- Email: [email protected]
On dinosaurs and medical textbooks
the former times to an Patients now insist on emphasis on their rights either to refuse a new treatment, or to withdraw from an existing treatment, if they do not believe that it affords them an acceptable quality of life. After cardiac disease, dialysis withdrawal is the second most frequent single cause of death among dialysis patients in the USA (17%)1,2 and Canada (14%).3 Among those 75 years or older, the frequency is even higher. A similar percentage (13%) has been reported by the Australian/New Zealand Registry.4 In Europe, deaths due to withdrawal from dialysis are rare, and this cause of death is not even listed in recent reports. This striking difference may be due to patient selection, to cultural or religious differences, or to reporting patterns. There needs to be agreement on definitions and guidelines to a standardised approach if we are going to understand the wide variation in reporting of deaths due to withdrawal. Major risk factors for withdrawal are the presence of
paternalism of patient autonomy.
from the medical
pre-existing comorbid diseases-eg, cancer, cachexia, atherosclerotic heart disease, peripheral vascular disease, and chronic obstructive pulmonary disease and an overall dissatisfaction with quality of life. Withdrawal is higher among whites, elderly people, and diabetics. There is no significant difference in incidence between the sexes or between the two main methods of dialysis modalities (haemodialysis, chronic ambulatory peritoneal dialysis).5,6 Nephrologists believe that they are adequately prepared to make decisions about withdrawing or withholding of treatment.7 However, it would help the patient and other health-care professionals if, before reaching a decision on this matter, nephrologists would consult with nurses, the social worker, the chaplain, and the psychiatrist-all of whom may provide an insight into the reasons behind the patient’s decision to refuse further treatment and can support the patient once he or she had made the decision for withdrawal. Whilst nephrologists agree that they should honour a competent patient’s request or an incompetent patient’s clearly expressed prior wishes,8 they do not agree on discontinuing dialysis in patients who become demented. Thus, in this circumstance, 32% of nephrologists would stop dialysis but 68% would continue it.This difference may reflect the surprising finding that most patients would not contemplate discontinuation of dialysis in the event that they developed dementia;9 probably they fear that their physician may misuse such a power over them either for their own or for society’s benefit. Competent patients who decide to withdraw from dialysis should be assured that they will not be abandoned but will continue to be cared for. Such care includes not only good intentions and kindness but also a palliative care plan that provides for psychological, philosophical, religious, and physical support to alleviate suffering and enhance the last days of life. 10 In this respect, I emphasise the liberal use of narcotics to alleviate pain, even at the risk of accelerating death. In a recent prospective study, Cohen et al" assessed the quality of dying in 11 patients in whom dialysis was discontinued and found it "good" in 7 and "poor" in 4. This observation indicates that, to improve the quality of dying in all, we should be prepared to consult and learn from our colleagues in palliative care more often than we do presently. Such consultation is relatively easy in
4
we should strive to do better for those who die at home. The important factor overall is that we should recognise when dialysis changes from being a measure that prolongs life to one that merely prolongs dying. At that point, we should help patients and their families accept the futility of further treatment and make the dying process as painless, peaceful, and dignified as possible.12
patients dying in hospital;
D G
Oreopoulos
Division of
Nephrology,
The Toronto
Hospital (Western Division),
Toronto, Ontario, Canada 1
2 3
4 5
Renal replacement therapy in the United States: data from the United States Renal Data. Am J Kidney Dis 1995; 25: 119-33. USRDS 1995 Annual Data Report. Bethesda, MD: USRDS, 1995: 87. Canadian Organ Replacement Register Report. Don Mills, Ontario: The Kidney Foundation of Canada, 1993. Disney APS, ed. ANZDATA report. Woodville, South Australia: Australian and New Zealand Dialysis and Transplant Registry, 1994. Nelson CG, Port FK, Wolf RA, Guire KE. The association of diabetic status, age and race to withdrawal from dialysis. J Am Soc Nephrol
Agodoa LY, Eggers PW.
1994; 4: 1608-14.
