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2008; Oxford University Press; Volume: 5; Issue: 2 Linguagem: Inglês
10.1111/j.1740-9713.2008.00285.x
ISSN1740-9713
Tópico(s)Infectious Encephalopathies and Encephalitis
ResumoSignificanceVolume 5, Issue 2 p. 50-53 NewsFree Access News First published: 29 May 2008 https://doi.org/10.1111/j.1740-9713.2008.00285.xAboutSectionsPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Vioxx data manipulated Merck, the makers of Vioxx, the anti-arthritis drug and painkiller that had to be withdrawn from sale because it was found to cause heart attacks, may have hidden its true death rate from the authorities for several years, according to a paper in the Journal of the American Medical Association (JAMA). Bruce Psaty, Professor of Medicine, and Richard Kronmal, Professor of Statistics, both from the University of Washington in Seattle, found discrepancies between internal Merck memos and information published by the company in two clinical papers and submitted to the US Food and Drug Administration (FDA). Internal company documents released during litigation in the USA suggest that Merck gave the FDA only selected data on deaths in its clinical trials, and failed to include people who had a fatal heart attack soon after coming off the drug. In April 2001, in studies to test the effectiveness of Vioxx in treating dementia, a Merck statistician found 34 deaths among 1069 patients treated with Vioxx, compared with 12 among 1078 on placebo—which would seem to imply a near three-fold increase. Published data on the trial however, gave the figures as 29 deaths in the Vioxx group and 17 in the placebo group. The manipulation was done, say the authors, in part by omitting some of the fatalities that occurred after patients stopped taking the drugs. “Deaths that had occurred more than 14 days after discontinuation of the trial drug apparently were not included” said Professor Psaty, “[Merck] were not being forthright. They minimised the appearance of risk.” FDA inquiries revealed that there were no independent data. Psaty and Kronmal's paper in JAMA was accompanied by another, by Dr Joseph S. Ross and others, revealing the extensive use of ghostwriters by Merck for their papers on the effectiveness of Vioxx. Heavily promoted as a gentler alternative to aspirin, with endorsements by celebrity athletes and the like, the promotional budget of Vioxx is said to have exceeded that of Pesi-Cola; worldwide sales totalled $2.5 billion. It was withdrawn in September 2004 but information was available well before that date to show that Vioxx posed serious potential harm to subjects in clinical trials. Unpublished data from as early as June 2000 showed that taking Vioxx significantly raised the rate of heart attacks, strokes, oedema and hypertension, according to subsequent analysis. Its withdrawal has been the most expensive in history. Twenty-seven thousand US lawsuits are current against Merck, on behalf of around 47 000 plaintiffs—survivors or relatives of those who have died—who claim the occurrence of heart attacks and other devastating side-effects, including loss of sight and paralysis, after taking the painkiller. In November 2007, Merck agreed a $4.85 billion settlement, without admitting guilt, for the majority of those cases. At least 300 cases are pending in the UK and many more worldwide. Kronmal is a paid consultant for families of patients who are suing Merck, but JAMA has required the authors to publish on the web all the company documents that they have analysed so that their charges can be independently assessed. A Merck attorney has stated that the company disclosed all its clinical results thoroughly and that “we completely disagree” with allegations that Merck misrepresented its findings. Breast cancer: screen for longer, or screen more often? Extending breast cancer screening to those who are 75 could cut death rates among older women by a third. But introducing annual checkups would save no more lives than the UK's current 3-yearly test. These results were presented to the European Breast Cancer Conference in Berlin in April. It is known that breast cancer risk increases with age. A comparison between the UK health policy, which invites women between the ages of 50 and 70 to health service clinics for screening, and that of the Netherlands, where screening for 70–75-year-olds was introduced in 1998, showed that the Dutch system had resulted in a fall of 30% in the mortality rate for the 75–79 age group by 2006. Jacques Fracheboud, of the Erasmus Medical Centre, Rotterdam, who carried out the analysis, said that screening was also more accurate in older women, with breast cancer being detected in 7.8 out of every 1000 patients referred by screening for diagnostic assessment, giving a successful prediction rate of 47%. The figure for women under 70 is 36%. “It is easier to find breast cancer in older women due to their breast tissue being less dense,” said Mr Fracheboud. He added that fears that screening the over-70s would not be cost-effective have not been borne out by experience. Increasing the frequency of breast cancer screening, however, would not be worthwhile. In the UK Breast Screening Frequency Trial, researchers led by Professor Roger Blaney of Nottingham City Hospital allocated nearly 100 000 women at random to have either annual or 3-yearly mammograms after their 50th birthday. The prediction was that annual screening would not result in a further reduction in breast cancer mortality. The actual mortality rates presented at the Berlin conference confirmed this to be the case. The trial started in 1989. Among those women who attended for screening there were 209 breast cancer deaths in the annual group and 231 in the 3-year control group after an average follow-up time of over 13 years. The researchers found no difference in mortality rates when they looked at only those cancers diagnosed during the 3-year screening periods. The difference in absolute risk of dying from