People with learning difficulties 'silenced with drugs'
- 2 September 2015
- Health
Professor Clive BallardAlzheimer's SocietyMore research is now needed to understand why this anti-depressant is having this effect on people with dementia and if there is an alternative treatment for depression that they could be prescribed”
Jessica HarrisCancer Research UKComparing the rates of two apparently unrelated issues across countries is a notoriously unreliable way of establishing whether they are truly linked”
A painkiller taken by millions can increase the risk of heart attack and stroke by 40%, the Daily Mail has today reported. The newspaper says that researchers are calling for the drug, called diclofenac, to be available on prescription only.
The news is based on a large review that looked at the cardiovascular risks associated with a class of widely used painkillers called non-steroidal anti-inflammatory drugs (NSAIDs). NSAIDs in high-dose formulations are usually only available on prescription, but some low-dose NSAIDs, including ibuprofen, naproxen and diclofenac, can be bought over the counter.
The review found that diclofenac raised the risk of heart problems by 22% when taken at over-the-counter doses and by 40% at prescription strength. Naproxen and low-dose ibuprofen were least likely to increase the risk of heart attacks and strokes.
While previous research has highlighted the cardiovascular risks of some NSAIDs, this review of observational studies provides some important new information about the risks associated with all currently available NSAIDs at different doses. As such, its findings will no doubt be important to future decisions about how these drugs should be used and regulated.
However, it is important to note that for a healthy individual who takes diclofenac, the increased risk to the heart is still very small. The nature of this research means it is not possible to estimate accurately how small this risk is. Anyone who is concerned about taking NSAIDs should not stop taking these drugs but should consult their doctor.
The study was carried out by researchers affiliated with Hull York Medical School, the Institute for Clinical Evaluative Sciences, the University of Toronto in Canada and the University of Newcastle in Australia. It received no external funding. The study was published in the peer-reviewed journal PLoS Medicine.
The research was covered fairly in most newspapers. In its print version of the story the Daily Mail featured a large front-page headline warning of a “Painkiller heart alert”, which may have been alarming. However, within the article itself the Daily Mail did feature prominent messages that patients should not panic and should not stop taking their medication. Both the Daily Mail and The Daily Telegraph reported that, for most healthy people, the increased risk of heart and other problems from diclofenac was small, and the reports featured in the Daily Mail, The Daily Telegraph and the Daily Express all included comments and advice from independent experts.
This was a systematic review comparing the risks of individual NSAIDs taken at typical doses by people at home, rather than in hospital. The researchers say that there are concerns about the risk associated with non-prescription NSAIDs available in low-dose forms, such as ibuprofen, naproxen and diclofenac.
The researchers point out that while some randomised trials have highlighted the cardiovascular risk of some NSAIDs, little is known about how the risks of individual drugs compare when used at different doses, for different lengths of time and in different populations. For this reason the researchers set out to examine the outcomes seen in controlled observational studies, which would better reflect the risks associated with the typical domestic use of NSAIDs rather than the risks associated with their use in the idealised setting of a clinical trial. To date, randomised trials of NSAIDs have reported only small numbers of heart and stroke problems.
The researchers searched a wide range of electronic databases for relevant studies published between 1985 and 2010 that had reported on the cardiovascular risks associated with the use of individual NSAIDs in population settings. They included only non-randomised, controlled observational studies in their literature search. These observational studies included case control, cohorts and case-crossover studies. They then assessed the methodological quality of the selected studies. From a total 459 potentially relevant papers, 51 studies met their criteria.
From the studies gathered, the researchers extracted and pooled information about the risk of major cardiovascular events associated with individual NSAIDs. They also assessed subsets of studies that provided relevant information to examine the risk of NSAIDs in different doses and in people with low and high existing risk of heart problems. To compare different drugs they carried out a further type of analysis, called a pair-wise comparison, where they indirectly compared each drug against another in turn, taking the results from separate trials.
The overall analyses included data from 30 case-control studies and 21 cohort studies involving more than 2.7 million individuals and featuring a total of 184,946 cardiovascular events.
