ScienceHealthyLongLife by Crabsallover

Aspirin - Peter Rothwell on Kausik Ray data

2012-01-10T22:16:00.000Z

reposted from: http://www.theheart.org/article/1338803.do

crabsallover highlights, key points, comments / links.

I await further trials analysis by Peter Rothwell later during 2012 which may show whether their is a net benefit of taking 75mg a day aspirin when heart disease, stroke and cancer reduction are compared with risk of fatal and non fatal stomach, brain and eye bleeding, in the over 50s.

Aspirin in primary prevention: New meta-analysis finds bleeding outweighs benefits for most

London, UK - A new meta-analysis said to provide "the largest evidence to date regarding the wider effects of aspirin treatment in primary prevention" has shown that cardiovascular benefits are offset by an elevated risk of bleeding [1].

Senior author Dr Kausik Ray (St George's University of London, UK) commented to heartwire: "On a routine basis I would not recommend aspirin use in primary prevention. And it certainly should not be put in a polypill for mass use."

The current study did not find a significant reduction in cancer mortality. However, the lead author of a previous meta-analysis that did show a reduction in cancer death with aspirin says follow-up in the current study was not long enough to show such an effect.

The new analysis, published online January 9, 2012 in the Archives of Internal Medicine, included nine randomized placebo-controlled trials with a total of 100 000 participants. Results showed that during a mean follow-up of six years, aspirin treatment reduced total cardiovascular events by 10%, driven primarily by a reduction in nonfatal MI, but there was a 30% increased risk of nontrivial bleeding events. The number needed to treat to prevent one cardiovascular event was 120, compared with 73 for causing a nontrivial bleed.

Effect of aspirin on vascular and nonvascular outcomes or death

Event	Odds ratio (95% CI)
Cardiovascular events	0.90 (0.85-0.96)
Nonfatal MI	0.80 (0.67-0.96)
Cardiovascular death	0.99 (0.85-1.15)
Cancer mortality	0.93 (0.84-1.03)
Nontrivial bleed	1.31 (1.14-1.50)

Possible benefit in those at high risk

The authors conclude that the "rather modest benefits" and the significant increase in risk of bleeding do not justify routine use of aspirin in the primary-prevention population. They say that further study is needed to identify subsets that may have a favorable risk/benefit ratio. They note that their results suggest an increased risk of nontrivial bleeding in individuals receiving daily (vs alternate-day) aspirin treatment and a particularly unfavorable risk/benefit ratio for individuals at lower baseline cardiovascular risk.

An editorial accompanying the paper suggests that aspirin may be considered in patients with a CHD risk of more than 1% per year [2], but Ray said he thought that was an "oversimplification" of the results.

"There may be a benefit in higher-risk individuals, and there is a case for personalized medicine here. But we showed that as the event rate increased in the placebo group, the reduction in MI with aspirin also increased, but so too did the bleeding risk. The bleeding risk is always greater than the MIs prevented, but it depends on whether you think a nonfatal MI is worse than a significant bleed. So we could do better if we knew who would bleed and who would have an event. I think we need a dual risk score as is done for warfarin."

The cardiovascular results from this latest analysis are in line with those from the 2009 Antithrombotic Trialists' (ATT) Collaboration, and there seems to be agreement on the conclusions regarding heart disease. But there is less agreement on the use of aspirin for the prevention of cancer.

Disagreement over cancer data

Lead author of last year's analysis showing a reduction in cancer mortality with aspirin, Dr Peter Rothwell(University of Oxford, UK) commented to heartwire: "This new meta-analysis just looks at the overall study results, and most of the studies only had three to four years of follow-up. That is not long enough to see a major effect on cancer mortality. In contrast, in our meta-analysis published last year we obtained individual patient data and followed patients long-term after the trials had finished, and in this way we were able to show a significant and impressive effect on cancer mortality."

Rothwell estimates that it takes at least five years to show an effect on cancer deaths, "but after this point you see quite an impressive effect." He noted that the new study also included both alternate and daily aspirin trials, but "all previous work has suggested that aspirin needs to be given every day to prevent cancer."

Rothwell says all previous work has suggested that aspirin needs to given every day to prevent cancer (NOT every other day)

He added: "Their results are completely compatible with our results. They did show a trend toward a reduction in cancer mortality, which we believe would have become significant if they had longer-term data or if they looked at individual patient data."

The UK newspapers were today full of reports saying there is no benefit of aspirin in cancer prevention, exactly the reverse of the headlines after Rothwell's study came out last year. Rothwell says he is concerned about this. "The message today that aspirin does not prevent cancer is premature.

The current study should not change advice on taking aspirin as a healthy person. It does not offer any additional information that we don't already know. We need to think about both risk of heart disease and cancer, and in general heart disease risk is coming down while cancer risk is increasing. There does appear to be a cancer benefit with long-term use, so if there is a family history of cancer I would think about taking aspirin. We have more studies with individual patient data coming out soon that will shed more light on the issue."

Rothwell says more studies with individual patient data coming out soon that will shed more light on the issue.

More data coming soon

Rothwell says official guidance on primary prevention varies from country to country. "At the moment, the guidelines on primary prevention are just focused on heart disease. They have not looked at the cancer data. There are some new guidelines due to come out over the next year, and these should start to discuss the cancer findings. "

Ray, however, is not so convinced by the cancer data. "Our meta-analysis is much larger than Rothwell's. They had 25 000 individuals whereas we have more than 100 000 patients. As usual, in this situation, when you see the bigger picture, you see 'regression to the truth.' "

Ray claims that because his meta analysis is bigger it is getting closer to the truth! Is that necessarily true?? Sounds like an over simplification to me.

Ray commented to heartwire that assuming the trend toward fewer cancer deaths in the current analysis was real, the use of aspirin would produce three and half extra nontrivial bleeds for one cancer death prevented. But he suggested that the cancer data may be biased. "Cancer often shows up as bleeding, and if you are taking aspirin, you are more likely to bleed so are more likely to be investigated, which could affect survival." He also points out that Rothwell's study mixed primary- and secondary-prevention populations, while his study looked at only healthy individuals.

He added: "The cancer data are far from certain. The major reason to give aspirin is to prevent heart attacks and strokes, and in healthy people this benefit is outweighed by the risk of bleeding. Aspirin is not the same as statins, which are known to reduce mortality in primary prevention. Aspirin doesn't affect atherosclerosis; it modifies plaque rupture, which is the final step. That is why it works better in patients with established heart disease. Primary-prevention efforts are much better directed at the basics of diet, exercise, and smoking and reducing cholesterol and blood pressure."

Aspirin - risks and benefits

2012-01-10T21:45:00.001Z

reposted from: http://www.bbc.co.uk/news/health-16479187 - Fergus Walsh, BBC reports

crabsallover highlights, key points, comments / links.

Listen to John Humphrys talk to Kausik Ray today about use of aspirin for healthy people and to Peter Rothwell last year. Further comment and related news stories.

Low dose aspirin is widely given to people with heart problems

More evidence has emerged of the conflicting benefits and risks of aspirin.

An analysis of nine medical trials involving over 100,000 people without a history of cardiovascular disease found that aspirin was more likely to do them harm than good.

Half the participants took aspirin, the other half a placebo; the studies lasted on average six years.

The researchers, writing in the Archives of Internal Medicine, found aspirin reduced the risk of cardiovascular disease by 10% but this was offset by a 30% increase in the risk of serious internal bleeds.

Professor Kausik Ray from St George's University of London told me: "Taking aspirin resulted in one fewer fatal heart attack for every 162 people over a six-year period. But among the same group you'd have about 2.5 extra serious bleeds, in the stomach or in the back of the brain, which could be fatal."

Whenever studies like this are published it immediately worries people who are taking the medication in question. So let's be clear. The strong advice - from these researchers and from other experts - is that those WITH a history of cardiovascular disease - such as heart attack or stroke - should continue with daily aspirin.

This is what's known as secondary prevention. And the evidence shows it works.

But aspirin is also prescribed as a primary prevention technique - for those without cardiovascular disease but who may be considered at risk of these conditions.

Indeed in 2005 guidelines were published which recommended low-dose daily aspirin for the over-50s who had a risk of cardiovascular disease - such as high blood pressure.

The guidelines are in the process of being updated and will be published later this year.

Dr Mike Knapton, associate medical director of the British Heart Foundation, welcomed the new research: "This is really helpful as it's been a bit of a murky area about who should receive aspirin. Now it's clear. If you have established heart disease you should take aspirin (unless there are contraindications) and if you don't fall into that category, then you should not."

Dr Knapton said simply being overweight, over 50, or with high blood pressure, were not enough on their own, despite them being risk factors. To fall into the group with cardiovascular disease you need to have symptoms such as angina (heart pain), and clogged arteries diagnosed following tests.

This research adds to other evidence that aspirin should only be used to ward off heart attacks and strokes in those with obvious cardiovascular disease.

This study does not settle another question - whether daily low dose aspirin can help prevent cancer over the long term. The researchers found no benefit over six years, but they admit that the effects of long-term use might not show up with regard to cancer until much later.

A major analysis of studies in 2010 (by Peter Rothwell) suggested daily low-dose aspirin could have a significant protective effect. Researchers at Oxford University followed up patients over two decades and found their overall risk of dying from cancer was cut by a fifth. That study suggested that the cancer prevention benefits outweighed the risks of internal bleeding.

Not for the first time, there is conflicting evidence on the effects of aspirin which - hopefully - future studies will resolve.

Update 11th January by Fergus Walsh

Thanks for your questions. I decided to take a daily low-dose aspirin following Prof Peter Rothwell's research last year based on the possible cancer reduction risk. I am continuing with that, but stress it is a personal decision - not a proposal to any readers of this blog. You can read my original blog post here.

Have two alcohol-free days each week

2012-01-10T21:24:00.001Z

reposted from: http://www.nhs.uk/news/2012/01January/Pages/avoid-alcohol-2-days-per-week.aspx

crabsallover highlights, key points, comments / links.

MPs have called for “two alcohol-free days each week and clearer guidelines on drinking”,The Guardian and other news sources reported. The news is based on a new report by the House of Commons Science and Technology Committee, which examined the UK’s alcohol guidelines.

Current Department of Health guidance recommends that men should not regularly drink more than 3–4 units of alcohol a day, while women should not regularly drink more than 2–3 units. “Regularly” is defined as drinking every day or on most days of the week. Guidelines also recommend that people do not drink alcohol for 48 hours after a heavy drinking session to let their bodies recover.

The Committee report looked at how well current government guidelines match the evidence on the effects of alcohol consumption, and how well they are communicated to and understood by the public.

After listening to submissions from medical bodies, charities and the alcohol industry, the Committee reached a range of conclusions, primarily that there should be a thorough review of the evidence regarding alcohol and health risks. In the meantime, they suggest that the public should be advised to have at least two alcohol-free days a week and that the sensible drinking limits should not be increased.

Calculating units

One unit equals 10ml or 8g of pure alcohol, which is around the amount of alcohol the average adult can process in an hour. This means that within an hour there should be, in theory, little or no alcohol left in the blood of an adult, although this will vary from person to person.

Using units is a simpler way of representing a drink's alcohol content, which is usually expressed by the standard measure ABV, which stands for alcohol by volume.

ABV is a measure of the amount of pure alcohol as a percentage of the total volume of liquid in a drink.

You can find the ABV on the labels of cans and bottles, sometimes written as "vol" or "alcohol volume" or you can ask bar staff about particular drinks.

For example, wine that says "12% ABV" or "alcohol volume 12%" means that 12% of the volume of that drink is pure alcohol.

You can work out how many units there are in any drink by multiplying the total volume of a drink (in ml) by its ABV (which is measured as a percentage) and dividing the result by 1,000.

Strength (ABV) x Volume (ml) ÷ 1,000 = units.

For example, to work out the number of units in a pint (568ml) of strong lager (ABV 5.2%):

5.2 (%) x 568 (ml) ÷ 1,000 = 2.95 units

Who produced the report?

The report came from the House of Commons Science and Technology Committee. The committee of MPs produced the report as they wanted to look at:

how evidence-based the current government guidelines on alcohol consumption are
how well the guidelines are communicated to the public
how well the public understands the current guidelines

To do this, they issued a call for interested parties to submit written evidence on this subject in July 2011. In response, a number of individuals and organisations contributed written and verbal evidence, including MPs, the Department of Health, the British Medical Association, the Royal College of Physicians and representatives of the alcohol industry.

What is current government advice?

Official UK government guidance recommends that men should not regularly drink more than 3–4 units of alcohol a day and women should not regularly drink more than 2–3 units a day. “Regularly” means drinking every day or on most days of the week. People are also recommended to take a break from alcohol for 48 hours after a heavy drinking session to let their bodies recover.

Pregnant women and women trying to conceive should not drink alcohol. If they choose to drink alcohol, they are advised not to drink more than 1–2 units of alcohol once or twice a week and not to get drunk, in order to minimise the risk to their baby. The National Institute for Health and Clinical Excellence (NICE) advises women to avoid alcohol in the first three months of pregnancy in particular, because of the increased risk of miscarriage.

What evidence did the report look at?

The Committee asked for people to submit evidence regarding the following questions:

What evidence are government guidelines on alcohol intake based on, and how regularly is the evidence base reviewed?
Could improvements be made to the evidence base and sources of scientific advice that are provided to the government on alcohol?
How well does the government communicate to the public its guidelines and the risks of alcohol intake?
How do the UK government's guidelines compare to those provided in other countries?

What did the report find?

The Committee found that:

The UK’s alcohol guidelines were broadly in line with those in other developed nations. However, the Committee noted that international comparisons should not be relied on as an indicator of how appropriate UK guidelines are, as national guidelines can be influenced by social and cultural factors, in addition to scientific evidence.
There is a lack of agreement among experts about the possible health benefits of alcohol, and a lack of conclusive evidence about the benefits of low alcohol consumption compared to being teetotal. The Committee judged that it seems likely that any potential benefits from alcohol consumption could be obtained through a healthy lifestyle, and that the potential for benefits should not be used as the basis for daily alcohol guidelines for all adults.
Public awareness of alcohol units seems to be high, but there is less understanding of how many units alcoholic drinks contain.
Some of the current government advice on alcohol consumption is unclear, in particular how advice on “regular” drinking relates to the advice to take a 48-hour break after heavy drinking episodes.

