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“Smoking cannabis from a pipe can significantly reduce chronic pain in patients with damaged nerves,” reported the BBC. It added that improvements in sleep and anxiety were also seen.

This news story is based on a small randomised controlled trial in 23 people, which found that a low dose of inhaled cannabis (lower than that needed to cause euphoria or a “high”) modestly improved reported pain in patients with neuropathic pain.

This is a well-conducted study, but its small size means that it is not possible to tell whether the results demonstrate a real association between cannabis and pain relief, or if they are due to chance.

More research in larger groups of people over a longer period of time is needed to see if the effects of cannabis for this type of pain can be replicated. In addition, there are health concerns related to the use of smoked cannabis, including mental health problems and lung damage.

It is important to point out that cannabis is a class B drug, which is illegal to possess or supply, and is not licensed in any form for medical use.

 

Where did the story come from?

The study was carried out by researchers from McGill University, Canada, and was funded by The Canadian Institutes of Health. The study was published in the (peer-reviewed) Canadian Medical Association Journal.
 
This research was covered well by The Daily Telegraph and the BBC, though the study did not find any evidence for effects on anxiety or depression, as the Telegraph headline suggests.

 

What kind of research was this?

This randomised controlled trial investigated whether cannabis can relieve neuropathic pain (neuralgia) – severe pain caused by the abnormal activity of nerve cells. Various events can set off neuropathic pain, including surgery, trauma or shingles.

The researchers say that although there are drug treatments for neuropathic pain, such as anticonvulsants, antidepressants, opioids and local anaesthetics, their effectiveness varies between patients. Some patients are put off taking them because of unpleasant side effects. They say there is anecdotal evidence that cannabis relieves chronic neuropathic pain and improves sleep. The researchers wanted to investigate whether these reported effects could be replicated under controlled experimental conditions.

This type of study design is the most appropriate way of determining whether a drug is effective. However, this was a very small trial in only 23 people, so it is not possible to conclude that the results are not down to chance alone.

 

What did the research involve?

The study recruited people who had experienced neuropathic pain for at least three months as a result of trauma or surgery. The participants ranked their current level of pain on a 10-point scale, and patients reporting pain intensity greater than four were included. Excluded from the study was anyone whose pain was due to cancer, those who had heart or lung disease, and those who had any type of substance abuse, a history of psychiatric disorders, or who were pregnant. In total 23 people were eligible to participate in the study.

The effect of smoking cannabis with the active ingredient, tetrahydrocannabinol (THC), was compared to smoking cannabis in which the THC had been removed (the control). Different potencies of THC were also compared to each other. Participants were not told the treatment they were given.

The control cannabis that had the THC removed was provided to the researchers by the US National Institute of Drug Abuse. The cannabis doses were prepared by blending the flowers and leaves of the plant to make three different potencies of the active drug (2.5%, 6.0% and 9.4% of THC).

Cannabis doses were delivered as single smoked inhalations taken through a pipe. The participants were instructed to inhale for five seconds as the cannabis was lit, hold the smoke in their lungs for 10 seconds, then exhale. The patients were observed taking the first dose. They then took subsequent doses at home, three times daily for five days. After 14 days, the participants swapped treatments so that those who had received the cannabis without THC then received cannabis containing the active drug. And those who had received active cannabis then received the placebo or a different dose of cannabis treatment.

In total, participants had four cycles of treatment where they received doses of 0%, 2.5%, 6% and 9.4% THC. Throughout the trial, the participants continued any routine medications that they were taking.

On the first day of each treatment period, the participants were asked about their feelings of pain, and how relaxed, stressed or happy they were. Their heart rate was also measured and a blood sample taken. During the five days of treatment or placebo, the participants were contacted by telephone and asked about their pain, how they were sleeping, their medication, and whether they were having any side effects. A urine sample was taken every day. On the fifth day of each treatment, a blood sample was taken and the participants were asked more questions about their pain, mood and quality of life.

 

What were the basic results?

The study had screened 113 participants but only 23 were eligible. Out of these, 21 completed all four cycles.

The researchers found that the average pain intensity was significantly lower on 9.4% THC cannabis (score 5.4 out of 10) than on 0% THC cannabis (6.1 out of 10) (p=0.023). However, no other comparisons between the different doses were statistically significant.

