblom Foundation and the US National Institutes of Health. Individual researchers also received support from various organisations. The study was published in the peer-reviewed scientific journal Nature.

Newspaper headlines have generally featured claims that the key to longevity has been discovered, which detracts from the reality that this was a study in worms. Also, this was early research and it is likely that a lot of further research will be needed before we can tell if this technology is applicable to humans.

 

What kind of research was this?

The researchers say that studies have shown that the maintenance of a careful balance of protein in cells is linked to cell longevity. They hypothesise that providing animals with treatments that promote this balance may improve lifespan. They tested this theory in a laboratory experiment using adult worms known as Caenorhabditis elegans. These small worms usually live in the soil but are commonly studied in laboratory settings. The particular substance studied is Thioflavin T (ThT). This is dye often used in a laboratory setting to stain cells that are examined under a microscope. It specifically marks the presence of fibrous protein complexes, such as the amyloid proteins implicated in Alzheimer’s disease.

 

What did the research involve?

The researchers tested a number of substances for their effects on the balance of proteins in worms. The substances were:

• Thioflavin T (ThT)
• Curcumin (turmeric)
• 2-(2-hydroxyphenyl)-benzoxazole (HBX)
• 2-(2-hydroxyphenyl) benzothiazole(HBT)
• 2-(2-aminophenyl)-1H-benzimidazole (BM)
• Rifampicin (an antibiotic)

The worms were exposed to the different substances and to different doses of them by saturating the medium in the dishes the worms were growing in. Every second day the researchers assessed whether the worms on the plate were alive, dead or lost, rating worms that did not respond to touch as dead.

In other experiments they used worms that had been genetically modified to have diseases in which proteins accumulated in muscle tissue. These proteins were amyloid beta and polyglutamine (polyQ) protein. Amyloid beta is also associated with lesions in Alzheimer’s disease.

Worms unable to regulate this protein develop lesions in their muscles and become paralysed. The researchers exposed these diseased worms to the ThT and to the other compounds to determine whether they were able to restore protein regulation in the worms. They also undertook a series of other experiments designed to help them understand what processes ThT was acting upon in order to affect lifespan.

 

What were the basic results?

Exposure to ThT throughout life increased the average lifespan of the worms by about 60% and by 43-78% beyond their untreated maximum lifespan. However, at high doses, ThT was toxic and reduced lifespan. At all ages, treatment with ThT resulted in reductions in rates of age-specific mortality and in age-related decline in spontaneous movement. This indicated improved health.

Treatment with ThT was able to restore movement in those worms that were paralysed by lesions of amyloid beta (the protein found in a brain with Alzheimer’s disease).

The effects of ThT on lifespan depended on the presence of other molecules (skn-1 transcription factor and a regulator molecular called HSF-1). The researchers say that ThT mimics the stress response that ultimately leads to better regulation of protein, stopping them from aggregating (i.e. collecting together to form clumps).

 

How did the researchers interpret the results?

The researchers conclude that their study has shown molecules that can mimic the stress response and target the complex processes that regulate the balance of proteins in cells may ‘provide opportunities for intervention in ageing and age-related disease’.

 

Conclusion

This well-described laboratory study has found that a dye commonly used in the laboratory to help identify the presence of protein complexes in cells actually interacts with these proteins in a beneficial way that could prevent them building up in cells. This effect appears to increase the lifespan of nematode worms and also to reduce (or reverse) the age-related paralysis that occurs when amyloid lesions build up in their muscle cells.

Amyloid beta lesions are responsible for Alzheimer’s disease in humans and many newspapers have made the leap from these discoveries to a potential ability to extend human longevity using the Thioflavin T (ThT) dye studied. It is too soon to know whether ThT could be safely given to humans and whether it will have any effect on the lifespan of individuals.

News headlines that have suggested that ThT is the key to long life are overly optimistic given the early stage of this research. For example, the Daily Mail reported that ThT ‘slowed the symptoms of dementia in worms bred to mimic aspects of Alzheimer’s’. It is not clear where this claim has come from or indeed, what the symptoms of dementia might be in a worm.

