“Deep brain stimulation is a promising therapy for epilepsy,” reported the BBC. The article said that patients who had resistant epilepsy (a type of epilepsy that does not respond to drug treatment) and who had regular seizures were selected for the new treatment.

Deep brain stimulation (DBS) is a surgical treatment in which electrodes are implanted into specific areas of the brain along with a device “like a pacemaker” that delivers small electrical impulses.
Following the surgery, there was a 41% reduction in seizures for patients who received brain stimulation, compared with a 14.5% decline in seizures in the control group.

The study points to a promising new treatment for a potentially large number of people with resistant epilepsy. The implant was given to epileptics who had specific types of epileptic seizures starting with a “partial seizure”. As such, the treatment may not be effective in people with other forms of epilepsy. This is likely to be less than the one-third of all people with epilepsy that was implied in news reports. The selection of patients suitable for treatment will need refining once long-term (defined as more than two years) complications are known, to ensure that each individual receives maximum benefit with minimal harm.

 

Where did the story come from?

This research was carried out by Dr Robert Fisher, director of the Epilepsy Centre at Stanford University, and colleagues from around the US, all members of the SANTE Study Group. The study was supported by Medtronic (the manufacturers of the device) and a National Institutes of Health grant.  The paper was published in the peer-reviewed medical journal Epilepsia.

The BBC also quotes the author of the study, who cautioned, “DBS therapy is invasive and serious complications can occur. Additional clinical knowledge would help to determine the best candidates for DBS therapy.”

 

What kind of research was this?

This was a double blind randomised trial of a new device implanted in the brain that is aimed at reducing the number of seizures in people with a specific form of epilepsy, in which attacks are set off by abnormal electrical disturbances in a limited region of the brain.

The devices were placed in an area of the brain where they could stimulate the anterior nuclei of the thalamus. This area lies deep within the centre of the brain, above the brain stem, and was chosen following several successful previous trials and animal studies in it. One of these randomised trials had shown a 50% reduction in the number of seizures in people with the implant. In this study, the researchers wanted to test the long-term effects and complications of the technique over a two-year period.

 

What did the research involve?

The carefully selected participants consisted of men and women aged 18 to 65 who were subject to “medically refractory partial seizures, including secondarily generalised seizures”. Partial seizures (also known as focal seizures) only affect a part of the brain when they first begin, without loss of consciousness. They can sometimes progress to a full generalised seizure in which consciousness is lost. To qualify, those recruited had to have at least six seizures a month, but no more than 10 a day, as recorded in a three-month daily seizure diary. The participants also had to have unsuccessfully tried at least three anti-epileptic drugs that had not achieved adequate seizure control, and to be taking between one to four drugs at the start of the study.

After three months of observation, during which the participants took note of the number of seizures they had in a diary, all had the device inserted, usually under general anaesthetic. The device was implanted in 110 patients. One month after surgery, participants were randomly allocated to receiving either treatment of no treatment in a way that ensured neither the patient nor the operator knew whether treatment was being received. The blinded phase lasted three months, after which all patients received non-blinded stimulation for nine months.

Treatment involved the electrodes being stimulated with five-volt pulses, on for one minute and off for five minutes. This sequence ran continuously for the patients in the active treatment group for three months.

The participants recorded the number of seizures in diaries and the researchers monitored the severity of seizures using the Liverpool Seizure Severity Scale (LSSS), which is an accepted scale. They also used a Quality of Life in Epilepsy (QoLIE-31) score along with neuropsychological testing. Appropriate statistical tests were then used to analyse the results.

 

What were the basic results?

Out of 157 enrolled participants, 110 underwent bilateral electrode implantations. The 54 patients allocated to stimulation and 55 patients in the control groups, were similar. One patient was excluded form the analysis as they had failed to complete enough diary entries.

The researchers say there were an average 19.5 seizures per month at the start of the study. In the last month of the blinded phase, the stimulated group had a 29% greater reduction in seizures compared with the control group.

At the end of the blinded phase, there was a 14.5% reduction in seizures in the control group compared to a 40.4% reduction in the stimulated group, before adjustments were made in the analysis. Complex partial and “most severe” seizures were significantly reduced by stimulation.

After two years, there was a 56% median (average) reduction in seizure frequency and 54% of patients had a seizure reduction of at least 50%. Fourteen patients were seizure-free for at least six months.

The researchers noted that five deaths occurred, none of which were related to the implantation or stimulation of the device. No participant had symptomatic bleed into the brain or brain infection. Two participants had temporary stimulation-associated seizures. There were 14 infections near the lead or stimulator, but none within the brain. There were significant differences between the groups through the three month blinded phase, with participants in the stimulated group more likely to report depression and memory problems as adverse events than in the non-stimulated group.

 

How did the researchers interpret the results?

The researchers say that bilateral stimulation of the anterior nuclei of the thalamus reduced seizures and the benefit persisted for two years of study. They say that complication rates were modest and that the benefit of DBS is shown for some epilepsy patients who were resistant to previous treatments.

 

Conclusion

This study provides reliable evidence of the effectiveness of this new treatment for drug-resistant epilepsy. It is important to state that the treatment will not be suitable for all patients with epilepsy.

The researchers say that epilepsy is relatively common with about 1% of the population having the condition. About a third of these people do not respond adequately to anti-epileptic drugs. Because the type of epilepsy studied in this trial was specifically “partial epilepsy”, it is not possible to say that one-third of people with resistant epilepsy could benefit from the treatment.