The Committee also noted that the government is working with the drinks industry, which has pledged to ensure that over 80% of alcohol products are labelled with alcohol unit content and the drinking guidelines by 2013. The Committee felt that if the government exercises proper scrutiny and oversight, the potential conflict of interest between sensible drinking messages and the drinks industry’s business objectives should not endanger the progress of the alcohol pledges.

What recommendations did it make?

The Committee recommended that:

There is a need to review the evidence on alcohol and health risks. It recommends that the Department of Health and the devolved health departments establish a nationwide expert working group to review the evidence base and whether the guidelines should be changed.
The working group should advise the government on whether the current alcohol guidelines are evidence-based and, if not, what they should be changed to.
In the meantime, there does not appear to be enough evidence to justify increasing the current drinking guidelines.
The government should provide specific alcohol guidelines for older people.
Lower drinking limits for women should be maintained.
Advice about drinking in pregnancy across the UK should be consistent. The Committee was satisfied that the UK's Chief Medical Officers had recently reviewed the evidence around this issue and come up with balanced guidance, but noted that their guidance differs from that of the Scottish Chief Medical Officer.

It is recommended that the government, industry and charities should emphasise:

the specific risks associated with drinking patterns, including the acute risks associated with individual episodes of heavy drinking and the chronic risks associated with regular drinking
that there are situations where it is not appropriate to drink at all, for example while operating machinery
that people should have some drink-free days every week

Recommendations on public information and understanding:

The concept of alcohol units should be retained, and efforts focused on helping people to translate alcohol units and sensible drinking guidelines into practice.
Alcohol guidelines should be viewed by the government as a source of information for the public, rather than a way to influence drinking behaviour.
If daily alcohol guidelines are kept, the government should consider simplifying them to advise that people take at least two alcohol-free days a week, as is the case in Scotland.
The Department of Health should consider introducing guidance for individual drinking episodes in their review of the evidence. This should only be introduced if the revised guidance states recommended limits in terms of weekly consumption rather than daily consumption, as two daily limits would be confusing.
There should be a website where people could obtain more individualised advice that takes into account factors such as weight, age, ethnicity and family history of alcohol problems. The resource should include links to sources of further information and support, and recommendations on whether to seek further expert medical advice. Charities and other organisations should develop ways to increase access to this type of advice for people who have limited or no access to the internet.

With regards to the drinks industry, the Committee recommended that:

The government should immediately set an interim alcohol labelling target for December 2012 to assess progress towards some of the alcohol-related pledges in the existing Public Health Responsibility Deal. These include a voluntary pledge by the drinks industry that by 2013 over 80% of products on the shelf should have "labels with clear unit content, NHS guidelines and a warning about drinking when pregnant". If targets are not met by the time of this interim review, the government should review the programme, including the possible need to make compliance with the labelling pledge mandatory.
The cooperation of the drinks industry is needed to achieve the Public Health Responsibility Deal's alcohol pledges. The government should exercise scrutiny and oversight to ensure that any conflicts of interest on the part of the drinks industry are reduced and managed.

Links to the headlines

Two drink-free days a week needed, MPs' report says. BBC News, January 9 2012

New binge-drinking daily limit advice as drinkers are told to have at least two alcohol-free days a week. Daily Mail, January 9 2012

Give yourself two alcohol-free days a week, MPs tell drinkers. Metro, January 9 2012

MPs call for two alcohol-free days each week and clearer guidelines on drinking. The Guardian, January 9 2012

Worm lifespan doubled - Cynthia Kenyon

2011-11-20T18:18:00.001Z

reposted from: http://www.facebook.com/ajax/sharer/?s=99&appid=2309869772&p%5B0%5D=680125715&p%5B1%5D=239216616142237

Refs: Unlocking the Secrets of Longevity Genes; March 2006; Scientific American Magazine; by David A. Sinclair and Lenny Guarente; 8 page(s)

crabsallover highlights, key points, comments / links.

Aubrey De Grey - Channel 4 - 2006 documentary

2011-11-10T08:20:00.001Z

reposted from: http://topdocumentaryfilms.com/do-you-want-to-live-forever/

crabsallover highlights, key points, comments / links.

thanks to Matthew Coussell of HASSNERS for letting me know about this 2006 Channel 4 programme.

Channel 4 Documentary says:-
"following the revolutionary life extension and immortality ideas of this somewhat eccentric scientist, Dr. Aubrey de Grey.

This show is all about the radical ideas of a Cambridge biomedical gerontologist called Aubrey de Grey who believes that, within the next 20-30 years, we could extend life indefinitely by addressing seven major factors in the aging process.

Channel 4 Documentary continues:-
"He describes his work as Strategies for Engineered Negligible Senescence (SENS). The SENS theory describes “seven deadly things” that erode the body’s youthfulness at the cellular level, eventually leading to death by old age. Aubrey de Grey means to apply exercise, gene therapy, stem cells, and other yet-to-be-discovered methods of medicine to counteract each of these age-advancing devices:

1. Cell death and atrophy: Treatable with exercise, stem cells, and chemicals which stimulate cell division.
2. Cancerous cells: Theoretically treatable with a type of gene therapy being developed, called Whole-body Interdiction of Lengthening of Telomeres (WILT).
3. Mutant mitochondria: Mutated DNA in the mitochondria causes a number of diseases. These can be prevented by moving the mitochondrial DNA into the cell nucleus, where the rest of the DNA resides.
4. Cell senescence (unwanted cells): Fat cells and other unwanted cruft can be removed surgically, or by stimulating the immune system to attack unwanted cells.
5. Extracellular crosslinks (loss of elasticity): Certain proteins, such as those in cells making up the arteries, become too rigid over time because they bond to each other. These bonds can be broken with certain chemicals (some in clinical trials even today).
6 Extracellular junk: “Plaque” which collects between cells can be eliminated by stimulating the immune system, and/or by using peptides called “beta-breakers.”
7. Intracellular junk: Molecular garbage can be prevented from overwhelming certain cells by introducing enzymes which are known to be effective against such molecules."

Aspirin, the cancer wonder drug

2011-11-05T13:56:00.001Z

reposted from: http://www.newscientist.com/article/dn21119-everyday-drugs-could-stop-cancers-before-they-hit.html?full=true

crabsallover highlights, key points, comments / links.

Aspirin, the cancer wonder drug

18:00 02 November 2011

If there was a daily pill you could take to reduce your risk of developing cancer, would you take it? At the very least, you would want to know the downside. Such a drug does exist, has few side effects, and can be purchased for peanuts in any pharmacy.

That wonder drug is aspirin. Evidence is piling up that a daily dose reduces the risk of dying from cancer by about a third (see "Everyday drugs could stop cancers before they hit"). For some cancers the results are even better.

As yet, there is no official advice to take aspirin to prevent cancer. Surely it can only be a matter of time. On the basis of similar – though admittedly stronger – evidence, doctors already advise millions of people to take low-dose aspirin to reduce their risk of having heart attacks and strokes. While the drug doesn't agree with everyone, severe adverse reactions are rare.

A handful of doctors claim that aspirin's benefits stem from the fact that it is a vital micronutrient which should be reclassified as a vitamin (New Scientist, 7 February 2004, p 36). That debate is still far from over. But the argument for even more widespread use of aspirin as a prophylactic is starting to look unstoppable.

Everyday drugs could stop cancers before they hit

18:00 02 November 2011 by Linda Geddes
Magazine issue 2837.

Editorial: "Aspirin, the cancer wonder drug"

People at high risk of cancer may soon be advised to take readily available drugs such as aspirin to reduce their chances of succumbing to one of the world's biggest killers.

Although cancer screening programmes already exist, offering women regular smear tests or mammograms, for example, to detect early signs of cervical or breast cancer, these look for precancerous changes to cells or suspicious lumps, rather than identifying people who are at high risk of cancer in the future. For many of these people, even those who possess a gene mutation that puts them at high risk, watchful waiting is the norm.

That could be about to change. It looks as if common drugs may be able to slash a person's chances of developing cancer – dubbed chemoprevention. "For people at high risk of cancer at least, chemoprevention is finally coming of age," says John Burn of Newcastle University, UK.

Breast cancer set the trend. Women over the age of 50 are often offered mammograms to detect early signs of cancer. Such screening has drawn controversy, as it can flag up harmless lumps as cancerous, leading women to undergo unnecessary investigation. However, mounting evidence suggests mammograms of healthy breasts might provide vital information on a woman's cancer risk in future, and that this information is not being put to good use.

"All the routine mammogram does is look for early cancers," says Jack Cuzick of the Wolfson Institute of Preventative Medicine in London. "But within this mammogram there's a lot of information about who is at risk." What's more, tamoxifen, a cheap drug that is already used to treat breast cancer, could significantly reduce the risk of the disease developing in the first place.

Several groups have found that healthy women with dense tissue in 75 per cent or more of the breast – around 5 to 10 per cent of the female population – were around four times as likely to develop breast cancer within 10 years following the diagnosis.

Breast density relates to the amount of connective and glandular tissue in the breast, and this produces hormones that can encourage cells to divide. "We think that this combination creates an environment in which changes are more likely to occur that can give rise to cancer in the future," says Norman Boyd of the Ontario Cancer Institute in Toronto, Canada.

Now, Cuzick and his colleagues have shown that treating women at high risk with tamoxifen can reduce breast density, cutting their risk of developing the most common form of breast cancer by up to 63 per cent. The results were presented at the Frontiers of Cancer Prevention Research meeting in Boston last week.

Tamoxifen does have some side effects, but for women whose mammograms suggest that they are at high risk, it could be an attractive option, says Cuzick.

Related drugs called aromatase inhibitors also show promise – one has been shown to reduce the occurrence of breast cancer by 65 per cent (The New England Journal of Medicine, DOI: 10.1056/NEJMoa1103507).

Chemoprevention isn't just focusing on breast cancer. Last week, a study in The Lancet showed that aspirin dramatically reduces the risk of developing colorectal cancer in people with a family history of the disease. "We set out to see if aspirin would prevent cancer, and it does," says Burn, who led the study.

This is especially significant for developing countries, where cancer rates are escalating at a staggering rate (see "Poor countries need cancer drugs").

Burn and his colleagues studied 861 people with a hereditary form of colorectal cancer called Lynch syndrome, who began taking two 300-milligram tablets of aspirin a day or a placebo at some point between 1999 and 2005. By 2010, there had been 19 new colorectal cancers in those who had taken aspirin and 34 in the placebo group. In people who had taken aspirin for more than two years the effects were even more pronounced (The Lancet, DOI: 10.1016/S0140-6736(11)61049-0).

"It provides the first evidence that aspirin is effective in reducing the very high risk of cancer that these individuals have," says Peter Rothwell of the University of Oxford, who earlier this year found that a daily dose of 75 mg of aspirin for more than five years reduced the risk of dying from all cancers by 34 per cent.

Both Burn and Rothwell say they now regularly take aspirin for cancer prevention, but emphasise that self-medication is a personal decision: everyone has to weigh up the pros and cons for themselves. "Up until now, the main reason to take aspirin was to prevent vascular events. I think it will become clear that cancer prevention is the main benefit of aspirin in healthy middle-aged people," says Rothwell.

Lung cancer is another disease where preventative therapy could reap rewards: especially for the millions of ex-smokers who remain at increased risk of disease. In a trial of 152 smokers and former smokers, a drug called iloprost significantly reduced abnormalities in cells lining the airways over the course of six months in those who had kicked the habit, but not in current smokers. "If this holds up, it suggests that former smokers could reduce their risk of developing lung cancer by taking a drug," says Robert Keith of the University of Denver in Colorado, who also presented his results in Boston last week. Iloprost is a synthetic version of a naturally occurring molecule called prostacyclin, which can suppress cell growth and division.

Bringing such preventative drugs to market may not be so easy, however. One of the biggest barriers is the need to test these drugs in large numbers of healthy individuals, which will inevitably produce side-effects in some people. "Chemoprevention is tremendously appealing, but it is a more difficult path to traverse than developing a therapeutic drug," says Michael Thun of the American Cancer Society.

It is also an issue for people like Cuzick, who want tamoxifen and related drugs made available as a precaution for people at high risk. "Treatment can't be the whole answer," he says. "We've got to do something about prevention."

Poor countries need cancer drugs

Surprisingly, cancer now kills more people in developing countries than malaria, AIDS and tuberculosis combined. More than 2.4 million lives could be saved each year using affordable and readily available drugs to prevent or treat cancer.

So says a report released last week by the Global Task Force on Expanded Access to Cancer Care and Control in Developing Countries(GTF.CCC).

Better drugs mean that more people in developing countries survive infectious diseases. But they are starting to fall prey to the same illnesses that strike in richer countries – cancer, cardiovascular disease and diabetes. By 2030, nearly 70 per cent of the projected 27 million new cancer cases each year will occur in those countries with the least infrastructure to deal with it. "Unless we take action now, these countries will be overwhelmed by the economic burden of disease," says David Kerr of the University of Oxford, who has set up a network of collaborations in India and Africa to improve cancer care. "It's not a success story to say we've avoided death in the first five years of life, and we've avoided death in childbirth, but we ignore what happens with cancer."

According to the report, 26 of 29 key drugs that could treat the most prevalent and curable cancers are off-patent, meaning people could receive a course of treatment for less than $100.

For example, the survival rate for childhood leukaemia in Canada is around 90 per cent, but in low-income countries, only 10 per cent survive because they do not have access to the drugs, even though they are off-patent.

"A couple of hundred million dollars would treat all of these childhood leukaemias," says Julio Frenk, Dean of Harvard School of Public Health and co-chair of the GTF.CCC. "It's just lack of access."

Low blood sugar 'affects food cravings'

2011-11-04T00:56:00.000Z

reposted from: http://www.nhs.uk/news/2011/09September/Pages/blood-sugar-desire-high-calorie-foods.aspx

crabsallover highlights, key points, comments / links.

“'Good' sugar is the secret to a slim figure,” according to The Daily Telegraph. The newspaper says that a new study has found that when our blood sugar levels drop we lose our ability to control desire and feel an increased urge to eat.

During the study researchers used scans to detect brain activity following a drop in glucose, which is the blood sugar that our cells use as a source of energy. They then compared their results to the participants’ desire to eat different foods and recorded how this related to their blood sugar levels. They found that small drops in blood sugar activated the region of the brain that produces a desire to eat, while adequate levels of blood sugar activated the region of the brain that controls impulses. Activation of this regulatory part of the brain by higher levels of blood sugar was found not to occur in obese individuals.