breast cancer was statistically insignificant between the two groups, the control group having an absolute risk of only 2% more than the study group. “When breast screening was set up there was a lot of criticism of the UK for having a 3-yearly interval” said Professor Blaney. “Screeners and advocacy groups said, without evidence, that it was too long an interval. These results indicate that our earlier predicted mortality figures were accurate and that there is no evidence in favour of shortening the current 3-year screening interval.” The current 3-yearly screening programme in the UK costs around £80 million a year. Professor Blaney added that women who pay privately for more frequent check-ups were, in his opinion, wasting their money. It's a boy! Women trying to get pregnant and hoping for that happy announcement in due course from the midwife should perhaps try eating more—and especially not skipping breakfast. Hitherto All-Bran and other breakfast cereals have claimed regular bowel movements as a health benefit for their consumption; now it seems that they can help mothers-to-be select the sex of their about-to-be-conceived child. Research shows a clear link between higher energy intake around the time of conception and the birth of sons. The findings are the first clear evidence that a mother can influence the sex of her child, and may help explain the falling birth-rate of boys in industrialised countries, including the UK and USA. The study focused on 740 first-time pregnant mothers in the UK who did not know the sex of their foetus. They were split into three groups according to the number of calories consumed per day around the time they conceived. 56% of the women in the group with the highest energy intake at conception had sons, compared with 45% in the lowest energy intake group. As well as consuming more calories, women who had sons were more likely to have eaten a higher quantity and wider range of nutrients, including potassium, calcium and sodium. There was also a strong correlation between women eating breakfast cereals and producing sons. Over the last 40 years there has been a small but consistent decline, of about one per 1000 births annually, in the proportion of boys being born in industrialised countries. Previous research has also shown a reduction in the average energy intake in the developed world. There is also evidence that skipping breakfast is now common in the developed world: in the USA, the proportion of adults eating breakfast fell from 86% to 75% between 1965 and 1991. Dr Fiona Mathews of the University of Exeter's School of Biosciences, lead author on the paper, said: “This research may help to explain why in developed countries, where many young women choose to have low calorie diets, the proportion of boys born is falling. Our findings are particularly interesting given the recent debates within the Human Fertilisation and Embryology Committee about whether to regulate ‘gender’ clinics that allow parents to select offspring sex, by manipulating sperm, for non-medical reasons. Here we have evidence of a ‘natural’ mechanism that means that women appear to be already controlling the sex of their offspring by their diet.” It is known that in many animals, particularly invertebrates but also including horses, cows and some species of deer, more sons are produced when a mother has plentiful resources or is high ranking. The explanation is thought to lie with the evolutionary drive to produce descendants. “If a mother has plentiful resources then it can make sense to invest in producing a son because he is likely to produce more grandchildren than would a daughter. However, in leaner times having a daughter is a safer bet” said Dr Mathews. Therefore, although sex is genetically determined by fathers, mothers appear to be able to favour the development of one sex of infant over the other. The mechanism is not yet understood in mammals, but it is known from IVF research that high levels of glucose encourage the growth and development of male embryos while inhibiting female embryos. In humans, skipping breakfast depresses glucose levels and so may be interpreted by the body as indicating poor environmental conditions and low food availability. “You are what your mother eats: evidence for maternal preconception diet influencing foetal sex in humans” is published in Proceedings of the Royal Society (http://journals.royalsociety.org/content/w260687441pp64w5/). The study was funded by the Sir Jules Thorn Charitable Trust. Migrant crime wave “a myth”—but not enough data A report from the Association of Chief Police Officers (ACPO) has concluded that the widely-held belief that migrants from Eastern Europe are fuelling a crime wave is a myth. Offending rates among mainly Polish, Bulgarian and Romanian immigrants are broadly in line with rates in the general population. “Any rise in crime has been broadly proportional to the number of people from those communities coming into this country”, said a source close to the report. “People are saying that crime is rising because of this influx. Given that one million people have come in, that doesn't make sense, as crime is significantly down.” Home Office figures published earlier this year gave a drop of 9% in overall crime. The report was co-authored by Peter Fahy, Chief Constable of the Cheshire Constabulary, and Grahame Maxwell, Chief Constable of the North Yorkshire force. It was based partly on the views of other chief constables and partly on Home Office crime statistics and was, therefore, said ACPO, “partly qualitative and partly quantitative”. Police data does not accurately distinguish the country of origin of offenders: it has only the category “white European” to include every one whose country of origin is within Europe, from Portugal to Eastern Europe and central Russia. The ACPO report called for more precise data collection. Chief constables did, however, report national variations in types of offence, based on the experiences of their