Can ibruprofen ward off Parkinson's?

reposted from: http://www.nhs.uk/news/2011/03March/Pages/ibruprofen-reduced-risk-parkinsons-disease.aspx

crabsallover highlights, key points, comments / links.

Taking ibuprofen just a few times a week could cut the risk of developing Parkinson's disease by a third, according to The Daily Telegraph.

The news is based on the publication of a large study that followed 136,197 middle-aged to elderly people over six years. It looked at whether regular use of the painkiller ibruprofen had any association with the risk of developing Parkinson’s disease. The study found that 291 people developed Parkinson’s, with those who regularly took ibuprofen having an approximately 30% lower risk of developing the disorder than those who did not. Other painkillers were also examined but were not associated with a reduced risk.

The study was well-designed but has some limitations, which mean it cannot prove that ibuprofen can help to protect against Parkinson’s. For example, only 28 people who developed Parkinson’s had used ibuprofen, making it hard to perform statistical comparisons of their behaviour. Also, early (pre-clinical) Parkinson’s may be present many years before obvious symptoms, so it is possible that participants may have already had undiagnosed Parkinson’s before their ibruprofen use was assessed.

Regular use of ibuprofen can have side effects, including a raised risk of stomach bleeds. Given the potential risks, people should not attempt to take ibuprofen as a preventative treatment against Parkinson’s disease at the current time.

Where did the story come from?

This US study was carried out by researchers from Brigham and Women’s Hospital, Harvard medical School, Harvard University School of Public Health, the National Institute of Environmental Health Sciences, and Massachusetts General Hospital. The research paper featured no information about external funding. The study was published in the peer-reviewed medical journal,Neurology.

In general, the study was reported accurately by the newspapers, although reports tended to be over-optimistic and did not mention the study’s limitations.

What kind of research was this?

This research was based on data from two prospective cohort studies, and it involved more than 136,000 participants. It looked at whether use of ibuprofen, other NSAIDs or paracetamol was associated with a lower risk of developing Parkinson’s disease: a progressive neurological disorder characterised by muscle tremor, stiffness and weakness.

This type of study, which can follow large groups of people for many years, is useful to assess the possible relationship between an intervention (in this case, use of ibuprofen and other painkillers) and an outcome (in this case, development of Parkinson’s disease). However, on its own it cannot prove a causal association between the two. Prospective cohort studies, which follow people in real time, are also considered to be more reliable than retrospective studies, which often ask people to recall events that have happened several years in the past.

The authors also pooled the results of their study with other previously-published trials to perform a meta-analysis of the relationship between NSAIDS, other painkillers and Parkinson’s.

The researchers discuss how neuroinflammation, a chronic, inflammation-like response in the central nervous system) may contribute to the development of Parkinson’s Disease. They point out that previous epidemiological studies suggest that use of NSAIDs in general, and ibuprofen in particular, may be related to a lower risk of developing Parkinson’s.

What did the research involve?

The researchers used data from two very large, long-term studies of health professionals. One was based in the US (the Health Professionals Follow-up Study, which began in 1986) and one was from the UK (the Nurses’ Health Study, which began in 1976). Both studies are based on participants completing questionnaires regarding the medical history and lifestyle of participants at the start of each study, with follow-up questionnaires mailed every two years.

The authors have already published earlier research from these groups, which found an association between non-aspirin NSAID use and a lower risk of PD. This new research was restricted to the years after the original study, using the 2000 US survey and the 1998 UK survey as their starting point. The total number of participants in these studies was 136,197.

The researchers established that participants were not diagnosed with Parkinson’s at the start of their study. They assessed the use of NSAIDs by questionnaire, with participants being asked if they regularly took (two or more times weekly) the painkillers aspirin, ibuprofen, other NSAIDs or paracetamol. Information on the participants’ use of these painkillers was updated every two years for both study groups. The questionnaires also recorded information on age, ethnicity, body weight, height and smoking status.

Participants were followed for six years. Those diagnosed with Parkinson’s over this period were identified using self-reports and diagnostic confirmation from relevant doctors.