While these are intriguing results, the study was small, only involving 14 participants. This means the results should be interpreted cautiously, as smaller sample sizes are prone to being influenced by chance.

Where did the story come from?

The study was carried out by researchers from Yale University School of Medicine and the University of Southern California Keck School of Medicine. It was funded by the US National Institutes of Health.

The study was published in the peer-reviewed Journal of Clinical Investigation.

The study was covered accurately by the media. However, no news outlets reported on the small sample size, which is a major limitation of the research. Both the Daily Mail and The Daily Telegraph reported that the results mean that maintaining glucose levels is the “secret to staying slim”, an interpretation that is not supported by this small, short-term study.

What kind of research was this?

This was a small human experiment that exposed participants to images of food and non-food, and measured how exposure to these images related to their desire for food and their brain activity under varying blood sugar conditions. The researchers aimed to detect whether the participants’ desire to eat when presented with external cues would differ according to their blood sugar levels.

The small number of participants involved in the study (14 in total) means the results should be interpreted cautiously, especially as the participants were further divided into smaller subgroups based on weight (five obese versus nine non-obese).

What did the research involve?

The researchers recruited 14 healthy participants - nine male and five female. They had an average age of 30 years and an average BMI of 25.6. Five of the participants were obese and nine were not obese.

The participants were given a lunch prepared by the researchers and then examined using a function magnetic resonance imaging (fMRI) brain scan. During the scan the researchers controlled the participants’ blood sugar by giving them varying levels of glucose and insulin intravenously. The researchers held insulin levels constant, and varied the glucose levels. Glucose levels were initially held at normal levels (euglycaemia), and then slowly dropped to low blood sugar levels (mild hypoglycaemia). This was done over the course of two hours.

During the euglycaemia and mild hypoglycaemia phases, researchers showed the participants images of high-calorie food, low-calorie food and non-food images. After each image was shown, the researchers asked the participants to rate how much they liked the item shown in the image, on a scale of 1 to 9 (higher score meant they liked it more). The researchers then asked the participants to rate how much they wanted the item shown, again on a scale of 1 to 9. The high-calorie images included pictures of cake, ice cream, lasagne, crisps and steak. The low-calorie images included pictures of fruits, vegetables and tofu.

In addition to the behavioural ratings described above, the researchers measured the participants’ brain activity when they were looking at each image. An fMRI is able to measure brain activity in real-time by detecting which brain cells are using oxygen. To activate, brain cells need both oxygen and glucose from the blood.

The researchers recorded how much the participants reported liking and wanting each item, and the areas of the brain that were activated by seeing each of the images. They then compared which brain regions were active during the normal sugar (euglycaemic) phase versus the low sugar (hypoglycaemic) phase. They also assessed whether glucose levels influenced the ability of the food pictures to affect both brain activity and the feeling of desire for food. This was assessed using the rating scale.

What were the basic results?

During the normal glucose level (euglycaemia) phase, the non-obese participants showed more activity in two areas of the brain than during the hypoglycaemia phase. These areas of the brain, the prefrontal cortex (PFC) and the anterior cingulated cortex (ACC), were significantly more active regardless of the type of image presented. These areas of the brain are responsible for controlling impulses. The difference in activation did not occur in obese participants.

During the mild hypoglycaemia, compared with the euglycaemia phase, the researchers found:

Hunger ratings were significantly greater, with an average of 5.7 points during the hypoglycaemic phase versus an average of 4.5 points during the euglycaemic phase. Hunger ratings were similar in both the obese and non-obese participants.
In both obese and non-obese participants, two areas of the brain called the insula and striatum were significantly more active when presented with bothigh- hand low-calorie food images. These areas of the brain are responsible for promoting feelings of desire and craving.
During hypoglycaemia wanting ratings were significantly higher (p=0.006) in response to high-calorie foods, but liking ratings were similar between the two phases.
There was no difference in brain activation in response to viewing low-calorie foods.

How did the researchers interpret the results?

The researchers concluded that small drops in glucose levels set in motion “adaptive mechanisms” that specifically increase the desire for high-energy and glucose-rich foods. That is, in response to blood sugar levels decreasing, the participants’ brains responded in ways that would increase desire to eat foods that would provide them with high levels of necessary sugars. They say that this activation occurred differently in obese people from in non-obese people.

The researchers say that, further to this, they were able to identify an interaction between blood glucose levels and external cues (the sight of food) that results in a drive to eat. They say that during the normal glucose phase, the activity in the PFC area of the brain (which controls impulses) decreased the desire for food in non-obese people. During the low glucose phase, however, a different region of the brain was activated in response to the sight of sugary foods. The activation of this region led participants to feel a desire for these foods.

Conclusion

This was a small human study that aimed to determine which areas of the brain were activated by the sight of food under different blood sugar levels. The use of both self-reported and brain imaging measurements provides information not only on physiological brain activity, but also on how this activity translates into consciously felt desires.

The researchers found that different areas of the brain are activated depending on the level of glucose available. When sufficient levels are present in the bloodstream, brain regions that control impulses seem to be activated. When low levels are present, brain regions that trigger desire and reward are more activated. The researchers say the level of activation of these regions differs depending on the weight of the individual.

When considering the implications of this research, it should be noted that the study was conducted under conditions that allowed the researchers to hold insulin levels constant artificially while manipulating glucose levels. This is not a state in which a person would find themselves naturally, as both insulin and glucose levels vary constantly. This feature of the study makes it difficult to generalise the results to a real world setting, particularly as, in everyday life, blood insulin levels would be expected to drop once sugar levels were too low.

This study has produced some interesting results but, ultimately, studies of this size are useful for generating theories rather than proving them. The sample size here (14 people) was very small and the results should be interpreted cautiously. Also, any comparisons between the obese and non-obese participants (five and nine people, respectively) are likely to be influenced by chance. Any further research attempts to confirm these results should involve more participants.

Links to the headlines

Why 'good' sugar is the secret to a slim figure. The Daily Telegraph, September 20 2011

The sweet science: Our uncontrollable cravings for treats are triggered by falls in blood sugar. Daily Mail, September 20 2011

Links to the science

Page KA, Seo D, Belfort-DeAguiar R et al. Circulating glucose levels modulate neural control of desire for high-calorie foods in humans.The Journal of Clinical Investigation, September 12 2011

Link between aspirin and eye condition unclear

2011-11-02T21:04:00.000Z

reposted from: http://www.nhs.uk/news/2011/10October/Pages/daily-aspirin-use-amd-vision-loss.aspx

crabsallover highlights, key points, comments / links.

“People who take a daily dose of aspirin are twice as likely to suffer blindness in later life,” The Daily Telegraph reported. The newspaper said that an international study of over 4,000 elderly people found that daily aspirin users are twice as likely to be diagnosed with a late-stage form of age-related macular degeneration(AMD), a common cause of vision problems in older people.

The study examined the association between aspirin use among older people and AMD. To examine the relationship, researchers tested the eyes of 4,691 adults aged over 65. They also assessed their aspirin use and other medical and lifestyle factors. The researchers found that people who took aspirin daily were more than twice as likely to have a more severe, later stage of AMD. This is known as “wet” AMD, and about 15% of people with AMD develop it. However, the relationship between aspirin use and other stages of AMD was not consistent, with aspirin users being no more likely to have mid-stage AMD.

As this study assessed AMD and aspirin use at the same time, it cannot show that regular aspirin use causes or increases the risk of vision problems. As such, we cannot tell whether aspirin use or vision problems came first. On the evidence provided by this particular study, it is not possible to tell how or whether the two are related, or if some unaccounted for factor is linked to both aspirin use and AMD. For example, aspirin is often prescribed to people with cardiovascular problems, which are themselves associated with smoking and obesity. Both of these are risk factors for AMD.

However, the study does raise questions about whether there could be an association between AMD and regular aspirin use, and the subject warrants further investigation.

Where did the story come from?

The study was carried out by researchers from a number of European centres, including Queen’s University, Belfast, and the London School of Hygiene and Tropical Medicine. It was funded by several organisations including the EU and the Macular Disease Society UK. The study was published in Ophthalmology,the peer-reviewed journal of the American Academy of Ophthalmology.

While headlines tended to overstate the certainty of the study’s findings, both the Daily Mail and the Telegraph pointed out that the study provided no evidence that aspirin use itself caused the participants’ AMD. The newspapers also explained that the relationship may be due to confounding factors. For example, it is possible that AMD was caused by cardiovascular disease, which might typically be treated using aspirin.

Some reports suggested that aspirin use was associated with “blindness”, but this may not reflect the nature of AMD. For example, the degree of visual impairment experienced by people with AMD can vary, and people may have distorted vision rather than no vision at all. Although it can cause severe visual impairment as central vision is lost (affecting everyday activities such as reading and writing), it does not usually affect peripheral vision and generally does not cause profound blindness.

What kind of research was this?

This cross-sectional study of nearly 4,700 older people explored the possible association between use of aspirin and the development of age-related macular degeneration (AMD). This type of study can provide a “snapshot” of health-related issues in a particular population at a certain point in time, but it cannot show cause and effect.

AMD (referred to in the research paper as aging macular disorder) is the most common cause of vision loss in people over 50. It occurs when problems affect the workings of the macula, the spot on the back of the eye that is responsible for central vision. This leads to a gradual loss of central vision, which is needed for detailed work and for tasks like driving or reading. However, it does not normally lead to complete blindness.

There are two main types of AMD, called wet and dry AMD. Dry AMD is the most common form. It usually progresses in stages causing gradual loss of vision over time. About 15% of people with AMD develop wet AMD. It is called wet because it is associated with the growth of abnormal new blood vessels in the retina, which are fragile and prone to bleeding.

The researchers say that while previous research has explored an association between aspirin use and AMD, findings have so far been inconsistent.

What did the research involve?

Between 2000 and 2003, researchers recruited participants aged 65 or over by randomly sampling people from national population registers of seven European countries. Participants were interviewed and given a structured questionnaire. This asked about their aspirin intake and other factors such as socioeconomic background, medical history, smoking and alcohol consumption. Aspirin intake was split into four categories ranging from “never” to “daily use”. Researchers also took into account other health measures, such a body mass index, blood pressure and cholesterol levels.

Participants underwent standard ophthalmic tests for AMD, with their AMD progression graded using a five-stage scale. A score of 0 indicated no AMD and the last stage – stage 4 – was also classified as being either dry or wet (not everyone with late-stage AMD will progress to the wet form). The classification system they used is a recognised international grading system.

The researchers then used standard statistical methods to analyse any association between aspirin use and AMD.

What were the basic results?

Of the initial 4,753 participants, the researchers excluded 62 for whom information on aspirin use was missing. This left 4,691 participants. They found that 36.4% (1,706) had early AMD (stages 0–3) and 3.3% (157) had late AMD (stage 4). Of those with stage 4 AMD, 108 had the wet form and 49 the dry form.

Within the whole study population, 41.2% took aspirin once a month, 7% at least once a week and 17.3% took aspirin daily.

After the researchers had adjusted for potential confounders, they calculated the associations between daily aspirin use and each grade of AMD. They found that there was:

a 26% increased risk of grade 1 AMD (odds ratio [OR] 1.26, 95% confidence interval [CI] 1.08–1.46)
a 42% increased risk of grade 2 AMD (OR 1.42, 95% CI 1.18–1.70)
no increased risk of grade 3 AMD
a more than double risk of grade 4 wet AMD (OR 2.22, 95% CI 1.61–3.05)
no increased risk of grade 4 dry AMD

How did the researchers interpret the results?

The researchers say that frequent aspirin use was associated with early AMD and wet late AMD. The risk rose with increasing frequency of aspirin use. They consider that, as aspirin acts on the body in several ways, it is possible that it affects blood vessels in the eye. However, further study of this is needed.

Conclusion

This large study had strengths, including the fact that it took a random sample of the population and established the presence of AMD using validated methods and accepted grading procedures for AMD. The researchers also tried to take account of other factors that could have affected the risk of AMD, in particular cardiovascular disease, smoking and excess weight, which are known risk factors for AMD.

The study’s major limitation is its cross-sectional design, which means it cannot establish cause and effect. As such, while the study has shown associations between aspirin use and vision problems, it cannot tell how or whether the two are directly related, nor which came first. While we could speculate that aspirin somehow causes AMD, it could also be suggested that AMD might be the result of cardiovascular conditions that require treatment with aspirin. Also, although the researchers attempted to adjust their analyses for confounders – including those known to be associated with AMD – other factors may be independently related to both aspirin use and AMD and could account for the observed relationship.

The relationship was also not completely consistent. Aspirin use was not associated with grade 3 AMD or grade 4 dry AMD. This suggests that the findings could possibly have happened by chance.

The limitations of the study’s design, together with the inconsistent results of other studies on the matter, mean it is hard to tell if there truly is an association between regular aspirin use and AMD. However, the possibility of an association seems worthy of further exploration. Ideally, this would involve examining people’s eyes to check they do not have AMD and following them over time to see whether people taking aspirin daily are more likely to develop the condition in the future.

Links to the headlines

Regular aspirin users at higher risk of sight problems, research suggests. The Daily Telegraph, October 4 2011

Over-65s who take a daily aspirin are 'twice as likely to suffer age-related sight loss'. Daily Mail, October 4 2011

Links to the science

de Jong PTVM, Chakravarthy U, Rahu M. Associations between Aspirin Use and Aging Macula Disorder. Ophthalmology, September 14 2011 (published online)

Reactive oxygen species (ROS) damage internal cell structure

2011-11-02T20:53:00.001Z

reposted from: http://www.nhs.uk/news/2011/11November/Pages/common-drug-may-slow-progeria.aspx

crabsallover highlights, key points, comments / links.

NHS.uk say:-

New pill to halt ageing, papers claim

NHS Choices Wed Nov 2, 2011 15:52

Scientists may have “found a cure for ageing”, the Daily Mirror reported. According to the newspaper, the answer could lie in a “forever young” drug that will allow us to grow old gracefully.

However, this seeminly marvelous news is based on a small study which looked at an extremely rare form of a genetic condition called progeria. This causes children’s bodies to rapidly age and leads to a number of physical health problems, limiting their lifespan to an average of around 13 years.

The researchers examined the cells of people with the condition and found that, compared to cells from healthy individuals, they produced five times the level of ‘reactive oxygen species’ (ROS), chemicals that are damaging to the internal cell structure. These higher ROS levels were associated with more breaks in the cells’ DNA and abnormal cell growth. However, when the cells were treated with a drug called N-acetylcysteine, which is already used to prevent liver damage in people who have overdosed on paracetamol, the researchers were able to largely prevent this DNA damage and improve cell growth and division.