The researchers looked at the drugs where there were 10 or more studies. Of drugs where there were 10 or more studies, researchers found that the highest overall risks were seen with rofecoxib and diclofenac, and the lowest with ibuprofen and naproxen. Compared with not using any NSAIDs, the researchers found:
In a subset of studies that looked at risk associated with lower doses they found:
It is important to note that the drug rofecoxib has already been withdrawn from the market because of its association with a raised risk of cardiovascular events. Including it in the study allows the risk associated with other drugs to be compared with the risks of rofecoxib.
Ibuprofen only posed a risk when taken at a higher dose and naproxen had no significant risk at any dose.
The researchers say the increase in risk was proportional for both high- and low-risk groups. This means that, relative to their risk if not using NSAIDS, the risks for both groups increased to the same extent. The risk of cardiovascular problems also rose early in the course of treatment. For some NSAIDs, risk was found to increase within the first month of taking the drug.
The researchers say the results of their review “are robust enough to inform clinical and regulatory decisions”.
This large review has published some important information on the cardiovascular risks associated with NSAIDs, including the risk associated with different doses and in populations at both high and low risk of cardiovascular events. It raises concerns about some of these risks, in particular the risk associated with the widely used non-prescription drug diclofenac.
As its authors point out, it had some limitations.
Patients using NSAIDs who are worried about side effects should not stop taking them, but instead consult their doctor.
Painkiller heart alert: Don't stop taking pills, but do talk to your GP, British scientists urge. Daily Mail, September 28 2011
Common painkillers can raise heart risk. The Daily Telegraph, September 28 2011
Health alert over common painkiller. Daily Express, September 28 2011
McGettigan P, Henry D. Cardiovascular Risk with Non-Steroidal Anti-Inflammatory Drugs: Systematic Review of Population-Based Controlled Observational Studies. PLoS Medicine 8(9)
End Quote Dr Clare Gerada Royal College of GPsDo not stop your medicines without taking advice first”
Giving children antibiotics can increase risk of irritable bowel syndrome and Crohn's disease later in life, the Daily Mail has reported. The newspaper article says that “scientists believe the drugs may encourage harmful bacteria and other organisms to grow in the gut, which trigger the conditions”.
This study looked at the medical records of over 500,000 children in Denmark, and found that children who had been prescribed antibiotics were more likely to develop inflammatory bowel disease (IBD) than those who had not received such prescriptions. IBD is a group of diseases which includes Crohn’s disease, but not (as suggested by the Mail) irritable bowel syndrome (IBS).
While this study has found a relationship between antibiotic use and IBD, it is not possible to say for certain why such a relationship exists. It might be that antibiotics do raise the risk of IBD, or that the infections being treated with them cause or trigger IBD, or that in some cases antibiotics were being used to treat symptoms of undiagnosed IBD that was later identified. These findings are worth further investigation.
It is important to remember that the risk of IBD in children is very low. In this study of more than half a million children, only 117 were diagnosed with the disease, despite almost 85% of the subjects taking at least one course of antibiotics.
The study was carried out by researchers from the Statens Serum Institut in Denmark and funded by Danish Medical Research Council and the Danish Agency for Science, Technology and Innovation. The study was published in the peer-reviewed medical journal Gut.
This study was reported by the Daily Mail, which has confused inflammatory bowel disease (investigated by this study) with irritable bowel syndrome, which is not an inflammatory bowel disease (and was not investigated in this study).
This was a nationwide Danish cohort study looking at whether there was a link between the use of antibiotics and inflammatory bowel disease (IBD) in childhood. The balance of microorganisms in the intestine has been suggested to be important in the development of IBD. As antibiotics can alter this balance, one suggestion is that their use could potentially affect the risk of IBD.
The main limitation of this type of study design is that the groups being compared (in this case, children exposed and unexposed to antibiotics) may differ in ways other than their use of antibiotics. Any such differences might potentially affect the results and therefore obscure the true relationship. Researchers can try to reduce the likelihood of this by taking such factors into account in their analyses.
Limitations of this nature could potentially be avoided by looking at the risk of IBD in children who had participated in randomised controlled trials of antibiotics, although the practical constraints of such studies mean they would not be likely to include the very large number of children that this study had.