Participants using 9.4% THC cannabis reported finding it easier to fall asleep and had better quality of sleep than those taking 0% THC. No differences in mood or quality of life were seen with the different THC potencies.

Of the reported side effects, none were serious or unexpected. The most frequent side effects reported by participants when taking 9.4% THC cannabis were headache, dry eyes, burning sensation, dizziness, numbness and cough. Feeling “high” and euphoric was reported once in the 2.5%, 6% and 9.4% THC cannabis treatment periods.

 

How did the researchers interpret the results?

The researchers said that the 25mg herbal cannabis with 9.4% THC, administered as a single smoked inhalation three times a day for five days, significantly reduced average pain intensity compared to placebo in adults with chronic post-traumatic or post-surgical neuropathic pain. They also said that there were improvements in measures of sleep quality, but that long-term safety and efficacy studies are needed.

 

Conclusion

This placebo-controlled trial found that cannabis containing 9.4% THC could reduce neuropathic pain compared to the placebo. However, this was a small trial with only 23 participants, so it is difficult to tell whether these results demonstrate a real association, or if they are due to chance. A much larger trial would be needed for a longer period to assess the long-term outcomes of such a treatment. Additionally there are health concerns related to the use of smoked cannabis, including mental health problems and lung damage. Further research is needed to assess such potential side effects over the long term.

The researchers say that their study provides a way of looking at the short-term effects of smoked cannabis in a placebo-controlled trial. It is important to point out that cannabis is a class B drug, which is illegal to possess or supply, and is not licensed in any form for medical use.

Links To The Headlines

Cannabis may relieve chronic nerve pain. BBC News, August 30 2010

Smoking cannabis ‘alleviates pain and depression’. The Daily Telegraph, August 30 2010

 

Links To Science

Ware MA, Wang T, Shapiro S, et al. Smoked cannabis for chronic neuropathic pain: a randomized controlled trial. Canadian Medical Association Journal 2010, Published online ahead of print August 30

The lives of 10,000 patients could be saved each year by a “breakthrough pill”, according to the Daily Express.

The news story comes from a study that looked at whether a drug called ivabradine could help prevent deaths or hospital admissions due to chronic heart failure. This relatively common condition occurs when the heart is no longer able to pump enough blood to meet the demands of the body. The study found that over an average of 23 months, patients taking the drug experienced fewer cardiovascular deaths or hospital admissions with worsening heart failure than people taking an inactive placebo pill.

Ivabradine is a drug that lowers the heart rate and is already prescribed for some people with angina. The results of this large, multinational study demonstrate that heart rate reduction could improve the outcome for people with chronic heart failure. However, as the authors note, its results only apply to patients with a certain type of chronic heart failure that meets specific criteria. It cannot be assumed that these results apply to all patients with chronic heart failure.

 

Where did the story come from?

The study was carried out by researchers from a number of centres in Europe and the US, including the University of Gothenburg, Sweden. It was funded by Servier, a French pharmaceutical company, which was also responsible for the study’s data management and final data analysis (although these were verified by an independent statistical centre). It was published in the peer-reviewed medical journal The Lancet.

The study was widely covered by the media, and reports featured quotes from experts that suggested the drug could save 10,000 lives a year.  It is unclear how this figure was reached. The study itself calculated that 26 patients would need treatment for one year to prevent one cardiovascular death or one hospital admission for worsening heart failure (the main outcomes of the study). The BBC’s headline that the drug may ‘prevent’ heart failure is misleading.

 

What kind of research was this?

This randomised controlled trial, in which both the researchers and participants were blinded, investigated whether the drug ivabradine had any effect on cardiovascular outcomes, symptoms and quality of life in patients with heart failure when used in addition to standard treatment. This kind of trial, in which patients are randomly assigned to either an active treatment or a placebo, is the best way to find out about the effects of medical treatments.

The researchers say that chronic heart failure, which affects 2-3% of the population in many industrialised countries, has a fairly poor prognosis and that the development of new medicines to treat it is crucial. In chronic heart failure, the heart is unable to pump enough blood around the body.  The researchers say that reducing the heart rate could be particularly important in improving some types of chronic heart failure. This is because a lower heart rate would allow more blood to enter the chambers of the heart between each beat and reduce the effect of low blood supply to the heart muscle.