The long-term risks of this treatment are not yet fully understood, as the authors acknowledge. The device is surgically implanted in the brain, a procedure not without its risks, and permanently having an implant would expose an individual to the risk of infection. As one of the researchers points out, “DBS therapy is invasive and serious complications can occur. Additional clinical knowledge would help to determine the best candidates for DBS therapy.” The selection of patients suitable for treatment will need refining to ensure that each individual receives maximum benefit with minimal harm.

Links To The Headlines

Brain stimulation a 'promising therapy' for epilepsy. BBC News, March 18 2010

Links To Science

Fisher R, Salanova V, Witt T et al. Electrical stimulation of the anterior nucleus of thalamus for treatment of refractory epilepsy. Epilepsia,
[Early View article online in advance of print] Published Online: 17 Mar 2010

The legal drug “meow meow” is being investigated in the wake of two teenagers’ deaths, says The Sun. The two boys from Scunthorpe are believed to have taken the stimulant, also known as mephedrone, shortly before their deaths. Several newpapers report that the synthetic drug is legally sold on the internet under names such as “M-CAT”, and “drone”, but is not subject to medical regulations because it is sold as plant fertiliser.

Detective Chief Inspector Mark Oliver, of Humberside police, reportedly told the BBC: “We have information to suggest these deaths are linked to M-CAT. We would encourage anyone who may have taken the drug or knows somebody who has taken the drug to attend a local hospital as a matter of urgency.” The substance is currently legal in the UK, but is part of an ongoing investigation by the Advisory Council on the Misuse of Drugs.

 

What is a 'legal high' drug?

Legal drugs and “legal highs” are substances used like illegal recreational drugs, such as cocaine or cannabis, but not covered by current drug misuse laws. They currently include a number of drugs such as mephedrone and salvia. Legal highs are marketed under dozens of different names, including, Legal E, Legal Cocaine, Fast Lane and Silver Bullet. To get advice on specific 'legal highs' and drugs talk to FRANK.

Although a drug may be referred to as being legal, this does not mean it is safe or approved for use; simply that it has not been declared illegal. For example they were banned last year, many common ‘legal highs’ were based on the drug GBL, BZP, and spice. Equally, the use of the term “legal drug” does not mean that a substance is a prescribed drug with a medical use. Because many legal highs are relatively new of and occupy a grey area within the law, they are often untested. This means no one can really be sure that they are safe.

 

What exactly is ‘meow meow’?

Meow meow is a common name for 4‐Methylmethcathinone, a synthetic substance based on the cathinone compounds found in the khat plant of eastern Africa, which locals chew for a amphetamine-like high. Meow meow can come in the form of capsules, tablets or white powder that users may swallow, snort or even inject. It acts as a stimulant and a "psychedelic", with reportedly similar properties to the drug ecstasy (MDMA).

Other street names for mephedrone, or meow meow, include 4MMC, M-CAT, meow, miaow or drone. It can be obtained relatively easily via the internet, where it is often sold as plant food, a “research chemical” or a “legal high”. It often features the label “not for human consumption”, which means it will not fall under the strict laws governing medical drugs. Meow meow may also come mixed with other stimulant substances or chemicals, or be an ingredient in other legal highs. 

A publication by the NorthWest Public Health Observatory reports that mephedrone can cost as little as £3 a hit.

 

What are its effects in the body?

Mephedrone users report that it stimulates the body, typically causing heightened awareness, excitement, alertness, lowered inhibitions and talkativeness. The NorthWest Public Health Observatory reports that the timing of the onset of effects can vary depending on how the drug was taken and whether the user has eaten food recently. Typically noticeable effects are likely to persist for two to three hours after being taken orally, but there is usually a one to four-hour period of insomnia after this.

However, effects of any recreational drug are always unpredictable and likely to vary from person to person and depending on the composition of a hit. A person taking mephedrone, or any other legal high, may experience paranoia, anxiety, overstimulation of the heart, sweating and chills, and effects on the nervous system, including light-headedness and fits. This is in addition to, or instead of, the “high” effects. The effects of recreational drug use can be as serious as coma or death.

 

Just how dangerous is mephedrone?

Although medical and scientific information on mephedrone is scarce, the risks are likely to be increased if it is used alongside alcohol, other stimulants or depressant substances. Many of the initial medical case reports on mephedrone suggest that it can particularly cause problems with breathing and the circulatory system, particularly when combined with alcohol. It seems sensible to assume that mephedrone is not safe unless rigorous scientific research proves otherwise.

 

What else do I need to know?

The Home Office sets out important advice to help parents talk to their children openly about the risks of drugs, both legal and illegal. Their advice on legal highs says that:

• You can never know what you’re taking in any drug, so the effects can be very unpredictable.
• Just because the drugs are legal to possess doesn’t mean they are safe.
• Legal highs can contain a range of potentially dangerous chemicals, and their chemical make-up changes all the time. This means you can never be 100% certain of what you have bought, and what the effects might be.
• Although legal, most of these substances are actually illegal to sell, supply, or advertise for human consumption, under medical legislation, due to their effects on the body.
• The chemicals in legal highs have, in most cases, never before been used as drugs, and their safety has not been tested.
• Suppliers may use descriptions such as bath salts, plant food, research chemicals, fertiliser and cleaning fluid, or statements such as “not for human consumption” in order to try to get around the law.
• Legal highs can carry a serious health risk and have been implicated in some cases of death.
• Risk is increased if the drug is combined with alcohol.

 

Where does the law stand?

In December last year some of the more common ‘legal highs’ were banned. These are:

• GBL and other chemicals derived by 1,4-Butanediol (1,4-BD) (to be criminalised when intended for human consumption only)
• BZP and its related compounds (mCPP, TFMPP etc)
• Synthetic cannabinoids (such as those found in ‘Spice’)

When Since the legislation came into force, GBL, BZP and their related compounds will come under class C legislation, the same class as ketamine and tranquillisers. Cannabinoid drugs such as “spice” now fall under higher, class B legislation, in line with cannabis and amphetamines.