The findings of this study are at a very early stage and suggest some potential ways to help people with rare but devastating forms of progeria. However, it is too great a leap too suggest that the research provides a “cure for ageing”, as some fanciful reports have done.

Where did the story come from?

The study was carried out by researchers from Durham University and the University of Bologna in Italy. It was funded by the European Commission and published in the peer-reviewed scientific journal Human Molecular Genetics.

Most news coverage on the research suggested that it could offer a way to slow or even stop routine human ageing. However, the media’s outlandish claims that scientists are on the verge of a “forever young drug” or a “cure for ageing” are not supported by this research.

Several newspapers focussed on the fact that the study used an existing drug called N-acetylcysteine, and implied that it could soon be used to block the effects of ageing. The drug is currently an ingredient in some eye drops and also has a role in treating paracetamol overdoses and poisoning, for which it is given intravenously for short periods. While it has been proven safe and effective for these uses, there are no guarantees that it would be safe or effective if taken orally in the long term.

Only the BBC’s coverage primarily focussed on progeria, the rare rapid-ageing condition that the research examined.

What kind of research was this?

This study was a laboratory-based investigation into the cause of and possible solutions to the genetic damage that occurs in a group of inherited degenerative disorders called laminopathies. These conditions are caused by mutations in a gene called LMNA, which normally produces a protein called lamin A. The lamin A protein plays an important role in keeping the structures within cells strong and stable.

The study focused on the most severe group of laminopathies, including the rare Hutchinson Gilford progeria syndrome (HGPS), which causes children’s bodies to age too quickly. This causes a range of effects, including restricting growth and loss of body fat and hair. Children with HGPS develop heart disease early in life, and have an average life expectancy of just 13 years.

Laboratory studies are the best way to determine exactly what happens in the individual cells of people with these types of genetic conditions. The results can help researchers explain the symptoms that people develop.

...

Previous studies have shown that skin cells from these patients have high levels of chemicals called reactive oxygen species (ROS). ROS can cause double strand breaks in DNA, and are thought to be involved in the accumulation of this type of DNA damage in normal ageing cells. Therefore, the researchers wanted to test whether ROS might be responsible for the DNA damage seen in cells from patients with laminopathies.

The researchers first compared the level of ROS produced by the cells, and then compared the level of damage caused by ROS in the cells. Specifically, they looked at how ROS caused DNA damage and disruption in the shape of the cells’ internal structures.

Finally, they investigated whether a drug called N-acetylcysteine could reduce the damaging effect of the ROS in the healthy and diseased cells. N-acetylcysteine is a chemical that “mops up” the damaging ROS and is already used to prevent liver damage in patients who have overdosed on paracetamol.

What were the basic results?

The researchers found that:

The cells from people with HGPS had ROS levels that were five times higher than those from healthy individuals.
The high ROS levels were linked to DNA damage (due to double strand breaks in the DNA).
The accumulation of DNA damage in these fibroblasts appeared to cause poor cell growth.
ROS-induced DNA damage could be repaired efficiently in cells from healthy individuals, but could not be repaired in the cells from people with HGPS.
Adding N-acetylcysteine to the cells of HGPS patients led to a significant increase their ability to grow and multiply. The cells also did not develop un-repairable ROS-induced DNA damage.

How did the researchers interpret the results?

The researchers say their findings suggest that the accumulation of ROS-induced DNA damage can “contribute significantly” to the problems seen in the cells of people with HGPS. They also state that N-acetylcysteine in combination with other treatments “might prove beneficial to HGPS patients”.

Conclusion

This laboratory-based study of isolated human cells provides interesting new evidence on how reactive oxygen species (ROS) potentially causes DNA damage in the accelerated ageing condition Hutchinson Gilford progeria syndrome (HGPS). It also highlights that N-acetylcysteine might be of use in treating patients with HGPS.

While this study provides interesting new findings, the following limitations should be considered:

This study experimented on isolated human cells in a laboratory, and it is not known what the effect of N-acetylcysteine would be if it was given to children with the illness.
This is early-stage research, the results of which will need to be confirmed in future studies. The effectiveness and safety of N-acetylcysteine is likely to need to be tested in animal models of the condition before it could be tested in people. However, the fact that N–acetylcysteine is already used as a treatment for paracetamol overdose may mean that human trials could be carried out sooner than for a completely new drug. That said, it would still need to be tested, particular its effects when taken in the long term.
A full randomised clinical trial of N-acetylcysteine may be difficult to conduct as the condition is so rare. The Progeria Research Foundation says that just 78 children are known to have the condition.
The newspapers suggest that the findings are applicable to normal ageing, and that N-acetylcysteine could be a “cure for ageing”. This study focussed on the effect of N-acetylcysteine on the cells of patients with HGPS, a rare, severe genetic condition. It is not possible to say from this study how the findings would apply to the normal ageing process.
HGPS is a genetic condition, and although N-acetylcysteine might be able to reduce or block some of the damage seen in the cells of people with HGPS, it will not remove the genetic mutation itself or allow the body to produce the important lamin A protein.
Regular cellular and physical ageing involves a complex mix of mechanisms. Even if N-acetylcysteine can block some of them, this does not mean that it could stop or greatly slow the overall ageing process.

These findings are at a very early stage and will aid further research into HGPS. However, it may take many years to confirm these findings through other studies and to assess the effects of N-acetylcysteine in HGPS patients. The implications of these findings for the ageing process of people without HGPS is unclear, and it is certainly too early to say that an “ageing pill” is just around the corner.

Links To The Headlines

Progeria may be treated by drug, researchers say. BBC News, November 2 2011

Breakthrough could lead to treatment for symptoms of growing old. The Daily Telegraph, November 2 2011

Scientists "find cure for ageing". Daily Mail, November 2 2011

Pill 'to combat ageing'. The Sun, November 2 2011

'Forever young' drug that lets you grow old gracefully could soon be reality. Daily Mail, November 2 2011

Links To Science

Richards SA, Muter J, Ritchie P et al. The accumulation of un-repairable DNA damage in laminopathy progeria fibroblasts is caused by ROS generation and is prevented by treatment with N-acetyl cysteine. Human Molecular Genetics, 2011 20 (20): 3997-4004

Avoid alcohol 3 days a week

2011-10-30T02:05:00.002Z

reposted from: http://www.nhs.uk/news/2011/10October/Pages/alcohol-advice-royal-college-physicians.aspx

crabsallover highlights, key points, comments / links.

NHS Choices Alcohol Tracker here.

Doctors have warned, “drinkers should have three alcohol-free days a week if they want to avoid the risk of liver disease,” the Daily Mail reported. It continued that the Royal College of Physicians (RCP) said that the current guidance must be rewritten as it implies that drinking every day is fine.

The new advice from the RCP is part of a submission to MPs on the House of Commons' Science and Technology Committee about current alcohol guidelines. This submission discusses their review of the evidence from 1995 as well as more recent research evidence and alcohol intake guidelines from other countries. The RCP concluded that the current wording of the UK guidelines appears to sanction daily or near daily drinking. It adds that the frequency of alcohol consumption is an important risk factor for the development of alcohol dependency and alcoholic liver disease.

To address what it sees as a problematic lack of emphasis on the frequency of drinking, the RCP suggests that the current advice on safe limits for alcohol intake should be stated in terms of weekly alcohol intake rather than daily unit limits, and that two or three days in the week should be completely alcohol free. It says that men should consume no more than 21 units a week and women should have no more than 14 units, provided the total amount is not drunk in one or two sessions.

The Department of Health (DH) has reportedly said that it has no plans to change its guidance at present. It recommends that men should not regularly drink more than 3-4 units of alcohol a day, while women should not regularly drink more than 2-3 units. ‘Regularly’ is defined as drinking every day or most days of the week. People are also advised to not drink alcohol for 48 hours after a heavy session to let their bodies recover.

Alcohol abuse is associated with an increased risk of liver disease, cancer and other conditions. Read our Live Well pages on alcohol to find out more.

Where is the advice from?

The advice comes from a report by the Royal College of Physicians (RCP). The RCP submitted its report to MPs on the House of Commons' Science and Technology Committee. As such, the advice given is for the government about its policy on recommended alcohol intake limits, rather than being aimed directly at the public.

The RCP believes that government advice on sensible drinking limits can play an important role in dealing with alcohol misuse. It says that it is essential government advice is based on evidence and that it is regularly reviewed. It continues that the last systematic review of the evidence by the government, to which interested parties could submit their views, was in 1995.

The RCP believes that current government guidelines on alcohol consumption could be improved to better reflect the evidence in a number of areas, such as:

overall levels of consumption that are ‘safe’ or within ‘sensible limits’
frequency of alcohol consumption
the physiological effects of ageing
the balance of the health benefits of alcohol consumption for coronary heart disease against wider alcohol-related health harm

The RCP would also like a clear, independent evaluation of the government’s strategy for communicating its guidelines and the risks of alcohol intake to the public.

What does the RCP advise?

The RCP believes that the current wording of the UK guidelines appears to sanction daily or near daily drinking. It says this is problematic, because the frequency of alcohol consumption is an important risk factor for the development of alcohol dependency and alcoholic liver disease. The RCP cites various studies to support its argument.

It also notes that someone drinking four units a day (the current upper limit for men in the UK) would be classed as a hazardous or high-risk drinker on the WHO’s gold standard tool for identifying people at risk of alcohol-related harm.

The RCP says that these potential problems with the current guidelines could be remedied by moving to a weekly limit and adding the recommendation to three alcohol-free days a week.

It recommends that in order that people keep their alcohol consumption within ‘safe limits’, men should consume no more than 21 units a week and women should have no more than 14 units. It says that most individuals are unlikely to come to harm at these levels, provided the total amount is not drunk in one or two sessions, and that there are two to three alcohol-free days a week. It says that above this limit the risk of death from all causes increases as alcohol consumption increases.

The RCP also notes that these recommendations are a best judgement based on the evidence, and were reached after a number of areas of uncertainty and inaccuracy were taken into account.

The RCP also suggests that recommended limits for safe drinking by older people in the UK require further consideration, as older people may be particularly vulnerable to harm from alcohol due to biological changes associated with ageing. It says that current guidelines are based predominantly on evidence for younger age groups and there is concern they are not appropriate for older people.

40. The current guidelines are based predominantly on evidence for younger age groups and there is concern that current guidelines are not appropriate for older people. The recent report ‘Our invisible addicts’ published by the Royal College of Psychiatrists in 2011, suggests that a ‘safe limit’ for older people is 11 units per week for men, or seven units per week for women. [16]

Ref: http://www.publications.parliament.uk/pa/cm201012/cmselect/cmsctech/writev/1536/ag22.htm

What evidence is this based on?

The RCP’s advice appears to be based on their review of evidence from 1995, and updated with other research evidence published since 1995.

What is current UK government advice?

Official UK government guidance recommends that men should not regularly drink more than 3-4 units of alcohol a day and women should not regularly drink more than 2-3 units a day. 'Regularly' is defined as drinking every day or most days of the week. It is also recommended that people not drink alcohol for 48 hours after a heavy session to let their bodies recover.

http://www.dh.gov.uk/en/Publichealth/Alcoholmisuse/DH_125368

Pregnant women and women trying to conceive should avoid drinking alcohol. If they do choose to drink alcohol, they are advised to not drink more than 1-2 units of alcohol once or twice a week and not to get drunk, to minimise the risk to the baby. The National Institute for Health and Clinical Excellence (NICE), advises women to avoid alcohol in the first three months of their pregnancy in particular, because of the increased risk of miscarriage.

How do the UK guidelines compare to other countries?

The RCP notes that comparing alcohol guidelines between different countries is difficult, as there are differences in the size of standard drinks and units. It reports that a recent analysis by the Australian government found that 15 countries recommended lower limits than the UK for men, and 12 countries recommended lower limits than the UK for women. Six countries recommended higher limits than the UK for men and six countries recommended higher limits than there are for UK women.

The RCP notes that although looking at the guidelines from other countries may be of interest, it is important that UK government guidelines are a considered and expert judgement on the risks of alcohol consumption, based on the scientific and medical evidence.

Where can I get more information?

More information on the effects of alcohol is available from the NHS Choices alcohol pages.

Links to the headlines

Avoid alcohol three days a week, doctors warn. BBC News, October 23 2011

Avoid alcohol three days a week, doctors warn. The Daily Telegraph, October 23 2011

Doctors say alcohol free days needed to protect liver. BBC News, October 23 2011

New guide for safe drinking. The Independent, October 23 2011

Don't drink on 3 days a week. As the liver crisis deepens, leading doctors warn of the dangers. Daily Mail, October 23 2011

OU MSc in Medicinal Chemistry 2011-2013

2011-10-29T11:36:00.004+01:00

In February 2011 I started the MSc in Medicinal Chemistry. I've just taken the first year exam. That's why I've only blogged here a few times since February - a bit busy on the course!

First randomised trial specifically for aspirin in cancer

2011-10-29T05:06:00.000+01:00

Prof. Sir John Burn

Crabsallover has followed the link between taking aspirin and reducation in Cancer since Peter Rothwell research results in 2010.

reposted from: http://www.nhs.uk/news/2011/10October/Pages/aspirin-cuts-lynch-syndrome-bowel-cancer-risk.aspx

crabsallover highlights, key points, comments / links.

Other studies over the past two decades have suggested Aspirin reduced cancer risk, but this was the first randomised control trial, specifically for aspirin in cancer, to prove it.

Aspirin cuts the risk of bowel cancer in people with inherited susceptibility to the disease,The Guardian has today reported. The newspaper said that a study of long-term aspirin use found it cut the risk of bowel cancer by more than 60% in these individuals.

Prof Sir John Burns (wikipedia) (won a Knighthood 2009) from Newcastle Uni (full list of John Burn publications) on the Today programme (2 min interview with Evan Davis) said

Burns mentioned very good research of Peter Rothwell looking at effect on aspirin on heart attack trials. Burns trial results:Out of 250 in trial group 23 cancers occurred in the placebo group but only 10 in the aspirin group. 63% fewer cancers! In some way aspirin knocks off the cells that are going to be cancerous in a few years time. One theory is that inflammation is involved in cancer progression, aspirins inhibit prostaglandin production. John Burns personal theory is that it is driving programmed cell death (apoptosis). Plants make salicylates (cf aspirin is a salicylate derived from white willow bark) which drive programmed cell death and protects the bark from infection.