The researchers looked at the healthcare records of all Danish children born between 1995 and 2003 who were not part of multiple births (e.g. twins or triplets). They obtained information on collections of antibiotic prescriptions, diagnoses of IBD and other factors that could affect results. They then looked at whether children who had received antibiotics were any more or less likely to subsequently develop IBD compared with children who had not received antibiotics.
The researchers drew data from various national registries to locate eligible children, their filled prescriptions and medical history. The researchers identified:
The researchers also obtained a range of information on factors which could affect results, including gender, birth order (whether the child was born first, second or third), level of urbanisation of the place of birth, birth weight, length of gestation, mother’s age at the child’s birth, educational level of mother in the year preceding the year of birth, and socioeconomic category of father in the year preceding the year of birth.
However, none of these factors were found to be independently associated with the risk of IBD, so they were not taken into account in the main analyses. These only took into account the child’s age and year of the diagnosis.
Overall, the researchers collected data on 577,627 children, with an average follow-up time of about 5.5 years. This provided over 3 million years of data in total. Most of the children (84.8%) had received at least one course of antibiotics.
Across both study groups 117 children developed IBD – 50 of these children had Crohn’s disease and 67 had ulcerative colitis. On average, diagnosis of these conditions was first recorded between the ages of three and four years old.
The researchers reported their outcomes using a measure called the "incidence rate ratio" [iRR], which is the relative proportion of people given a new diagnosis in two different groups within a specified period of time. They found that children who had collected an antibiotic prescription were 84% more likely to develop IBD during follow-up than those who did not [iRR 1.84, 95% confidence interval [CI] 1.08 to 3.15].
When looking at the different types of IBD separately, antibiotics were only associated with an increased risk of Crohn’s disease [iRR 3.41] but not ulcerative colitis. The risk of being diagnosed with Crohn’s disease was greater in the first three months after the prescription collection [iRR 4.43], and greater in children who received seven or more courses of antibiotics [iRR 7.32].
The researchers concluded that their study is the “first prospective study to show a strong association between antibiotic use and [Crohn’s disease] in childhood”. This suggests that antibiotics or the conditions for which they are prescribed (infections) could potentially increase the risk of IBD or trigger the disease in people who are susceptible.
However, they note that as with all studies of this type, it cannot prove that antibiotics or the illnesses they were prescribed to treat cause IBD. They say that a possible explanation might be that the children had been prescribed antibiotics to treat intestinal symptoms caused by undiagnosed Crohn’s disease that would later be identified.
Overall, this large study has suggested a link between antibiotic use and IBD, although it should not be assumed that antibiotic use is necessarily the cause of the condition. There are a number of alternative explanations for the association, such as the possibility that antibiotics had been given to the children to deal with symptoms of Crohn’s disease that had not yet been diagnosed. Further research will be needed to clarify the situation.
The strengths and limitations of this research must also be considered when interpreting its results:
As the authors acknowledge, it is not possible to say whether the link found is due to the antibiotics, the infection that prompted the need for antibiotics or treatment of existing but undiagnosed IBD.
Fergus Walsh | 15:35 UK time, Monday, 8 November 2010
The condition, known as cryptorchidism, affects about one in 20 boys in the UK. It is known to be a risk factor for male fertility problems later in life and an increased risk of testicular cancer.
1,463 pregnant women in Finland completed written questionnaires and 834 women in Denmark did the same or took part in a telephone interview. The researchers found that women significantly under-reported the use of painkillers in the written questionnaire because they did not consider mild painkillers to be "medication".
The study showed that women who used more than one painkiller simultaneously (such as paracetamol and ibuprofen) had a seven-fold increased risk of giving birth to sons with some form of undescended testes compared to women who did not take the drugs.
The second trimester appeared to be a particularly sensitive time. Any analgesic use at this point more than doubled the risk of the condition. Simultaneous use of more than one painkiller during this time appeared to increase the risk 16-fold.