Although it is illegal to supply or advertise mephedrone for human consumption it is not currently illegal to possess it. The Government and its Advisory Council on Misuse of Drugs (ACMD) constantly monitor the risks of both legal and illegal substances, and have set a goal to tackle legal highs that pose a significant risk to health. According to the Home Office its ongoing review of mephedrone and other cathinone compounds is one of its current priorities.

Although mephedrone has been linked with recent deaths, details of the latest cases are as yet largely unconfirmed and are the subject of ongoing police investigation.

There have been published case reports of two people admitted to A&E who were confirmed to have mephedrone in their bodies.

Links To The Headlines

Arrests after teenage M-CAT users die in Lincolnshire. BBC News, March 17 2010

Head teacher Mike Stewart: "We need help". BBC News, March 17 2010

Calls for ban on mephedrone after teenage deaths. The Guardian, March 17 2010

Arrests over Meow drug teen deaths. Daily Mirror, March 17 2010

Three arrested over deaths of teenagers believed to have taken ‘meow meow’. The Times, March 17 2010

Two held after ‘meow’ deaths. The Sun, March 17 2010

Police investigate deaths of two teens linked to mephedrone. The Daily Telegraph, March 17 2010

“Vitamin D is better than vaccines at preventing flu,” reported The Times. The newspaper said that children’s risk of getting flu could be halved if they take vitamin D, a finding that has implications for flu epidemics.

This trial of 430 schoolchildren in Japan found that taking daily vitamin D supplements in winter decreased their risk of seasonal flu, compared to taking an inactive tablet. The news headline is misleading, as the vitamin D supplementation was only compared with this inactive placebo, not with flu vaccines.

Vitamin D is produced through exposure to natural daylight and is also present in various food sources. Most people should therefore be able to gain all the vitamin D that they need without taking supplements. Exceptions to this include pregnant women, the elderly or people who cover up their skin or rarely go outdoors. These people are advised to take 10 micrograms (0.01mg) a day.

It is important not to take above the recommended daily dose of any supplements. The FSA recommends that taking 25 micrograms (0.025 mg) or less of vitamin D supplements a day is unlikely to cause any harm.

 

Where did the story come from?

This study was carried out by Mitsuyoshi Urashima and colleagues from the Jikei University School of Medicine in Tokyo and other hospital departments of Japan. The medical schoo provided financial support. The study was published in the (peer-reviewed) American Journal of Clinical Nutrition.

Overall, The Times reported this study accurately. But its headline (“Vitamin D better than vaccines”) is misleading, as it suggests that the vitamin was compared to vaccines. It has only been compared with an inactive placebo, so it has not been proved that the vitamin is more effective than flu vaccines.

 

What kind of research was this?

This was a randomised, placebo-controlled trial investigating how vitamin D supplementation affects the incidence of seasonal flu in school children.

This type of study, a randomised controlled trial, is the best way to investigate the effectiveness of a treatment. The trial was double blinded, meaning that neither participants nor researchers knew who was getting which treatment. Randomisation should balance out differences between the groups; important ones in this case being the varying amounts of vitamin D each child received naturally through their diet and daylight exposure, and their variable exposure to people with flu.

As the trial was only four months’ long, its findings do not indicate the longer-term effects of taking vitamin D supplements.

 

What did the research involve?

The trial was conducted in 12 hospitals in Japan between December 2008 and March 2009. Researchers enrolled 430 healthy schoolchildren aged between 6 and 15 (with an average age of 10). They did not include children who were taking vitamin D supplements as part of treatment for a specific disease. However, children could be included if they were taking vitamin and nutrient supplements for general health.

General medical questionnaires were completed by the parents that included information on the child’s health and family medical history. Parents were given tablet bottles containing either vitamin D or a placebo and told that the children should take three tablets, twice daily (total dose 1,200 international units [IU] of vitamin D, or inactive placebo).

The researchers assessed the participants’ compliance by seeing how many tablets there were left at follow-up sessions (one bottle should have been consumed within 15 days).

After the study, parents completed follow-up questionnaires on whether their children had caught influenza A (diagnosed by nose and throat swab by a doctor), which was the main outcome of interest to the researchers. Influenza B and other illnesses were secondary outcomes. They also questioned the child’s compliance with study drugs, typical consumption of oily fish, eggs and shitake mushrooms, outdoor activities, school absence and other possible adverse effects of the tablets.

 

What were the basic results?

Of the children who were enrolled, 334 (77.7%) completed the study, with a similar number of children dropping out from both the treatment and placebo groups. Compliance was reported to be 96% and was similar between groups. Influenza A was diagnosed in 49 children; 18 in the vitamin D group and 31 in the placebo group; which was calculated as a 42% risk reduction from taking vitamin D (relative risk (RR) 0.58, 95% confidence interval (CI) 0.34 to 0.99).

In subgroup analyses, a number of patterns in risk reduction were found. Risk of flu was significantly less in the treatment group only between days 30 and 60 of the study, not before or after this period.

Risk reduction was greatest in children who had not taken other vitamin D supplements before or during the study. The researchers found that 6% of those who developed flu in the treatment group and 16.5% of those with flu in the placebo group had never taken additional supplements of vitamin D (RR of flu with treatment: 0.36, 95% CI 0.17 to 0.79).

Risk reduction was also only significant for those who started nursery school after the age of three. This could be broken down into 7.5% of those with flu in the treatment group and 20.5% of those with flu in the placebo group (RR of flu with treatment: 0.36, 95% CI 0.17 to 0.78).