The benefits of one standard treatment for heart failure, called beta-blockers, seem to be linked in part to its heart rate-lowering properties. However, beta-blockers can have undesirable effects for heart failure patients. Ivabradine, say the researchers, seems to reduce heart rate without these side effects on the heart. It is currently licensed for use in people with angina who have a normal, regular heartbeat (sinus rhythm), either in combination with a beta-blocker or without if a beta-blocker is unsuitable or not tolerated.

 

What did the research involve?

The study was undertaken in 677 medical centres in 37 countries. Researchers enrolled 6,558 patients with moderate to severe heart failure associated with left ventricular systolic dysfunction (where contraction of the lower left heart chamber pumps an inadequate amount of blood to the rest of the body). The patients had to meet various other selection criteria, including being on stable background treatment and having a resting heart rate of at least 70 beats a minute.

Between October 2006 and June 2009, the patients were randomly assigned to receive either ivabradine or an inactive placebo drug. Both groups continued to take their standard heart failure medications, including beta-blockers. Neither patients nor researchers knew which patients were in which group. The dose of ivabradine was started at 5mg twice a day and was increased (up to a maximum dose of 7.5 mg twice a day) or decreased according to the change in each patient’s heart rate.

The patients were followed up for an average of 22.9 months. Researchers looked primarily at the “combined outcome” of cardiovascular death or admission to hospital with worsening heart failure (i.e. the occurrence of either or both outcomes). They also separately looked at a number of secondary outcomes, including deaths from any cause and all hospital admissions. All the results were analysed using standard statistical methods.

 

What were the basic results?

A small number of patients were removed from the study due to various problems. After these exclusions, final results were available for 3,241 patients in the ivabradine group and 3,264 patients in the placebo group. The main results were as follows:

• 24% of patients taking ivabradine experienced cardiovascular death and/or admission to hospital because of worsening heart failure, compared to 29% of those taking placebo (an 18% reduction in risk, hazard ratio [HR] 0.82, 95% confidence interval [CI] 0.75 to 0.90).
• When the results were analysed separately, 16% of patients taking ivabradine were admitted to hospital with worsening heart failure, compared to 21% taking a placebo (a 26% risk reduction, HR 0.74, 95% CI 0.66 to 0.83).
• 3% of patients on ivabradine died of heart failure, compared with 5% taking a placebo (a 26% risk reduction, HR 0.74, 95% CI 0.58 to 0.94).

Adverse effects were also examined:

• 5% of ivabradine patients had bradycardia (an abnormally low heart rate) compared to 1% of the placebo group.
• 3% of patients on ivabradine had blurred vision compared to 1% of the placebo group.
• 21% of patients on ivabradine withdrew from the study compared to 19% of patients on the placebo.

The researchers note that the overall effects of ivabradine were less marked in patients taking at least 50% of a standard dose of beta-blockers.

 

How did the researchers interpret the results?

The researchers concluded that ivabradine significantly reduced the major risks associated with heart failure when added to standard treatments. They also said the findings suggest that those with higher heart rates will benefit most.

Treatment with ivabradine was also associated with a reduction in heart rate of 15 beats a minute. Heart rate is an important physical factor that contributes to heart failure and reducing it can interrupt progression of the disease, the study authors suggest.

 

Conclusion

This large, well-conducted study has demonstrated the role that heart rate reduction may have in improving outcomes of people with heart failure. It found that the drug ivabradine, which slows heart rate, significantly reduced cardiovascular deaths and hospital admissions due to heart failure when combined with standard treatments.

The findings of this research could have implications for the treatment of some, but not all, patients with heart failure. As the researchers note, its results apply to a specific group of patients with both a stable, regular baseline heart rate of at least 70 beats a minute and left ventricular systolic function (an enlargement of the lower left chamber of the heart that means it is unable to pump enough oxygenated blood to the rest of the body). People with irregular heartbeat patterns, such as atrial fibrillation or flutter, were also excluded from the study. Overall, the effect of ivabradine in this trial cannot be said to be applicable to everyone with chronic heart failure.

