- Email: [email protected]
Still life in oxidation hypothesis of atherogenesis
CORRESPONDENCE
However, that should not be confused with the standard by which therapeutics are assessed for IBS or any other disease state. We did collect quality of life data in this and its companion study using IBSQoL, a validated disease specific instrument,3 and benefit was seen. Allen W Mangel Gastroenterology, Glaxo Wellcome, Research Triangle Park, NC 27709, USA 1
2
3
Mangel A, Camilleri M, Chey W, et al. Alosetron, a 5HT3 receptor antagonist, in the treatment of non-constipated female IBS patient. Am J Gastroenterol 1999; 94: 2677 (abstr). Jones R, Holtmann G, Rodrigo L, et al. Alosetron relieves pain and improves bowel function compared with mebeverine in female nonconstipated irritable bowel syndrome patients. Aliment Pharmacol Ther 1999; 13: 1419–27. Hahn BA, Kirchdoerfer LJ, Fullerton S, et al. Evaluation of a new quality of life questionnaire for patients with irritable bowel syndrome. Aliment Pharmacol Ther 1997; 11: 547–52.
Still life in oxidation hypothesis of atherogenesis Sir—In his provocative and timely viewpoint, Barry Halliwell (April 1, p 1179)1 draws attention to the paradox of the growing experimental evidence linking the oxidative modification of LDL to atherogenesis and the generally disappointing outcome of trials of antioxidants in the prevention of coronary heart disease (CHD). He suggests that one explanation might be that the antioxidants administered may not have altered antioxidant status in the desired direction. We have reported that even high doses of antioxidants, although delaying the early phase of LDL oxidation in which conjugated dienes are formed, failed to influence the subsequent formation of lipid peroxides.2 It is the breakdown of lipid peroxides that leads to the atherogenic modification of LDL. Furthermore, we have found that supplementation with vitamin E, like the synthetic antioxidant probucol, increases the transfer of cholesteryl ester between This might be lipoproteins.3 counterproductive in the prevention of atheroma, because it may, for example, increase the formation of small, dense LDL, which is more susceptible to oxidation. HDL, unlike physical antioxidants, protects against the accumulation of lipid peroxides on LDL over several hours by a mechanism, which is unaffected by oral supplementation with physical antioxidants, such as
THE LANCET • Vol 356 • July 8, 2000
vitamins and selenium.2 This effect seems to be the result of the enzyme, paraoxonase (PON1) located on HDL.4 Thus, one consequence of the poor results of antioxidant trials should not be the rejection of the oxidation hypothesis of atherogenesis, but rather that greater attention should be paid to other antioxidant mechanisms, such as PON1. Serum PON1 activity is profoundly decreased in CHD.5 It may be possible to devise dietary or pharmacological interventions to increase PON1 activity, which could lead to the true test of the oxidant hypothesis in clinical trials. *P N Durrington, M I Mackness Department of Medicine, Manchester Royal Infirmary, Manchester M13 9WL, UK 1 2
3
4
5
Halliwell B. The antioxidant paradox. Lancet 2000; 355: 1179–80. Mackness MI, Abbott CA, Arrol S, Durrington PN. The role of high density lipoprotein and lipid-soluble antioxidant vitamins in inhibiting low-density lipoprotein oxidation. Biochem J 1993; 294: 829–35. Arrol S, Mackness MI, Durrington PN. Vitamin E supplementation increases the resistance of both LDL and HDL to oxidation and increases cholesteryl ester transfer activity. Atherosclerosis (in press). Mackness MI, Mackness B, Durrington PN, et al. Paraoxonase and coronary heart disease. Cur Opin Lipidol 1998; 9: 319–24. Ayub A, Mackness MI, Arrol S, Mackness B, Patel J, Durrington PN. Serum paraoxonase after myocardial infarction. Arterioscler Thromb Vasc Biol 1999; 19: 330–35.