Prof Sir John Burn, from Newcastle University, said there were 30,000 adults in the UK with Lynch syndrome.

If all were given the treatment he said it would prevent 10,000 cancers over 30 years and he speculated that this could possibly prevent 1,000 deaths from the disease.

However, there would also be side effects.

"If we can prevent 10,000 cancers in return for 1,000 ulcers and 100 strokes, in most people's minds that's a good deal," he said.

"People who've got a clear family history of, particularly, bowel cancer should seriously consider adding low dose aspirin to their routine and particularly those people who've got a genetic predisposition."

One of the questions asked by the research into aspirin was whether healthy people with no family risks should take the drug.

The lower the risk of heart attack or cancer, the lower the benefit of taking aspirin, yet there are still potentially deadly side effects.

Sir John said that it was a "finely balanced argument" and that he decided the risks were worth it for him.

"I think where we're headed for is people that are in their 50s and 60s would look very seriously at adding a low dose aspirin to their daily routine because it's giving protection against cancer, heart attack and stroke.

"But if they do that they've got to have their eyes wide open. They will increase their risk of ulcers and gastrointestinal bleeds and very rarely they will have a stroke caused by the aspirin."

View John Burns interviewed by Dominic Hughes, BBC

Fergus Walsh, BBC Health Correspondent, reports having taken aspirin daily for 11 months since the Peter Rothwell trial results.

Those on the John Burn trial took 600mg aspirin daily which is a much bigger dose than the 75 mg that many middle-aged people like me take to reduce their risk of cardiovascular disease. I wrote last year: "If I get an intestinal bleed in a few months time and am taken to hospital needing a blood transfusion, then it will be easy to argue that I got it wrong."

Well, so far so good.

John Burn also looked at other cancers eg womb and found a 50% reduction (Telegraph interview)

John Burn explains his trials and the biochemistry (8min 20s) of Aspirin mechanism to prevent cancers. It might be making faulty cells fall on their sword.

100,000 years ago we used to forage on plants that used salicylates to defend themselves. Now our diet is free of salicyates. Above paper in picture is

J. Burn, P. D. Chapman, D. T. Bishop and J. Mathers (1998). Diet and cancer prevention: the Concerted Action Polyp Prevention (CAPP) Studies. Proceedings of the Nutrition Society, 57 , pp 183-186 doi:10.1079/PNS19980030 (full pdf)

Another 10 min video on mechanism of action of aspirin (technical)

another presentation by John Burn - trial results and biochem (5min 50s) "as in plants, salicylates initiate apoptosis (programmed cell death) among genetically abnormal stem cells that have yet to become cancer."

OUS827 library search: BOWEL CANCER PREVENTION: ASPIRIN INDUCES COX-2 INDEPENDENT ENDOTHELIAL CELL APOPTOSIS FACILITATING ANGIOGENESIS ARREST.
By: Johnson, A. S.; Arthur, H. M.; Burn, J.; Wilson, R. G.. Gut, Apr2004 Supplement 3, Vol. 53, pA21-A21,
Conclusion: Both aspirin and celecoxib caused dose dependent reduction in cell viability, proliferation, and angiogenesis. Celecoxib produced these effects at levels in excess of normal serum levels when it is no longer COX-2 selective. Aspirin induces apoptosis via a COX-2 independent mechanism which may facilitate angiogenesis arrest and play a critical role in limiting tumour growth.

The Lancet Podcast of the 28th October 2011 press conference (20mins) - John Burn & Tim Bishop

taking 600mg / day aspirin gives 60% prevention of cancer - 75mg gives 25% prevention (13 mins) .. but a low dose will avoid a lot of ulcers.. (14 mins).. CaPP3 trials will give clue to best dose 75mg / 300mg / 600mg per day to offset cancer. CaPP3 website now launched!

Press Release embargo 28th October 2011

The Lancet comments (subscription required)
'The long-term results of CAPP2 are also invaluable for the continued assessment of aspirin for prevention of sporadic colorectal cancer, which is not currently recommended mainly because of concerns about toxic effects and continuing uncertainty about dose and duration.10 With aspirin's well established vascular benefits and recent evidence of benefit for colorectal and other cancers in pooled cardiovascular randomised trials,11 Burn and colleagues' findings might at last tip the scales in favour of aspirin as the chemopreventive agent of choice for many individuals.

Does this long-term follow-up analysis allow a definitive conclusion, say for standard regulatory approval, about aspirin's ability to prevent colorectal cancer? In isolation, no, since the results of the primary analysis were not significant for the ITT (Intention-To-Treat) population. The data strongly support routine use of aspirin, however, for patients with Lynch syndrome as an adjunct to intensive cancer surveillance. As the first randomised trial of aspirin with colorectal cancer as the primary endpoint, CAPP2 also certainly moves us closer to a more definitive answer on aspirin's overall role in the prevention of colorectal cancer. Unfortunately, prohibitive logistics make a randomised trial of aspirin prevention with a colorectal cancer endpoint in a sporadic-risk population unlikely. Therefore, these results from CAPP2 and previous evidence arguably support more general recommendations to consider aspirin for prevention of colorectal cancer in the context of individualised risk-benefit assessments.

Cancer Research UK comment 'People with Lynch syndrome are about 10 times more likely that the general population to develop cancer, particularly of the bowel and womb, and often at a young age.'

My dentist takes a daily baby aspirin & Vitamin D

2011-07-11T10:40:00.004+01:00

My dentist has taken a daily baby aspirin for 20-25 years because of research showing reduction in colon cancer (his father died of colan cancer). Would that research be from CPS II data which demonstrated a decreased risk of colon cancer in people who take aspirin regularly?...

Thun, M. J., Namboodiri, M. M. & Heath, C. W. Jr. Aspirin use and reduced risk of fatal colon cancer. N. Engl. J. Med. 325, 1593–1596 (1991). (cited in Ann M. Bode and Zigang Dong, 508, July 2009, Volume 9, www.nature.com/reviews/cancer)

He also takes a Vitamin D spray daily (as a dentist he works out of the sun!)

Jack Cuzick 'really exited' about use of aspirin to prevent cancer

2011-07-02T06:22:00.000+01:00

reposted from:

crabsallover highlights, key points, comments / links.

http://scienceblog.cancerresearchuk.org/2011/07/01/expert-opinion-professor-jack-cuzick/

Cancer Research UK: What single research publication has most excited you recently?

Jack Cuzick: One of the things that came as a bit of a surprise – and we’re very actively pursuing now – is the publication from Peter Rothwell and colleagues about the fact that aspirin when taken regularly for a period of 5 years or longer appears to lead to about a 20 percent reduction in cancer overall – not just one type, but many types. The major effects seem to be in colorectal cancer, oesophageal cancer and maybe stomach cancer, but also some effects for other cancers as well.

I think this is really exciting, and we’re very actively looking at how this might be implemented – whether low dose is enough, what age you should start, whether the effects are as clear in women as they are in men, etc.

But something as simple as a daily low-dose aspirin could produce a 20 percent reduction in all deaths from cancer would be a huge step forward.

(Read more about this research)

Cancer Research UK: So why is it that we’re not all being told to take aspirin on a daily basis to reduce cancer risk?

Jack Cuzick: Like all drugs, aspirin does have some side effects. The biggest concern with aspirin is gastrointestinal bleeding, and that’s been one of the issues where, when the benefits were only thought to be heart disease, they seemed to be pretty evenly balanced with the increased risk of GI bleeds.

Now with the additional benefit of cancer, the balance may be much more favourable, but again it is a concern, and one of the things that will be important if we are going to try and pursue this will be to identify who’s at high risk of bleeding so that those people would not be offered aspirin.

Instead we’d offer to people where the benefits clearly outweigh the side effects.

Janusz Jankowski et al comment on Peter Rothwell, Asprin & Cancer, 14 May 2011, The Lancet

2011-06-07T23:24:00.002+01:00

reposted from: http://download.thelancet.com/pdfs/journals/lancet/PIIS0140673611606661.pdf?id=e16241398b8eb460:3c68b886:1306b6f6506:38b41307479634423 and Reply:
http://download.thelancet.com/pdfs/journals/lancet/PIIS0140673611606703.pdf?id=e16241398b8eb460:3c68b886:1306b6f6506:38b41307479634423

crabsallover highlights, key points, comments / links.

Janusz Jankowski, Hugh Barr, John deCaestecker, Peter Watson, Stephen Attwood, Paul Moayyedi

We write with regard to the Article by Peter Rothwell and colleagues,1 which indicates that low-dose aspirin might prevent cancer. Although we strongly endorse Rothwell and colleagues’ publication, we urge caution.

If we presume that aspirin does have a chemoprotective role, it clearly does not work for everyone since at best 25% of people are estimated to get a cancer prevention benefit but this figure could be as low as 20%.

This “aspirin resistance” in patients seems to be present widely in the population so we do not know who should respond.2

Genetic studies such as those undertaken by the Esophageal Adenocarcinoma Genetic Linkage (EAGLE) consortia are needed to assess which individuals will respond best to the chemopreventive eff ects of low dose aspirin.

Additionally, meta-analysis of cardiac trials with reassess ment of causes of cancer deaths might have in advertently introduced bias. For example, the number of cases of gastrointestinal cancer death in Rothwell and colleagues’ study was 182 out of almost 20 000 cases. In particular there were only 23 oesophageal cancers. Patients in these trials, especially those using aspirin, might have had complications that resulted in earlier presentation.

The AspECT chemoprevention trial 3 was specifi cally designed to look at the effect of aspirin on oesophageal cancer development but will also give information on effects on colon cancer development as well as on cardiac deaths. To date, the data monitoring team and the trial steering team have not divulged any obvious trend between the four groups of this trial (low-dose proton-pump inhibitor [PPI], high-dose PPI, low-dose PPI with low-dose aspirin [300 mg], and high-dose PPI with low-dose aspirin). We need trials such as AspECT to report their preliminary findings of genetic stratification for response, as well as risk/benefi t, dose, and length of therapy.

JJ has a consultancy to AstraZeneca Oncology, which makes esomeprazole—one of the agents in the AspECT trial. JJ has also received grants in aid from AstraZeneca previously. All authors are co-investigators in the AspECT trial. *Janusz Jankowski, Hugh Barr, John deCaestecker, Peter Watson, Stephen Attwood, Paul Moayyedi j.a.jankowski@qmul.ac.uk Leicester Royal Infi rmary, Leicester LE7 7HH, UK (JJ, JdC); Gloucestershire Royal Hospital, Gloucester, UK (HB); Belfast Hospital Trust, Belfast, UK (PW); Northumbria Healthcare NHS Foundation Trust, Tyne and Wear, UK (SA); and Gastrointestinal Division, McMaster University Medical Centre, Hamilton, ON, Canada (PM)

1 Rothwell PM, Fowkes FG, Belch JF, Ogawa H, Warlow CP, Meade TW. Eff ect of daily aspirin on long-term risk of death due to cancer: analysis of individual patient data from randomised trials. Lancet 2011; 377: 31–41.
2 Jankowski J, Hunt R. Cyclooxygenase-2 inhibitors in colorectal cancer prevention: better the devil you know. Cancer Epidemiol Biomarkers Prevent 2008; 17: 1858–61.
3 Das D, Chilton AP, Jankowski JA. Chemoprevention of oesophageal cancer and the AspECT trial. Recent Results Cancer Res 2009; 181: 161–69.

Peter Rothwell Reply
We thank Janusz Jankowski and colleagues for their comments. However, our estimate of the effect of aspirin on death due to oesophogeal cancer was based on 68 events and not 23 as Jankowski and colleagues state. The 20-year risk of death due to adenocarcinoma of the oesophagus, the predominant histological subtype in Barretts’ oesophagus, was substantially reduced by allocation to aspirin in the trials (hazard ratio 0·36, 95% CI 0·21–0·63, p=0·0001). It is difficult to conceive of how this estimate might have been biased by inclusion of some trials that included patients with established vascular disease, as Jankowski and colleagues suggest. Moreover, the effect was significant in both of the large randomised trials of daily aspirin versus control in primary prevention that we studied—ie, the Thrombosis Prevention Trial1 (0·42, 0·22–0·78, p=0·004) and the British Doctors Aspirin Trial 2 (0·45, 0·19–0·99, p=0·04). The figure shows a pooled analysis of the effect in these two trials. Additionally, our estimates of the effect of aspirin on risk of death due to gastrointestinal cancers as a whole were based on more than 500 deaths and not on 182 as stated by Jankowski and colleagues, with a highly statistically robust reduction in 20-year mortality (0·65, 0·53–0·78, p<0·0001).

Luca Mascitelli role of Aspirin in reducing Iron, Cancer effect, 14 May 2011, The Lancet

2011-06-07T23:24:00.001+01:00

reposted from:

crabsallover highlights, key points, comments / links.
http://download.thelancet.com/pdfs/journals/lancet/PIIS0140673611606703.pdf?id=e16241398b8eb460:3c68b886:1306b6f6506:38b41307479634423
and http://download.thelancet.com/pdfs/journals/lancet/PIIS0140673611606673.pdf?id=e16241398b8eb460:3c68b886:1306b6f6506:38b41307479634423
Luca Mascitelli, Mark R Goldstein
Peter Rothwell and colleagues 1 provide new evidence that long-term daily aspirin lowers mortality from several common cancers. However, the mechanisms underlying this beneficial effect are not clearly understood. A plausible anti-tumour mechanism of long-term aspirin use that was not considered is aspirin-mediated chronic iron loss, as previously suggested.2

Loss of stored iron is known to be possible even in aspirin users with clinically undetectable occult gastric bleeding. Indeed, long-term aspirin use has been shown to be associated with roughly 20% lower serum ferritin concentrations—a good indicator of body iron stores—than in non-users;3 treatment with other non-steroidal anti-infl ammatory drugs had no signifi cant effect on serum ferritin concentrations.