It is also important to note that the results were achieved alongside the patients’ existing treatment programmes, which included beta-blockers, so no conclusions can be drawn about the effects of ivabradine in the absence of these drugs or as a replacement for them. As the researchers also point out, in many cases the recommended target doses of these other standard heart failure medications had not been reached, so it is not known whether this particular population would have been able to tolerate high doses of a beta-blocker.

Overall, the research supports the potential beneficial role of ivabradine in particular subgroups of people with heart failure.

Links To The Headlines

Ivabradine pill may prevent heart failure for thousands. BBC News, 29 August 2010

Cheap heart-failure drug could save thousands of lives. The Daily Telegraph, 29 August 2010

Pill for chest pains ‘could save 10,000 lives a year’. The Guardian, 29 August 2010

£10 heart pill could save 10,000 UK lives. The Sun, 29 August 2010

Thousands in heart drug boost. Daily Express, 29 August 2010

Links To Science

Swedberg K, Komajda M, Böhm M et al. Ivabradine and outcomes in chronic heart failure (SHIFT): a randomised placebo-controlled study. The Lancet, Early Online Publication, 29 August 2010

"Eating broccoli and plantain could reduce bouts of Crohn’s disease,” reported The Daily Telegraph. It said researchers have found that certain types of soluble fibre from these plants can help to prevent bacteria from sticking to the gut’s walls, thereby limiting the progress of the disease.

This study looked at whether fibres from various edible plants affected the transport of E. coli bacteria across specialised cells found in the lining of the bowel. The researchers also looked at whether substances called emulsifiers (commonly found in processed foods) altered the transfer of bacteria across these cells.

They found that fibres from broccoli and plantain reduced the transmission of bacteria across cells by between 45% and 82%, while leek and apple fibres had no effect. One emulsifier, called polysorbate 80, seemed to increase the transmission of bacteria across these cells.

This preliminary laboratory study has not shown that eating broccoli or plantain reduces attacks of Crohn’s and the findings have no immediate implications for the prevention or treatment of the disease. Nevertheless, these early findings are of scientific interest and may lead the way into clinical trials investigating whether certain plant foods and dietary modifications could have an effect on disease activity in people with Crohn’s.

 

Where did the story come from?

The study was carried out by researchers from the University of Liverpool, Linkoping university, Sweden, the University of Aberdeen and Provexis Plc (a company that makes medical dietary supplements and products and that provided the plant preparations used in the study). It was funded by the Wellcome Trust, the National Institute for Health Research, the National Association for Colitis and Crohn’s Disease, the Medical Research Council and the Swedish Research Council.
The study was published in the (peer-reviewed) medical journal Gut.

Both the BBC and The Daily Telegraph correctly reported that this was a laboratory study. However their headlines (“Broccoli boosts healthy gut” – BBC) did not reflect the fact that this research used extracts of the vegetable in a laboratory-based setting rather than testing broccoli consumption in people.

 

What kind of research was this?

Crohn’s disease is a chronic (long-term) condition that causes inflammation of the lining of the digestive system. Inflammation can occur anywhere in the digestive system, from the mouth to the anus (back passage). Common signs and symptoms include pain and diarrhoea (often with blood and mucus) while other effects on the body include weight loss, skin problems and arthritis.

Genetic factors are known to play a role in the development of the disease, but a role for environmental factors has also been speculated. These environmental factors may include diet and bacteria present in the gut. This laboratory research aimed to look at whether uptake of bacteria by gut cells from people with Crohn’s was affected by certain plant soluble fibres from foods as well as substances found in processed foods.

There is a high prevalence of Crohn’s disease in developed countries where the typical diet is low in fibre and high in processed food. The researchers also point out that parts of the world such as Africa, India and Central America, where plantains are a dietary staple, have low rates of inflammatory bowel disease as well as colon cancer. Therefore diet could be having an impact on Crohn’s disease.

In the digestive system, potentially harmful micro-organisms and molecules are transported away from the bowel to the lymph tissue, so that they can be recognised by the immune system and an immune response mounted. The cells involved in transporting these foreign organisms to the lymph tissue are called ‘membranous’ or ‘microfold’ cells (M-cells) and can be found in the lining of the bowel wall.