Kjellstrand C. Stopping dialysis: different views. In: Oreopoulos DG, Michelis MF, Herschorn S, eds. Nephrology and urology in the aged patient. Dordrecht: Kluwer, 1993: 563-68. 7 Moss AH, Stockings CB, Sachs GA, Siegler M. Variation in the attitudes of dialysis unit medical directors towards decisions to withhold and withdraw dialysis. JAm Soc Nephrol 1993; 4: 229-34. 8 Singer PA. Nephrologists’ experience with an attitudes towards decisions to foregoing dialysis. J Am Soc Nephrol 1992; 2: 1235-40. 9 Cohen L, Germain M, Woods A, Gilman ED, McCul JD. Patient attitudes and psychological considerations in dialysis discontinuation. Psychosomatics 1993; 34: 395-401. 10 Schneiderman LJ, Faber-Langendoen K, Jecker NS. Beyond futility to an ethic of care. Am J Med 1994; 96: 110-14. 11 Cohen LM, McCul JD, German M, Kjellstrand CM. Dialysis discontinuation: a good death? Arch Intern Med 1995; 155: 42-47. 12 Oreopoulos DG. Is there time to say no to life? Perit Dial Int 1994; 14: 6
205-08.
On dinosaurs and medical textbooks Almost all species in the past failed. If they died out gradually quietly and if they deserved to die because of some inferiority, our good feelings about earth can remain intact. But if they die violently and without having done anything wrong, then our planet may not be such a safe place.-David M Raup, 1991
and then
The embers of the age-old argument about educational value, or lack of it, of textbooks have been rekindled recently. In a robust presentation to a House of Lords Select Committee, Chalmers suggested that many patients lose their lives because doctors rely on information obtained from outdated texts and clinical teaching based on archaic practice.’ He chose to illustrate his point with the statement in the last edition of the Oxford Textbook of Medicine (OTM) that thrombolytic drugs were still of unproven value and safely in the treatment of myocardial infarction.2 Not surprisingly, this criticism gave food for thought to the media-and to us, the editors of the OTM. Chalmers is not the first to express such views on the value of medical textbooks. In reviewing Price’s Textbook of Medicine, a close ancestor of the OTM, the late Prof Tony Mitchell suggested that textbooks were likely to suffer the same fate as dinosaurs in that their very weight would preclude their survival. He pointed out that they are all usually out of date before they are published, and
well as being a health hazard because of their of limited educational value to their readers. weight, The story of the time-lag between the apparent demonstration of the benefit of thrombolytic agents and their widespread use in clinical practice is an interesting example of the difficulties that face editors of textbooks and doctors at large. The second edition of the OTM was written in the mid-1980s and published in 1987. In 1985, a systematic review concluded that, taken several small randomised controlled trials suggested that fibrinolytic therapy reduced the risk of premature death after myocardial infarctionafinding that was confirmed by a large trial published in 1986.4 Despite these results critical reviews in leading medical journals at that time remained cautious about the role of fibrinolytics .5-7 After discussing all the evidence, a Lancet editoriaF concluded "It would be inappropriate for streptokinase immediately to become routine treatment for patients with suspected myocardial infarction. The results so far apply only to the initial 21 days after myocardial infarction. A similar benefit shown in the Western Washington Study of intracoronary streptokinase had disappeared when treated and control groups were compared after a year. It is a good principle never to base clinical practice on a single clinical trial; there have been many claims for a reduction of 20% in the fatality rate from acute myocardial infarction for a variety of other agents that have ultimately not been accepted into routine practice." In the event, thrombolysis was not widely recommended until the late 1980s, and only after the publication of the results of a megatrial.8 While this approach to new therapy, reflected in the advice given in the 1987 edition of the OTM, might seem overcautious, recent experiences in the case of magnesium for the treatment of myocardial infarction suggest that it is not entirely misplaced. A meta-analysis carried out in 1993 concluded that magnesium treatment is an "effective, safe, simple, and inexpensive innovation that should be introduced