- Email: [email protected]
LESSONS IN THE SURGICAL TREATMENT OF EPILEPSY
366
damage? First, neurological damage sometimes
significantly associated
brain
outcome was
several risk factors.i5 However, the risk of permanent damage is probably only 0-2%.23 Second, there is a risk, probably greater after cardiac than after general surgery, of subtle intellectual impairment. Although such effects become more likely with increasing age and duration of surgery,2,4 there are apparently no absolute predictors for development. is There is much to be said for conducting bypass under alphastat acid-base control, with continuous online monitoring of arterial carbon dioxide tension, a membrane oxygenator, and an arterial line filter; but to exclude any or all of these aspects of technique is not negligent. Postoperative cerebral dysfunction deserves more thorough investigation after all types of surgery.
with neuropsychological the fall in haemoglobin concentration during the procedure. This latter variable was also associated with the development of retinal infarcts postoperatively. The lack of any association of the defect with any aspect of extracorporeal support seems surprising. The investigators were also unable to establish that use of a membrane-type oxygenator (in 66 % of patients) rather than a bubble oxygenator conferred any neuropsychological benefit. This result accords with preliminary data obtained by mechanical methods such as arterial line filtration16 and also with a flat sheet membrane vs a bubble-type oxygenator17 to reduce arterial microemboli. Although the quantities of particulate and probably gaseous microemboli delivered to the patient were significantly reduced, but not abolished, by these methods16,17 there was no dramatic improvement in neuropsychological outcome. Two years after CAS, Klonoff et ap8 reported an improvement in patients’ physical activity, personal satisfaction, and work ability, attributed to the success of the operation in relieving angina and preoperative anxiety; these researchers suggest that, overall, the anxiolytic action outweighs any neurological defect. Why has cerebral impairment after open-heart surgery not been the subject of a barrage of pharmacological interventions, especially as there is now considerable scope for such approaches?19,20 Use of antiaggregatory agents such as the prostacyclins has not been beneficial, probably because the desired action is unobtainable without severe hypotension." Nussmeyer and her colleagues reported that neuropsychological outcome was vastly improved if the patients were given thiopentone for cerebroprotection,z2 but the dose used (35 mg/kg) meant that all patients required postoperative catecholamines to support their arterial pressure and the profound sedation produced by such a dose imposed the need for prolonged ventilatory support (typically 24 hours). This latter effect brings its own dangers--eg, inadvertent disconnection leading to hypoxia. In addition, the need for prolonged intensive care would reduce the available beds and might lead to longer hospital stays and longer waiting lists. What do you says to your patient or close relative who requires cardiac surgery and is worried about 16. Treasure T. Intervennons to reduce cerebral injury during cardiac surgery-the effect of artenal line filtration. Perfusion 1989; 4: 147-52. 17. Smith PLC. Interventions to reduce cerebral injury during cardiac surgeryintroduction and the effect of oxygenator type. Perfusion 1989; 4: 139-45 18. Klonoff H, Clark C, Kavanagh-Gray D, Meigala H, Munro I. Two year follow up study of coronary bypass surgery. J Thorac Cardiovasc Surg 1989; 97: 78-85. 19. Weir DL, Jones JG. Cerebral ischaemia; pathophysiology and treatment. In. Kaufmann L, ed. Anaesthesia review 5. London: Churchill Livingstone, 1988: 131-44. 20 Royston D. Interventions to reduce cerebral injury during cardiac surgery-the effect of physical and pharmacological agents. Perfusion 1989; 4: 153-61. 21 Blauth C, Brady A, Arnold J, Schulenberg WE, Frackowiak R, Taylor KM A double blind clinical trial of Iloprost during cardiopulmonary bypass. Perfusion 1987; 2: 271-76. 22. Nussmeyer NA, Arlund C, Slogoff S Neuropsychological complications after cardiopulmonary bypass: cerebral protection with a barbiturate. Anesthesiology
1986; 64: 165-70.