The researchers used standard statistical techniques to assess the possible relationship between use of NSAIDs and Parkinson’s. They adjusted their findings to take account of possible “confounders” which might have affected results, including age, smoking and caffeine intake. Researchers also excluded patients with gout, since high uric acid levels also lower PD risk. They excluded PD cases identified in the first two years of follow-up, to avoid the possibility of reverse causation, i.e. people not taking NSAIDs because of their PD.

What were the basic results?

During six years of follow-up, the researchers identified 291 people who had developed PD. They found that:

• After adjusting for age, smoking, caffeine use and other possible confounders, people using ibuprofen had a significantly lower PD risk than non-users (relative risk [RR], 0.62, 95% confidence interval [CI] 0.42 to 0.93).
• The higher the dose of ibuprofen taken each week, the lower the risk. This is called a dose–response relationship.
• Use of other painkillers, including aspirin, paracetamol and other NSAIDs, had no significant association with risk of PD.
• When researchers combined their results with other published studies in a meta-analysis, they again saw a reduced incidence of Parkinson’s disease with ibuprofen use (pooled RR of Parkinson’s 0.73, 95% CI 63 to 0.85).
• In the meta-analysis, other types of analgesics were once again not found to be associated with lower Parkinson’s disease risk.

How did the researchers interpret the results?

The researchers say their results suggest that ibuprofen should be investigated further as a “potential neuroprotective agent” against Parkinson’s disease. They add that there is some evidence that “inflammatory mechanisms” may contribute to the progressive damage to nerve cells. They argue that ibuprofen therefore possibly has protective properties against this process. They suggest that these protective properties are not shared by other NSAIDs.

Conclusion

The strengths of this study lie in its large sample size and high follow-up rate (95% and 94% in the UK and US studies, respectively). Because the study was prospective, following people in real time, there was also less chance of “recall bias” (where participants inaccurately recall the use of painkillers). In addition, the researchers controlled for important confounding factors, such as age, smoking, body mass index, caffeine and alcohol intake. The way they assessed NSAID use, intended to cover both prescription and over-the-counter use, is also thought to be reliable.

However, as the authors note, it does have some limitations:

• NSAID use was self-reported and therefore potentially subject to error.
• The studies involved US and UK health professionals rather than random samples of men and women. Their use of NSAIDs would not necessarily reflect the pattern of use seen in the general population. The authors point out that the biological effects of ibuprofen on Parkinson’s disease would be the same, however.
• It is possible that ibuprofen was used to treat conditions that are themselves associated with a lower risk of PD. That said, the primary use of ibuprofen was for muscle and joint pain, which is not associated with PD risk.
• Although they adjusted for confounders, other factors that might influence the results cannot be ruled out.

Importantly, although this was a large study, it should be noted that the number of people who developed Parkinson’s disease was small (28 Ibruprofen users and 263 non-users). Carrying out statistical comparisons in such few participants can be problematic as it increases the possibility of presenting inaccurate risk associations. The potential for inaccuracy is even greater when subdividing them by dose taken. For example, only nine people with Parkinson’s had taken ibuprofen once or twice a week; four people used it three to five times a week; and 10 people, more than six times. Though they observed a trend for higher dose to be associated with lower risk, this may therefore be inaccurate. 

A further limitation that might have affected results is the study’s short follow-up period: as an accompanying editorial points out, early signs of “preclinical” PD may be present up to 20 years before obvious symptoms. It is possible that gastrointestinal symptoms, for example, could cause a person with very early Parkinson’s to be less likely to take ibuprofen regularly (because it would be contraindicated).

In conclusion, this study is of interest but it cannot show a causative association between ibuprofen use and the development of Parkinson’s. Further research is required to investigate whether ibuprofen could be “neuroprotective”. 

Regular use of ibuprofen and other NSAIDs can have side effects, including stomach bleeds, particularly in the elderly, and a slightly increased risk of heart attack and stroke. Given these risks, and the uncertainy over whether it is associated with a lower risk of Parkinson’s disease the use of ibuprofen as a preventative treatment against Parkinson’s cannot be recommended at the current time.