 

How did the researchers interpret the results?

The researchers conclude, “Vitamin D supplementation during the winter may reduce the incidence of influenza A, especially in specific subgroups of schoolchildren.”

 

Conclusion

This randomised controlled trial of 430 schoolchildren found that taking daily vitamin D supplements for the four winter months reduced children’s risk of being diagnosed with seasonal flu compared to taking an inactive tablet. There are a few important points:

• The Times headline, “Vitamin D better than vaccines”, is misleading, as it implies that the vitamin has been trialled against vaccines. It has only been compared with an inactive placebo drug, so there is no evidence that the vitamin is more effective than seasonal flu vaccines or any other vaccine, including the swine flu vaccine.
• Subgroup analyses found that there were some differences in the effect of vitamin D depending on certain characteristics, such as if the child had never taken supplements before, or if they started school later than their peers. However, there were very small numbers of children with flu in each of these groups (eight in the treatment group who had never before taken supplements vs. 22 in the placebo group). When calculating differences between such small numbers of cases there is a higher likelihood of chance findings.
• The trial did not last long enough to examine the long-term safety effects of taking vitamin D. In particular, the researchers say they did not measure the potentially adverse effects of vitamin D on calcium metabolism. People taking supplements should not take more than the recommended daily maximum.
• The sample was relatively small and the research needs to be replicated in larger numbers of people over a longer period to confirm these results.
• Although compliance was reportedly high in this study, this may be an issue in real life situations. Few children are going to be happy taking three tablets twice a day on a regular basis.

Vitamin D is produced through our exposure to natural daylight and is also present in various food sources including oily fish, dairy and fortified cereals and margarine. Most people should therefore be able to gain all the vitamin D that they need through natural sources, without needing to take supplements. Exceptions to this include pregnant women, the elderly or people who cover up their skin or rarely go outdoors.

It is important not to take more than the recommended daily dose of any supplement. 

Links To The Headlines

Vitamin D better than vaccines at preventing flu, report claims. The Times, March 17 2010

Links To Science

Urashima M, Segawa T, Okazaki M, et al. Randomized trial of vitamin D supplementation to prevent seasonal influenza A in schoolchildren. American Journal of Clinical Nutrition 2010; March 2010

A genetic discovery means that “damaged human limbs could one day regrow by themselves”, according to the Daily Mirror. The reported research found that switching off a particular gene in mice meant that they could grow healthy tissue to replace tissue that was missing or damaged.

This study highlights a role for this gene, called p21, in tissue regeneration in mice. However, while many biological pathways are similar across different species, there may still be differences. Therefore these findings in mice will need confirmation that they apply in human cells and tissues too.

The healing of a wound is a complex process, and a number of factors will play a contributing role. This research provides a better understanding of the process and may contribute to the development of medical approaches to improve wound healing. However, such developments will take time, and we are still a very long way off being able to regrow entire human limbs.

 

Where did the story come from?

Dr Khamilia Bedelbaeva and colleagues from the Wistar Institute in Philadelphia and Washington University carried out this research. The study was funded by the US National Institutes of Health and several research support foundations, including the Harold G. and Leila Y. Mathers Foundation, the F.M. Kirby Foundation and the W.W. Smith Foundation. The study was published in the peer-reviewed scientific journal Proceedings of the National Academy of Sciences USA.

The Daily Mirror, Guardian, and Daily Express have reported on this complex research. The Guardian provides good overall coverage of it, while the Mirror and Express focus more on the possibility of regrowing lost limbs in humans, which is a distant hope. The Express does include a quote from the researchers saying that to get major organs or limbs to repair “will need decades of work”.

 

What kind of research was this?

This was animal research attempting to identify genes that are involved in the regeneration of damaged or missing tissue. Some animals, such as salamanders, can regenerate different organs, tissues, and even limbs if they are lost or damaged, without leaving scars.

This ability is generally not seen in mammals, but one strain of mice called the “Murphy Roths Large” (MRL) mouse can partially regrow amputated toes and grow tissue to close puncture wounds to their ears without scarring. The researchers investigated this strain to see how they differed from other strain that did not have this healing capability.

This type of study helps researchers to understand the biology of tissue regeneration. However, although many biological pathways share similarities across different species there are a number of differences. This means that findings in mice may not be directly applicable to humans, and any findings would need to be confirmed using tests on human tissue. Equally, even if laboratory tests on human cells confirm the presence of a particular biological pathway, this does not necessarily mean that this knowledge will lead to a successful treatment for human disease.

 

What did the research involve?

The researchers took uninjured skin cells from MRL mice and from normal mice and grew them in the laboratory. They then compared the characteristics of these cells to see how they differed throughout their cellular lifecycle. The study particularly focused on how they prepare for and undergo cell division, as these functions are important in repairing and regrowing damaged or missing tissue.

The researchers also looked specifically at the activity of a gene called p21, which regulates whether cells are able to divide and plays a role in stopping damaged cells from dividing. They looked to see whether wound healing in mice that had been genetically engineered to lack the p21 gene differed from wound healing in normal mice.

 

What were the basic results?

The researchers found that uninjured skin cells of MRL mice had characteristics similar to the cells of animals that are able to regenerate tissue successfully, such as salamanders. These skin cells also had similarities to mammalian stem cells, which can also regenerate tissue.

In particular, a greater proportion of the MRL skin cells had copied their DNA in preparation for division into two cells if needed; for example, if they needed to regenerate lost or damaged tissue. Cells that do this are more likely to be able to regenerate quickly. In the non-MRL mice, fewer skin cells had reached this stage.

