946
Treatment decisions still have to be made, patients will continue to be treated, and useful information can be derived by finding out what happens to patients after treatment and comparing this to expectations from other data sources, including RCTs. The risk with cross design synthesis is that the more expensive, time-consuming, and reliable component-RCTswill increasingly be replaced by database analyses. Formal methods of combining results from different study techniques can confuse rather than clarify the issues and should not substitute for informed interpretation of all the evidence. Accounting Office. Cross design synthesis: a new strategy for medical effectiveness research. Washington, DC: GAO, 1992. 2. Gurwitz JH, Col NF, Avorn J. The exclusion of the elderly and women from clinical trials in acute myocardial infarction. JAMA 1992; 268: 1. General
1417-22. 3. Varnauskas E. Twelve year
follow-up of survival in the randomised European coronary surgery study. N Engl J Med 1988; 319: 332-37. 4. Editorial. Databases for health care outcomes. Lancet 1989; ii: 195-96. 5. Hartz AJ, Kuhn EM, Pryor DB, et al. Mortality after coronary angioplasty and coronary artery bypass surgery (the National Medicare Experience). Am J Cardiol 1992; 70: 179-85. 6. Green SB, Byar DP. Using observational data from registries to compare treatments: the fallacy of omnimetrics. Stat Med 1984; 3: 361-70. 7. Hlatky MA, Califf RM, Harrell FE, Lee KL, Mark DB, Pryor DB. Comparison of predictions based on observational data with the results of randomised controlled clinical trials of coronary artery bypass surgery. JACC 1988; 11: 237-45. 8. Califf RM, Harrell FE, Lee KL, et al. The evolution of medical and surgical therapy for coronary artery disease: a 15-year perspective. JAMA 1989; 261: 2077-86. 9. Hlatky MA. Using databases to evaluate therapy. Star Med 1991; 10: 647-52. 10. Petitti DB, Perlman JA, Sidney S. Postmenopausal estrogen use and heart disease. N Engl J Med 1986; 315: 131-32. 11. Davey Smith G, Phillips AN, Neaton JD. Smoking as "independent" risk factor for suicide: illustration of an artifact from observational epidemiology? Lancet 1992; 340: 709-12. 12. Roper WL, Winkenwerder W, Hackbarth GM, Krakauer H. Effectiveness in health care: an initiative to evaluate and improve medical practice. N Engl J Med 1988; 319: 1197-202. 13. Risks in 2 angina treatments weighed. International Herald Tribune 1992 14.
Aug 27: 7. Eddy DM, Hasselblad V, McGivney W, Hendee W. The value of mammography screening in women under age 50 years. JAMA 1988;
259: 1512-19. 15. Editorial. Breast cancer screening in women under 50. Lancet 1991; 337: 1575-76. 16. Roos NP, Wennberg JE, Malenka DJ, et al. Mortality and reoperation after open and transurethral resection of the prostate for benign prostatic hyperplasia. N Engl J Med 1989; 320: 1120-24. 17. Andersen TF, Bronnum-Hansen H, Sejr T, Roepstorff C. Elevated mortality following transurethral resection of the prostate for benign hypertrophy! But why? Med Care 1990; 28: 870-79. 18. Concato J, Horowitz RI, Feinstein AR, Elmore JG, Schiff SF. Problems of comorbidity in mortality after prostatectomy. JAMA 1992; 267: 1077-82. 19. Blumberg MS. Potentials and limitations of database research illustrated by the QMMP AMI Medicare mortality study. Stat Med 1991; 10: 637-46. 20. Chalmers I, Dickerson K, Chalmers TC. Getting to grips with Archie Cochrane’s agenda. BMJ 1992; 305: 786-88. 21. Berlin JA, Colditz GA. A meta-analysis of physical activity in the prevention of coronary heart disease. Am J Epidemiol 1990; 132: 612-28. 22. Law MR, Thompson SG. Low serum cholesterol and the risk of cancer: an analysis of the published prospective studies. Cancer Causes Control
1991; 2: 253-61. JE, Tosteson H, Ridker PM, et al. The primary prevention of myocardial infarction. N Engl J Med 1992; 326: 1406-16.
23. Manson 24.
Naylor CD. Two cheers for meta-analysis: problems and opportunities in aggregating results of clinical trials. Can Med Assoc J 1988; 138:
891-95. 25. Kassirer JP. Clinical trials and meta-analysis: what do N Engl J Med 1992; 327: 273-74.
they do for us?.