Links To The Headlines

Yellow dye used to test Alzheimer’s could hold key to living longer. Daily Mail, March 31 2011

Found – dye that may help us to live longer. Daily Express, March 31 2011

Links To Science

Alavez S, Vantipalli MC, Zucker DJS et al. Amyloid-binding compounds maintain protein homeostasis during ageing and extend lifespan. Nature, Published online 30 March 2011

DIY health testing kits have made headlines, with several newspapers reporting that they could do more harm than good. Home test kits designed to detect ailments from high cholesterol to cancer, can be misleading, offer false reassurance or trigger false alarms, and use language that is often confusing, the media reported.

The stories are based on a new report by the consumer organisation Which? on six widely available home testing kits. It found many problems with the tests, including gaps in information, difficulty of use, “baffling” language, the risk of false alarms or false reassurance and misleading naming.

According to Which? people would be better off saving their money and going straight to the GP – who would have to carry out tests to confirm any ‘diagnosis’ made by such kits in any case.

It is always preferable to consult a medical practitioner if you have any health concerns. A GP will conduct an appropriate assessment and will be able to discuss any concerns that you have and advise which further examinations, investigations or further assessments – if any – are appropriate.

 

What did the research involve?

Which? asked two experts to assess a selection of home testing kits and to look at their packaging, leaflets and websites. The experts were Dr Danielle Freedman, consultant pathologist from the Royal College of Pathologists, and GP Dr Paul Singer.

The Plain English Campaign was also asked to assess the information provided with the packs.

Which? also asked 64 members of the public to look at the information available when buying a test, to see whether the average person would be able to use the kits correctly. They were then given in-depth interviews about the information available at the point of purchase.

The test kits examined were for the following medical conditions:

Bowel cancer

The Boots Home test kit, £12.25, says it may help in the early detection of bowel cancer.

Prostate problems such as prostate cancer

The Selfcheck Health Test, £15.99, says it measures blood levels of prostate specific antigen (PSA), a marker for prostate problems.

Cholesterol

Care Diagnostica Cholesterol Health Care Test, £9.99, says it can detect high cholesterol levels.

Diabetes

Boots home test kit, £12.25, claims it may help in the early detection of diabetes.

Urinary tract infection

Atlas Urinary Tract Test, £4.49, says it is an aid in the diagnosis of urinary tract infection.

Stomach ulcers

Simplicity Stomach Ulcer Screening Test, £12.00, says it is a “screen” for stomach ulcers.

 

What were the findings?

Detailed findings about the six tests are as follows:

Boots Home test kit

Which? says the kit, which tests for blood in the stools, is not as accurate as the screening test used by the NHS because it is based on only one bowel motion and “of little use as a screen for early bowel cancer”. Information is misleading – for example, it is referred to as a “diagnostic device” on the website. The pack gives no guidance on how to collect a stool sample, nor does it mention that you’re likely to need a repeat test by your GP, or that there’s a free NHS screening programme for the over-60s.

Selfcheck Health Test

Which?  points out that although raised levels of PSA can indicate prostate cancer, raised PSA levels can be caused by other things (including benign enlargement, infection and inflammation of the prostate). Because of this, there is a good chance that this finger prick test could lead to false alarms, while negative results may give false reassurance. The pack fails to state that the test is unsuitable for people with certain medical conditions such as prostatitis (acute or chronic inflammation of the prostate) or, in some circumstances, unsuitable for use after sexual activity or cycling. Consumers reported that information about the test was not always clear. Selfcheck recommends regular prostate testing for men over 40, but this is not supported by NHS screening policies. It was also difficult to use: the Which? tester “didn’t even collect half the blood needed”.

Care Diagnostica Cholesterol Health Care Test

The test involved a finger prick test that measures cholesterol in the blood, which can indicate a higher risk of heart disease. However, the Which? medical experts said there are other risk factors for heart disease, such as smoking, diabetes and obesity. They say the test results should be considered in combination with these factors to get a more accurate idea of risk, and this should be clearly explained to avoid “false reassurance”. The wording on the pack was judged to be “inappropriate for a general audience”. The Which? tester also found that the lancet which draws blood from the finger was broken and unusable.

Boots Home Test Kit

This test, which measures the level of glucose in the blood, could worry people unnecessarily as it doesn’t mention that glucose levels can be raised after a meal. The package does not clearly state who the test is unsuitable for, what might interfere with the results and when it should not be used. Which? says that although the leaflet contains some useful information in the event of an abnormal result, it also uses some confusing language. Lack of clarity over high glucose levels and an actual diagnosis of diabetes could lead to “some unduly and unnecessarily frightened people”.

