Comment
the answer is yes; only after licensing in the USA and after marketing surveillance was troglitazone found to cause liver failure and withdrawn.14 Why do we still use ineffective treatments? One reason is that our expectations for the benefits of treatment are too high.14 We have to recognise that treatments can sometimes do more harm than good, occasionally on a devastating scale.15 The duty of doctors is to do good for patients; however, that sometimes means doing nothing—watching and careful observation should not be replaced by blind optimism. It is in everyone’s interest that the findings of this review, and others, are in the public domain. *Carl Heneghan, Rafael Perera
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Centre for Evidence Based Medicine, Department of Primary Health Care, University of Oxford, Oxford OX3 7LF, UK
[email protected]
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We declare that we have no conflict of interest.
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Yasunaga H. Risk of authoritarianism: fibrinogen-transmitted hepatitis C in Japan. Lancet 2007; 370: 2063–67. World Health Organization. Fact sheet number 164. Revised October, 2000. http://www.who.int/mediacentre/factsheets/fs164/en/ (accessed May 10, 2007). Perz JF, Armstrong GL, Farrington LA, Hutin YJ, Bell BP. The contributions of hepatitis B virus and hepatitis C virus infections to cirrhosis and primary liver cancer worldwide. J Hepatol 2006; 45: 529–38.
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NIH consensus conference statement. Management of hepatitis C. June 10–12, 2007. http://consensus.nih.gov/2002/2002HepatitisC2002 116html.htm (accessed May 11, 2007). Abocar A. Criminal charges laid in Canadian blood scandal. Reuters (Toronto), Nov 21, 2002. http://www.aegis.com/news/re/2002/RE021126. html (accessed May 11, 2007). The Daily Record (Scotland), Oct 31, 2005. http://www.dailyrecord. co.uk/news/tm_objectid=16314330&method=full&siteid=66633&headlin e=clinton-s-scottish-court-warning--name_page.html (accessed May 11, 2007). Hoofnagle JH, Gerety RJ, Tabor E, Feinstone SM, Barker LF, Purcell RH. Transmission of non-A, non-B hepatitis. Ann Intern Med 1977; 87: 14–20. Aach RD, Szmuness W, Mosley JW, et al. Serum alanine aminotransferase of donors in relation to the risk of non-A, non-B hepatitis in recipients: the transfusion-transmitted viruses study. N Engl J Med 1981; 304: 989–94. Franciscus A. HCV Advocate. Japanese state and firm blamed for hepatitis C infection. http://209.41.169.29/news/newsRev/2006/NewsRev-158. html#13 (accessed May 18, 2007). Echt DS, Liebson PR, Mitchell LB, et al. Mortality and morbidity in patients receiving encainide, flecainide, or placebo. The Cardiac Arrhythmia Suppression Trial. N Engl J Med 1991; 324: 781–88. Vandenbroucke JP. Thalidomide: an unanticipated adverse event. http://www.jameslindlibrary.org (accessed May 10, 2007). Graham DJ, Campen D, Hui R, et al. Risk of acute myocardial infarction and sudden cardiac death in patients treated with cyclo-oxygenase 2 selective and non-selective non-steroidal anti-inflammatory drugs: nested case-control study. Lancet 2005; 365: 475–81. Evans I, Thornton H, Chalmers I. New—but no better or even worse. In: Evans I, Thornton H, Chalmers I (eds). Testing treatments: better research for better healthcare. London: British Library Publishing Division, 2006: 1–13. Doust J, Del Mar C. Why do doctors use treatments that do not work? BMJ 2004; 328: 474–75. Chalmers I. Well informed uncertainties about the effects of treatments. BMJ 2004; 328: 475–76.