South-East Asia in the twenty-first
century Over the past fifty years, the population in every country in South-East Asia has more than doubled. Fortunately food production has increased slightly faster than populations and the great epidemics have at least been contained. The last major famine was in 1943 in Bengal and there have been no epidemics of cholera, smallpox, and plague to match those in the 19th and early 20th centuries. Yet this story, which reflects much credit on the people and the health services in each country, is one of only limited successes. All the old health problems, except smallpox, remain, although some of them are less
pressing. In World Health Organisation terms the SouthEast Asia region (SEAR) consists of Bangladesh,
Bhutan, India, Indonesia, Maldives, Myanmar (Burma), Nepal, Sri Lanka, and Thailand; Malaysia, Pakistan, and Singapore are included in neighbouring regions. Nearly 1 -3 billion people-about a quarter of the world’s population-live in SEAR, and the health services in each country face broadly similar pressures. As a guide to development of the most appropriate policies for the region, the WHO regional director, Dr U. Ko Ko, asked Dr C. Gopalan to undertake a review. Gopalan’s report,1 which is refreshingly free of sociological and medical jargon, is available. Over 30% of the population live in towns, and five towns in the region are expected to have a population of over 10 million by the year 2000. Many urban dwellers live in shanty towns, where there are immense difficulties in providing potable water and effective sewerage systems. The high population density favours the spread of infectious diseases, especially those causing diarrhoea. Many women in urban slums, unlike their counterparts in the country, have to seek work in factories, shops, or as domestic servants, which restricts opportunities for breastfeeding and for preparing wholesome meals for older children. Huge rises in the number of elderly individuals are predicted for early in the next century in India, Indonesia, Sri Lanka, and Thailand. Old people in these countries are traditionally respected and cared for in their homes, as part of an extended family. The demographic changes that are now taking place will inevitably put many families under stress and the need for geriatric services throughout the region will
now
increase steadily. The increase in population has not been only among the poor. There are now many prosperous middle-class people with affluent lifestyles. Obesity, diabetes, hypertension, and ischaemic heart disease have followed in the wake of their prosperity, and are certain to place greatly increased demands on health services. Large health education programmes will be
required.
947
The great increase in agricultural production, largely due to the green revolution, has enabled farmers in the region to grow sufficient cereals, mainly rice and wheat, to meet the needs of all people. That there are groups who are undernourished and hungry is due to social and economic factors that prevent the equitable distribution of a supply that is overall sufficient. Yet the green revolution has not been all benefit. For example, there has been little increase in production of pulses and, as a result, their overall availability in India during the past 30 years has fallen from 66 to 33 g/head daily. Protein quality of diets must have diminished accordingly, especially in poor households that are predominantly vegetarian. The revolution also bypassed horticulture: supplies of fruit and fresh vegetables are still subject to seasonal glut and scarcity. Until horticultural resources are harnessed and managed effectively, vitamin A deficiency will remain widespread. The new agriculture depends upon intensive irrigation and use of chemical fertilisers. In some areas traditional organic manures have been almost completely jettisoned. Consequently there is a risk that crops will become deficient in essential mineral nutrients such as zinc, and contaminated with toxic chemicals, a risk greatly increased by the use of pesticides and herbicides. As a counter-measure there should be extensive but realistic legislation on food standards, but this will only be effective if there are efficient inspection and analytical procedures backed up by continuing research. The health services in the region will also have to take an interest in environmental protection. Deforestation, soil erosion, and industrial pollution, of both the atmosphere and rivers, are having severe adverse effects in parts of South-East Asia. Whereas most of the report is concerned with strategies for action against broad causes of disease and ill-health, one chapter in Gopalan’s report deals with three specific nutritional disorders-iodine deficiency goitre, hypovitaminosis A, and iron-deficiency anaemia-that continue to cause much ill-health in the region, although the knowledge and means to prevent them are available. The report calls for national goitre commissions with authority to enforce the regulations for distribution of iodised salts. That many thousands of babies are still being bom condemned through lack of a little iodine to a life as cretinous deaf mutes is a scandal that should no longer be tolerated. Severe vitamin A deficiency leads to keratomalacia and blindness and is associated with a high mortality. Reports from hospitals and clinics suggest that keratomalacia is much less frequently seen than formerly, at least in large medical centres, but how much moderate deficiency, widespread in the region, contributes to mortality from measles, respiratory infections, and diarrhoeal diseases is hard to quantify.23 Moderate deficiency is generally held to be an important factor contributing to child morbidity
and mortality in many communities. The paradox is that in such communities there is an abundant source of the vitamin from p-carotene in the fruits and green leaves of plants growing nearby. The report calls for intensive research to develop acceptable recipes based on food rich in 0-carotene and for education to see that these recipes become part of family diets. Such education should be a top priority in antenatal care and in home science courses in colleges. Agricultural research is needed to develop cultivation of plants especially rich in the provitamin, both in home gardens and commercially. Existing programmes for giving children periodic very large doses of synthetic vitamin A may well be continued but Gopalan does not see this as the answer. He calls for "the immediate adoption of a clear policy, backed by political will and commitment" whereby such programmes are tapered off progressively as production of P-carotene rich foods and their introduction into the diets of women and children gets going. Iron deficiency anaemia is widespread in the region; most of those affected are women, with a greatly increased risk from pregnancy. A main contributory cause is the poor availability of iron from cereal-based vegetarian diets, but the relative importance of other causes requires investigation. The strategy for prevention advocated is to encourage girls to take iron/folate tablets from marriage onwards. This report needs to be read widely by leaders of public opinion, who should strive to ensure the great benefits arising from new medical knowledge become available to all the people. Ultimately, a higher level of education is the key to successful health policies in the
region. 1.