detectives. Poles are more frequent drink-drivers, and London-based Romanians are using children to commit petty robberies. “Cultural differences such as attitudes to offences like drink driving may exist, but can be exaggerated”, said Peter Fahy. “The influx of Eastern Europeans has created pressures on forces in some areas, including local rumour and misunderstandings fuelling tensions, but the evidence does not support theories of a large scale crime wave generated through migration. Better forecasting and data-sharing between local agencies to pick up changes in local populations more quickly is necessary to help anticipate the issues. Given the number coming into the country, the problems have been very few in terms of criminality.” A second report, more quantitivelybased, from the Institute for Public Policy Research, found that migration from Eastern Europe has been much faster, more evenly distributed around the country, and less permanent in nature than previous waves of immigration. Drawing data from the Labour Force Survey, national insurance number applications, the Workers Registration Scheme and the International Passenger Survey, it looked at migrants from the eight countries that joined the European Union in 2004—Poland, the Czech Republic, Estonia, Hungary, Latvia, Lithuania, Slovakia and Slovenia—and from Romania and Bulgaria, both of which joined in 2007. Poles are now the largest foreign national group in the UK, having been only 13th-largest in 2004. Post-enlargement migration was “very different” from previous migration to Britain, said the report. “In contrast to previous migrants, it is financially and logistically possible for migrants from the new EU member states to come to the UK on a temporary or seasonal basis, and to regularly visit home while living in Britain.” Of the million migrant workers who came to Britain from 2004-accession countries, about half have already left the UK. The report found an employment rate of 84% among post-enlargement migrants, which is among the highest of all immigrant groups, and is nine percentage points higher than the UK-born average. East European migrants work, on average, 4 hours longer per week than UK-born workers, it said; and very few post-enlargement migrants claim state benefits. Only 2.4% of those registering for national insurance numbers between May 2004 and December 2007 did so in order to claim benefits. Youth gangs: beliefs but no data Street gangs of teenagers and so-called feral youths have attracted high-profile attention in the media. They are responsible, it is claimed, for more than just graffiti. Several recent court cases in Britain have seen defendants accused of violence up to and including murder, often for the smallest of apparent motives. Just one recent case was of four youths who kicked an elderly cyclist to death in an underpass. They are not just a British phenomenon. Street gangs are seen as a major social problem worldwide. Current estimates suggest that in the USA alone there are currently 24 000 gangs with 760 000 members. A frequently-proposed strategy to keep young people integrated within society is to provide clubs and activities for sports and other more acceptable pastimes. Others advocate cognitive-behavioral intervention to steer youths away from gangs. Two Cochrane reviews1, 2 examined these key approaches and found no evidence whatsoever to back either of them. Such strategies have been implemented at various times and places, and money has been spent on them, but it seems that their effectiveness has never been researched. Despite studying 2696 publications relating to youth gangs, the reviewers were unable to find any randomised controlled trials or quasi-randomised controlled trials that studied these issues. “This lack of research is surprising given the scale of the problem,” says lead researcher Dr Paul Montgomery, of the University of Oxford's Centre for Evidence-based Intervention. “There is an urgent need rigorously to evaluate the various gang prevention strategies that people suggest and try to implement, if we are going to be able to direct resources well and build future gang prevention programmes that have a good chance of working.” Vitamins: beliefs despite data One in three women and one in four men regularly take vitamin supplements. The food supplement pill industry is reported to be worth some $60 billion worldwide, so the findings from the Cochrane meta-analysis of the effect of such pills, which was revealed in April, was greeted with extensive publicity, and with celebrity fans of such supplements quoted in newspapers and other media pouring scorn on its conclusions. However, “The bottom line is that current evidence does not support the use of antioxidant supplements in the general healthy population or in patients with certain diseases” is how the lead author, Goran Bjelakovic, summed up its conclusions. The researchers identified 67 trials, involving 232 550 people, as being suitable for inclusion in the review. A third of these trials included healthy participants (164 439 people) and two-thirds of the trials involved people with a variety of different diseases (68 111 people). The average age of participants in the studies was 62 and the average length of follow-up was 3.4 years. Overall, there was no reduction in mortality from taking antioxidant supplements. Of all the participants in the trials, 13.1% of those taking antioxidants died and 10.5% of those taking placebo or no treatment died. A statistical analysis combining all the studies found there to be no significant effect of antioxidant supplements on mortality—neither an increased nor a decreased risk. The trials studied covered different types of supplement, and significantly differed from each other in the degree of bias that could have been introduced. When they looked at trials with a low risk of bias only, the risk of mortality from taking supplements just reached statistical significance, showing a 5% increased risk of