Global health and Japan’s foreign policy In 2008, Japan will host two major conferences, the Fourth Tokyo International Conference on African Development (TICAD IV) and the G8 Hokkaido Toyako Summit. At this important diplomatic juncture, Japan will take up and call for a stronger engagement of the international community in global health. In 2000, during the G8 Kyushu Okinawa Summit, Japan launched the Okinawa Infectious Diseases Initiative1 and appealed for international collaboration. This led to the establishment of the Global Fund to Fight AIDS, Tuberculosis and Malaria. The UN Millennium Summit, in 2000, laid the foundation for the Millennium Development Goals (MDGs), including health goals to be achieved by 2015. Also in 2000, a historical statement announced the eradication of poliomyelitis in WHO’s Western Pacific region.2 Since then, international awareness about the need to tackle infectious diseases has increased. The Global Fund now saves 3000 lives each day; it has saved 1·5 million www.thelancet.com Vol 370 December 15, 2007
so far. And yet, 6 million people still die every year from AIDS, tuberculosis, or malaria. We still face serious challenges in maternal, newborn, and child health. In sub-Saharan Africa, 166 in 1000 children die before their fifth birthday, which is 20 times higher than the number in developed countries. The risk of death related to pregnancy and childbirth is one in 16, which is 200 times higher for women in sub-Saharan Africa than for those in developed countries. At this rate, we are likely to miss the health-related MDGs. One vital aspect of health is water and sanitation. In a developed country such as Japan, nearly everyone has access to safe drinking water. In sub-Saharan Africa, the proportion is only 56%. For adequate sanitation facilities, including toilets, nearly all the developed world has access, compared with only 37% in sub-Saharan Africa. Next year we reach the midpoint for the achievement of the MDGs by 2015. At TICAD IV, Japan intends to take up the issue of health in Africa, and at the G8 Summit,
Published Online November 26, 2007 DOI:10.1016/S01406736(07)61726-7
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Comment
Masahiko Koumura
the wider issue of global health. The objective will be to develop a common framework for action shared by the international community. Where should the international community go from here? Human security is a concept that is very relevant to cooperation in the 21st century. That is to say, it is vitally important that we not only focus on the health of individuals and protect them, but also strive to empower individuals and communities through health-system strengthening. To date, international efforts in the health sector have largely centred on measures against infectious diseases. From now on, it is essential to promote a comprehensive approach to strike at the root of the problem, especially through the promotion of research and development and strengthening of health systems, including humanresource development and retention. Disturbingly, subSaharan Africa contains 11% of the world’s population and 25% of the disease-related burden, but the region has only 3% of the world’s health workers. The importance of human-resource development and retention on a considerable scale is self-evident. The disease-specific and comprehensive approaches complement each other. Striking a good balance between them will be at the core of the international framework that we aim to develop at Toyako. The effectiveness of integrating two intersecting approaches has been empirically proven by Japan’s experiences. Postwar Japan focused on the promotion of maternal and child health and tackled infectious diseases, 1984
such as tuberculosis. A holistic approach included the spread of vaccinations and regular health check-ups at health centres and schools, provision of nutritional education, and school lunches, which together led to overall improvements in the population’s health. Japan has shared its experience with developing countries by, for example, dissemination of the Maternal and Child Health Handbook in Indonesia.3 It began when one Indonesian doctor came across this handbook during training organised by the Japan International Cooperation Agency. This empowerment tool for mothers has reached several other countries in Asia and the rest of the world, for example, in Palestine. The development and retention of human resources is important for the running of health systems. Basic education and gender equality are essential, because they underpin health systems. The development of road networks is also relevant. We may have to transport patients, doctors, nurses, and medical supplies quickly. We also need means of communication that are readily available. The proposed framework for action cannot be promoted by the Japanese government alone. Diverse stakeholders will have to collaborate. Developing countries, including those in Africa, must have ownership of the health agenda. The Hideyo Noguchi Africa Prize4 will be supporting various health efforts in Africa, and will be presented for the first time at the TICAD IV. Major developed countries, including the G8 and international organisations, need to show clear political will to support the efforts of developing countries as their partners. New emerging donor countries, NGOs, the business sector, and private foundations also have roles to play. No less important, any proposed framework for action cannot be formulated by health experts alone. We need experts from various fields to be involved in this process. The TICAD IV and G8 Summit next year will be excellent opportunities for the international community to strengthen their collaboration and build a framework based on a participatory approach suited to the 21st century. Japan, as G8 chair and host to TICAD, will aim to achieve this. Masahiko Koumura Minister for Foreign Affairs, Chiyoda-ku, Tokyo 100-8919, Japan
[email protected] I declare that I have no conflict of interest.