Gopalan C. Nutrition in developmental transition in South-East Asia. Regional Health Paper SEARO no 21. New Delhi: World Health Organisation Regional Office for South-East Asia. ISBN 92-
2.
Gopalan C. Vitamin A deficiency and childhood mortality. Lancet 1992;
90221909. 340: 177-78. 3. Sommer A. Vitamin A 340: 482-89.
deficiency and childhood mortality. Lancet 1992;
Grand Rounds in The Lancet The second in our series Grand Rounds appears this week on p 948 and, like the first, (see Lancet 1992; 339: 1146-49) comes from University College London Medical School, UK. At these meetings there has been a strong emphasis on communicating advances in basic research as they apply to the clinical subject in question. Hence the title of the meeting, which draws attention to the collaboration between physicians and scientists and which emphasises the difference between these rounds and standard casepresentations. Would you like to contribute to this series? We intend to publish similar peer-reviewed reports from other centres world wide. Readers wishing to submit such a report can obtain a copy of our editorial guidelines for this series by writing to the Editor.
Treatment decisions still have to be made, patients will continue to be treated, and useful information can be derived by finding out what happens to patients after treatment and comparing this to expectations from other data sources, including RCTs. The risk with cross design synthesis is that the more expensive, time-consuming, and reliable component-RCTswill increasingly be replaced by database analyses. Formal methods of combining results from different study techniques can confuse rather than clarify the issues and should not substitute for informed interpretation of all the evidence. Accounting Office. Cross design synthesis: a new strategy for medical effectiveness research. Washington, DC: GAO, 1992. 2. Gurwitz JH, Col NF, Avorn J. The exclusion of the elderly and women from clinical trials in acute myocardial infarction. JAMA 1992; 268: 1. General
1417-22. 3. Varnauskas E. Twelve year
follow-up of survival in the randomised European coronary surgery study. N Engl J Med 1988; 319: 332-37. 4. Editorial. Databases for health care outcomes. Lancet 1989; ii: 195-96. 5. Hartz AJ, Kuhn EM, Pryor DB, et al. Mortality after coronary angioplasty and coronary artery bypass surgery (the National Medicare Experience). Am J Cardiol 1992; 70: 179-85. 6. Green SB, Byar DP. Using observational data from registries to compare treatments: the fallacy of omnimetrics. Stat Med 1984; 3: 361-70. 7. Hlatky MA, Califf RM, Harrell FE, Lee KL, Mark DB, Pryor DB. Comparison of predictions based on observational data with the results of randomised controlled clinical trials of coronary artery bypass surgery. JACC 1988; 11: 237-45. 8. Califf RM, Harrell FE, Lee KL, et al. The evolution of medical and surgical therapy for coronary artery disease: a 15-year perspective. JAMA 1989; 261: 2077-86. 9. Hlatky MA. Using databases to evaluate therapy. Star Med 1991; 10: 647-52. 10. Petitti DB, Perlman JA, Sidney S. Postmenopausal estrogen use and heart disease. N Engl J Med 1986; 315: 131-32. 11. Davey Smith G, Phillips AN, Neaton JD. Smoking as "independent" risk factor for suicide: illustration of an artifact from observational epidemiology? Lancet 1992; 340: 709-12. 12. Roper WL, Winkenwerder W, Hackbarth GM, Krakauer H. Effectiveness in health care: an initiative to evaluate and improve medical practice. N Engl J Med 1988; 319: 1197-202. 13. Risks in 2 angina treatments weighed. International Herald Tribune 1992 14.