Links to the headlines

Ibuprofen could help fight off Parkinson's Disease. The Daily Telegraph, March 3 2011

Parkinson's disease risk 'could be cut by a third' through ibuprofen use. Daily Mail, March 3 2011

Ibuprofen may reduce risk of getting Parkinson's disease by a third.The Guardian, March 3 2011

Ibuprofen 'cuts Parkinson's risk'. BBC News, March 3 2011

Links to the science

Gao X, Chen H, Schwarzschild MA, Ascherio A. Use of ibuprofen and risk of Parkinson disease. Neurology, [Published online before print] March 2, 2011

Dedicated to John Head, aged 80+, who is being treated for Prostate Cancer.

reposted from: http://www.nhs.uk/news/2011/03March/Pages/new-prostate-cancer-test-studied.aspx

crabsallover highlights, key points, comments / links.

“Thousands of lives could be saved by a new cancer test,” the Daily Express reported today. It said that the new test for prostate cancer “detects twice as many cases as the current method”.

This story is based on a study in 288 men with and without prostate cancer, which assessed whether a urine test that measures levels of a protein called EN2 could detect the disease. Cases of prostate cancer had been confirmed through biopsy. The study found that testing for the protein could accurately identify 66% of men with prostate cancer, and correctly rule out the disease in almost 90% of men without the disease.

This study has identified a potential new marker for prostate cancer. The results are promising, but the research is at an early stage, and much further study is needed. The performance of the test will need to be confirmed in larger samples of men from the general population. After this, studies would need to examine how the test affects outcomes such as the numbers of men dying from prostate cancer, and those having unnecessary biopsies. Newspaper estimates that the test will be ready within months are probably overly optimistic.

Where did the story come from?

The study was carried out by researchers from the University of Surrey and other research centres in the UK. It was funded by Cancer Research UK and the Prostate Project Foundation. The authors were also supported by The University of Cambridge, Hutchison Whampoa Limited, the NIHR Cambridge Biomedical Research Center, the Department of Health, and the Medical Research Council.

The study was published in the peer-reviewed medical journal Clinical Cancer Research.

The Daily Express, Daily Mail, Mirror, and The Daily Telegraph covered this research. The papers vary in their predictions of how soon the test might be available; the Mail suggests it could be in general use within months, while the Telegraph claims “within 18 months”. The Express suggests that the test could cost less than £100. However, the test’s performance is still being assessed in the laboratory. It is too early to say if it is reliable and accurate enough to be put into general use, when that may be, or how much it might cost. It is much too early to know whether the test “could save thousands of lives” as some papers suggest.

What kind of research was this?

This laboratory research investigated whether testing for a protein called engrailed-2 (EN2) might detect prostate cancer. This protein belongs to a family of proteins that are usually produced in cells in the embryo but are also switched back on in cancerous cells. The researchers wanted to test whether this protein was produced by prostate cancer cells, and whether it might be a good marker for prostate cancer.

Currently, prostate cancer is detected by measuring the levels of prostate specific antigen (PSA) in the blood. PSA levels are also used to monitor the effects of treatment. PSA is made by normal prostate cells as well as cancerous prostate cells, and men vary in their natural levels of PSA. Raised PSA levels may indicate the presence of prostate cancer, but can also occur in men with non-cancerous enlargement of the prostate. This means that the PSA test misses some cancers (false negatives), and it may suggest that cancer is present in some men who do not have the disease (false positives). The performance of the test depends on the level of PSA selected as the “threshold” for indicating the possible presence of cancer. It also depends on the population tested. Different studies have reported that the PSA test detects between 15% and 44% of prostate cancers.

Therefore, researchers are looking into whether they can develop a better test for prostate cancer. This study aimed to test the diagnostic accuracy of the EN2 urine test (its sensitivity and specificity) and to define a useful threshold for the test, i.e. what a ‘normal’ and ‘abnormal’ level for the protein might be.

What did the research involve?

The researchers first tested whether the EN2 protein was produced by prostate cancer cells and non-cancerous prostate cells grown in the laboratory. They also tested for EN2 in normal and cancerous prostate tissue samples from men with prostate cancers. Prostate tissue samples from men with the non-cancerous condition “benign prostatic hyperplasia” were also tested, as were tissue samples from men with the pre-cancerous condition “high-grade prostatic intraepithelial neoplasia”.