Sir—Barry Halliwell1 addresses the questions for the selection of patients suitable for treatment with antioxidants according to their antioxidant status, and how to follow up the effect of antioxidant therapy. We agree with him that these topics are crucial in designing future studies of antioxidants. One of the main purposes of antioxidant therapy is to reduce arterial-wall inflammation induced by oxidative stress. Measuring the markers of inflammation could be used as surrogate endpoints of antioxidant therapy. Emerging data show that soluble fractions of cellular adhesion molecules (CAM) and C-reactive protein (CRP) could be useful in this respect.2 Increased oxidative stress and induction of redox-sensitive genes by activating nuclear factor B is a common final pathway of action of the classic risk factors: hypercholesterolaemia, hypertension, smoking, and diabetes. The induction of these genes is followed by increased arterial wall inflammation and increased expression of CAM by endothelial cells.3 These changes promote interaction by circulating monocytes with endo-
thelium, followed by migration in subendothelial space. It has been shown that CAM concentration correlates with the extent of carotid atherosclerosis and is a good predictor of further ischaemic events.4 Existing data on the effect of antioxidants on concentration of CAM are spare and controversial. Another very important question raised by Halliwell is that in some invivo circumstances, and depending on the dose of antioxidants, antioxidants could be damaging. Our own unpublished data show that the use of moderate doses of combinations of antioxidants with different modes of action (scavenging free radicals and suppressing formation of free radicals), reduces the concentration of soluble vascular cell adhesion molecule 1 and soluble intracellular cell adhesion molecule 1 in high-risk postmenopausal women. Use of a combination of antioxidants resembles much more the antioxidant-rich diet supplementation on which the positive data from epidemiological studies is based. The antioxidant hypothesis faces similar difficulties to the hypothesis of cardioprotective effects of hormonereplacement therapy. The encouraging data from mechanistic and observational studies are not confirmed in randomised controlled trials. Data from the Postmenopausal Estrogen/ Progestin Intervention (PEPI) trial show that all used hormone combinations increase the concentration of CRP in the first year, followed by decreased concentration of CAM later on in the follow-up.5 One of the suggested cardioprotective effects of hormone-replacement therapy, beyond a lipid-lowering effect, is the antioxidant activity. Measuring of CRP with highly specific tests could also provide information on the effects of antioxidants on vascular wall. The measurement of inflammatory markers in nested case-control studies in the cohort of the patients from large antioxidants trials like the Cambridge Heart Antioxidant Study (CHAOS), the Gruppo Italiano per lo Studio della Sopravvivenza nell’ Inforto (GISSI) Prevention Study, and the Heart Outcomes Prevention Evaluation (HOPE) study could provide interesting data as to who are the winners and who are the losers in antioxidant therapy. *A Goudev, D Georgiev, S Kuyrkchiev, V Ganev, I Kehayov Departments of *Biochemistry and Internal Medicine, Medical University, Sofia 1431, Bulgaria; Second Obstetric and Gynaecology Hospital, Sheinovo 19, Sofia; and Institute of Immunology, Bulgarian Academy of Science, Sofia (e-mail: [email protected])
165
For personal use only. Not to be reproduced without permission of The Lancet.
CORRESPONDENCE 1 2
3
4
5
Halliwell B. The antioxidant paradox. Lancet 2000; 355: 1179–80. Libby P, Ridker P. Novel inflammatory markers of coronary risk. Theory versus practice. Circulation 1999; 100: 1148–50. Liao F, Andalibi A, Qiao JH, et al. Genetic evidence for a common pathway mediating oxidative stress, inflammatory gene induction and aortic fatty streak formation in mice. J Clin Invest 1994; 94: 877–84. Hwang S, Ballantyne C, Sharrett AR, et al. Circulating adhesion molecules VCAM-1, ICAM-1 and E-selectin in carotid atherosclerosis and incident coronary heart disease cases. The Atherosclerosis Risk in Communities (ARIC) Study. Circulation 1997; 96: 4219–25. Ridker P, Hennekens C, Rifai N, Buring J, Manson J. Hormone replacement therapy and increased plasma concentration of C-reactive protein. Circulation 1999; 100: 713–16.
Sir—Barry Halliwell1 draws attention to a valid point on the apparent lack of effectiveness and possibly harmful effects of -carotene supplements, something that seems to have been missed in most studies. Although diets rich in -carotene protect against cancer development, carotene is not the protective agent.2 It may well be a good indicator of general carotenoid consumption, but it is not necessarily the most appropriate carotenoid with respect to antioxidant properties. The unusual behaviour of -carotene in membranes was noted as long ago as 1984 by Burton and Ingold3 who concluded that “-carotene is not a conventional antioxidant” and at high oxygen partial pressures it may even act as a pro-oxidant. Analysis of plant material always reveals the presence of six carotenoids, of which -carotene is usually the most abundant. The remaining five compounds are present at much lower concentrations but they are by no means any less important. For example, two of these dietary components (zeaxanthin and lutein) are thought to be essential for the wellbeing of the retina.4 Diets that are high in -carotene will also contain much lower concentrations of these rare carotenoids and supplements of pure -carotene alone cannot be expected to reproduce the same effects as a balanced intake provided by a diet rich in fruit and vegetables. Moreover, taking unnaturally high doses of pure -carotene is inadvisable because the general carotenoid status of circulating lipoproteins may be upset, with potentially dangerous consequences. Michael J Fryer Department of Biology, John Tabor Laboratories, University of Essex, Colchester, Essex CO4 3SQ, UK (e-mail: [email protected]) 1
Halliwell B. The antioxidant paradox. Lancet 2000; 355: 1179–80.