Atlas Urinary Tract Test

This tests for white blood cells, red blood cells and nitrites in the urine, which can indicate a urinary tract infection (UTI). Consumers thought this test could be useful, and frequent UTI sufferers may find that the test helps to indicate when they need to visit the GP. Experts were concerned about the difficulties of interpreting the results. The Plain English Campaign said the leaflet uses “overly scientific and technical language”. Which? points out that as with many of the tests, many people would need re-testing by the GP to decide whether treatment is needed.

Simplicity Stomach Ulcer Screening Test

Which? says that this finger prick tests is misleading since it actually tests for a bacteria (helicobacter pylori) rather than stomach ulcers, and it cannot tell people if they have a current infection. Only a minority of people with the bacteria will develop an ulcer. Information with the kit is “vague” and the company’s website “unduly frightening”. Plain English Campaign called the information on the leaflet “overwhelming”. It was difficult to use: the tester only managed to get three-quarters of the blood needed after two finger pricks.

 

What does the report recommend?

Which? says that while self-test health kits could be a useful tool, the lack of clear information about how to use them could do more harm than good. Which? chief executive, Peter Vicary-Smith, says:

“As your GP may well have to carry out their own tests to confirm a positive diagnosis anyway, you may be better off saving your money and going straight to your GP.”

Which? will be contributing its report to the European review of self-testing devices.

 

What do other sources say?

Other experts are reported as agreeing that some of these tests can be misleading. The Prostate Cancer Charity said it did not encourage the use of PSA testing because this can result in false reassurance or create unnecessary anxiety. The charity Diabetes UK also advises people who are worried that they may have the condition not to use glucose test kits. Cancer Research UK said that anyone worried about the risk of cancer should see their doctor.

Boots is reported as saying that self-testing health kits should always be used with advice from a GP or pharmacist.

 

What should I do?

Many people find it difficult to see the GP or may be unwilling to talk to a doctor about their health concerns. Self-test health kits are widely available and may seem appealing by offering people the chance to test for various conditions in the comfort and privacy of their own home. However, this report, which has looked at six widely available home testing kits, concluded that they can be difficult to use, do not always give clear or adequate information, and can lead to unnecessary anxiety or false reassurance.

Although the report was limited to only six kits and they were assessed by only two experts, the findings are worth noting. The current lack of legislation for these home testing kits may mean that these problems are common among testing kits in general.

If you are considering using a home testing kit of any kind, it is worth bearing in mind these potential drawbacks, as well as the expense. The Department of Health advises people to be cautious when using home-testing kits. A spokesperson told the BBC, "anyone who is concerned that they may be suffering from an infection or illness should contact their GP practice, pharmacist or other health professional for advice.”

It is always preferable to consult a medical practitioner if you have any health concerns. A GP will conduct an appropriate assessment and can discuss any of your concerns and advise which further examinations, investigations or further assessments – if any – are appropriate. NHS Direct can also provide advice on 0845 4647.

Links To The Headlines

Concern at self-test health kits. BBC News, March 31 2011

Home health tests ‘could do more harm than good’. The Daily Telegraph, March 31 2011

DIY health testing kits ‘could do more harm than good’. Daily Mail, March 31 2011

‘Hit and miss’ warning on home health tests. The Independent, March 31 2011

Links To Science

5 need to knows about home self-test health kits. Which 2011

“Pregnant women who take paracetamol could be increasing the risk of their child developing asthma,” the Daily Express has reported.

The news is based on a review that systematically combined the findings from six previous studies examining whether paracetamol use in pregnancy is associated with asthma in early childhood. It should be noted that the review looked at cases of wheeze, which may not necessarily indicate asthma. Of the six studies examined, three found a significant association with paracetamol use and three did not. When pooled, the results suggested a 21% higher risk of wheeze for children whose mothers had used the painkiller.

There are important limitations to the review, particularly the fact that it looked at wheeze rather than asthma. The contradictory results of the individual studies and the lack of adjustment for factors such as parental smoking also undermine the reliability of the results. However, the findings of this initial review are important, and the topic is worthy of further research to try to clarify any possible association.

Expectant mothers should not be overly concerned. There are many causes of childhood asthma, and exposing the developing foetus or child to smoke is likely to be a more important one. Paracetamol remains safe for use at standard adult dose if required during pregnancy or breastfeeding.