In the next part of their study, the researchers compared the levels of EN2 in urine samples from 82 men with biopsy-confirmed prostate cancer, with 102 men without the disease.

Some of the urine samples were collected from men who had been referred to their specialist Uro-Oncology clinic. These men were referred because they had urinary symptoms that could be a sign of prostate cancer, or had no symptoms but were concerned that they might have prostate cancer (due to a family history of prostate cancer, for example) or had an abnormal PSA test. These men had been referred for testing to determine whether they did or did not have prostate cancer. Of these men, 82 had prostate cancer confirmed on biopsy. Fifty-eight had negative biopsies and were included in the control group of men without prostate cancer.

The researchers also collected urine samples from additional control men aged over 40, who had normal levels of PSA (below 2.5 nanogrammes per mL). These men either had blood in their urine but had no malignancies in their urinary system (urothelial malignancy) detected on testing (17 men), or they had no symptoms or family history of prostate cancer (27 men). The researchers also had urine samples from 10 men with the pre-cancerous condition “high grade prostatic intraepithelial neoplasia”.

Men already being treated for known prostate cancer, or with any known cancer in the past 10 years, or with a urinary tract infection, were not eligible to take part in the study. Urine samples were collected from the first passage of urine of the day. They were taken before any biopsies were performed or any hormone therapy received, and at least 24 hours after any digital rectal examination.

The researchers testing the urine samples did not know which men had cancer. Blood samples for PSA testing were also collected before the urine samples were collected. The researchers looked at whether the levels of EN2 in a man’s urine were related to the levels of PSA in his blood.

To confirm their results, another research centre tested urine from a further 81 patients with prostate cancer and 13 men without prostate cancer.

What were the basic results?

The researchers found that the EN2 protein was being made and secreted by prostate cancer cells grown in the laboratory, but not in normal prostate cells.

They also found EN2 protein in 92% of 184 prostate cancer tissue samples, but in none of the 20 normal prostate tissue samples. The EN2 protein was not detected in prostate tissue samples from men with “benign prostatic hyperplasia”, nor in prostate tissue samples from men with “high grade prostatic intraepithelial neoplasia”.

The urine tests showed that 66% of the men with prostate cancer had EN2 protein in their urine. About 12% of men without prostate cancer had EN2 protein in their urine. The researchers report that using a cut-off value of 42.5 ng/mL of EN2 protein in the urine appeared to be optimal, giving a sensitivity of 66% and specificity of almost 90%. This suggests that in combination with other tests it may be useful at ruling out disease in normal men and confirming disease in those with cancer.

On average, levels of EN2 protein in the urine of men with prostate cancer were 10.4 times higher than those in men without prostate cancer. Independent testing of urine samples from another 94 men at another laboratory found that 58% of the prostate cancer patients in this sample had EN protein in their urine, compared with 15% of control men without the disease.

Of the 10 men with the pre-cancerous condition “high grade prostatic intraepithelial neoplasia”, three had EN2 protein in their urine. A second biopsy taken within six months of the first found that two of these three men had prostate cancer.

The level of EN2 in the men’s urine was not related to the level of PSA in their blood.

How did the researchers interpret the results?

The researchers concluded that EN2 protein in the urine is a good candidate marker for the presence of prostate cancer. They say that a larger study across multiple centres “to further evaluate the diagnostic potential of EN2 is justified”.

Conclusion

This study has identified a potential new marker for prostate cancer. This research is at an early stage, and much further research is needed. The test’s accuracy will need to be confirmed in larger samples of men from non-specialist settings to show how effective it is at screening for prostate cancer in the general population. After this, studies would need to examine how the test affects outcomes such as the numbers of men dying from prostate cancer, and those having unnecessary biopsies.

Though promising, these findings also need to be considered with some pragmatism. Even if the EN2 test performs well in larger scale testing, the test would not necessarily replace PSA testing. The authors suggest that the tests could be used together in prostate cancer diagnosis. Also, if the combined tests did indicate that cancer might be present, the results would still need confirmation by prostate biopsy.

There is a need for improved prostate cancer tests, particularly those that can detect early prostate cancer accurately. There is a lot of research going on in this area. More research will be needed to determine how well these newer tests perform when compared with current tests, and which of them performs the best.