occurs, for which there
are
LESSONS IN THE SURGICAL TREATMENT OF EPILEPSY A DYSEMBRYOPLASTIC neuroepithelial tumour has lately been described in a group of 39 patients from Paris and from Rochester, Minnesota, all of whom had medically intractable partial complex seizures with secondary generalisation in 6 patients (15%).1 Total or subtotal removal of these tumours led to complete freedom from seizures in 81 % of the 37 patients available for follow-up over a mean of 9 years and to improvement in the remainder. The patients had had seizures for 2-18 years. In most cases the tumour was in the frontal lobe (31 %) or in the temporal lobe (62%), and it was visible on a computerised tomographic (CT) scan in 91 % of the 22 patients who were examined. In the Paris group, the patients represented 75% of those undergoing epilepsy surgery between 1964 and 1983. This report should draw attention to certain guidelines for the surgical treatment of epilepsy. First, the principle that focal seizures suggest focal pathology is well illustrated by this group of patients. The original study of 471 epileptics by Gastaut showed that in only 11 % of patients with generalised seizures could a CT scan abnormality be demonstrated, compared with 63% of those with partial complex seizures.2 Similar findings have been described by Yang et al in children.3 Experience in the use of magnetic resonance imaging (MRI) for detection of such lesions is growing, and reports suggest that tumours may be shown by this technique when they are unrecognised or invisible by CT scanning.4 In specialist epilepsy centres the frequency of such lesions is probably 20-25%.5 Unfortunately, the Taggart DP, Reece IJ, Wheatley DJ. Cerebral deficit after elective cardiac surgery. Lancet 1987; i: 47. 1. Daumas-Duport C, Scheithauer BW, Chodkiewicz JP, Laws ER, Vedrenne C. Dysembryoplastic neuroepithelial tumor: a surgically curable tumor of young patients with intractable partial seizures. Neurosurgery 1988; 23: 545-56. 2. Gastaut H, Gastaut HL. Computerised transverse axial tomography in epilepsy Epilepsia 1976, 17: 325-36. 3 Yang PJ, Berger PE, Cohen ME, Duffner PK. Computed tomography and childhood seizure disorders. Neurology 1979; 29: 1084-88. 4. Sperling MR, Wilson G, Engel J, Babb TL, Phelps M, Bradley W. Magnetic resonance imaging in intractable partial epilepsy: correlative studies. Ann Neurol 1986; 20: 57-62 5. Adams CBT, Anslow OWP, Molyneux A, Oxbury J Radiological detection of surgically treatable lesions. In: Engel J, ed Surgical treatment of the epilepsies. New York: Raven, 1987: 213-33.
23.
367
provision of MRI facilities, or funding for access to them, is often inadequate. Treatment of drug-resistant epilepsy by surgery has been carried out for over a hundred years and there are about fifty centres
in the western world where such skills
are
available.
Morbidity, both physical and intellectual, and mortality are commendably low for these procedures. Mortality overall is now less than 1 % and for anterior temporal lobectomy is less than 0-5%. Likewise, overall morbidity is less than 5% and serious morbidity less than 2%.6 The results for seizure control are also good overall--even if we exclude hemispherectomy, which is better. Resective surgery renders 50% of patients seizure free. In patients with tumours such as those described above, or with other benign tumours, complete freedom from seizures is achieved in 70% or more.5,7,8 About 45% of patients with partial complex seizures are poorly controlled.9 If the Paris figures are representative, then at least 7-5% of them have a remediable lesion that can be demonstrated by non-invasive brain imaging.
INFORMING PATIENTS ABOUT CLINICAL DISAGREEMENT THE public are not generally aware of the extent of variation and disagreement in clinical practice. Patients may witness medical debate around the bedside and accept that their doctor may have to try several treatments to get the best result, but there is widespread belief that most clinical decisions are uniform and made with certainty. Many patients would therefore be surprised to fmd that, if admitted for elective surgery, their chances of having a preoperative chest radiograph could vary from 10 to 50% depending on the surgical unit;10 that general practitioners may vary four-fold in their decisions to refer patients with the same diagnosis to hospital;" and that age and sex standardised haemorrhoidectomy rates could be about five times higher in one district than another within the same regional health authority.12 Such variations in practice within small areas are more likely to be due to differences between doctors in diagnostic style and therapeutic beliefs than in supply and organisation of services. 13 In the USA, Brook and colleagues have been examining how clinical disagreement might explain geographical variations in the use of common medical procedures.14,15
6. Van Buren
J Complications of surgical procedures in the diagnosis and treatment of epilepsy. In Engel J, ed. Surgical treatment of the epilepsies. New York: Raven, 1987: 465-76.
Polkey CE. Neurosurgery. Chap 13. In: Laidlaw J, Richens A, Oxley J, eds. A textbook of epilepsy Edinburgh: Churchill-Livingstone, 1988 484-510. 8. Wieser HG ’Selective amygdalo-hippocampectomy’: indications, investigative technique and results. In: Symon L, ed. Advances and technical standards in neurosurgery. Vol 13. Vienna: Springer Verlag, 1986: 39-133. 9. Dreifuss FE. Goals of surgery for epilepsy. In: Engel J, ed. Surgical treatment of the epilepsies. New York: Raven, 1987: 31-50. 10. National Study by the Royal College of Radiologists. Preoperative chest radiology. Lancet 1979; ii 83-86. 11. Wilkin D, Smith A. Variation in general practitioners’ referrals to consultants. J R Coll 7.