 

Where did the story come from?

The study was carried out by researchers from the Medical Research Institute of New Zealand, the University of Otago Wellington, New Zealand, and the University of Southampton. No sources of funding were reported. The study was published in the peer-reviewed medical journal, Clinical and Experimental Epidemiology.

The Daily Express has accurately reflected the reporting of this review, though the review itself has several important limitations which mean that further, carefully conducted and reported research is needed to clarify these associations.

 

What kind of research was this?

This was a systematic review which aimed to investigate whether paracetamol use in pregnancy may be associated with asthma in infancy and childhood. A previous systematic review had noted an association between paracetamol use in a child or an adult and the risk of them developing wheeze or asthma.

A systematic review of cohort studies is the best way of gathering together the global evidence regarding a particular exposure (paracetamol) and subsequent development of a disease outcome (asthma). All reviews involve a degree of limitation due to the variation in study methods, the populations included, follow-up periods and methods of outcome assessment used in the individual studies.

 

What did the research involve?

The authors searched medical databases and reference lists for relevant randomised controlled trials or observational studies published up to 2010. Eligible studies were either RCTs of women randomised to paracetamol or a placebo drug during pregnancy, or cohort studies that had compared a group of women who had used paracetamol during pregnancy against a control group who had not used paracetamol. All studies had investigated how this affected the likelihood of wheeze or asthma in the child.

The gathered studies were assessed in detail for quality and the methods used. The main outcome that the reviewers were interested in was ‘current wheeze’, which was defined as wheeze in the 12 months prior to the assessment. The reviewers pooled the odds of asthma or wheeze in those who took paracetamol and those who did not, and used them to calculate a ratio of risk. During this process they applied statistical processes that took into account the differences in methods and results of the various studies.

 

What were the basic results?

Six studies met the inclusion criteria: five cohort studies and one cross-sectional survey. No RCTs were identified. Studies assessed children between the ages of 2.5 and 7 years, and all looked at how paracetamol use during pregnancy related to the outcome of current wheeze. Only one of the five cohorts reported the specific period of pregnancy during which paracetamol was used (20-32 weeks). The review classified women as either users or non-users of paracetamol, but did not look at dosage or length of paracetamol use.

The six studies gave very variable results. Three of them found a significant association between paracetamol use and current wheeze. Three of them found no association. All of these risk associations were reported to be unadjusted for any confounders. When the authors of the current review pooled these six results, they found that there was a 21% increased chance of current wheeze in the child if the mother had used paracetamol during pregnancy (OR 1.21, 95% CI 1.02 to 1.44).

 

How did the researchers interpret the results?

The researchers conclude that “the use of paracetamol during pregnancy is associated with an increased risk of childhood asthma”. They say that further research is now required “to determine the impact of paracetamol during pregnancy on the risk of wheezing in offspring so that appropriate public health recommendations can be made”.

 

Conclusion

The findings of this study should be interpreted carefully, particularly as the six observational studies included in the review had variable results: three had found a significant association between pregnant paracetamol use and wheeze, and three did not. While the odds ratio when pooling these six results found a statistically significant association, this finding should also be considered in light of some important limitations:

• The review categorised paracetamol use in each study as either ‘yes’ or ‘no’. Only one of the pooled studies specifically looked at paracetamol use during the latter half of pregnancy (20-32 weeks). This, along with wide differences in the categorisation of paracetamol doses in the individual studies, means that when pooling the results, only the broad considerations of whether women had used paracetamol or not could be used. This, therefore, cannot inform us about dosage or duration of use, for example.
• The review reported that there was considerable variation across the included studies in the adjustments they made for confounders. The review did not explicitly report these. It presented its summary odds ratio of 1.21 as an unadjusted summary calculated without consideration of any confounders. This means that there are other factors, both measured or unmeasured, that could vary between paracetamol users and non-users, which could also account for the difference seen. The authors mention maternal smoking, respiratory disease, length of pregnancy, pet ownership and social class as possible confounders.
• The main outcome of the review was ‘current wheeze’, defined as wheeze in the 12 months prior to the assessment. As asthma is notoriously difficult to diagnose during infancy and childhood; sometimes a nocturnal cough can be the only symptom. Likewise a wheeze can commonly occur with respiratory tract infections in a child who does not have asthma. Therefore it not possible to know for certain whether the children categorised as having ‘current wheeze’ actually had asthma.