166
2 3
4
Rowe PM. -carotene takes a collective beating. Lancet 1996; 347: 249. Burton GW, Ingold KU. -carotene: an unusual type of lipid antioxidant. Science 1984; 224: 569–73. Schalch W. Carotenoids in the retina. In: Emerit I, Chance B, eds. Free radicals and ageing. Basel: Birkhauser Verlag, 1992: 280–98.
Combating medical errors Sir—We read with concern Richard Cook’s comments on the Institute of Medicine’s (IOM) report on quality “To err is human”,1 reported by Norra MacReady in her March 18 news feature.2 Unlike Cook, we fully support the systems analysis approach to adverse event prevention proposed in the IOM report and believe the IOM report provides the foundations to improving patient care. The report provides practical advice in the area of improving medication safety which is in line with the suggestions of R E Ferner and J K Aronson in their commentary in the same issue of The Lancet.3 The basic principles expounded by the IOM about leadership, respect of human limits in process design, promoting effective team functioning, anticipating the unexpected, and creating a learning environment are the core of any successful and safe system. The report offers a comprehensive description of the nature, severity, and possible causes of the adverse events, and provides a detailed theoretical framework for analysing and managing these events. We consider the major limitation of the report to be in the area of implementation and change management. That is to say: have the theoretical principles been translated into practice? What obstacles will be faced and how can they be overcome? Do these changes actually improve patients’ safety? What is the impact of these changes on other aspects of the health system? Perhaps expecting answers to these questions is unfair. They key to successful programme implementation and change management often resides in an understandng of local issues and the provision of local solutions. Further, as far as we can tell, the information needed to answer these questions is, unfortunately, not yet available. Several disturbing statements are made by Cook. The assertion that “in the end safety is a dynamic quality created by people at the sharp end” is simply another way to apportion blame to an individual practitioner or sector rather than adopting a systems
approach. This takes us no closer to eradicating scapegoating, which most agree is fundamental to developing a systems approach. Cook’s suggestion to analyse “what it is that permits health-care practitioners to be successful so much of the time” is predicated on the belief that current practice is safe. There is little evidence to support this assumption and a great deal of work that indicates current practice is suboptimum and at times dangerous. Concentrating only on the systems that reflect successful and safe practice considerably limits our ability to understand and solve the existing problems. We would like to make an additional observation concerning the commentary by Ferner and Aronson dealing with medication. We suggest that their approach—favouring the introduction of technical changes “to improve the prescribing, dispensing, and giving of drugs, to remove some of the factors that impair performance, and to make thorough checks to detect errors before they cause harm”—is an example of an attempt to begin to formulate a systematic methodology. They, like those at the IOM, recommend mandatory reporting systems for errors, or where these are not in place the immediate establishment of voluntary schemes. This of course leaves many questions unresolved and these require extensive public discussion. As becomes evident from a brief perusal of the IOM report, the content of what ought to be mandatorily reported is far from clear, as is what information is to be public, anonymous, or made confidential through any future statutory scheme. Recommendations are made in general terms but a potential legislator would require far more detail. In conclusion, until we move away from the tendency to punish both in our legal frameworks and in our own minds, the IOM’s valuable insights and recommendations will be beyond our grasp, as will the improvement of quality. *Joseph Ibrahim, Jenny Majoor, Bebe Loff Health Services Management Program, Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Victoria 3004, Australia 1
2
3
Kohn L, Corrigan J, Donaldson M. To err is human: building a safer health system. Washington DC: Institute of Medicine, National Academy Press, 1999. MacReady N. Second stories, sharp ends: dissecting medical errors. Lancet 2000; 355: 994. Ferner RE, Aronson JK. Medication errors, worse than a crime. Lancet 2000; 355: 947–48.
THE LANCET • Vol 356 • July 8, 2000
For personal use only. Not to be reproduced without permission of The Lancet.