into clinical practice without delay."9 Yet the results of a megatrial published only 2 years later indicate that magnesium has little or no role in the treatment of myocardial infarction.10 In view of the complexities and paucity of evidencebased medicine, what are authors of textbooks to do in this rapidly changing scene? Are textbooks of any value at all? We think that they are. Medical practice is becoming increasingly specialised, complex, and global in scope. No student or practitioner can own a library of monographs and journals that covers the whole of internal medicine, so medical textbooks still have an important part to play in providing a sound basic account of the many disorders that comprise medical practice. Textbook accounts of common and rare disorders provide students and doctors with a "way in" to the published work on the bulk of diseases that they are likely to encounter. But in their approach to therapy textbooks must remain extremely cautious; the recent experiences with magnesium and myocardial infarction emphasise the uncertainties of some of our current analytical approaches,"’" and underline the importance of evidence from large trials and the value of allowing time to elapse to obtain wide experience of new treatments. Yet however thoroughly their evidence is researched at the time of publication, textbooks can only be used as the backbone to an understanding of disease; hence
as
are
together,
must always be augmented by journals and other aids to keeping up with medical advances. It has been argued that dinosaurs did not die out but simply evolved wings and took off; all of the 8600 species of birds living today carry some vestig es of their reptilian ancestors. 14 No doubt with the advent of CD-ROM and continual updating systems12 "textbooks" will look very different in 50 years time. We hope that, like the birds, they will still carry the evolutionary remnants of the best of their forebears-a thorough description of the protean manifestations of disease backed up by advice on diagnosis and management based on reliable evidence that has had time to be evaluated in day-to-day practice.
they
DJ
Weatherall, J G G Ledingham, D A Warrell
Institute of Molecular Medicine and Nuffeld Department of Clinical Medicine, John Radcliffe Hospital, Oxford, UK House of Lords Select Committee of Science and Technology. SubCommittee I: Medical Research and the NHS Reforms. London: HM Stationery Office 1995. Pentecost BL. Myocazrdial infarction. In: Weatherall DJ, Ledingham JGG, Wzrtrell DA, eds. Oxford textbook of medicine, 2nd ed.. Oxford: Oxford University Press, 1987: 13: 167-82. Yusuf S, Collins R, Peto E, et al. Intravenous and intracoronary fibrinolytic therapy in acute myocardial infarction: overview of results on mortality, reinfarction and side effects from 33 randomised controlled trials. Eur Heart J 1985; 6: 556-85. Gruppo Italiano per lo Studio della St reptochinasi nell’Infarto Miocardico (GISSI). Effectiveness of intravenous thrombolytic treatment in acute myocardial infarction. Lancet 1986; i: 397-402. Kennedy JW, Ritchie JL, Davis KB, et al. The western Washington randomised trial of intracoronary streptokinase in acute myocardial infarction. N Engl J Med 1985; 312: 1073-78. Mitchell JRA. Back to the future: so what will fibrinolytic therap[y offer your patients with myocardial infarction? BMJ 1986; 292:
1
2
3
4
5
6
973-78. 7 8
9
10
11 12
13 14
Editorial. Streptokinase in acute myocardial infarction. Lancet 1986; i: 421-22. ISIS-2 Collaborative Group. Randomised trial of intravenous streptokinase, oral aspirin, both, or neither, among 17 189 cases of suspected acute myocardial infarction: ISIS-2 Lancet 1988; ii: 349-60. Yusuf S, Koon T, Woods K. Intravenous magnesium in acute myocardial infarction. An effective, safe, simple and inexpensive intervention. Circulation 1993; 87: 2043-46. ISIS-4 Collaborative Group. ISIS-4: a randomised factorial trial assessing early oral captopril, oral mononitrate, and intravenous magnesium in 58 050 patients with suspected acute myocardial infarction. Lancet 1995; 345: 669-85. Egger M, Davey Smith G. Misleading meta-analysis. BMJ 1995; 310: 752-54. Chalmers I, Haynes B. Reporting, updating, and correcting systematic reviews of the effects of health care. BMJ 1994; 309: 862-65. Charlton BG. Mega-trials: methodological issues and clinical implications. J R Coll Physicians Lond 1995; 29: 96-100. Raup DM. Extinctions: bad genes or bad luck? New York: W W Norton, 1991.