The p21 gene, that can stop cells dividing in unfavourable conditions, is not active in mouse embryo stem cells. The researchers found that this division-blocking gene was also inactive in the MRL cells. Mice genetically engineered to lack the p21 gene showed enhanced healing of damaged ear tissue akin to that found in MRL mice, rather than the limited healing ability of normal mice.

 

How did the researchers interpret the results?

The researchers concluded that there is a link between how cells prepare for and undergo cell division (the cell cycle) and tissue regeneration.

 

Conclusion

This study illustrates a role for the p21 gene in tissue regeneration in mice. Although many biological pathways share similarities between different species, there may also be distinct differences. Therefore findings on p21 in mice will need confirmation in human cells and tissues. Wound healing is a complex process, and even if p21 has a role in human healing a number of additional factors will also play a role.

This study may lead to a better understanding of the human healing process. Realistically, it would be more likely to help in the development of treatments to aid wound healing rather than growing back whole limbs. However, even developing a treatment for wound healing based on this research would take a long time, and unfortunately such a treatment may eventually prove to unfeasible or unsuccessful.

Links To The Headlines

Regrow limbs by yourself. Daily Mirror, March 16 2010

Genetic discovery promises healing without scars. Guardian, March 16 2010

Gene switch that helps lost limbs grow back. Daily Express, March 16 2010

Links To Science

Bedelbaeva K, Snyder A, Gourevitch D et al. Lack of p21 expression links cell cycle control and appendage regeneration in mice. PNAS Published online before print March 15, 2010

“Hair loss 'almost halves the risk of prostate cancer',” the Daily Mail reported. The news is based on a study looking at hair loss in about 2,000 men aged between 35 and 74, about half of whom had prostate cancer.

This study does appear to suggest a possible association between male pattern baldness that begins before the age of 30, and a reduced risk of prostate cancer. No link was found between baldness in later life and prostate cancer risk. However, other studies have had contradictory findings, with some linking hair loss to an increased risk of prostate cancer. This study also has some limitations, including having to rely on men’s recollections of whether they began to lose their hair by age 30 – up to 44 years in the past for some.

These inconsistent results and the limitations to the current study make it difficult to draw firm conclusions about the relationship between male pattern baldness and prostate cancer. Further well-designed prospective cohort studies looking at this question are needed.

 

Where did the story come from?

Dr Jonathan L Wright and colleagues from the University of Washington and Fred Hutchinson Cancer Research Center carried out this research. The study was funded by the National Institutes of Health and the Fred Hutchinson Cancer Research Center. The study was published in the peer-reviewed medical journal Cancer Epidemiology.

The Daily Mail and The Daily Telegraph report the research and both papers make the important point that other studies have had different findings. However, both papers concentrate on the figure of a 45% reduction in the risk of prostate cancer – the largest risk reduction calculated in the study. This figure only applies to men aged 60 or over who showed hair loss at the top of the head and forehead at age 30, a fact not reported by the newspapers. In addition, the small numbers of men in this analysis are likely to make it less reliable than the overall analyses, which showed smaller reductions in risk.

 

What kind of research was this?

This case-control study looked at the relationship between early onset male pattern baldness and prostate cancer. The researchers thought that similar factors might be involved in the development of the two conditions as they are both affected by how much testosterone men’s bodies produce. They report that previous studies have had mixed conclusions – some finding male pattern baldness to be associated with an increased risk of prostate cancer, with others finding no such association. However, some of these studies were quite small and assessed male pattern baldness in different ways.

This study design compares past exposures/events in people with a disease and those without the disease. If an exposure/event is more common in people with the disease than those without the disease, then it could potentially be related to the cause of the disease. This type of study has some limitations. Firstly, cases and controls need to come from the same population, so that any differences between them are more likely to be related to the disease. Secondly, this type of study is usually retrospective – looking back at exposures in the past. It can be difficult for people to remember what happened in the past, which can reduce the reliability of results. If a link is found in a case-control study, ideally this link should be confirmed in a prospective cohort study that follows people over time and looks at whether their hair loss is related to their risk of prostate cancer later in life.

 

What did the research involve?

The researchers enrolled 999 men aged 35 to 74 who had been diagnosed with prostate cancer between 2002 and 2005 in one county in Washington (cases), and 942 age-matched men without prostate cancer (controls). They then assessed the men’s hair loss at age 30, and in the year before diagnosis for cases, or a similar date (called the reference date) for matched controls. Whether or not the extent of hair loss at these two ages differed between cases and controls was then assessed.

Participants gave information about their lifestyles, medical and family history, whether they had been screened for prostate cancer in the past five years, and whether they used drugs that could affect their testosterone metabolism, such as finasteride (a drug used to treat male pattern baldness and some prostate problems). Hair loss was assessed by showing participants drawings of heads with different extents of hair loss and asking which one best represented their hair loss at the two ages of interest. The drawings showed men with little or no hair loss, loss at the forehead only, or loss at the top of the head and the forehead.

Comparisons were then made between cases and controls in the odds of having hair loss at either time point.

The researchers also looked at whether the pattern of hair loss – at forehead only, or at the top of the head and forehead – had an effect, and whether effects were different in men aged 60 or over. Analyses took into account the men’s ages, race, prostate screening history, family history of prostate cancer, body mass index and use of finasteride.

 

What were the basic results?

The researchers found that about 25% of men who had prostate cancer had shown hair loss at age 30, compared to about 20% of men who did not have prostate cancer. This represented a 29% reduction in the odds of prostate cancer in men who had hair loss at age 30 (odds ratio [OR] 0.71, 95% confidence interval 0.56 to 0.91). If they looked only at men who were aged 60 and over at cancer diagnosis, the reduction in risk was 37% for men who showed hair loss at age 30.