However, that should not be confused with the standard by which therapeutics are assessed for IBS or any other disease state. We did collect quality of life data in this and its companion study using IBSQoL, a validated disease specific instrument,3 and benefit was seen. Allen W Mangel Gastroenterology, Glaxo Wellcome, Research Triangle Park, NC 27709, USA 1
2
3
Mangel A, Camilleri M, Chey W, et al. Alosetron, a 5HT3 receptor antagonist, in the treatment of non-constipated female IBS patient. Am J Gastroenterol 1999; 94: 2677 (abstr). Jones R, Holtmann G, Rodrigo L, et al. Alosetron relieves pain and improves bowel function compared with mebeverine in female nonconstipated irritable bowel syndrome patients. Aliment Pharmacol Ther 1999; 13: 1419–27. Hahn BA, Kirchdoerfer LJ, Fullerton S, et al. Evaluation of a new quality of life questionnaire for patients with irritable bowel syndrome. Aliment Pharmacol Ther 1997; 11: 547–52.
Still life in oxidation hypothesis of atherogenesis Sir—In his provocative and timely viewpoint, Barry Halliwell (April 1, p 1179)1 draws attention to the paradox of the growing experimental evidence linking the oxidative modification of LDL to atherogenesis and the generally disappointing outcome of trials of antioxidants in the prevention of coronary heart disease (CHD). He suggests that one explanation might be that the antioxidants administered may not have altered antioxidant status in the desired direction. We have reported that even high doses of antioxidants, although delaying the early phase of LDL oxidation in which conjugated dienes are formed, failed to influence the subsequent formation of lipid peroxides.2 It is the breakdown of lipid peroxides that leads to the atherogenic modification of LDL. Furthermore, we have found that supplementation with vitamin E, like the synthetic antioxidant probucol, increases the transfer of cholesteryl ester between This might be lipoproteins.3 counterproductive in the prevention of atheroma, because it may, for example, increase the formation of small, dense LDL, which is more susceptible to oxidation. HDL, unlike physical antioxidants, protects against the accumulation of lipid peroxides on LDL over several hours by a mechanism, which is unaffected by oral supplementation with physical antioxidants, such as
THE LANCET • Vol 356 • July 8, 2000
vitamins and selenium.2 This effect seems to be the result of the enzyme, paraoxonase (PON1) located on HDL.4 Thus, one consequence of the poor results of antioxidant trials should not be the rejection of the oxidation hypothesis of atherogenesis, but rather that greater attention should be paid to other antioxidant mechanisms, such as PON1. Serum PON1 activity is profoundly decreased in CHD.5 It may be possible to devise dietary or pharmacological interventions to increase PON1 activity, which could lead to the true test of the oxidant hypothesis in clinical trials. *P N Durrington, M I Mackness Department of Medicine, Manchester Royal Infirmary, Manchester M13 9WL, UK 1 2
3
4
5
Halliwell B. The antioxidant paradox. Lancet 2000; 355: 1179–80. Mackness MI, Abbott CA, Arrol S, Durrington PN. The role of high density lipoprotein and lipid-soluble antioxidant vitamins in inhibiting low-density lipoprotein oxidation. Biochem J 1993; 294: 829–35. Arrol S, Mackness MI, Durrington PN. Vitamin E supplementation increases the resistance of both LDL and HDL to oxidation and increases cholesteryl ester transfer activity. Atherosclerosis (in press). Mackness MI, Mackness B, Durrington PN, et al. Paraoxonase and coronary heart disease. Cur Opin Lipidol 1998; 9: 319–24. Ayub A, Mackness MI, Arrol S, Mackness B, Patel J, Durrington PN. Serum paraoxonase after myocardial infarction. Arterioscler Thromb Vasc Biol 1999; 19: 330–35.