A protective effect of iron loss on cancer mortality was confi rmed in a randomised trial in which patients were randomly assigned to reduction in iron stores by calibrated phlebo tomies or to observation. Over 4·5 years, the risk of new cancers was signifi cantly lower in the iron reduction group than in controls.4 Furthermore, in patients with new cancers, those with iron reduction had highly signifi cantly lower cancerspecifi c and all-cause mortality than controls. These findings are plausible in view of the growing number of published studies on the role of iron in carcinogenesis.2 In this setting, we have also proposed that lower stored iron concentrations mediated by inhibition of iron absorption by polyphenols present in the diet might exert an anti-cancer mechanism.5 Future studies of aspirin action should therefore include assessment of the eff ects of the intervention on iron status. If iron loss is found to be a mechanism, this consequence of aspirin use can be clinically replicated by other methods without incurring the risk of major aspirin-induced haemorrhage.2

We declare that we have no confl icts of interest. *Luca Mascitelli, Mark R Goldstein lumasci@libero.it Medical Service, Comando Brigata alpina “Julia”, Via S Agostino 8, 33100 Udine, Italy (LM); and Fountain Medical Court, Bonita Springs, FL, USA (MRG)

1 Rothwell PM, Fowkes FG, Belch JF, Ogawa H, Warlow CP, Meade TW. Eff ect of daily aspirin on long-term risk of death due to cancer: analysis of individual patient data from randomised trials. Lancet 2011; 377: 31–41.
2 Mascitelli L, Pezzetta F, Sullivan JL. Aspirin-associated iron loss as an anticancer mechanism. Med Hypotheses 2010; 74: 78–80.
3 Milman N, Ovesen L, Byg K, Graudal N. Iron status in Danes updated 1994, I: prevalence of iron defi ciency and iron overload in 1332 men aged 40-70 years. Infl uence of blood donation, alcohol intake, and iron supplementation. Ann Hematol 1999; 78: 393–400.
4 Zacharski LR, Chow BK, Howes PS, et al. Decreased cancer risk after iron reduction in patients with peripheral arterial disease: results from a randomized trial. J Natl Cancer Inst 2008; 100: 996–1002.
5 Mascitelli L, Goldstein MR. Inhibition of iron absorption by polyphenols as an anti-cancer mechanism. QJM 2011; 104: 459–61.

Peter Rothwell Reply
Luca Mascitelli and Mark Goldstein raise the issue of the possible eff ect of aspirin treatment on iron loss as a mechanism for the reduction in cancer deaths. We deliberately did not review the many suggested mechanisms by which aspirin might reduce the risk of death due to cancer, but it is possible that reduced iron stores might contribute. There are currently insuffi cient data on the associations between iron stores and cancer risk to determine whether their pattern closely mirrors that of the effects of aspirin on deaths due to the specific cancers that we noted.

Mark Nelson, risk of bleeding with Asprin, Peter Rothwell reply

2011-06-07T23:24:00.000+01:00

reposted from: http://download.thelancet.com/pdfs/journals/lancet/PIIS0140673611606703.pdf?id=e16241398b8eb460:3c68b886:1306b6f6506:38b41307479634423
and http://download.thelancet.com/pdfs/journals/lancet/PIIS0140673611606685.pdf?id=e16241398b8eb460:3c68b886:1306b6f6506:38b41307479634423

crabsallover highlights, key points, comments / links.

Mark Nelson

Although Peter Rothwell and colleagues 1 provide the strongest evidence to date for the effect of aspirin in cancer prevention, they do not consider the well known adverse effects of aspirin, and focused on one potential benefit of aspirin in a study largely confined to middle-aged men.

Risk and benefit increase with age.2 Although the results look impressive when presented in proportional reduction terms, they are less so in “real” terms (14 000 people took aspirin for at least 4 years for a saving of about 100 cancer deaths). It is important, therefore, to be aware that a small proportion of those who develop serious adverse events, such as haemorrhagic stroke and major gastrointestinal bleeding, could reduce or reverse the benefi t.2–4

In older people, for whom serious adverse events are much more common and their consequences potentially more serious, the risk/benefi t equation will probably be different. The ASPirin in Reducing Events in the Elderly (ASPREE) trial5 examines whether the benefits of daily aspirin outweigh the risks in people aged 70 years or older. The ASPREE primary endpoint is extension of life free from dementia and disability. The trial will be able to show the true overall benefi t of routine use of aspirin in older people for primary prevention beyond simply counting individual adverse events.

I have received travel support from Bayer Healthcare—a manufacturer of aspirin. This company is also providing aspirin for ASPREE, of which I am a principal investigator. Mark Nelson mark.nelson@utas.edu.au Menzies Research Institute/University of Tasmania, Private Bag 23, Hobart, Tasmania 7001, Australia

1 Rothwell PM, Fowkes FG, Belch JF, Ogawa H, Warlow CP, Meade TW. Effect of daily aspirin on long-term risk of death due to cancer: analysis of individual patient data from randomised trials. Lancet 2011; 377: 31–41.
2 Hernandez-Diaz S, Rodriguez LA. Incidence of serious upper gastrointestinal bleeding/ perforation in the general population: review of epidemiologic studies. J Clin Epidemiol 2002; 55: 157–63.
3 He J, Whelton PK, Vu B, Klag MJ. Aspirin and risk of hemorrhagic stroke: a meta-analysis of randomized controlled trials. JAMA 1998; 280: 1930–35

Peter Rothwell Reply
Mark Nelson raises the issue of the risk of bleeding on aspirin. We deliberately made no specific recommendations about the widespread use of aspirin in healthy individuals, but we did discuss the issue of bleeding in some detail. Our analyses showed that taking aspirin daily for 5–10 years would reduce all-cause mortality (including any fatal bleeds) during that time by about 10% in relative terms. Subsequently, there would be further delayed reductions in risk of cancer death even if aspirin was stopped. In healthy middle-aged individuals, the risk of major bleeding on aspirin is relatively low (about 0·2 per 1000 patients per year—only a small proportion of which are fatal),3 and is already off set in many groups by the small reduction in risk of ischaemic vascular events.3 The reduction in risk of cancer is therefore additional to this existing balance in which the bleeding risk is already taken into account. However, the risk of bleeding on aspirin increases steeply with age and so we did not comment on use of aspirin in healthy individuals older than 75 years. The results of the ASPREE trial will be of great importance in this respect.

We agree with L H Opie that, in individuals without previous vascular events, both the relative and absolute reductions in risk of death due to cancer on aspirin versus control are larger than the equivalent reductions in risk of fatal vascular events, and that eff ects on cancer outcomes will dominate the overall risk/benefi t equation, particularly when the delayed eff ects on cancer death beyond the end of the trials is also factored in.

I have received honoraria for talks, advisory boards, and clinical trial committees from several pharmaceutical companies with an interest in antiplatelet agents, including AstraZeneca, Bayer, Boehringer Ingelheim, Sanofi -Aventis/ Bristol-Myers Squibb, and Servier.
Peter M Rothwell, on behalf of all authors peter.rothwell@clneuro.ox.ac.uk Stroke Prevention Research Unit, University Department of Clinical Neurology, John Radcliffe Hospital, Headington, Oxford OX3 9DU, UK

1 Medical Research Council’s General Practice Research Framework. Thrombosis prevention trial: randomised trial of low-intensity oral anticoagulation with warfarin and low-dose aspirin in the primary prevention of ischaemic heart disease in men at increased risk. Lancet 1998; 351: 233–41.
2 Peto R, Gray R, Collins R, et al. Randomised trial of prophylactic daily aspirin in British male doctors. BMJ 1988; 296: 313–31.
3 Antithrombotic Trialists’ (ATT) Collaboration. Aspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials. Lancet 2009; 373: 1849–60.

Lancet Correspondence on Peter Rothwell studies on Aspirin & Cancer, 14 May 2011

2011-06-07T21:39:00.001+01:00

This is an important series of 4 letters published May 2011 about Peter Rothwells work on Aspirin and Cancer followed by a comment by Peter Rothwell.

reposted from: http://download.thelancet.com/pdfs/journals/lancet/PIIS0140673611606661.pdf
and Peter Rothwells comments: http://download.thelancet.com/pdfs/journals/lancet/PIIS0140673611606703.pdf?id=e16241398b8eb460:3c68b886:1306b6f6506:38b41307479634423

crabsallover highlights, key points, comments / links.

The new data on cancer help to clarify the net benefit of aspirin, particularly if aspirin were included with a statin and bloodpressure- lowering drugs in a combined formulation (Polypill). Aspirin causes substantially fewer major extracranial bleeds that require a blood transfusion than the number of CVD events and cancer deaths prevented (table).

Aspirin in the prevention of cancer, N J Wald, J K Morris, M R Law
Peter Rothwell and colleagues, in their meta-analysis of randomised trials (Jan 1, p 31),1 show that low-dose long-term aspirin use reduces the risk of several cancers. Before this information was available, the balance of benefit and harm in taking aspirin in the primary prevention of coronary heart disease and stroke (cardiovascular disease [CVD]) was uncertain. The new data on cancer help to clarify the net benefit of aspirin, particularly if aspirin were included with a statin and bloodpressure- lowering drugs in a combined formulation (Polypill).

The table shows the estimated number of first CVD events and cancer deaths prevented in England and Wales in 1 year on the basis of a Polypill (composed of three blood-pressure lowering drugs at half standard dose and a statin at standard dose such as simvastatin 40 mg), with or without aspirin.

In people aged 55–89 years, for example, 186 000 CVD events and cancer deaths would be prevented. The table shows that 120 such outcomes would be prevented in 1000 people over a period of 20 years (or 170 per 1000 over 35 years).2–6

Aspirin causes substantially fewer major extracranial bleeds that require a blood transfusion than the number of CVD events and cancer deaths prevented (table). However, the risk of an aspirin-induced major extracranial bleed increases with age.4

The estimates for such bleeds shown in the table among people aged 55 years over a period of 20 years are based on observed data and are likely to be accurate, but the numbers in people older than 75 years are uncertain— they would be twice those shown if the age trend to 75 years continues to 90 years.

Given the results published by Rothwell and colleagues,1 the balance of the evidence is in favour of including aspirin in a Polypill strategy to prevent CVD and cancer.

NW and ML hold a European and Canadian patent (pend ing in the USA) for the Polypill, filed in April 2000.

*N J Wald, J K Morris, M R Law n.j.wald@qmul.ac.uk Wolfson Institute of Preventive Medicine, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London EC1M 6BQ, UK
1 Rothwell PM, Fowkes FG, Belch JF, Ogawa H, Warlow CP, Meade TW. Eff ect of daily aspirin on long-term risk of death due to cancer: analysis of individual patient data from randomised trials. Lancet 2011; 377: 31–41.
2 Law M, Wald N, Morris J. Lowering blood pressure to prevent myocardial infarction and stroke: a new preventive strategy. Health Technol Assess 2003; 7: 31.
3 Offi ce for National Statistics. Mortality statistics: deaths registered in 2009. London: Stationery Offi ce, 2010. http://www.statistics.gov.uk/ downloads/theme_health/dr2009/dr-09.pdf (accessed April 27, 2011).
4 Antithrombotic Trialists’ (ATT) Collaboration. Aspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials. Lancet 2009; 373: 1849–60.
5 Law MR, Wald NJ, Rudnicka AR. Quantifying the eff ect of statins on low density lipoprotein cholesterol, ischaemic heart disease, and stroke: systematic review and meta-analysis. BMJ 2003; 326: 1423–27.
6 Wald NJ, Law MR. A strategy to reduce cardiovascular disease by more than 80%. BMJ 2003; 326: 1419–23.

Author’s reply
We agree with N J Wald and colleagues that our results and their analyses do suggest that aspirin should be included in Polypill regimens, although the balance of risk and benefit is less certain in older individuals owing to the increase in risk of bleeding with age.

New clues to how humble painkiller stifles cancer growth

2011-05-31T14:19:00.000+01:00

reposted from: https://msds.open.ac.uk/students/course.aspx?c=S807_2011B

crabsallover highlights, key points, comments / links.

Thursday 26 May 2011

Cancer Research UK Press Release

CANCER RESEARCH UK scientists have shed light on how a common class of painkillers – which includes ibuprofen – may interact with a key protein that fuels the growth of many different types of cancer, according to a study published in the journal Chemical Communications today (Thursday).

Ibuprofen is one of several profens - a particular group of non-steroidal anti-inflammatory drugs (NSAIDs) - being investigated for their ability to prevent cancer.

The University of Bath research team* carried out an analysis of drugs in the same class as ibuprofen and discovered that they are all processed by the body in exactly the same way – through a protein called AMACR, which converts the drug into its active form.

AMACR is overactive in almost all prostate cancers, some bowel cancers and several other types of cancer and is thought to fuel the growth of the disease by boosting the cell’s energy supply.

So understanding how drugs like ibuprofen might alter AMACR activity could help scientists better understand how they are able to block cancer growth.

Lead author Dr Matthew Lloyd, said: “Our study is the first to test other drugs in the same family as ibuprofen systematically and show that they‘re all processed by the same protein in the body. Some early laboratory studies have suggested that high doses of ibuprofen can halt the growth of prostate cancer cells, but the reasons for this aren’t well understood.

“Understanding more about how this protein is acting in cells and what molecules it interacts with could provide important clues to how this process works, hopefully opening up new avenues of research for treating prostate cancer in the future.”

Dr Julie Sharp, senior science information manager at Cancer Research UK, said: “This research is part of an international effort to understand how drugs like ibuprofen could prevent, or slow down, the development of cancer. But there are risks as well as benefits and long term use of these drugs can have side effects, such as bleeding and stomach ulcers. Understanding more about how these drugs work on a molecular level is a crucial step in being able to develop better targeted drugs with fewer side effects in future.”

ENDS

For media enquiries please contact the Cancer Research UK press office on 020 3469 8300 or, out-of-hours, the duty press officer on 07050 264 059.

Woodman et al., Chiral inversion of 2-arylpropional-CoA esters by human alpha-methyylacyl-CoA racemase 1A (P504S) – a potential mechanism for the anti-cancer effects of ibuprofen (2011), Chemical Communications, DOI: 10.1039/ClCC10763A.

Dichloracetate DCA links

2011-05-26T21:20:00.000+01:00

reposted from:
http://www.nature.com/news/2010/100512/full/news.2010.236.html#B2
http://www.newscientist.com/blogs/shortsharpscience/2011/05/cure-for-cancer-resurfaces-and.html
http://www.newscientist.com/article/dn10971
http://en.wikipedia.org/wiki/Dichloroacetic_acid
http://en.wikipedia.org/wiki/Talk:Dichloroacetic_acid
http://scienceblogs.com/insolence/2010/05/dichloroacetate_dca_and_cancer_deja_vu_a.php
http://www.dca.med.ualberta.ca/Home/Media/articles.cfm
crabsallover highlights, key points, comments / links.