Links to the headlines

Thousands of lives could be saved by a new cancer test. Daily Express, March 2 2011

Prostate cancer test is 'twice as good', say researchers. BBC News, March 2
2011

Accurate new prostate cancer test could save thousands of lives. Daily Mirror, March 2 2011

Urine test for prostate cancer 'in 18 months'. The Daily Telegraph, March 2 2011

New test to spot prostate cancer could be in use in surgeries within months. Daily Mail, March 2 2011

Links to the science

Morgan R, Boxall A, Bhatt A,et al.Engrailed-2 (EN2): A Tumor Specific Urinary Biomarker for the Early Diagnosis of Prostate Cancer.Clinical Cancer Research 2011, Published OnlineFirst March 1

Further reading

Ilic D, O'Connor D, Green S, Wilt TJ. Screening for prostate cancer.Cochrane Database of Systematic Reviews 2006, Issue 3

(Another) urine test for prostate cancer

reposted from: http://www.bbc.co.uk/blogs/thereporters/ferguswalsh/2011/03/another_urine_test_for_prostate_cancer.html

crabsallover highlights, key points, comments / links.

Fergus Walsh (BBC News) Tue Mar 01 2011 16:19:39 GMT+0000 (GMT Standard Time) Share

An encouraging development in the diagnosis of prostate cancer - the most common cancer in men. Scientists at the University of Surrey have developed a urine test which - in an early trial - was at least twice as good at detecting prostate cancer than the current test.

Last October, Cancer Research UK scientists in Cambridge also announced early results of a prototype urine test. The CRUK researchers looked at levels of a protein found in urine called MSMB, and in a small study were able to diagnose prostate cancer from urine samples with about 50% accuracy.

The team at the University of Surrey focussed on another protein, Engrailed-2 (EN2) which is made by prostate cancers and secreted into urine. In a study of nearly 300 men published in the US journal Clinical Cancer Research, they found the test was able to detect prostate cancer with 66% accuracy, and with few so-called "false positives" - where cancer was supposedly detected when the patient was free of the disease. The research was funded by the University of Surrey and The Prostate Project charity.

The standard blood test checks prostate-specific antigen (PSA) levels. Among many problems with the blood test are that PSA levels can vary widely between men and at different time. Furthermore, a raised level may indicate other prostate conditions which are not cancerous.

False positives are a significant problem with the PSA test. A raised level may prompt a significant period of anxiety for patients and mean that they undergo a needle biopsy. Here the problem can be false negatives - so a cancer may be missed if the needle does not sample the right area.

Professor Malcolm Mason from CRUK said: "There is a desperate need for a better prostate cancer test than PSA, and this latest candidate, EN2, is very welcome. However, more work needs to be done to find out whether or not EN2 is capable of distinguishing between aggressive prostate cancers that need treatment, and non-aggressive ones that don't. Almost certainly, this new marker would be used as part of a combination of several markers, including PSA.

Both the Surrey and Cambridge urine tests are promising. Indeed there are frequent research papers showing the potential of biomarkers in blood and urine for detecting cancer and other diseases. But most still have a long way to go. A blog in the Guardian last year discussed the problems involved with using these "biological fingerprints" for detecting disease.

Men hoping to benefit from the Surrey research may have to wait some time at the prostate cancer urine test is still experimental. Dr Richard Morgan, senior lecturer in Molecular Oncology at the University of Surrey said: "We are preparing several large studies in the UK and in the US and although the EN2 test is not yet available several companies have expressed interest in taking it forward."

Govt advisers urge people to limit red and processed meat intake

reposted from: http://info.cancerresearchuk.org/news/archive/cancernews/2011-02-25-Govt-advisers-urge-people-to-limit-red-and-processed-meat-intake-?rss=true

crabsallover highlights, key points, comments / links.

Friday 25 February 2011

A government-commissioned report has advised people who eat the highest levels of red and processed mean to limit their consumption of the foods in order to reduce the risk of bowel cancer.

Previous studies have indicated that substances in red meats such as beef, lamb and pork, and processed meats - including those that are smoked, cured, salted or chemically preserved - may increase people's risk of developing the disease.