Sir—Barry Halliwell1 addresses the questions for the selection of patients suitable for treatment with antioxidants according to their antioxidant status, and how to follow up the effect of antioxidant therapy. We agree with him that these topics are crucial in designing future studies of antioxidants. One of the main purposes of antioxidant therapy is to reduce arterial-wall inflammation induced by oxidative stress. Measuring the markers of inflammation could be used as surrogate endpoints of antioxidant therapy. Emerging data show that soluble fractions of cellular adhesion molecules (CAM) and C-reactive protein (CRP) could be useful in this respect.2 Increased oxidative stress and induction of redox-sensitive genes by activating nuclear factor B is a common final pathway of action of the classic risk factors: hypercholesterolaemia, hypertension, smoking, and diabetes. The induction of these genes is followed by increased arterial wall inflammation and increased expression of CAM by endothelial cells.3 These changes promote interaction by circulating monocytes with endo-
thelium, followed by migration in subendothelial space. It has been shown that CAM concentration correlates with the extent of carotid atherosclerosis and is a good predictor of further ischaemic events.4 Existing data on the effect of antioxidants on concentration of CAM are spare and controversial. Another very important question raised by Halliwell is that in some invivo circumstances, and depending on the dose of antioxidants, antioxidants could be damaging. Our own unpublished data show that the use of moderate doses of combinations of antioxidants with different modes of action (scavenging free radicals and suppressing formation of free radicals), reduces the concentration of soluble vascular cell adhesion molecule 1 and soluble intracellular cell adhesion molecule 1 in high-risk postmenopausal women. Use of a combination of antioxidants resembles much more the antioxidant-rich diet supplementation on which the positive data from epidemiological studies is based. The antioxidant hypothesis faces similar difficulties to the hypothesis of cardioprotective effects of hormonereplacement therapy. The encouraging data from mechanistic and observational studies are not confirmed in randomised controlled trials. Data from the Postmenopausal Estrogen/ Progestin Intervention (PEPI) trial show that all used hormone combinations increase the concentration of CRP in the first year, followed by decreased concentration of CAM later on in the follow-up.5 One of the suggested cardioprotective effects of hormone-replacement therapy, beyond a lipid-lowering effect, is the antioxidant activity. Measuring of CRP with highly specific tests could also provide information on the effects of antioxidants on vascular wall. The measurement of inflammatory markers in nested case-control studies in the cohort of the patients from large antioxidants trials like the Cambridge Heart Antioxidant Study (CHAOS), the Gruppo Italiano per lo Studio della Sopravvivenza nell’ Inforto (GISSI) Prevention Study, and the Heart Outcomes Prevention Evaluation (HOPE) study could provide interesting data as to who are the winners and who are the losers in antioxidant therapy. *A Goudev, D Georgiev, S Kuyrkchiev, V Ganev, I Kehayov Departments of *Biochemistry and Internal Medicine, Medical University, Sofia 1431, Bulgaria; Second Obstetric and Gynaecology Hospital, Sheinovo 19, Sofia; and Institute of Immunology, Bulgarian Academy of Science, Sofia (e-mail: [email protected])
165
For personal use only. Not to be reproduced without permission of The Lancet.
CORRESPONDENCE 1 2
3
4
5
Halliwell B. The antioxidant paradox. Lancet 2000; 355: 1179–80. Libby P, Ridker P. Novel inflammatory markers of coronary risk. Theory versus practice. Circulation 1999; 100: 1148–50. Liao F, Andalibi A, Qiao JH, et al. Genetic evidence for a common pathway mediating oxidative stress, inflammatory gene induction and aortic fatty streak formation in mice. J Clin Invest 1994; 94: 877–84. Hwang S, Ballantyne C, Sharrett AR, et al. Circulating adhesion molecules VCAM-1, ICAM-1 and E-selectin in carotid atherosclerosis and incident coronary heart disease cases. The Atherosclerosis Risk in Communities (ARIC) Study. Circulation 1997; 96: 4219–25. Ridker P, Hennekens C, Rifai N, Buring J, Manson J. Hormone replacement therapy and increased plasma concentration of C-reactive protein. Circulation 1999; 100: 713–16.
Sir—Barry Halliwell1 draws attention to a valid point on the apparent lack of effectiveness and possibly harmful effects of -carotene supplements, something that seems to have been missed in most studies. Although diets rich in -carotene protect against cancer development, carotene is not the protective agent.2 It may well be a good indicator of general carotenoid consumption, but it is not necessarily the most appropriate carotenoid with respect to antioxidant properties. The unusual behaviour of -carotene in membranes was noted as long ago as 1984 by Burton and Ingold3 who concluded that “-carotene is not a conventional antioxidant” and at high oxygen partial pressures it may even act as a pro-oxidant. Analysis of plant material always reveals the presence of six carotenoids, of which -carotene is usually the most abundant. The remaining five compounds are present at much lower concentrations but they are by no means any less important. For example, two of these dietary components (zeaxanthin and lutein) are thought to be essential for the wellbeing of the retina.4 Diets that are high in -carotene will also contain much lower concentrations of these rare carotenoids and supplements of pure -carotene alone cannot be expected to reproduce the same effects as a balanced intake provided by a diet rich in fruit and vegetables. Moreover, taking unnaturally high doses of pure -carotene is inadvisable because the general carotenoid status of circulating lipoproteins may be upset, with potentially dangerous consequences. Michael J Fryer Department of Biology, John Tabor Laboratories, University of Essex, Colchester, Essex CO4 3SQ, UK (e-mail: [email protected]) 1
Halliwell B. The antioxidant paradox. Lancet 2000; 355: 1179–80.