The findings of this review, as the authors conclude, are clearly worthy of further study to see whether an association could exist between paracetamol use in pregnancy and asthma or wheeze in the child. However, given the uncertainty surrounding these initial findings, pregnant women should not be overly concerned by this possible association until this further research is complete.

Asthma is a relatively common condition in children and can be increased by several risk factors or triggers. A family history of asthma and other allergic conditions, combined with environmental irritants, are the most established triggers. Key among these is exposure to smoke in infancy and childhood. Other research has linked smoking while pregnant to risk of asthma in the child.

Paracetamol use in pregnancy, or while breastfeeding, is currently not known to be associated with any harms to the developing foetus or infant. Current advice is that it remains safe for use during pregnancy at the recommended adult dose (up to 1g every 4-6 hours, with a maximum of 4g in any 24-hour period).

Links To The Headlines

Asthma link to pills. Daily Express, March 30 2011

Links To Science

Eyers S, Weatherall M, Jefferies S and Beasley R. Paracetamol in pregnancy and the risk of wheezing in offspring: a systematic review and meta-analysis. Clinical & Experimental Allergy, 41, 482–489

Trace levels of radioactive material have been detected in the UK following the recent failure of the Fukushima nuclear power plant in Japan. While some media reports have suggested this could be dangerous, the levels of radiation detected are extremely low. The arrival of these trace amounts of radiactive material poses no health risk to people the UK.

The radiation from these airborne particles is well below the normal, harmless levels of background radiation that we are naturally exposed to every day.

The Health Protection Agency (HPA), which is monitoring situation, has said: “Any radiation that could potentially reach the United Kingdom would be miniscule and no threat to people’s health. There is no health risk to people living in the UK from the release of radioactive material from the Japanese nuclear power plant.”

The radioactive isotope detected in the UK, called iodine 131, is found only in the brief period following specific nuclear events, after which it rapidly decays. The presence of these particles suggests the radioactive material came from Japan, rather than being due to a significant rise in UK radiation levels.

The HPA also said that levels of radioactive iodine may rise in the coming days and weeks, but this would still be "significantly below any level that could cause harm to public health".

Links To The Headlines

No risk from Japanese radiation. Daily Mirror, March 30 2011

Scotland’s on radiation alert. The Sun, March 30 2011

Radioactive particles from Fukushima nuclear plant are detected in OXFORDSHIRE as experts warn Japan has ‘lost race’ to save reactor. Daily Mial, March 30 2011

Tsunami nuclear fallout hits UK. Daily Express, March 30 2011

“Doctors cause a third of stubborn high blood pressure,” reported the BBC News. The news service reports that some cases of hard-to-treat high blood pressure may actually be caused by patient nervousness at being seen by a doctor.

The news is based on a Spanish study which compared blood pressure measurements taken in a doctor’s surgery and measurements gathered using a 24-hour monitoring device in people believed to have resistant hypertension. Resistant hypertension was defined in this study as high blood pressure that had not responded to concurrent use of three or more high blood pressure medications. The study found that 37% of patients with resistant hypertension (based on the doctor’s surgery measurements) actually had blood pressure within the normal range when it was measured with 24-hour monitoring. This suggests that an anxious response to being in a doctor’s surgery may affect a proportion of patients’ blood pressure readings.

At present, NICE recommends that raised blood pressure is confirmed on at least two further readings at a separate time. However, recent draft recommendations issued by NICE have called for the introduction of home-based or ambulatory blood pressure monitoring to confirm diagnoses of high blood pressure. These are expected to be approved later this year.

 

Where did the story come from?

The study was carried out by researchers from The University of Barcelona, and it was funded by Lacer Laboratories, Spain.

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

The Daily Mail reported that “thousands are wrongly treated for high blood pressure”.  However, this should not be assumed on the basis of this research alone: the study only looked at a subgroup of people with high blood pressure – those who had been diagnosed with resistant hypertension, i.e. high blood pressure despite being treated with multiple anti-hypertension medications. Also, the study did not assess whether these people had originally been misdiagnosed with hypertension or whether their medication was actually just working to control what would have otherwise been high blood pressure. The study was also in Spain, where the medical practices for treating hypertension may vary from those used in the UK.