Potential cancer drug DCA tested in early trials

2011-05-26T00:37:00.000+01:00

reposted from: Cancer Research UK comments: http://scienceblog.cancerresearchuk.org/2010/05/12/potential-cancer-drug-dca-tested-in-early-trials/

crabsallover highlights, key points, comments / links.

I read about DCA in Cancer Research UK newsfeed on 16th May 2011. It was also mentioned by Guy
http://www.meetup.com/HASSNERS/messages/boards/thread/11130311/20#42889221 on 25th May 2011.

Update, 16th May 2011: Several websites are reporting that last week ‘cancer was cured without anyone reporting on it’. This is not true and seems, we think, to have arisen from a misreading of the date on the most recent paper on DCA (which was published on May 12th 2010 – i.e. this time last year).

Everything we wrote in the post and comments below stands – DCA is still only a ‘potential’ cancer treatment, and more research is needed to find out whether it’s safer or more effective than existing therapies.

- Henry

DCA has been tested in a small trial

The controversial drug DCA (dichloroacetate) is in the headlines again, after researchers in Canada carried out a small-scale clinical trial of the drug in five patients with advanced brain tumours.

Over the past year or two there have been several articles in the news and on the internet about DCA, which was claimed to be cheap, safe and “kill most cancers”.

Understandably this caused a great deal of interest, especially as DCA is an off-patent drug and appears to be non-toxic to humans (although it can cause significant side effects, as we’ll see later).

But before we jump to conclusions and hail DCA as a ‘wonder drug’, we need to look at the science behind the headlines.

What is DCA and how does it work?

Mitochondria are the 'power stations' in our cells

All our cells need energy to grow and function, including cancer cells. Simply put, our cells usually generate energy by breaking down sugar (glucose). To do this, they use a process known as the Krebs cycle, which takes place in tiny structures within the cell called mitochondria (the ‘power stations’ of the cell).

But cancer cells bypass this cycle and produce energy using a simpler process, known as glycolysis, which takes place outside the mitochondria in the cell’s cytoplasm (the main part of the cell).

Mitochondria play a crucial role in cells. As well as generating energy for the cell, they can also trigger the cell to die if it is faulty – a process that helps stop cancers from forming in the first place.

Because cancer cells seem to switch off their mitochondria, scientists think this is one way in which cancer cells are able to evade death and remain immortal.

DCA, or dichloroacetate, is a very simple chemical and is similar to some of the chemicals involved in the Krebs cycle. In 2007, researchers at the University of Alberta (led by Evangelos Michelakis) found that adding DCA to cancer cells grown in the lab kick-starts the Krebs cycle, turning the mitochondria back on again. This caused the cancer cells to stop multiplying and die. The team discovered that DCA didn’t affect healthy cells, because their mitochondria were functioning normally.

DCA has been tested as a treatment for children and adults with certain rare metabolic disorders. This means that, at the doses needed to treat these diseases at least, DCA has been through clinical trials aimed at assessing its safety. Based on their results, the researchers have proposed that DCA could also be useful in treating cancer.

To begin to investigate if this is indeed the case, Michelakis and his team started by carrying out experiments on cancer cells grown in the lab. The team also studied rats that had been injected with cancer cells. They found that DCA could slow the growth of the rats’ tumours, and reduce their size. This did not prove that the cancers were completely cured, or that DCA could prevent cancers from growing.

It is important to stress that DCA had not then been tested as a cancer treatment in humans, despite the implication in news headlines that it “kills most cancers”. There are many research papers produced by scientists around the world every year that reveal potential new treatments for cancer. But it is important that every discovery is carefully investigated to make sure that it is effective and safe for use in patients, and DCA is no exception.

The University of Alberta researchers received approval for a human cancer trial in September 2007, involving 50 patients. Now they have published the first results from five of those patients in the journal Science Translational Medicine.

The new trial

In this study, Michelakis and his team gave DCA to five patients with advanced glioblastoma, a type of brain tumour, in combination with surgery, radiotherapy and a drug called temozolomide. It’s important to point out that the aim of this study was not to find out whether DCA could treat glioblastoma, but to figure out the safest dose to use for cancer patients. We already know that the drug can be safely given to humans – although it can cause side effects – but this is the first time it has been tested in people with cancer.

The study shed light on the dose that could be given to patients without causing nerve problems or other serious side effects. Four patients were still alive after 18 months, and three showed some shrinkage of their tumour, but it is impossible to tell with such a small study whether this is longer than might be expected. And, given that they were also receiving other treatment, it’s hard to know if it was due to DCA at all.

As well as this small trial, the researchers also looked at the effect of DCA on tumour samples from 49 other glioblastoma patients. They found that DCA could switch mitochondria back on in the cancer cells, although – crucially – it’s still not clear exactly how it’s doing this.

Finally, the team looked at tumour samples taken from the five patients on the trial, both before and after treatment with DCA, and found that the drug was again helping to switch mitochondria on. They also discovered other differences in the cancer cells’ metabolism before and after treatment.

A key gap in this trial is that, as we’ve mentioned above, it’s not clear exactly how DCA is working. The researchers suggest that the drug may target cancer stem cells and prevent the growth of blood vessels into tumour, although they didn’t actually prove this.

Is it safe?

These results show that lower doses of DCA could, at least in theory, be given to cancer patients while avoiding some of the damaging side effects seen at higher doses. For example, a clinical trial of DCA for a childhood disease found that the drug caused significant side effects, affecting the nervous system. It is also known to be an environmental pollutant. And researchers have found that DCA can actually cause cancer in animals.

This is not necessarily a barrier to the use of DCA as a treatment for cancer – there are a number of powerful cancer drugs that are carcinogens themselves. And this is why we need to test them in clinical trials (as Michelakis and his team have begun to do here) to discover how they can be safely used to treat patients while minimising any harmful effects.

Why can’t we use it now?

It is understandable that people with cancer will want to try everything possible to help treat their disease. However, there is still no evidence – yet – to support the immediate use of DCA to treat cancer patients.

The trial in Canada is being conducted under stringent conditions both to ensure the validity of the results and to protect the participants from any unforeseen effects. Further clinical trials of DCA using more patients will help determine whether the treatment is more effective than the cancer therapies that are currently available.

There are reports that people are buying personal supplies of DCA from sources such as the internet. Cancer Research UK would strongly advise against this, as DCA still has not been shown to actually treat tumours successfully in patients. And it may be harmful when given to cancer patients without accurate dosing and medical supervision.

What will happen in the future?

It is clear that DCA is an intriguing drug – one of many currently being investigated by scientists around the world. It will be interesting to see the results of more extensive lab-based experiments and larger clinical trials of DCA. And cancer cell metabolism is certainly a productive area of research that we’re actively funding.

The fact that DCA is off-patent is no barrier to its development as a treatment for cancer. For example, Cancer Research UK has secured a licence for an off-patent drug called fenretinide, which could be used to treat rare childhood cancers.

And there is certainly no “conspiracy” by pharmaceutical companies to prevent research into DCA – there is just not enough evidence at the moment to support its widespread use to treat patients.

While these results are intriguing, it is unlikely that this one compound represents “the cure” for cancer – and it is also unlikely that DCA is the “wonder drug” that the headlines portray. Cancer is a complex and multi-faceted disease, and it can be caused by a range of different faults within the cell. It is unlikely that any single drug could ever treat all forms of the disease.

There are many promising new treatments for cancer currently in development, funded by organisations across the globe – including Cancer Research UK. If anything, these new results show why research is so important in bringing safe and effective treatments to people with cancer – they don’t provide definitive answers, but they support further investigations which may yield benefits for patients in the future.

Kat

Further reading:

A more detailed analysis of the new research can be found atRespectful Insolence – DCA and cancer: Deja vu all over again

References:

P. Kaufmann, K. Engelstad, Y. Wei, S. Jhung, M. C. Sano, D. C. Shungu, W. S. Millar, X. Hong, C. L. Gooch, X. Mao, J. M. Pascual, M. Hirano, P. W. Stacpoole, S. DiMauro, D. C. De Vivo (2006). Dichloroacetate causes toxic neuropathy in MELAS Neurology, 66, 324-330

Michelakis ED, et al (2010). Metabolic modulation of glioblastoma with dichloroacetate. Science translational medicine, 2 (31) PMID: 20463368

S BONNET, S ARCHER, J ALLALUNISTURNER, A HAROMY, C BEAULIEU, R THOMPSON, C LEE, G LOPASCHUK, L PUTTAGUNTA, S BONNET (2007). A Mitochondria-K+ Channel Axis Is Suppressed in Cancer and Its Normalization Promotes Apoptosis and Inhibits Cancer Growth Cancer Cell, 11 (1), 37-51 DOI: 10.1016/j.ccr.2006.10.020

Open University, S807, Molecules in Medicine MSc.

2011-05-25T05:08:00.000+01:00

February 2011 - I've started a 3 year part-time MSc in Science.

First year study: Open University, S807, Molecules in Medicine.

Conference reviews cancer prevention benefits of prophylactic aspirin

2011-05-25T04:56:00.001+01:00

reposted from: http://www.alphagalileo.org/ViewItem.aspx?ItemId=103955&CultureCode=en via Google 'aspirin', 'cancer' alert

crabsallover highlights, key points, comments / links.

Conference reviews cancer prevention benefits of prophylactic aspirin

24 May 2011 ecancermedicalscience

Recent evidence linking aspirin use with a reduced risk of several cancers could change the risk benefits analysis in favour of wider use of aspirin, concluded a meeting organized by the Aspirin Foundation. The report of the meeting “Aspirin, Salicylates and Cancer”, held November 2010 at the Royal Society of Medicine, has just been published in ecancermedicalscience.

In the report Gareth Morgan, from Older People’s Services, NHS Wales, outlined the current evidence on aspirin and cancer prevention; while Peter Rothwell, from Oxford University, explored the effects of aspirin on colon cancer risk; and Sir John Burn, from Newcastle University, looked at aspirin in the prevention and treatment of hereditary colorectal cancer.

Based its safety profile aspirin is the chemoprevention agent of choice in colorectal cancer, said Dion Morton from the University of Birmingham. The fact that aspirin reduces the risk of colorectal cancer with a latency of 10 years indicates that adenoma prevention, rather than down-staging cancer or preventing progression is probably the mechanism involved. He proposed a trial in which patients with high risk adenoma should be randomised to adjunctive treatment with aspirin or placebo.

Jack Cuzick, from Cancer Research UK, said that the cost of Phase II studies for early validation of the role of aspirin in cancer prevention could be minimised by the use of biomarkers and precursor lesions as end points.

Gordon McVie, from the European Institute of Oncology, Italy, said that several issues remain unresolved including the dose-response relationship in the prevention of colorectal cancer and the effect of enteric coating. The combinations of aspirin with other treatments, he added, was an avenue worth exploring in clinical trials.

Concluding the conference chairman, Peter Elwood, from the University of Cardiff, said that evidence of the risks and benefits of taking aspirin should be presented to the public in a package of measures to preserve health to allow them to make informed choices.

http://www.ecancermedicalscience.com/view-article.asp?doi=10.3332/ecancer.2011.213&type=abstract

download free conference report: http://www.ecancermedicalscience.com/cache/pdf/10.3332-ecancer.2011.213.pdf

Full bibliographic informationG Morgan, P Rothwell, J Burn, A Chan, L Mur, D Morton, J Cuzick, G McVie, "Aspirin, Salicylates and Cancer: report of a meeting at the Royal Society of Medicine, London, 23 November 2010". E cancer 2011, 5:213 DOI: 10.3332/ecancer.2011.213.

Aspirin in the prevention of cancer

2011-05-19T08:53:00.000+01:00

reposted from: http://www.lancet.com/journals/lancet/article/PIIS0140-6736(11)60669-7/fulltext

crabsallover highlights, key points, comments / links.

The Lancet, Volume 377, Issue 9778, Page 1651, 14 May 2011

doi:10.1016/S0140-6736(11)60669-7 Cite or Link Using DOI

Aspirin in the prevention of cancer

LH Opie a

That aspirin can help to prevent cancer1 has caught the public's attention. How does this benefit compare with the rather modest benefit in lessening cardiovascular events previously reported in those at low cardiovascular risk? In a previous study of such patients,2 the prevention was only three events in women and four in men among 1000 people studied over 6·4 years. The cost was 2·5 major bleeds per 1000 per 5 years in women and three in men, so the overall benefit was truly modest. By contrast, the cancer prevention rates in the study by Rothwell and colleagues1 included 15 gastrointestinal cancer deaths per 1000 people over 5 years. These benefits vastly outweighed the risk of major bleeds.

In view of these new facts, we should no longer be reserved about recommending aspirin even for those at low cardiovascular risk. However, we are still lacking firm data on when aspirin should be started in those at low risk, and at which dose. The doses of aspirin protecting from cancer in Peter Rothwell and colleagues' study1 were in the range of 75—300 mg daily. My guess is to start at a low dose—say 75 mg—in the early 50s.

I delare that I have no conflicts of interest.

References

1 Rothwell PM, Fowkes FG, Belch JF, Ogawa H, Warlow CP, Meade TW. Effect of daily aspirin on long-term risk of death due to cancer: analysis of individual patient data from randomised trials. Lancet 2011; 377: 31-41. Summary | Full Text | PDF(502KB) |CrossRef | PubMed

2 Berger JS, Roncaglioni MC, Avanzini F, Pangrazzi I, Tognoni G, Brown DL. Aspirin for the primary prevention of cardiovascular events in women and men: a sex-specific meta-analysis of randomized controlled trials. JAMA 2006; 295: 306-313. CrossRef |PubMed

a Hatter Cardiovascular Research Institute, University of Cape Town Medical School, Observatory, Cape Town 7925, South Africa

Call for all to take statins after 55

2011-05-06T22:49:00.000+01:00

reposted from: http://www.nhs.uk/news/2011/05May/Pages/statins-for-all-55-plus.aspx

crabsallover highlights, key points, comments / links.

"All those over 55 should be offered drugs to lower cholesterol and blood pressure, according to a new study," reported BBC News. It said the report suggests that when assessing the risk of heart problems, offering treatment to all over-55s had the same results as testing for cholesterol or blood pressure problems. The authors have also argued it would be simpler and more cost-effective.

Scientists warn about future flu strains

2011-03-12T00:28:00.000Z

reposted from: http://www.nhs.uk/news/2011/03March/Pages/call-for-vaccination-against-h2n2-flu.aspx

crabsallover highlights, key points, comments / links.

Governments should start vaccinations against a lethal strain of the influenza virus circulating in birds and pigs, The Independent has reported.