Cultural shift in
Italy’s drug policy
beginning of 1994 there was a "cultural shift" in drug policy as a result of a law aimed at rationalising drug classification and reimbursement by the National Health Service (NHS). With the populace reeling in shock at the revelations of widespread corruption surrounding drug registration, indications, and pricing, the pressure of public opinion was overwhelming and the changes brought about by the new law were wideranging and swift. One year later it is a good time to take
At the Italian
stock. The Committee for Drugs (CUF-Comitato Unico per il Farmaco), in accordance with the law, set about
5
paternalism of patient autonomy.
from the medical
pre-existing comorbid diseases-eg, cancer, cachexia, atherosclerotic heart disease, peripheral vascular disease, and chronic obstructive pulmonary disease and an overall dissatisfaction with quality of life. Withdrawal is higher among whites, elderly people, and diabetics. There is no significant difference in incidence between the sexes or between the two main methods of dialysis modalities (haemodialysis, chronic ambulatory peritoneal dialysis).5,6 Nephrologists believe that they are adequately prepared to make decisions about withdrawing or withholding of treatment.7 However, it would help the patient and other health-care professionals if, before reaching a decision on this matter, nephrologists would consult with nurses, the social worker, the chaplain, and the psychiatrist-all of whom may provide an insight into the reasons behind the patient’s decision to refuse further treatment and can support the patient once he or she had made the decision for withdrawal. Whilst nephrologists agree that they should honour a competent patient’s request or an incompetent patient’s clearly expressed prior wishes,8 they do not agree on discontinuing dialysis in patients who become demented. Thus, in this circumstance, 32% of nephrologists would stop dialysis but 68% would continue it.This difference may reflect the surprising finding that most patients would not contemplate discontinuation of dialysis in the event that they developed dementia;9 probably they fear that their physician may misuse such a power over them either for their own or for society’s benefit. Competent patients who decide to withdraw from dialysis should be assured that they will not be abandoned but will continue to be cared for. Such care includes not only good intentions and kindness but also a palliative care plan that provides for psychological, philosophical, religious, and physical support to alleviate suffering and enhance the last days of life. 10 In this respect, I emphasise the liberal use of narcotics to alleviate pain, even at the risk of accelerating death. In a recent prospective study, Cohen et al" assessed the quality of dying in 11 patients in whom dialysis was discontinued and found it "good" in 7 and "poor" in 4. This observation indicates that, to improve the quality of dying in all, we should be prepared to consult and learn from our colleagues in palliative care more often than we do presently. Such consultation is relatively easy in
4
we should strive to do better for those who die at home. The important factor overall is that we should recognise when dialysis changes from being a measure that prolongs life to one that merely prolongs dying. At that point, we should help patients and their families accept the futility of further treatment and make the dying process as painless, peaceful, and dignified as possible.12
patients dying in hospital;
D G
Oreopoulos
Division of
Nephrology,
The Toronto
Hospital (Western Division),
Toronto, Ontario, Canada 1
2 3
4 5
Renal replacement therapy in the United States: data from the United States Renal Data. Am J Kidney Dis 1995; 25: 119-33. USRDS 1995 Annual Data Report. Bethesda, MD: USRDS, 1995: 87. Canadian Organ Replacement Register Report. Don Mills, Ontario: The Kidney Foundation of Canada, 1993. Disney APS, ed. ANZDATA report. Woodville, South Australia: Australian and New Zealand Dialysis and Transplant Registry, 1994. Nelson CG, Port FK, Wolf RA, Guire KE. The association of diabetic status, age and race to withdrawal from dialysis. J Am Soc Nephrol
Agodoa LY, Eggers PW.
1994; 4: 1608-14.