The Daily Mail and the BBC News did highlight draft NICE guidelines which propose that home or ambulatory blood pressure monitoring should be used to confirm any initial diagnosis of hypertension.

 

What kind of research was this?

The researchers say that a proportion of the high blood pressure measurements taken at the doctor’s office may be affected by the “white coat effect”, where a person’s blood pressure may be affected by the anxiety they feel while visiting the doctor. In turn, these readings may go on to form the basis of a patient’s treatment strategy.

This was a cohort study which followed patients with persistent resistant hypertension (high blood pressure). It compared their blood pressure readings, which were taken in a doctor’s office and obtained using a blood pressure monitoring device that could measure their blood pressure as they went about their daily lives. In this study, resistant hypertension was defined as blood pressure that remained above the target threshold (140/90mmHg) despite the concurrent use of three hypertensive agents at full doses, one of them being a diuretic.

The ambulatory blood pressure monitoring (ABPM) used in this study was performed using a device that was worn by the patient over a 24-hour period in order to measure their blood pressure in 20-minute intervals throughout the day. This method allows doctors to assess fluctuations in blood pressure and examine whether blood pressure remains high for extended periods of the day.

The Spanish researchers say that these devices are currently used in a small proportion of referred patients. They wanted to use this technology to record data from a large group of patients with hypertension according to measurements taken in their doctor’s office.

 

What did the research involve?

The study was carried out in Spain and recruited patients who were registered with the Spanish Ambulatory Blood Pressure Monitoring (ABPM) registry. This registry was set up to promote the use of ABPM in clinical practice. The patients were recruited from this registry if:

• they had enough information regarding office blood pressure measurements and had ABPM data of good quality.
• they had resistant hypertension that was uncontrolled despite using more than three blood pressure medications (including one diuretic).
• their doctor’s office BP measurements were over 140 and/or 90 mm Hg – the commonly accepted threshold for defining high blood pressure.

In total, the researchers analysed data on 8,295 patients with resistant hypertension (this population with resistant hypertension was approximately 12% of patients with hypertension).

The patients wore the ABPM device for 24 hours, and their blood pressure was measured every 20 minutes. The majority of patients’ measurements using this device had been on working days, during which the participants were asked to maintain their usual activities. Daytime and night time periods were defined according to the patient’s self-reported data of going to bed and getting up times.

The researchers classified patients based on how their blood pressure during the night related to their daytime BP (expressed as a percentage). People were classified as:

• extreme dippers if their systolic or diastolic BP fell by more than 20% in the night
• dippers if it fell between 10 and 20%
• non-dippers if it fell between 0 and 10%
• risers if BP increased during night time

The researchers also looked at data on the patients’ age, sex, height, weight, smoking status and whether they had diabetes. All of these factors which may have influenced their blood pressure.

 

What were the basic results?

Using the ABPM data, the researchers found that 5,182 of the 8,295 patients (62.5%) who had been diagnosed with resistant hypertension in a clinical setting had true resistant hypertension when assessed using ambulatory 24-hour blood pressure monitoring and cut-off values of more than 130 and/or 80mm Hg. The other 3,113 patients (37.5%) showed BP values below this cut-off and were classified as having “white coat” resistant hypertension.

The patients with true resistant hypertension tended to be younger, male, have a longer duration of hypertension, and have a worse cardiovascular risk profile. For example, being smokers, having diabetes and having heart or kidney damage.

The researchers found that the group with true resistant hypertension had a higher proportion of ‘riser’ pattern patients (i.e. BP increased during the night) than the group with white coat hypertension. (22% vs. 18%; p<0.001).

 

How did the researchers interpret the results?

The researchers estimated that “resistant hypertension is present in 12% of the treated hypertensive population”, but say that “among them more than one third have normal ambulatory blood pressure”. They emphasise a need to use ambulatory blood pressure monitoring in order to make a correct diagnosis of resistant hypertension and to manage this condition.

Although they found that a worse cardiovascular risk factor profile was associated with true resistant hypertension, they emphasised that this association is weak.

 

Conclusion

This research in a relatively large Spanish cohort has assessed the prevalence of true resistant hypertension in a population that had been diagnosed with this condition using blood pressure measurements taken in the doctor’s surgery. The observation that approximately a third of the assessed population’s blood pressure was within a normal range over the 24-hour period suggests that diagnoses should take into account “white coat hypertension”, or blood pressure changes as a response to being in the doctor’s surgery.