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Japanese Anti-Tuberculosis Association. Okinawa Infectious Diseases Initiative: summary of midterm evaluation report. March, 2004. http://www.mofa.go.jp/policy/oda/evaluation/2003/okinawa.pdf (accessed Nov 22, 2007). World Health Organization, Regional Office of the Western Pacific. Polio success story. 2005. http://www.wpro.who.int/sites/epi/polio_success/ PolioSuccess02XX.htm (accessed Nov 22, 2007).
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Ministry of Foreign Affairs of Japan. Maternal and Child Health (MCH) Handbook projects. http://www.mofa.go.jp/policy/environment/ wssd/2002/type2/1-1-6.html (accessed Nov 22, 2007). Hideyo Noguchi Africa Prize. Factsheet. http://www.cao.go.jp/noguchisho/ gaiyo-e.html (accessed Nov 22, 2007).
Preimplantation aneuploidy screening: a research tool for now
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be seen. The testing of all chromosomes would probably even increase observed aneuploidy rates.5 Mosaicism (ie, differences in the chromosomal constitution of some cells during early development of the embryo) is another possible reason for confusion.6 A single blastomere might thus be classified as abnormal, whereas the remaining (not examined by biopsy) blastomeres in the embryo are normal. The opposite can also occur, contributing greatly to false-positive or false-negative results. Of course, if only one blastomere is examined, mosaicism cannot be detected. Test results could theoretically improve with the study of two blastomeres. The removal of two blastomeres has been argued as being detrimental for embryonic implantation potential.7 But two arguments against this idea are convincing. Reported rates of embryo implantation after the removal of one blastomere (17·6%) were similar to those after two were removed (17·1%).2,4 Moreover, in a randomised trial in women aged 37 years or younger, implantation rates of day-5 blastocysts were similar with or without preimplantation aneuploidy screening after the removal of one blastomere (47·4% vs 42·8%).8 A final reason for confusion is lack of knowledge about the natural course of mosaicism;9 mosaic preimplantation embryos might be self-correcting. Theoretically, preimplantation aneuploidy screening seems a solid technique with the potential to improve embryo selection and clinical outcomes in IVF. Unfortunately, its clinical usefulness has not been confirmed by existing data from well-designed trials. However, more randomised studies are underway. The disappointing results of studies of aneuploidy screening suggest that at present science has to overcome the mysteries of embryo biology. Detailed fundamental research about the biology of a cleaving embryo is mandatory. The conclusion seems justified that, on the basis of current evidence, aneuploidy screening should be considered as a research tool and not be advocated for routine care of patients.
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Sebastiaan Mastenbroek and colleagues have reported that the use of preimplantation aneuploidy screening to select chromosomally normal embryos for in-vitro fertilisation (IVF) does not improve rates of pregnancy at 12 weeks.1 Their randomised trial in more than 400 women aged 35–41 years compared outcomes of up to three IVF cycles with or without screening. The pregnancy rate was significantly decreased in the aneuploidy screening arm (25% vs 37%; rate ratio 0·69, 95% CI 0·51–0·93). A clear distinction should be made between preimplantation aneuploidy screening and preimplantation genetic diagnosis, in which IVF is done in couples with a known genetic disease, solely to obtain embryos for diagnosis. In principle, only non-affected embryos are implanted. This method is preferred by some women over prenatal diagnosis during pregnancy, because it avoids the need for termination if an affected fetus is diagnosed. Aneuploidy screening (counting abnormal chromosome numbers) was developed to improve embryo selection in infertile couples, by implanting only euploid embryos.2,3 Promising data that suggest higher pregnancy rates and reduced miscarriage rates after such screening have been reported over the past decade. This technique is currently advocated widely for patients with advanced maternal age (more than 37 years), for patients who present with repeated implantation failure (ie, unsuccessful previous IVF), in women who have had repeated miscarriages, and for the IVF technique of single-embryo transfer. Unfortunately, all previous studies were observational, uncontrolled, and often in selected populations of patients. Two large randomised trials have shown no benefit of preimplantation aneuploidy screening for pregnancy and delivery rates.1,4 Several possible reasons for this lack of benefit are proposed: technical reasons include both damage to the remaining embryo during blastomere biopsy, reducing its developmental potential; and limitations of current fluorescence in-situ hybridisation technology (90% accuracy) that allows only a few chromosomes to
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