Kjellstrand C. Stopping dialysis: different views. In: Oreopoulos DG, Michelis MF, Herschorn S, eds. Nephrology and urology in the aged patient. Dordrecht: Kluwer, 1993: 563-68. 7 Moss AH, Stockings CB, Sachs GA, Siegler M. Variation in the attitudes of dialysis unit medical directors towards decisions to withhold and withdraw dialysis. JAm Soc Nephrol 1993; 4: 229-34. 8 Singer PA. Nephrologists’ experience with an attitudes towards decisions to foregoing dialysis. J Am Soc Nephrol 1992; 2: 1235-40. 9 Cohen L, Germain M, Woods A, Gilman ED, McCul JD. Patient attitudes and psychological considerations in dialysis discontinuation. Psychosomatics 1993; 34: 395-401. 10 Schneiderman LJ, Faber-Langendoen K, Jecker NS. Beyond futility to an ethic of care. Am J Med 1994; 96: 110-14. 11 Cohen LM, McCul JD, German M, Kjellstrand CM. Dialysis discontinuation: a good death? Arch Intern Med 1995; 155: 42-47. 12 Oreopoulos DG. Is there time to say no to life? Perit Dial Int 1994; 14: 6
205-08.
On dinosaurs and medical textbooks Almost all species in the past failed. If they died out gradually quietly and if they deserved to die because of some inferiority, our good feelings about earth can remain intact. But if they die violently and without having done anything wrong, then our planet may not be such a safe place.-David M Raup, 1991
and then
The embers of the age-old argument about educational value, or lack of it, of textbooks have been rekindled recently. In a robust presentation to a House of Lords Select Committee, Chalmers suggested that many patients lose their lives because doctors rely on information obtained from outdated texts and clinical teaching based on archaic practice.’ He chose to illustrate his point with the statement in the last edition of the Oxford Textbook of Medicine (OTM) that thrombolytic drugs were still of unproven value and safely in the treatment of myocardial infarction.2 Not surprisingly, this criticism gave food for thought to the media-and to us, the editors of the OTM. Chalmers is not the first to express such views on the value of medical textbooks. In reviewing Price’s Textbook of Medicine, a close ancestor of the OTM, the late Prof Tony Mitchell suggested that textbooks were likely to suffer the same fate as dinosaurs in that their very weight would preclude their survival. He pointed out that they are all usually out of date before they are published, and
well as being a health hazard because of their of limited educational value to their readers. weight, The story of the time-lag between the apparent demonstration of the benefit of thrombolytic agents and their widespread use in clinical practice is an interesting example of the difficulties that face editors of textbooks and doctors at large. The second edition of the OTM was written in the mid-1980s and published in 1987. In 1985, a systematic review concluded that, taken several small randomised controlled trials suggested that fibrinolytic therapy reduced the risk of premature death after myocardial infarctionafinding that was confirmed by a large trial published in 1986.4 Despite these results critical reviews in leading medical journals at that time remained cautious about the role of fibrinolytics .5-7 After discussing all the evidence, a Lancet editoriaF concluded "It would be inappropriate for streptokinase immediately to become routine treatment for patients with suspected myocardial infarction. The results so far apply only to the initial 21 days after myocardial infarction. A similar benefit shown in the Western Washington Study of intracoronary streptokinase had disappeared when treated and control groups were compared after a year. It is a good principle never to base clinical practice on a single clinical trial; there have been many claims for a reduction of 20% in the fatality rate from acute myocardial infarction for a variety of other agents that have ultimately not been accepted into routine practice." In the event, thrombolysis was not widely recommended until the late 1980s, and only after the publication of the results of a megatrial.8 While this approach to new therapy, reflected in the advice given in the 1987 edition of the OTM, might seem overcautious, recent experiences in the case of magnesium for the treatment of myocardial infarction suggest that it is not entirely misplaced. A meta-analysis carried out in 1993 concluded that magnesium treatment is an "effective, safe, simple, and inexpensive innovation that should be introduced into clinical practice without delay."9 Yet the results of a megatrial published only 2 years later indicate that magnesium has little or no role in the treatment of myocardial infarction.10 In view of the complexities and paucity of evidencebased medicine, what are authors of textbooks to do in this rapidly changing scene? Are textbooks of any value at all? We think that they are. Medical practice is becoming increasingly specialised, complex, and global in scope. No student or practitioner can own a library of monographs and journals that covers the whole of internal medicine, so medical textbooks still have an important part to play in providing a sound basic account of the many disorders that comprise medical practice. Textbook accounts of common and rare disorders provide students and doctors with a "way in" to the published work on the bulk of diseases that they are likely to encounter. But in their approach to therapy textbooks must remain extremely cautious; the recent experiences with magnesium and myocardial infarction emphasise the uncertainties of some of our current analytical approaches,"’" and underline the importance of evidence from large trials and the value of allowing time to elapse to obtain wide experience of new treatments. Yet however thoroughly their evidence is researched at the time of publication, textbooks can only be used as the backbone to an understanding of disease; hence
as
are
together,
must always be augmented by journals and other aids to keeping up with medical advances. It has been argued that dinosaurs did not die out but simply evolved wings and took off; all of the 8600 species of birds living today carry some vestig es of their reptilian ancestors. 14 No doubt with the advent of CD-ROM and continual updating systems12 "textbooks" will look very different in 50 years time. We hope that, like the birds, they will still carry the evolutionary remnants of the best of their forebears-a thorough description of the protean manifestations of disease backed up by advice on diagnosis and management based on reliable evidence that has had time to be evaluated in day-to-day practice.