166
2 3
4
Rowe PM. -carotene takes a collective beating. Lancet 1996; 347: 249. Burton GW, Ingold KU. -carotene: an unusual type of lipid antioxidant. Science 1984; 224: 569–73. Schalch W. Carotenoids in the retina. In: Emerit I, Chance B, eds. Free radicals and ageing. Basel: Birkhauser Verlag, 1992: 280–98.
Combating medical errors Sir—We read with concern Richard Cook’s comments on the Institute of Medicine’s (IOM) report on quality “To err is human”,1 reported by Norra MacReady in her March 18 news feature.2 Unlike Cook, we fully support the systems analysis approach to adverse event prevention proposed in the IOM report and believe the IOM report provides the foundations to improving patient care. The report provides practical advice in the area of improving medication safety which is in line with the suggestions of R E Ferner and J K Aronson in their commentary in the same issue of The Lancet.3 The basic principles expounded by the IOM about leadership, respect of human limits in process design, promoting effective team functioning, anticipating the unexpected, and creating a learning environment are the core of any successful and safe system. The report offers a comprehensive description of the nature, severity, and possible causes of the adverse events, and provides a detailed theoretical framework for analysing and managing these events. We consider the major limitation of the report to be in the area of implementation and change management. That is to say: have the theoretical principles been translated into practice? What obstacles will be faced and how can they be overcome? Do these changes actually improve patients’ safety? What is the impact of these changes on other aspects of the health system? Perhaps expecting answers to these questions is unfair. They key to successful programme implementation and change management often resides in an understandng of local issues and the provision of local solutions. Further, as far as we can tell, the information needed to answer these questions is, unfortunately, not yet available. Several disturbing statements are made by Cook. The assertion that “in the end safety is a dynamic quality created by people at the sharp end” is simply another way to apportion blame to an individual practitioner or sector rather than adopting a systems
approach. This takes us no closer to eradicating scapegoating, which most agree is fundamental to developing a systems approach. Cook’s suggestion to analyse “what it is that permits health-care practitioners to be successful so much of the time” is predicated on the belief that current practice is safe. There is little evidence to support this assumption and a great deal of work that indicates current practice is suboptimum and at times dangerous. Concentrating only on the systems that reflect successful and safe practice considerably limits our ability to understand and solve the existing problems. We would like to make an additional observation concerning the commentary by Ferner and Aronson dealing with medication. We suggest that their approach—favouring the introduction of technical changes “to improve the prescribing, dispensing, and giving of drugs, to remove some of the factors that impair performance, and to make thorough checks to detect errors before they cause harm”—is an example of an attempt to begin to formulate a systematic methodology. They, like those at the IOM, recommend mandatory reporting systems for errors, or where these are not in place the immediate establishment of voluntary schemes. This of course leaves many questions unresolved and these require extensive public discussion. As becomes evident from a brief perusal of the IOM report, the content of what ought to be mandatorily reported is far from clear, as is what information is to be public, anonymous, or made confidential through any future statutory scheme. Recommendations are made in general terms but a potential legislator would require far more detail. In conclusion, until we move away from the tendency to punish both in our legal frameworks and in our own minds, the IOM’s valuable insights and recommendations will be beyond our grasp, as will the improvement of quality. *Joseph Ibrahim, Jenny Majoor, Bebe Loff Health Services Management Program, Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Victoria 3004, Australia 1
2
3
Kohn L, Corrigan J, Donaldson M. To err is human: building a safer health system. Washington DC: Institute of Medicine, National Academy Press, 1999. MacReady N. Second stories, sharp ends: dissecting medical errors. Lancet 2000; 355: 994. Ferner RE, Aronson JK. Medication errors, worse than a crime. Lancet 2000; 355: 947–48.
THE LANCET • Vol 356 • July 8, 2000
For personal use only. Not to be reproduced without permission of The Lancet.