There was no difference in the proportion of men in the case and control groups who only started losing hair after the age of 30, suggesting that hair loss after 30 was not related to prostate cancer risk.

Different patterns of baldness were associated with different reductions in risk of prostate cancer. Loss of hair at the forehead only and loss of hair at both the forehead and top of the head at age 30 were associated with a reduction of 25% to 31% in the odds of prostate cancer. This reduction was only statistically significant for loss of hair at the forehead only – possibly because this type of hair loss is more common. When looking at men aged 60 and over, men showing loss of hair at the top of the head and forehead at age 30 had a 45% reduction on the odds of prostate cancer compared to men with little or no hair loss.

 

How did the researchers interpret the results?

The researchers concluded, “early-onset [male pattern baldness] was associated with a reduced relative risk of [prostate cancer] in this population-based study”. They suggest that further research into why this may be the case is needed.

 

Conclusion

Though this study suggests there is an an association between early onset male pattern baldness and risk of prostate cancer, the findings are not conclusive. Its strengths include its relatively large size and that it assessed men’s baldness at a standard point in time (at age 30). However, there are a number of points to consider:

• Hair loss was assessed retrospectively, and this may reduce the reliability of these reports, particularly for hair loss at age 30, which may become increasingly difficult to recall the further in the past this date was.
• Some of the analyses of specific subgroups of men, particularly those examining patterns of baldness in men aged 60 and over, only included small numbers of men, and therefore these results should be interpreted cautiously.
• Although the researchers took into account some factors that could be affecting the results in their analyses, other unknown or unmeasured factors could be having an effect.
• The researchers report that some previous studies have produced conflicting results, whereby hair loss had been associated with an increased risk of prostate cancer. The researchers suggest that this is because of differences in when hair loss was assessed. A more detailed systematic review and analysis of all studies on this issue would give a clearer idea of whether male pattern baldness is associated with prostate cancer in any way.

The conflict between these findings and those from previous studies – and the limitations of the current study – mean that it is difficult to draw firm conclusions about the relationship between male pattern baldness and prostate cancer. Further well-designed prospective cohort studies looking at this question are needed.

Links To The Headlines

Good news for bald men at last: Hair loss 'almost halves the risk of prostate cancer'. Daily Mail, March 16  2010

Baldness linked to good health. The Daily Telegraph, March 16 2010

Baldness 'could be good for your health' say scientists. BBC News, March 16 2010 

Links To Science

Wright JL, Page ST, Lin DW, Stanford JL. Male pattern baldness and prostate cancer risk in a population-based case–control study. Cancer Epidemiology 2010; published online February 22 2010

 

The secret of keeping fit is to “do less exercise”, says the Daily Express. The newspaper claims that new research shows that short bursts of intense activity are enough to keep most people fit, “blowing away the myth that staying in shape takes hours of dedication”.

The news is based on a small study in seven healthy men, comparing their fitness levels before and after a two-week programme of short cycling sessions. After the course of six sessions the researchers found the men had improved exercise performance and metabolism in their muscles.

However, this study did not compare this exercise regime with others, or look at any long-term benefits of exercise, such as any reduction in heart disease or obesity. This, and other limitations, means the research does not support the claims that short bursts of intensive exercise offer as much benefit as the officially recommended, more frequent, but less intensive exercise. Government guidelines suggest 30 minutes of moderate-intensity exercise taken five times a week.

 

Where did the story come from?

This study was carried out by Dr Jonathan Little and colleagues from McMaster University in Canada. The research was funded by the Natural Sciences and Engineering Research Council of Canada and individual researchers were supported by grants from various health research organisations. The study was published in the peer-reviewed Journal of Physiology.
 
Newspapers have reported on the study in some detail, but most fail to discuss the shortcomings of this small, non-comparative study. A few do report that the short-term changes assessed in this study, muscle metabolic capacity and functional performance, do not equate with long-term cardiovascular health. This is very preliminary evidence towards the reported theory that “less really can be more when it comes to exercise”.

 

What kind of research was this?

In this before-and-after experiment, seven men undertook six training sessions over a period of two weeks, with researchers comparing their performance and muscle health before the sessions with that seen after the training programme.

 

What did the research involve?

Seven healthy men were enrolled in this study. Their average age was 21, and they were reported to be healthy and “recreationally active” two or three times a week, although none were “engaged in a structured exercise training programme”. They were asked to maintain normal diet and routine levels of physical activity throughout the study but to refrain from any sporting activities beyond the exercise programme.

During each of their six exercise sessions (on Monday, Wednesday and Friday for two weeks), they did short bursts of high-intensity cycling. In each session they performed 8 to 12 repetitions of a one-minute burst at 100% of their individual maximum power output (as determined by previous tests), followed by a recovery period, which was 75 seconds of low-intensity cycling. The time commitment for each training session was around 30 minutes including warm-up and recovery.

Timed cycling trials were used to assess the participants’ exercise capacity 72 hours after the end of their final training session. Tissue samples were also taken from their “skeletal muscle”, the  type of muscle tissue that powers movement and activities like running, walking and lifting. These tissue samples (taken from a muscle in the quadriceps) were assessed for their protein content and general metabolism and compared with a tissue sample taken prior to training.

Researchers used a statistical test called a “paired Student’s t-test” to compare the participants’ results after their training with their results prior to it. This is an appropriate statistical analysis method that takes into account the fact that this is a before-and-after study.

 

What were the basic results?

The researchers found that the time taken to complete the cycling trials improved by about 10% after training and that there was an increase in the average power during the trial. The activity of various enzymes in muscle cells also improved, as did the cells' protein content.

 

How did the researchers interpret the results?