they
DJ
Weatherall, J G G Ledingham, D A Warrell
Institute of Molecular Medicine and Nuffeld Department of Clinical Medicine, John Radcliffe Hospital, Oxford, UK House of Lords Select Committee of Science and Technology. SubCommittee I: Medical Research and the NHS Reforms. London: HM Stationery Office 1995. Pentecost BL. Myocazrdial infarction. In: Weatherall DJ, Ledingham JGG, Wzrtrell DA, eds. Oxford textbook of medicine, 2nd ed.. Oxford: Oxford University Press, 1987: 13: 167-82. Yusuf S, Collins R, Peto E, et al. Intravenous and intracoronary fibrinolytic therapy in acute myocardial infarction: overview of results on mortality, reinfarction and side effects from 33 randomised controlled trials. Eur Heart J 1985; 6: 556-85. Gruppo Italiano per lo Studio della St reptochinasi nell’Infarto Miocardico (GISSI). Effectiveness of intravenous thrombolytic treatment in acute myocardial infarction. Lancet 1986; i: 397-402. Kennedy JW, Ritchie JL, Davis KB, et al. The western Washington randomised trial of intracoronary streptokinase in acute myocardial infarction. N Engl J Med 1985; 312: 1073-78. Mitchell JRA. Back to the future: so what will fibrinolytic therap[y offer your patients with myocardial infarction? BMJ 1986; 292:
1
2
3
4
5
6
973-78. 7 8
9
10
11 12
13 14
Editorial. Streptokinase in acute myocardial infarction. Lancet 1986; i: 421-22. ISIS-2 Collaborative Group. Randomised trial of intravenous streptokinase, oral aspirin, both, or neither, among 17 189 cases of suspected acute myocardial infarction: ISIS-2 Lancet 1988; ii: 349-60. Yusuf S, Koon T, Woods K. Intravenous magnesium in acute myocardial infarction. An effective, safe, simple and inexpensive intervention. Circulation 1993; 87: 2043-46. ISIS-4 Collaborative Group. ISIS-4: a randomised factorial trial assessing early oral captopril, oral mononitrate, and intravenous magnesium in 58 050 patients with suspected acute myocardial infarction. Lancet 1995; 345: 669-85. Egger M, Davey Smith G. Misleading meta-analysis. BMJ 1995; 310: 752-54. Chalmers I, Haynes B. Reporting, updating, and correcting systematic reviews of the effects of health care. BMJ 1994; 309: 862-65. Charlton BG. Mega-trials: methodological issues and clinical implications. J R Coll Physicians Lond 1995; 29: 96-100. Raup DM. Extinctions: bad genes or bad luck? New York: W W Norton, 1991.
Cultural shift in
Italy’s drug policy
beginning of 1994 there was a "cultural shift" in drug policy as a result of a law aimed at rationalising drug classification and reimbursement by the National Health Service (NHS). With the populace reeling in shock at the revelations of widespread corruption surrounding drug registration, indications, and pricing, the pressure of public opinion was overwhelming and the changes brought about by the new law were wideranging and swift. One year later it is a good time to take
At the Italian
stock. The Committee for Drugs (CUF-Comitato Unico per il Farmaco), in accordance with the law, set about
5