Aug 27: 7. Eddy DM, Hasselblad V, McGivney W, Hendee W. The value of mammography screening in women under age 50 years. JAMA 1988;
259: 1512-19. 15. Editorial. Breast cancer screening in women under 50. Lancet 1991; 337: 1575-76. 16. Roos NP, Wennberg JE, Malenka DJ, et al. Mortality and reoperation after open and transurethral resection of the prostate for benign prostatic hyperplasia. N Engl J Med 1989; 320: 1120-24. 17. Andersen TF, Bronnum-Hansen H, Sejr T, Roepstorff C. Elevated mortality following transurethral resection of the prostate for benign hypertrophy! But why? Med Care 1990; 28: 870-79. 18. Concato J, Horowitz RI, Feinstein AR, Elmore JG, Schiff SF. Problems of comorbidity in mortality after prostatectomy. JAMA 1992; 267: 1077-82. 19. Blumberg MS. Potentials and limitations of database research illustrated by the QMMP AMI Medicare mortality study. Stat Med 1991; 10: 637-46. 20. Chalmers I, Dickerson K, Chalmers TC. Getting to grips with Archie Cochrane’s agenda. BMJ 1992; 305: 786-88. 21. Berlin JA, Colditz GA. A meta-analysis of physical activity in the prevention of coronary heart disease. Am J Epidemiol 1990; 132: 612-28. 22. Law MR, Thompson SG. Low serum cholesterol and the risk of cancer: an analysis of the published prospective studies. Cancer Causes Control
1991; 2: 253-61. JE, Tosteson H, Ridker PM, et al. The primary prevention of myocardial infarction. N Engl J Med 1992; 326: 1406-16.
23. Manson 24.
Naylor CD. Two cheers for meta-analysis: problems and opportunities in aggregating results of clinical trials. Can Med Assoc J 1988; 138:
891-95. 25. Kassirer JP. Clinical trials and meta-analysis: what do N Engl J Med 1992; 327: 273-74.
they do for us?.
South-East Asia in the twenty-first
century Over the past fifty years, the population in every country in South-East Asia has more than doubled. Fortunately food production has increased slightly faster than populations and the great epidemics have at least been contained. The last major famine was in 1943 in Bengal and there have been no epidemics of cholera, smallpox, and plague to match those in the 19th and early 20th centuries. Yet this story, which reflects much credit on the people and the health services in each country, is one of only limited successes. All the old health problems, except smallpox, remain, although some of them are less
pressing. In World Health Organisation terms the SouthEast Asia region (SEAR) consists of Bangladesh,
Bhutan, India, Indonesia, Maldives, Myanmar (Burma), Nepal, Sri Lanka, and Thailand; Malaysia, Pakistan, and Singapore are included in neighbouring regions. Nearly 1 -3 billion people-about a quarter of the world’s population-live in SEAR, and the health services in each country face broadly similar pressures. As a guide to development of the most appropriate policies for the region, the WHO regional director, Dr U. Ko Ko, asked Dr C. Gopalan to undertake a review. Gopalan’s report,1 which is refreshingly free of sociological and medical jargon, is available. Over 30% of the population live in towns, and five towns in the region are expected to have a population of over 10 million by the year 2000. Many urban dwellers live in shanty towns, where there are immense difficulties in providing potable water and effective sewerage systems. The high population density favours the spread of infectious diseases, especially those causing diarrhoea. Many women in urban slums, unlike their counterparts in the country, have to seek work in factories, shops, or as domestic servants, which restricts opportunities for breastfeeding and for preparing wholesome meals for older children. Huge rises in the number of elderly individuals are predicted for early in the next century in India, Indonesia, Sri Lanka, and Thailand. Old people in these countries are traditionally respected and cared for in their homes, as part of an extended family. The demographic changes that are now taking place will inevitably put many families under stress and the need for geriatric services throughout the region will
now
increase steadily. The increase in population has not been only among the poor. There are now many prosperous middle-class people with affluent lifestyles. Obesity, diabetes, hypertension, and ischaemic heart disease have followed in the wake of their prosperity, and are certain to place greatly increased demands on health services. Large health education programmes will be
required.