The researchers say that the results of their study demonstrate that low volume HIT (high-intensity training) is a “potent stimulus for increasing skeletal muscle [energy releasing] capacity and improving exercise performance”. They also say that the results shed light on ways in which exercise training potentially promotes changes in the metabolism in skeletal muscle.

 

Conclusion

This small observational study has demonstrated an improvement in muscle health following low-volume, high-intensity training in seven healthy men. There are a number of points to keep in mind when considering the results of this research, including:

• The small sample size. The study included only seven men with an average age of 21. The researchers report that they were healthy and “recreationally active two or three times a week”, but that “none were engaged in a structured exercise training programme”. The results of the study cannot therefore be taken to represent the wider population, particularly older people.
• This study lacked a comparator group. While newspapers have reported that short bursts of high-intensity exercise are as effective as longer-term training is, the research featured no direct comparison between the two. Although the researchers say that their programme was “designed to be more practical and attainable for the general population”, they do not claim that their exercise programme was better than other types or durations of exercise.
• Given that the participants were all healthy, active young men, it is likely that they were doing other forms of activity and exercise outside of their experimental training programme. The Department of Health recommendations on physical activity say that activities of daily life, including walking, gardening and cleaning, can all count as forms of exercise.
• The Department of Health document At least five a week acknowledges that there is “growing support for the benefits of accumulating activity in shorter bouts of activity of 10 minutes or more, interspersed throughout the day”, and reports that equivalent total volumes of short activities have demonstrated positive effects similar to a single, long bout of activity. This particular study, although using a weak design, adds further evidence that low-volume, high-intensity training is good for muscles and their metabolism. However, how well it compares to other regimens is yet to be established.
• Research needs to establish how suitable short bursts of intensive exercise are for different groups of people, particularly older people or people with health problems like arthritis or high blood pressure.

These findings are interesting, but it remains to be seen whether the improvements in muscle metabolism and exercise performance observed in this study are the same as those seen with other levels of exercise. Furthermore, it remains to be seen whether they will translate into the longer-term health benefits (such as reductions in heart disease, strokes and obesity) that are associated with the levels of exercise recommended by the Department of Health.

While this type of research may suggest theoretical benefits to short bursts of intensive exercise, it does not change the fact that regular, moderate-intensity exercise is good for our health. The current recommendations of 30 minutes’ physical activity a day, five days a week, are based on rigorous reviewing of the evidence and discussion with experts.

Links To The Headlines

Short bursts of exercise will make you fitter quicker. The Independent, March 15 2010

10 minutes of fast sprints beat 10 hours of cycling. Metro, March 15 2010

Short blasts of exercise as good as hours of training, scientists find. The Daily Telegraph, March 12 2010

The secret of keeping fit- Do less exercise. Daily Express, March 12 2010

Links To Science

Little JP, Safdar A, Wilkin GP et al. A practical model of low-volume high-intensity interval training induces mitochondrial biogenesis in human skeletal muscle: potential mechanisms. The Journal of Physiology, 588, 1011-1022. March 15 2010

“Two key treatments do not halt diabetes in people with early signs of the disease,” BBC News reported. The story is based on a large trial assessing the effects of two approved diabetes medications, valsartan and nateglinide, on the development of diabetes and cardiovascular disease in high-risk populations.

As BBC News reports, the results indicate that neither drug reduced the risk of cardiovascular disease, and there was only a small reduction in the risk of diabetes with valsartan. This trial was in people showing an early warning sign for diabetes, not in people with the disease. Anyone taking these drugs should not change their treatment on the basis of this study.

There is good evidence that changing diet and exercise are the best ways of reducing the risk of diabetes in those with raised glucose levels, an early indicator of the condition. Systematic reviews in high risk populations have shown that a change in physical activity and diet could reduce the number of new diabetes cases by about 37%. In comparison, this trial found that valsartan reduced diabetes by only 14%.

 

Where did the story come from?

The study was carried out by the NAVIGATOR study group, consisting of a number of researchers with affiliations to various research and medical institutions in the UK and around the world. The study was funded by Novartis Pharma, the manufacturer of both drugs trialled in this research. The papers were published in the (peer-reviewed) New England Journal of Medicine.

This large randomised controlled trial in people with impaired glucose tolerance across 40 countries was accurately described by BBC News. The results of the study are published as two separate papers in the medical journal, one for each drug.

 

What kind of research was this?

The NAVIGATOR study (Nateglinide and Valsartan in Impaired Glucose Tolerance Outcomes Research) is a large, double-blind, randomised-controlled trial. This research investigated whether two drugs, nateglinide (a diabetes treatment) and valsartan (a blood pressure treatment) could lower the risk of developing diabetes or new cardiovascular events in people at higher risk of these conditions. Both drugs were used in combination with a lifestyle-modification programme.

Specifically, the participants had impaired glucose tolerance (where the concentration of glucose in the blood soon after drinking a glucose drink is raised) and had known cardiovascular disease or cardiovascular risk factors. Previous research suggests that impaired glucose tolerance is an early warning sign for the later development of diabetes and is linked closely with cardiovascular risk, more so than the level of blood glucose after fasting. The means that impaired glucose tolerance may be a distinct target for therapies to prevent diabetes.

 

What did the research involve?

The researchers recruited 9,306 participants from 806 centres in 40 countries. All had impaired glucose tolerance and one or more cardiovascular risk factors or known cardiovascular disease. The participants were randomised to receive just nateglinide (up to 60mg three times a day), just valsartan (up to 160mg a day), both drugs, or a placebo.

All participants were also given a lifestyle-modification programme aimed at helping them to achieve and maintain 5% weight loss, to reduce their intake of saturated and total dietary fat and to increase their physical activity to 150 minutes a week. Patients were seen every six months for the first three years and then annually for a total of about six-and-a-half years. During each study visit, the participants’ fasting plasma glucose levels were measured. Oral glucose tolerance tests were performed annually.