The scientists behind the research believe painkillers may be part of the reason for the increase in male reproductive disorders in recent decades, possible by interfering with the role of the male hormone testosterone. Research carried out on rats in Denmark and France found that painkillers disrupted androgen production, leading to insufficient supplies of testosterone during the crucial early period of gestation when the male organs were forming. The effects of the painkillers on the rats was comparable to that caused by similar doses of known endocrine (hormone) disrupters such as phthalates - a family of chemical compounds used in the manufacture of plastics such as PVC.
Dr Henrik Leffers, senior scientist at Righospitalet in Copenhagen, who led the research, said: "If exposure to endocrine disruptors is the mechanisms behind the increasing reproductive problems among young men in the Western World, this research suggests that particular attention should be paid to the use of mild analgesics during pregnancy, as this could be a major reason for the problems".
But the study is not without limitations. The researchers could not find a statistically significant effect among the Finnish women, which was the larger group, but did find significant effects among the Danish women.
Dr Leffers said: "We do not quite understand why the Finnish cohort does not show the same associations as the Danish cohort." However, he said the telephone interviews used in Denmark gave the "most reliable information" and this may explain some of the differences. He added: "The prevalence of cryptorchidism is much lower in Finland (2.4%) compared to Denmark (9.3%) and, therefore, this would require a larger cohort to find the same number of cases."
Pregnant women in the UK are already advised to avoid taking ibuprofen or aspirin, unless they are advised to do so by their doctor.
Instead they are told they can take paracetamol. The NHS Choices website puts it like this:
Paracetamol has been used routinely through all stages of pregnancy to reduce a high temperature (fever) and relieve pain. There is no clear evidence that paracetamol has any harmful effects on the baby.
As with any medicine that is used during pregnancy, paracetamol should be taken at the lowest effective dose for the shortest possible time.
This raises a further concern with the research. Of the individual painkillers, ibuprofen and aspirin approximately quadrupled the risk of cryptorchidism. Paracetamol doubled the risk, but this was not statistically significant. This suggests that a link between paracetamol use alone in pregnancy and male fertility problems is not clear-cut.
Dr Leffers said: "Although we should be cautious about any over-extrapolation or over-statement, the use of mild analgesics constitutes by far the largest exposure to endocrine disruptors among pregnant women."
Prof Richard Sharpe of the Medical Research Council's Human Reproductive Sciences Unit at the University of Edinburgh, said:
"The studies are top quality from groups with considerable expertise. The association between painkiller (paracetamol) use in early pregnancy and increased risk of cryptorchidism in sons has been independently confirmed in another study from Denmark (MS Jensen et al. November 2010, Epidemiology). Painkillers/paracetamol are likely to be one of several factors that cause cryptorchidism - some environmental chemicals are also implicated - it is probably the sum of all such exposures that determines the outcome.
Pregnant women who are alarmed by these studies should note the following:
It is only prolonged use that has an effect - taking occasional painkiller for a headache will have no adverse effect (and the stress, worry and sickness from not taking something for a bad headache may be worse for the mother and baby).
Most women in this study who used paracetamol did not have a baby boy with cryptorchidism.
Prolonged use of painkillers in pregnancy should not be contemplated without medical approval. For certain, taking paracetamol as a 'feel good' factor should be avoided (by all of us!).
It is sound common sense to minimize your exposure (and therefore your baby's exposure) to all drugs, environmental (pesticides, paints, household chemical exposures) and lifestyle (smoking, alcohol, cosmetics usage) chemicals during pregnancy wherever possible."
Update at 17:00
Basky Thilaganathan, Spokesperson for the Royal College of Obstetricians and Gynaecologists, said:
"The findings need to be interpreted with caution. Firstly, the study shows an association rather than causation; it is entirely possible that mothers took these analgesics for an ailment (for example, a viral infection) in pregnancy that may have been the real cause for the noted problems. Secondly, the dose-dependent effect was seen in one study cohort but not another, raising the possibility that this preliminary study may be prone to inadvertent bias of patient recruitment and ascertainment. Furthermore, the definition of cryptorchidism is broad and clinical, rather than specific and the overall number of cases is so small that a small change in affected numbers would have nullified the findings.
"Given these limitations, the findings of the study should be interpreted with caution and it would be inappropriate to spread alarm to pregnant women on this basis."
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