947
The great increase in agricultural production, largely due to the green revolution, has enabled farmers in the region to grow sufficient cereals, mainly rice and wheat, to meet the needs of all people. That there are groups who are undernourished and hungry is due to social and economic factors that prevent the equitable distribution of a supply that is overall sufficient. Yet the green revolution has not been all benefit. For example, there has been little increase in production of pulses and, as a result, their overall availability in India during the past 30 years has fallen from 66 to 33 g/head daily. Protein quality of diets must have diminished accordingly, especially in poor households that are predominantly vegetarian. The revolution also bypassed horticulture: supplies of fruit and fresh vegetables are still subject to seasonal glut and scarcity. Until horticultural resources are harnessed and managed effectively, vitamin A deficiency will remain widespread. The new agriculture depends upon intensive irrigation and use of chemical fertilisers. In some areas traditional organic manures have been almost completely jettisoned. Consequently there is a risk that crops will become deficient in essential mineral nutrients such as zinc, and contaminated with toxic chemicals, a risk greatly increased by the use of pesticides and herbicides. As a counter-measure there should be extensive but realistic legislation on food standards, but this will only be effective if there are efficient inspection and analytical procedures backed up by continuing research. The health services in the region will also have to take an interest in environmental protection. Deforestation, soil erosion, and industrial pollution, of both the atmosphere and rivers, are having severe adverse effects in parts of South-East Asia. Whereas most of the report is concerned with strategies for action against broad causes of disease and ill-health, one chapter in Gopalan’s report deals with three specific nutritional disorders-iodine deficiency goitre, hypovitaminosis A, and iron-deficiency anaemia-that continue to cause much ill-health in the region, although the knowledge and means to prevent them are available. The report calls for national goitre commissions with authority to enforce the regulations for distribution of iodised salts. That many thousands of babies are still being bom condemned through lack of a little iodine to a life as cretinous deaf mutes is a scandal that should no longer be tolerated. Severe vitamin A deficiency leads to keratomalacia and blindness and is associated with a high mortality. Reports from hospitals and clinics suggest that keratomalacia is much less frequently seen than formerly, at least in large medical centres, but how much moderate deficiency, widespread in the region, contributes to mortality from measles, respiratory infections, and diarrhoeal diseases is hard to quantify.23 Moderate deficiency is generally held to be an important factor contributing to child morbidity
and mortality in many communities. The paradox is that in such communities there is an abundant source of the vitamin from p-carotene in the fruits and green leaves of plants growing nearby. The report calls for intensive research to develop acceptable recipes based on food rich in 0-carotene and for education to see that these recipes become part of family diets. Such education should be a top priority in antenatal care and in home science courses in colleges. Agricultural research is needed to develop cultivation of plants especially rich in the provitamin, both in home gardens and commercially. Existing programmes for giving children periodic very large doses of synthetic vitamin A may well be continued but Gopalan does not see this as the answer. He calls for "the immediate adoption of a clear policy, backed by political will and commitment" whereby such programmes are tapered off progressively as production of P-carotene rich foods and their introduction into the diets of women and children gets going. Iron deficiency anaemia is widespread in the region; most of those affected are women, with a greatly increased risk from pregnancy. A main contributory cause is the poor availability of iron from cereal-based vegetarian diets, but the relative importance of other causes requires investigation. The strategy for prevention advocated is to encourage girls to take iron/folate tablets from marriage onwards. This report needs to be read widely by leaders of public opinion, who should strive to ensure the great benefits arising from new medical knowledge become available to all the people. Ultimately, a higher level of education is the key to successful health policies in the
region. 1.
Gopalan C. Nutrition in developmental transition in South-East Asia. Regional Health Paper SEARO no 21. New Delhi: World Health Organisation Regional Office for South-East Asia. ISBN 92-
2.
Gopalan C. Vitamin A deficiency and childhood mortality. Lancet 1992;
90221909. 340: 177-78. 3. Sommer A. Vitamin A 340: 482-89.
deficiency and childhood mortality. Lancet 1992;
Grand Rounds in The Lancet The second in our series Grand Rounds appears this week on p 948 and, like the first, (see Lancet 1992; 339: 1146-49) comes from University College London Medical School, UK. At these meetings there has been a strong emphasis on communicating advances in basic research as they apply to the clinical subject in question. Hence the title of the meeting, which draws attention to the collaboration between physicians and scientists and which emphasises the difference between these rounds and standard casepresentations. Would you like to contribute to this series? We intend to publish similar peer-reviewed reports from other centres world wide. Readers wishing to submit such a report can obtain a copy of our editorial guidelines for this series by writing to the Editor.