Gen Pract 1987; 37: 350-53. 12 McPherson K, Wennberg JE, Hovind OB, Clifford P. Small area variations in the use of common surgical procedures: an international comparison of New England, England, and Norway. N Engl J Med 1982; 307: 1310-14. 13. Wennberg JE, Gittlesohn A. Variations in medical care among small areas. Sci Am 1982, 246: 120-34. 14 Park RE, Fink A, Brook RH, et al Physician ratings of appropnate indications for six medical and surgical procedures Am J Publ Health 1986; 76: 766-72. 15 Chassin MR, Kosecoff J, Park RE, et al. Does inappropnate use explain geographic variations in the use of health services? A study of three procedures JAMA 1987; 258: 2533-37.
They found considerable dissent among clinical experts on the indications for coronary
angiography, coronary artery bypass graft surgery (CABG), cholecystectomy, upper gastrointestinal endoscopy, colonoscopy, and carotid endarterectomy.14 There was even more discord on the indications for coronary angiography and CABG among a panel of doctors in the UK.’6 Moreover, in a survey of several thousand patients who had had at least one of these procedures, Chassin et al found that many of the indications were those open to considerable disagreement. 15 So, this work confirms previous suspicions-whether patients have major diagnostic and therapeutic procedures often depends on whom they consult. Brook’s group have lately suggested that when a doctor plans a procedure under circumstances without firm scientific justification, then the patient has a right to know that other doctors might disagree.l’ Informing patients about clinical variability and disagreement may become more relevant in the UK because Working for Patients18 implies that substantial differences may be created in clinical practice. Thus, self-governing hospitals will be able to provide some services and not others, thereby creating discrepancies in supply locally. General practice budgets will encourage doctors to consider more carefully the financial implications of their decisions, so introducing another element into the decision-making process and promoting greater discord. At the same time, patients are to be encouraged to shop around to register with the doctor who best suits their needs. We hope that doctors will provide more information about the services on offer—eg, well-women clinics and blood pressure screening. But to what extent should doctors inform patients that they carry out certain procedures and others do not? When a surgeon is advocating cholecystectomy for symptomless gallstones, should the patient be told that another surgeon in the same hospital probably would not operate under the circumstances? Greater participation by patients in clinical decisionmaking is laudable in many respects; involvement of patients in mapping out their own destiny with less abrogation of this task to the medical profession must surely encourage greater self-responsibility for health. And people should know about the risks and benefits of medical procedures to which they might be subjected. However, there are limitations in providing such information. Disagreement is so rife throughout medicine that explanations to patients may be time consuming and in many cases complex and confusing. Randomised controlled trials have multiplied, but "firm scientific" evidence often remains inconclusive. It is often impossible to discuss the nuances of the evidence, and emphasising controversy may instil unnecessary alarm. Members of the general public usually seek medical care because they recognise the knowledge and skill of doctors. On the whole, patients trust doctors’ judgments. The extent to which patients are involved in clinical decisions should obviously depend on medical circumstances and on the patient’s desires and capabilities. To inform someone about clinical disagreement when he is not in a position to make a rational choice seems same
foolhardy. RH, Kosecoff JB, Park RE, et al. Diagnosis and treatment of coronary disease: comparison of doctors’ attitudes in the USA and the UK. Lancet 1988; i: 750-53. 17. Park RE, Fink A, Brook RH, et al. Physician ratings of appropriate indications for three procedures: theoretical indications vs indications used in practice. Am J Publ Health 1989; 79: 445-47. 18 Working for Patients (Cm 555). London: HM Stationery Office, 1989. 16. Brook
damage? First, neurological damage sometimes
significantly associated
brain
outcome was
several risk factors.i5 However, the risk of permanent damage is probably only 0-2%.23 Second, there is a risk, probably greater after cardiac than after general surgery, of subtle intellectual impairment. Although such effects become more likely with increasing age and duration of surgery,2,4 there are apparently no absolute predictors for development. is There is much to be said for conducting bypass under alphastat acid-base control, with continuous online monitoring of arterial carbon dioxide tension, a membrane oxygenator, and an arterial line filter; but to exclude any or all of these aspects of technique is not negligent. Postoperative cerebral dysfunction deserves more thorough investigation after all types of surgery.