Current UK guidelines recommended that an initial diagnosis of high blood pressure is confirmed on at least two further surgery visits. However, The National Institute for Health and Clinical Excellence (NICE) has recently issued revised draft guidance for hypertension. It recommends that 24-hour ambulatory blood pressure monitoring (ABPM) should be used to confirm the diagnosis of hypertension if the first and second blood pressure measurements taken during a consultation with a doctor are both higher than 140/90mmHg. While these proposed changes in diagnoses are still subject to revision, it is expected that they will be introduced later this year.

Links To The Headlines

Doctors cause a third of stubborn high blood pressure. BBC News, 29 March 2011

Fear of doctors may cause blood pressure misdiagnosis. Daily Mirror, 29 March 2011

37% ‘wrongly treated for high blood pressure’ because their heart rate jumps through fear of GPs. Daily Mail, 29 March 2011

Links To Science

de la Sierra A, Segura J, Banegas JR, et al. Clinical Features of 8295 Patients With Resistant Hypertension Classified on the Basis of Ambulatory Blood Pressure Monitoring. Hypertension 2011, Published online before print March 28

A study suggests “a pill could help people cure themselves of a fear of heights”, reported The Daily Telegraph. It said, “Scientists have discovered that giving people a tablet of the stress hormone cortisol can help reduce their phobia.”

This news story is based on a randomised controlled trial in 40 people with acrophobia (fear of heights). It compared the effect of cortisol against a placebo when given one hour before three sessions of virtual reality–based exposure therapy (a simulation of an elevator ride).

The researchers found that although both groups improved after the virtual reality therapy, people who also had cortisol rated their improvement as greater. Objective scores of anxiety (how much the participants sweated) also showed that those given cortisol showed less anxiety than the placebo group a month after the therapy sessions.

This preliminary study shows promising early results for this combined treatment. However, it is still early research in only 40 people. Follow-up studies are needed to replicate these findings and to gauge the extent of this effect. It will also be necessary to see if these results can be reproduced in more challenging real life situations.

 

Where did the story come from?

The study was carried out by researchers from the University of Basel, Switzerland and other universities and institutions in Europe. Funding was provided by the Swiss National Science Foundation and the Basel Scientific Society.

The study was published in the (peer-reviewed) journal Proceedings of the National Academy of Sciences of the United States of America.

The research was generally covered accurately by The Daily Telegraph and the Daily Mail.

What kind of research was this?

This was a double-blind, randomised controlled trial. The researchers were interested in whether taking cortisol, a stress hormone, helps to relieve fear in people with a phobia of heights when combined with a behavioural therapy called exposure therapy.

Exposure therapy is a behavioural therapy technique in which people with phobias, in a limited and structured manner, are exposed to their fears after being shown different relaxation and coping techniques, aimed at decreasing the intensity of their fear response. In this study, to prepare the participants for the exposure, they were given educational materials about exposure therapy and instructions on how to cope with their former avoidance strategies during the pre-treatment assessment. However, no cognitive behavioural techniques such as breathing or relaxation techniques were used.

Cortisol is a stress hormone released from the adrenal gland. It has many functions, including increasing blood sugar, but it is also thought to affect learning and memory processes. Cortisol is a type of hormone called a glucocorticoid. Previous animal research using other glucocorticoid hormones has shown them to be effective at promoting ‘extinction processes’ (lessening of fear during exposure to a fear-inducing stimulus). Therefore, the researchers wanted to see whether glucocorticoids could be useful in enhancing exposure therapy in humans.

A randomised double-blind placebo controlled trial is the best method of assessing whether a treatment is effective for a condition.

 

What did the research involve?

The study recruited 40 people who had a specific phobia of heights (acrophobia), which was defined according to psychiatric criteria listed in the Diagnostic and Statistical Manual of Mental disorders, Fourth Edition (DSM-IV).

The participants were given three sessions of exposure therapy using virtual exposure to heights. Virtual reality exposure to heights has been shown to be effective for treating people with acrophobia. One hour before each session, half the participants were given a cortisol pill, while the half were given a placebo pill. Neither the participants nor the person giving them the pills knew which pills were placebos.