The main outcomes of interest were the number of people who developed diabetes and the number who experienced events related to cardiovascular health. There were two cardiovascular endpoints, a “composite cardiovascular” outcome (nonfatal myocardial infarction, nonfatal stroke, hospitalisation for heart failure or unstable angina or arterial revascularisation) and a “core cardiovascular” outcome (death from a cardiovascular cause, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure).

Two papers based on this research have been published. The first looks at the effects of nateglinide (with or without valsartan) compared to placebo (with or without valsartan). The second compared the effects of valsartan (with or without nateglinide) with placebo (with or without nateglinide). The researchers also broke down their analysis by a variety of factors including gender and levels of fasting glucose, to see whether there were any particular differences between subgroups.

 

What were the basic results?

The groups were broadly similar at baseline (beginning of the study) to each other on a range of characteristics, as expected in a properly randomised study. There were 1,532 (33%) people in the valsartan group (with or without nateglinide) who developed diabetes, compared with 1,722 (37%) with placebo (with or without nateglinide). This indicated a significant 14% reduction in the risk of diabetes (Hazard Ratio (HR) 0.86, 95% Confidence Interval (CI) 0.80 to 0.92).

The ‘composite cardiovascular’ outcome occurred in 672 people (15%) in the valsartan group and 693 people (15%) in the placebo group, while the core cardiovascular outcome occurred in 8% of people in both groups. Statistical tests show the drugs had no significant effect on the risk of having either a composite or core cardiovascular event.

In people taking nateglinide (with or without valsartan), 1,674 (36%) developed diabetes compared to 1,580 (34%) of people receiving a placebo (with or without valsartan). This represented a non-significant increased risk of diabetes with treatment (HR 1.07, 95% CI 1.00 to 1.15).

For cardiovascular events, 658 people (14%) experienced a composite cardiovascular event in the nateglinide group (with or without valsartan), compared with 707 (15%) in the placebo group (with or without valsartan). This represents a non-significant change in risk (HR 0.93, 95% CI 0.83 to 1.03). About 8% in each group experienced the core cardiovascular outcome (no significant difference between the groups). More patients in the neteglinide group reported hypoglycaemia.

 

How did the researchers interpret the results?

When combined with a lifestyle intervention, valsartan at a daily dose of 160mg reduced the risk of diabetes but did not affect cardiovascular outcomes in patients with impaired glucose tolerance. The researchers say that no safety concerns were identified.

They conclude that nateglinide did not reduce the incidence of diabetes or cardiovascular outcomes for people with impaired glucose tolerance and cardiovascular disease or cardiovascular risk factors, compared with placebo. The drug was given at a dose of 60mg, three times a day, and was combined with a lifestyle-modification programme.

 

Conclusion

Overall, this large, industry-funded study found that nateglinide had no effect on the incidence of diabetes or cardiovascular disease in this population and that valsartan had a small effect on diabetes risk but not on cardiovascular outcomes.

This was well-conducted research and used the most robust study design for comparing the effectiveness of one treatment with another. There are some points to highlight, including the fact that 20% of participants in each trial arm dropped out of the study (they either withdrew their participation, died or were lost in the follow-up). Other important points relating to the research and its interpretation are raised in an accompanying editorial in the journal, written by Dr. David Nathan from the Diabetes Centre at Harvard Medical School.

The main aim of the trial was to determine whether using nateglinide or valsartan to lower glucose could reduce the risk of diabetes and cardiovascular outcomes in high-risk individuals when used in combination with a lifestyle-modification programme.

However, Dr Nathan explains that the study was not able to answer this question because the average glucose levels in the nateglinide group two hours after a glucose challenge were higher than in the placebo group in the annual oral glucose-tolerance tests. This is a paradoxical finding that the researchers have attempted to explain saying that it may be because the nateglinide was not administered on the mornings of the glucose tolerance tests (although there is no data to support this).

The editorial also says it is possible that the effects of the medications may have been masked by the large effects of the lifestyle intervention that all participants were receiving. The finding that valsartan did not affect cardiovascular outcomes is surprising and contradicts other research. It is possible that the high drop-out rates and the use of other medications in the placebo group may explain the lack of significance here.

Dr. Nathan concludes that these results do not support the theory that reducing postprandial hyperglycemia has a specific role in preventing diabetes or reducing cardiovascular disease. He says, “The prevention of diabetes remains a critical public health priority, but for now we should steer away from these two drugs and use effective lifestyle interventions and, in selected persons, metformin to combat the epidemic.”

This is sensible advice, as systematic reviews have shown a reduction of about 37% of new cases of diabetes with physical activity and diet for people whose profiles were similar to those in this trial. This compares with only 14% with the drug valsartan used in this trial.

Diet and exercise remain the most important way of reducing the risk of developing diabetes in those showing early signs of elevated glucose.

Links To The Headlines

No quick drug fix for high diabetes risk. BBC News, March 15 2010

Links To Science

Nathan DM. Navigating the Choices for Diabetes Prevention. NEJM [published online] March 14 2010

The NAVIGATOR Study Group. Effect of Nateglinide on the Incidence of Diabetes and Cardiovascular Events. NEJM [published online] March 14 2010

The NAVIGATOR Study Group. Effect of Valsartan on the Incidence of Diabetes and Cardiovascular Events. NEJM [published online] March 14 2010

“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 β 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.

This news is based on a trial on the effectiveness of therapeutic massage in treating generalised anxiety disorder (GAD), compared to thermotherapy (a heat-based treatment) 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