mortality. Looking at trials of different supplements separately, the researchers also found increased risk of death from any cause from vitamin A (16%), beta-carotene (7%) and vitamin E (4%), but all of these results only just reached statistical significance. There were no significant effects on mortality from either vitamin C or selenium. The researchers conclude that there is “no evidence to support antioxidant supplements for primary or secondary prevention [of mortality]” and that vitamins A, E and beta-carotene may even increase risk of mortality. Further trials should be closely monitored for potential harmful effects. They say also that “antioxidant supplements need to be considered medicinal products and should undergo sufficient evaluation before marketing”. As the authors acknowledge, most trials used supplement doses that were much higher than those found in a normal diet and sometimes higher than recommended daily intake levels. Their results do not apply to people who have specific deficiencies in these antioxidants. Boys in trees—falling data This month's Statistic That Tells Us Most about Modern Life: boys are now twice as likely to get injured falling out of bed than falling out of trees. The figures come from accident and emergency departments in England. Seven years ago admissions from the two sources of injury were equal. Now bed-fall injuries predominate by a factor of two. This might mean one or more of several things. Boys might now be getting fitter and therefore better at climbing trees and so fall out of them less often than they used to. Alternatively, they might be spending more time in bed than they used to, thus increasing their chances of falling out. Or trees are getting smaller, and therefore less dangerous, so falls from them result in fewer hospitalisations. Or bedroom carpets are getting harder than they used to be, so bed-fall injuries are becoming more severe. Or, thanks to modern cramped housing, more children are sleeping in bunk beds, falls from the upper levels of which are likely to be more injurious. Or boys are becoming more phlegmatic and no longer report falls from trees, whereas falls from beds are noticed by their alarmed parents, who haul them off to the nearest casualty department. Other possible explanations are welcomed. It might be that the stresses of modern life induce more nightmares than hitherto, which cause poor young lads to thrash about in their sleep and so plummet from their beds to the floor. Sadly, though, the most obvious conclusion is probably the right one. Fewer boys live near climbable trees, and those that do spend less time outdoors playing cowboys and indians and other activities that might involve tree-climbing and more time indoors watching television or playing computer-games. Not for nothing is today's youth known as “the X-box generation”. Figures for computer-related accidents to young boys, however, are not available. We await statistics from the ONS for repetitive strain injuries and computer-screen-induced vision problems among the under-nines. Watch this space. Obesity and “the Force”: may the data be with you In 2003, National Statistics announced that there were 390 127 Jedis in England and Wales. That was the number of people who recorded their religion on the 2001 Census form as “Jedi”, the belief system from the Star Wars series of films. National Statistics categorised these entries under “No religion”. A potentially useful, or useless, correlation has now emerged from this. Research by Kevin McDonald of Glamorgan University compared Jedi statistics with a list of local authorities ranked by obesity risk. (Sadly, no research grant was available for this important work.) Prior to the 2001 Census there had been an email campaign encouraging people to declare themselves as Jedi. The campaign claimed, erroneously, that if more than 10 000 people declared themselves to be Jedi, then it would become a recognised religion. It was notable that amongst the local authorities in which the Jedi religion had fewest declared adherents were Easington (0.16%), Knowsley and Sedgefield (each with less than 0.20%). Two of the areas with greatest support for Jedi-ism (if that is the correct term) were Wandsworth (1.9%) and Lambeth (1.9%). “The obesity risk survey showed that obesity risk is 22% higher than average in Easington, and Knowsley and Sedgefield both feature in the top 10 of the list. Wandsworth and Lambeth featured in the bottom 10 of the list, where obesity risk is less than average. There appeared to be a negative correlation between obesity risk and the level of Jedi ‘religion’ in local authorities” said McDonald. Further investigation of the complete data sets bore out this correlation. “Spearman's rank correlation coefficient was calculated for the two ranked data sets. With n = 376 and no missing values, Spearman's ρ = –0.707 (3 d.p.) p < 0.0001, showing that there was indeed a negative correlation between the Jedi ‘religion’ and the risk of obesity. As Jedi membership rises, risk of obesity declines.” McDonald offers no explanations for this correlation but given the current reported levels of obesity in England and Wales, and forecasts for this to increase, he does suggest that encouraging exercise with light sabres might be useful. May the Force be with him. References 1Fisher, H., Montgomery, P. and Gardner, F. E. M. (2008) Opportunities provision for preventing youth gang involvement for children and young people (7–16). Cochrane Database of Systematic Reviews, Issue 2, Art. No. CD007002, DOI: 10.1002/14651858. CD007002.pub2. Google Scholar 2Fisher, H., Gardner, F. E. M. and Montgomery, P. (2008) Cognitive-behavioural interventions for preventing youth gang involvement for children and young people (7–16). Cochrane Database of Systematic Reviews, Issue 2, Art. No. CD007008, DOI: 10.1002/14651858. CD007008.pub2. Google Scholar Volume5, Issue2June 2008Pages 50-53 ReferencesRelatedInformation
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