The news is based on an article written by US vaccine researchers, who said that an old flu strain known as H2N2, which caused a pandemic in the 1950s and 60s, could easily start circulating again in humans. The researchers also conducted a small test of 90 people, which showed that people under the age of 50 have little or no immunity to the strain. They argue that creating a new vaccination programme to deal with this strain of flu could save lives by preventing a potential pandemic.

The emergence of different flu strains and the question of whether vaccines are needed against them is an important public health issue, particularly in light of the rapid spread of swine flu in 2009. However, it can be hard to initially tell how widely a new or re-emergent strain of flu will spread or how severely it will affect people. In the case of H2N2, the disease does not currently circulate in humans and any pre-emptive vaccine programme will need further investigation before it can be justified.

Where did the story come from?

The report was written by researchers working at the Vaccine Research Centre of the US National Institutes of Health. The researchers did not report any sources of external funding. The report was published in the peer-reviewed journal Nature.

The research article was faithfully reported by both the BBC andThe Independent. The BBC included comments from an independent UK expert, who questioned whether the public would want another vaccine against a disease that does not presently exist. The Independent’s headline, which stated that we should “vaccinate against killer flu virus now”, does not reflect the conclusion of the research article, which suggested we should examine the issue rather than begin vaccinations. In addition, it is not possible to tell whether the H2N2 flu virus would be likely to kill if it began circulating in a modern population.

What kind of report was this?

This commentary, written by vaccine researchers, argued that government regulatory authorities should plan for a vaccination programme against an old flu strain called H2N2. They warned that this strain is circulating in birds and pigs and could jump to humans, as the H1N1 swine flu strain did in 2009.

In their comment article, the researchers reported details of a small study they conducted, in which they tested 90 US residents for antibodies against the H2N2 flu strain. Their results suggested that people under the age of 50 have little or no immunity to the strain, while resistance dramatically increases in people older than 50. They say this pattern of immunity is similar to that found in H1N1.

What does the report say?

The researchers point out that the emergence of a new strain of the H1N1 virus in 2009 took the world by surprise. The public health community had assumed that any future pandemic flu strain would arise from a “major genetic reshuffling” of existing flu viruses to produce a new virus that had never circulated in humans before. As it turned out, the virus that emerged bore a remarkable resemblance to one that had already caused a pandemic 90 years earlier: H1N1 Spanish flu, which killed about 50 million people worldwide. A version of this virus had circulated in pigs for nearly a century and was able to eventually transfer back to humans and cause a new pandemic at a time when immunity levels had waned.

The authors of this comment article say that the unexpected origin of the H1N1 pandemic provides a “cautionary tale” for the public health community, and that the H2N2 strain constitutes a possible public health threat as it could re-emerge in a similar way. They argue that government regulatory agencies should develop a pre-emptive vaccine programme against H2N2.

The researchers draw a number of parallels between the H1N1 and H2N2 viruses. For example, they have both caused pandemics: from 1957 to 1968, an H2N2 strain caused 1–4 million deaths worldwide. Like the 1918 strain, the H2N2 virus has not circulated in humans for several decades but continues to do so among birds and pigs.

To examine people’s levels of immunity to this class of virus, between 2003 and 2007 the researchers tested stored blood samples for antibodies against H2N2 strains in a small cohort of 90 people in the US. The researchers admit that ideally the test needs to be repeated in several thousand individuals, but say their study suggests that people under the age of 50 have little or no immunity to H2N2, and immunity is far stronger in people over 50 (as was also the case for H1N1).

The researchers argue that governments should plan a pre-emptive vaccination programme to prevent the re-emergence of H2N2 in humans, perhaps based on the vaccine against H2N2 licensed for use against the 1957-68 pandemic. They suggest several possible strategies for doing this:

Manufacture the vaccine licensed in 1957 and immunise enough of the world’s population to provide “herd immunity” to the rest (i.e. vaccinate a large enough proportion of people so that the virus cannot easily spread to non-vaccinated individuals).
Stockpile the vaccine so supplies are ready in the event of an outbreak (which they point out would be more expensive and less effective than routine vaccination).
Make “master lots” of H2N2 vaccine and increase production as soon as signs of an outbreak occur (they argue this would be cheaper but less effective than either of the above methods).

What do these researchers conclude?

The researchers looked at the pros and cons of developing a pre-pandemic vaccine, including cost, the obstacles to distributing vaccines internationally, potential public distrust of vaccines and the limitations that are placed on public health resources. However, they finally concluded that another major flu pandemic is likely to cost far more and create a far greater health burden than a pre-emptive vaccination programme. Such a strategy would save lives and “spare the world a major public-health crisis”, they concluded.

Conclusion

The researchers raise important questions about the possibility of a future flu pandemic caused by the H2N2 virus, and about whether vaccination programme planning could be used to prevent it. However, many issues need further consideration, including a detailed assessment of the probability of the H2N2 strain jumping to humans, whether it would pose a serious health threat, how long it would take to emerge and which groups of people would be vulnerable. It is important to note that infection with the H1N1 virus, although dangerous for some population groups, did not make most people seriously ill.

As the researchers point out, there are concerns over whether it makes sense to expose individuals to vaccines for a virus that is not currently circulating in humans, although they say the previously licensed H2N2 vaccine has a proven safety and efficacy record. Also, the virus that might emerge in humans may have evolved or mutated to the point where the current H2N2 vaccine no longer provides immunity, although the researchers argue that this is unlikely. As the researchers note, more studies of the existing H2N2 vaccine would be required to confirm its safety and efficacy and to establish who to immunise and when.

The question of whether vaccines should be prepared against the possibility of new, emergent and sometimes dangerous strains of flu is an important public health issue, particularly given the nature of the 2009 swine flu pandemic, in which a new strain of the H1N1 virus emerged and spread quickly.

With new or re-emergent strains of flu, immunity levels are often low, and it can be difficult to initially tell how widely a new strain will spread, or how severely it will affect people. In the case of H2N2, the disease does not currently circulate in humans, so there is still uncertainty over whether it is necessary to plan a vaccine programme and whether existing vaccines would work against an emerging strain. It is also not clear whether the public would find it acceptable to receive or have the government fund a vaccine against a non-circulating disease.

While this research paper rightly argues that an H2N2 vaccination should be investigated, such an examination will need to be informed by evidence on the medical and logistic issues involved, particularly whether available vaccines would be likely to provide protection against future strains.

Links to the headlines

Call to vaccinate against possible H2N2 flu pandemic. BBC News, March 10
2011

Vaccinate against killer flu virus now, say experts. The Independent, March 10 2011

Links to the science

Nabel GJ, Wei CJ, Ledgerwood JE. Vaccinate for the next H2N2 pandemic now. Nature, 10 March 2011, volume: 471, Pages: 157–158

Mediterranean diet - high in fruit & veg & olive oil, low in meat

2011-03-10T08:49:00.000Z

reposted from: http://www.nhs.uk/news/2011/03March/Pages/mediterranean-diet-obesity-blood-pressure-diabetes.aspx

crabsallover highlights, key points, comments / links.

Eating a Mediterranean diet “can reduce the risk of developing conditions such as diabetes, obesity and high blood pressure”, The Daily Telegraphhas today reported. Mediterranean diets are typically high in fruit and vegetables, low in meat and use olive oil in place of dairy fats.

The news comes from a new review of research on the Mediterranean diet that combined and analysed the results of 50 studies in more than 500,000 people. Among the most notable findings were that those eating the diet had lower blood pressure, lower blood sugar and higher levels of ‘good’ cholesterol. The study also found an overall reduction in symptoms of metabolic syndrome, which is a combination of risk factors that increase the likelihood of cardiovascular disease.

This new review did not assess the development of heart disease and diabetes, but it has demonstrated that the Mediterranean diet reduces the development of metabolic syndrome and its components, which are often precursors to the development of these conditions. There were some differences between the gathered studies that suggest that the results should be interpreted somewhat cautiously, although the trends seen do support other research about this dietary pattern.

Where did the story come from?

The study was carried out by researchers from universities in Athens and Ioannina in Greece and in Naples, Italy. The authors do not specify whether they received external funding. The study was published in the peer-reviewed Journal of the American College of Cardiology.

The press has covered this study well, although headlines stating that the Mediterranean diet “cuts risk of heart disease” may incorrectly imply that the study directly measured outcomes of heart disease. The study was concerned with a range of risk factors that are likely to precede heart disease, such as high blood pressure.

What kind of research was this?

This is certainly not the first time that research on the Mediterranean diet has made headlines, with numerous individual studies on the diet having received press coverage. However, this systematic review and meta-analysis provides the most up-to-date assessment of the evidence for the diet as a way to reduce the risk of developing cardiovascular disease in adults.

Specifically, the authors combined the results from 50 previous studies that had measured the effects of the diet on metabolic syndrome, a cluster of risk factors in adults that together can considerably raise the likelihood that a person will develop diabetes or heart disease. Metabolic syndrome is defined formally as the presence of any three of the following:

high blood pressure (greater than 130/85mmHg or active treatment for hypertension)
high blood sugar (fasting plasma glucose >5.6mmol/L or active treatment for hyperglycaemia)
high blood fat (triglycerides ≥1.7mmol/L)
low levels of ‘good cholesterol’ (<1.03mmol/L for men or <1.29mmol/L for women)
a large waist circumference (≥102cm in men and ≥88cm in women or ≥90cm in Asian men and ≥80cm in Asian women)

Lifestyle interventions, particularly changes in diet and increases in physical activity, are established ways to prevent metabolic syndrome and, consequently, to reduce the likelihood of cardiovascular disease and diabetes. The Mediterranean diet is generally considered to consist of a high concentration of good oils (monosaturated fatty acids), usually from olives and olive oil; daily consumption of fruit, vegetables, wholegrains and low-fat dairy; weekly fish, poultry, nuts and legumes; low red meat consumption and moderate alcohol consumption. It has been linked to reduced risk of cardiovascular disease, cancer and diabetes.

This study takes a new angle by specifically looking at the effects diet has on the risk factors that often precede the development of cardiovascular diseases.

What did the research involve?

The researchers set out to identify all English language research studies published up to April 30 2010, that assessed the effects of a Mediterranean diet on the development of metabolic syndrome or its components. They searched well known medical databases including PubMed, Embase and the Cochrane Central Register of Controlled Trials. They did not exclude studies on the basis of study design at this stage.

Their search initially identified 474 studies, but after excluding those that did not meet specific inclusion criteria (such as those that failed to be randomised if they were trials, those that failed to compare the Mediterranean diet against another diet or those that missed some of the key components of the Mediterranean diet) they were left with 50 studies that were eligible for analysis. There were 2 cohort studies, 35 randomised controlled trials and 13 cross-sectional studies. They provided a total study population of 534,906 individuals.

The researchers extracted the results data from each study, specifically the reports of changes in or progression of metabolic syndrome or any of the main components (waist circumference, blood pressure, blood cholesterol, blood fat or blood glucose). The results were then pooled using the statistical techniques of meta-analysis. The researchers differed the techniques according to whether they were combining the results from the randomised controlled trials, the cohort studies or the cross-sectional studies. The researchers also rated the quality of each study to help provide a measure of their confidence in the results obtained from the pooling.

From their analyses, the researchers then reported how a Mediterranean diet affects the risk of metabolic syndrome and some of its separate components. Although 50 studies were included overall, the different outcomes they each addressed meant that fewer studies could be included in the meta-analyses relating to each specific outcome. For example, in total, only eight studies assessed the effect of Mediterranean diet on the development or progression of the entire set of metabolic syndrome risk factors. Only two of these were randomised controlled trials, two were cohort studies and four were cross-sectional studies.

What were the basic results?

The Mediterranean diet was found to protect against the development or progression of metabolic syndrome, reducing the risk by about 50%. The Mediterranean diet was also protective against some of the individual components of the syndrome, with people who consumed it having, on average, a 42cm smaller waist circumference, higher levels of good cholesterol (1.17mg more), lower blood triglycerides (-6.14mg lower), lower blood pressure and lower blood glucose.

How did the researchers interpret the results?

The researchers conclude that their results “are of considerable public health importance” because the dietary pattern can be easily adopted by all population groups and is a cost-effective approach to the primary and secondary prevention of metabolic syndrome and its individual components.

Conclusion

This was a well conducted systematic review and meta-analysis, although the interpretation of some of its extensive results is not straightforward. The researchers have performed different sub-analyses, each separately pooling all cross-sectional studies, all cohort studies and all controlled trials. They then reported the results of these groups separately and also combined the results from cohort studies and trials in some cases.

The most noteworthy results are probably those obtained from pooling randomised controlled trials. Randomised controlled trials have the most appropriate study design for assessing the effects of receiving an intervention compared with not receiving it. Pooling just those results from randomised controlled trials showed Mediterranean diet reduced the risk of developing or progressing metabolic syndrome overall, as well as all of the individual components that make up the syndrome. These are the important results of the study, as combining the results of cohort studies and cross-sectional studies has limitations. Neither cohort studies nor cross-sectional studies can prove cause and effect.

There are some other points to keep in mind when interpreting the results:

Although the researchers excluded studies that did not describe the full Mediterranean diet, the precise pattern of food was likely to vary across the included studies as was the way it was administered and the recommendations given. There were also differences in the diets consumed by the control groups and in whether dietary change was being recommended as part of wider lifestyle changes or not.
Importantly, some of the analyses combined studies that were very different from one another in terms of the sample size, study duration, trial quality and context of intervention. These analyses had a high ‘statistical heterogeneity’, which is a way of measuring whether it is appropriate to pool them or not (higher heterogeneity means pooling is less appropriate). The researchers say that this “introduces a warning about the generalisation of the present results”.
The outcomes were related to risk factors for cardiovascular disease, not the disease itself. It is, therefore, an extrapolation, although perhaps not an unrealistic one, to claim that this study proves that the Mediterranean diet has an effect on cardiovascular disease outcomes.

Overall, this research provides further evidence of the benefits of eating a Mediterranean-style diet and quantifies the benefit in terms of the individual risk components of metabolic syndrome.

Links to the headlines

Mediterranean diet 'cuts risk of heart disease'. The Daily Telegraph, March 8 2011

Links to the science

Kastorini CM, Milionis HJ, Esposito K et al. The Effect of Mediterranean Diet on Metabolic Syndrome and its Components: A Meta-Analysis of 50 Studies and 534,906 Individuals. Journal of the American College of Cardiology, 2011; 57:1299-1313