Studies in people with Crohn’s have found that they have greater amounts of E. coli bacteria in their gut tissue. Many of the E. coli isolated from people with Crohn’s also have special characteristics which make them more able to stick to and live in gut wall cells, and are called AIEC strains (adherent invasive E. coli strains). In people with Crohn’s disease, the initial inflammations occur in the areas of the digestive tract where these M-cells are found, so the researchers were particularly interested in looking at the effect of the dietary substances being tested on the uptake of AIEC strains by these cells.

This laboratory study set out to investigate whether certain soluble plant fibres from foods, as well as substances found in processed foods, have any effect on the transmission of the bacteria across these cells.

 

What did the research involve?

The laboratory research used strains of E. coli that had been isolated from six people with Crohn’s, as well as five control samples from people without Crohn’s. The plant-based sources of dietary fibre they tested were prepared from broccoli, leek, apple and plantain (a member of the banana family usually cooked as a vegetable). They also included two common food emulsifiers used in processed foods.

The researchers took human colon cells and grew them in the laboratory in conditions which encouraged them to develop into M cells. They tested these cells to make sure that they could successfully transport bacteria, to show that they had developed into M-cells.

They then carried out a number of tests on the M-cells and the ‘parent’ colon cells that they had been grown from. The cells were grown as a layer a single cell thick in special containers in such a way that the cell layers had solutions above and below them which did not mix. The researchers then applied bacteria to the upper surface of this layer and incubated it for up to four hours. After this time they tested to see how much bacteria had been transported across the cells to reach the solution underneath the cell layer. They then tested the effects of the different preparations on the transmission of E. coli across the cell layers. They applied the soluble fibre or other food substance onto the cells before applying the bacteria and measured whether this affected the transport of E. coli across the cell layer. They also tested the effect of the same substances on E. coli transport across normal tissue samples taken from the intestines of people without Crohn’s. They then analysed all the data, using validated statistical methods.

 

What were the basic results?

As the researchers expected, more E. coli was transported across the layers of specialised M-cells than across the layers of the ‘parent’ human colon cells. The difference in transport across M-cells and the parent colon cells was greater when they used AIEC stains of E. coli from people with Crohn’s disease than when they used E. coli from people without Crohn’s disease.

They also found that:

• both the preparations of plantain and broccoli markedly reduced the transport of E. coli across these specialised M-cells (range 45.3-82.6%).
• apple and leek preparations had no significant effect on E. coli transport across the M-cells.
• one of the emulsifiers called polysorbate-80, increased E. coli transport across the cells, particularly the non-specialised colon cells.
• the plantain extract also reduced E. coli transport across the normal human intestine tissue samples, and polysorbate-80 increased transport across this tissue.

 

How did the researchers interpret the results?

The researchers say that transport of E coli across M-cells is reduced by soluble plant fibres such as plantain and broccoli, but increased by the emulsifier polysorbate 80. They suggest that fibre supplementation might protect against Crohn’s disease relapse by preventing bacterial invasion of intestinal mucosa, and that the effect of the food emulsifier could explain why Crohn’s rates are higher in developed countries where processed foods are common.

 

Conclusion

This carefully conducted laboratory study indicates that soluble fibres from certain plant foods can reduce the transport of E coli strains associated with Crohn’s, and their transfer across specialised cells of the bowel lining. It also shows that one emulsifier used in food processing has the opposite effect, by increasing transport.

This is early research aimed at furthering our understanding of how dietary and environmental factors might have a role in the development of Crohn’s. However, the findings have no current implications for the prevention or treatment of the disease, and it cannot be concluded from this study alone that any of these substances affect the development of Crohn’s. The study has not shown that eating broccoli or plantain reduces disease activity in Crohn’s. Even if there was an effect, it is unclear how much broccoli or plantain might be effective, or whether effective supplements of these substances could be developed.

These early findings are nevertheless of interest and may lead the way into later clinical trials investigating whether certain plant foods and dietary modifications could have an effect on disease activity in people with Crohn’s.

Links To The Headlines

Broccoli and plantain could fight Crohn’s disease. The Daily Telegraph, August 26 2010

Broccoli ‘boosts’ healthy gut. BBC News, August 26 2010

 

Links To Science

Roberts Cl, Keita AV, Duncan SH, et al. Translocation of Crohn’s disease Escherichia coli across M-cells: contrasting effects of soluble plant fibres and emulsifiers. Gut 2010; online first