Three to five days after the last treatment session, the participants had a post-treatment session and were assessed once more a month later. These post-treatment assessments were compared to assessments made before the treatment had commenced.

The success of the treatment was assessed by giving the participants questionnaires in which they were asked to rate how fearful they felt when considering 20 situations that could cause fear of heights. Examples of these situations include driving over a bridge or sitting on an aeroplane. Participants were asked to rank these on a seven-point scale. Questions also asked about the possible consequences of scenarios involving heights. This was to assess the participants’ attitude to heights, and the likelihood that they would avoid being in a scenario involving heights, or their behaviour in such a case.

The participants were also asked about their anxiety levels during virtual reality therapy and during a real life situation involving height (going up an outdoor staircase with three levels). During the real life test (Behavioural Avoidance Test), participants were given one point for each level they climbed and one point for looking down for 30 seconds at each level.

As a more objective measure, fear was estimated using the ‘skin conductance response test’. This test measures the moisture levels on the skin. It is used to measure fear as the skin produces sweat in response to stress.

 

What were the basic results?

The researchers found that based on their scores on the acrophobia questionnaire all of the participants benefited from the virtual reality therapy for acrophobia. The participants who also had cortisol however, showed a significantly greater improvement at post-treatment and at one month follow-up (p=0.031).

The researchers used a statistical technique called Cohen’s d to calculate the difference between the average (mean) “effect size” of the cortisol pills compared to the average effect of the placebo. This technique calculated the difference to be somewhere just over a ‘medium effect’ at d=0.6 for the effect size at both post-treatment and one month follow-up. For this d statistic, a value of 0.2 to 0.3 is considered to be a “small” effect. Around 0.5 is a “medium” effect, and more than 0.8 is a “large” effect.

Cortisol was also found to decrease “danger expectancy” at follow-up (effect size, d=0.6). However, the researchers did not find a difference between the cortisol and placebo groups on the attitude toward heights questions and on the behavioural avoidance test.

At the post-treatment session, the cortisol group had lower levels of anxiety during the virtual reality height exposure according to subjective measures of discomfort (SUD) in which the participants were asked to rank their anxiety from 0 “no anxiety at all” to 100, “extreme anxiety”. This difference was not maintained at follow-up one month later.

The objective measure of anxiety, the skin conductance test, showed that the cortisol group had a smaller exposure-induced increase in sweat compared to the placebo group at follow-up. However, due to technical reasons, the researchers were only able to collect skin conductance data from 25 of the participants at one hour post-treatment (11 from the placebo group, 14 from the cortisol group) and from 20 participants at follow-up (9 from the placebo group and 11 from the cortisol group). 

 

How did the researchers interpret the results?

The researchers said that cortisol enhances the effect of virtual reality exposure therapy for people with a fear of heights as assessed by the acrophobia questionnaire – a standard questionnaire used to assess fear of heights.

They call for further studies “to investigate the cortisol effects in more challenging real-life situations”. They say that studies which look at pharmacological or behavioural treatments that enhance extinction or reconsolidation of fears after therapy may “not only help to better understand the role of memory processes in fear reduction but may also contribute to the development of novel therapeutic strategies to treat anxiety disorders”.

 

Conclusion

This study shows that cortisol treatment prior to virtual reality exposure therapy sessions for acrophobia can have a beneficial effect compared to placebo with virtual reality exposure. The researchers also point out that virtual reality-based exposure therapy for fear of heights has been shown to be effective. This is supported by this study.

However, this was a small preliminary study with only 20 people in each group (and only data for 25 people using the only objective measure of anxiety, the skin conductance test). Further research is needed to assess optimum treatment programmes and the safety and effectiveness of cortisol in addition to long-term behavioural therapy.

As the participants had a psychiatric diagnosis of acrophobia, it is not clear whether this study is relevant to people with less severe fear of heights. The researchers also say that it is necessary to see if the results seen in this study can be reproduced in more challenging real life height situations.

Links To The Headlines

Scared of heights? Take this pill. The Daily Telegraph, March 29 2011

Fear of heights could be treated with dose of stress hormone. Daily Mail, March 29 2011

Links To Science

de Quervain DJ-F, Bentz D, Michael T, et al. Glucocorticoids enhance extinction-based psychotherapy. PNAS 2011, published online before print March 28