For instance, a compound called haem - which gives red meat its colour - is broken down into harmful chemicals in the gut, and these chemicals can damage DNA in the cells lining the bowel.

In 1998, the Committee on Medical Aspects of Food and Nutrition Policy (COMA) suggested that people who eat large amounts of red and processed meat should cut back because of the possible risks.

However, red meat is an important source of iron, which is essential for health.

The Scientific Advisory Committee on Nutrition (SACN) has now reviewed the implications of reducing red and processed meat consumption and produced recommendations that aim to strike a balance between reducing the risk of bowel cancer and ensuring a sufficient intake of iron.

Its report concludes that red and processed meat is "probably" associated with an increased risk of bowel cancer.

Writing in a preface to the report, committee chair Professor Alan Jackson said: "Since the evidence does not allow quantification of the amount of red and processed meat that may be linked with increased colorectal cancer risk, SACN is advising high consumers of red and processed meat to consider reducing their intakes."

The research suggests that limiting consumption to about 70g (cooked weight) per day "would have little effect on the proportion of the population with iron intakes below the lower limit of recommended intake for iron".

This means about three rashers of bacon, three average slices of ham, or just under two large sausages per day.

At present, around 33 per cent of men and eight per cent of women are thought to consume more than 100g of red or processed meat each day.

Sara Hiom, Cancer Research UK's director of health information, said: "Eating lots of red and processed meat can increase your risk of bowel cancer and possibly stomach cancer. Red meat includes all forms of fresh, minced and frozen beef, lamb and pork. Processed meat includes sausages, bacon, ham and salami. White meat such as chicken is not likely to increase your risk of cancer. We advise people to eat smaller and fewer portions of red meat and to try using beans or pulses instead of meat in their recipes."

A large European study called EPIC, which was part-funded by Cancer Research UK, found that people who ate two 80g portions of red or processed meat each day were 30 per cent more likely to develop bowel cancer than those who ate just 20g per day.

She advised: "Keeping a healthy weight helps to reduce your risk of cancer so we recommend a balanced diet with plenty of fruit, vegetables and fibre and low in red and processed meat, salt and saturated fat."

Reference

• Scientific Advisory Committee on Nutrition - Iron and Health Report (2011)

New European guidelines on bowel cancer screening and diagnosis

reposted from: http://info.cancerresearchuk.org/news/archive/cancernews/2011-02-07-New-European-guidelines-on-bowel-cancer-screening-and-diagnosis-?rss=true

crabsallover highlights, key points, comments / links.

Tuesday 8 February 2011

The first-ever set of EU guidelines for bowel cancer screening and diagnosis has been published.

Coordinated by the International Agency for Research on Cancer (IARC) - the World Health Organisation's cancer research agency - the guidelines were drawn up by more than 90 experts from 32 countries.

Bowel cancer is the second most common cause of cancer deaths in Europe and the fourth worldwide, but screening can help to detect the disease at an early stage when it is easier to treat.

The new guidelines aim to improve the quality of screening across EU member states by providing benchmarks for all stages of the screening process, from the initial invitation and organisation through to diagnosis and the management of bowel abnormalities.

IARC director Dr Christopher Wild, said: "These guidelines are the result of a major international cooperation and the authors, editors and other contributors are to be congratulated.

"We must now turn to their widespread application to promote the vital international exchange of information and experience between programmes that is essential for continuous quality improvement across national borders."

Dr Wild also underlined the importance of primary prevention of bowel cancer alongside national screening programmes.

He revealed: "Reducing exposure to modifiable risk factors for colorectal cancer, such as physical inactivity, obesity, consumption of alcoholic beverages, red or processed meats and tobacco smoking, combined with screening will translate to a significantly reduced burden of this cancer."

Dr Jodie Moffat, Cancer Research UK's health information manager, said: "We welcome these new bowel cancer guidelines. The cancer screening programmes that we have in this country together save several thousand lives every year, but making sure that every step in a programme works as it should is crucial to its effectiveness. It's important that the right balance between risk and benefit is kept."

Reference

• European guidelines for quality assurance in colorectal cancer screening and diagnosis First Edition