with neuropsychological the fall in haemoglobin concentration during the procedure. This latter variable was also associated with the development of retinal infarcts postoperatively. The lack of any association of the defect with any aspect of extracorporeal support seems surprising. The investigators were also unable to establish that use of a membrane-type oxygenator (in 66 % of patients) rather than a bubble oxygenator conferred any neuropsychological benefit. This result accords with preliminary data obtained by mechanical methods such as arterial line filtration16 and also with a flat sheet membrane vs a bubble-type oxygenator17 to reduce arterial microemboli. Although the quantities of particulate and probably gaseous microemboli delivered to the patient were significantly reduced, but not abolished, by these methods16,17 there was no dramatic improvement in neuropsychological outcome. Two years after CAS, Klonoff et ap8 reported an improvement in patients’ physical activity, personal satisfaction, and work ability, attributed to the success of the operation in relieving angina and preoperative anxiety; these researchers suggest that, overall, the anxiolytic action outweighs any neurological defect. Why has cerebral impairment after open-heart surgery not been the subject of a barrage of pharmacological interventions, especially as there is now considerable scope for such approaches?19,20 Use of antiaggregatory agents such as the prostacyclins has not been beneficial, probably because the desired action is unobtainable without severe hypotension." Nussmeyer and her colleagues reported that neuropsychological outcome was vastly improved if the patients were given thiopentone for cerebroprotection,z2 but the dose used (35 mg/kg) meant that all patients required postoperative catecholamines to support their arterial pressure and the profound sedation produced by such a dose imposed the need for prolonged ventilatory support (typically 24 hours). This latter effect brings its own dangers--eg, inadvertent disconnection leading to hypoxia. In addition, the need for prolonged intensive care would reduce the available beds and might lead to longer hospital stays and longer waiting lists. What do you says to your patient or close relative who requires cardiac surgery and is worried about 16. Treasure T. Intervennons to reduce cerebral injury during cardiac surgery-the effect of artenal line filtration. Perfusion 1989; 4: 147-52. 17. Smith PLC. Interventions to reduce cerebral injury during cardiac surgeryintroduction and the effect of oxygenator type. Perfusion 1989; 4: 139-45 18. Klonoff H, Clark C, Kavanagh-Gray D, Meigala H, Munro I. Two year follow up study of coronary bypass surgery. J Thorac Cardiovasc Surg 1989; 97: 78-85. 19. Weir DL, Jones JG. Cerebral ischaemia; pathophysiology and treatment. In. Kaufmann L, ed. Anaesthesia review 5. London: Churchill Livingstone, 1988: 131-44. 20 Royston D. Interventions to reduce cerebral injury during cardiac surgery-the effect of physical and pharmacological agents. Perfusion 1989; 4: 153-61. 21 Blauth C, Brady A, Arnold J, Schulenberg WE, Frackowiak R, Taylor KM A double blind clinical trial of Iloprost during cardiopulmonary bypass. Perfusion 1987; 2: 271-76. 22. Nussmeyer NA, Arlund C, Slogoff S Neuropsychological complications after cardiopulmonary bypass: cerebral protection with a barbiturate. Anesthesiology
1986; 64: 165-70.
occurs, for which there
are
LESSONS IN THE SURGICAL TREATMENT OF EPILEPSY A DYSEMBRYOPLASTIC neuroepithelial tumour has lately been described in a group of 39 patients from Paris and from Rochester, Minnesota, all of whom had medically intractable partial complex seizures with secondary generalisation in 6 patients (15%).1 Total or subtotal removal of these tumours led to complete freedom from seizures in 81 % of the 37 patients available for follow-up over a mean of 9 years and to improvement in the remainder. The patients had had seizures for 2-18 years. In most cases the tumour was in the frontal lobe (31 %) or in the temporal lobe (62%), and it was visible on a computerised tomographic (CT) scan in 91 % of the 22 patients who were examined. In the Paris group, the patients represented 75% of those undergoing epilepsy surgery between 1964 and 1983. This report should draw attention to certain guidelines for the surgical treatment of epilepsy. First, the principle that focal seizures suggest focal pathology is well illustrated by this group of patients. The original study of 471 epileptics by Gastaut showed that in only 11 % of patients with generalised seizures could a CT scan abnormality be demonstrated, compared with 63% of those with partial complex seizures.2 Similar findings have been described by Yang et al in children.3 Experience in the use of magnetic resonance imaging (MRI) for detection of such lesions is growing, and reports suggest that tumours may be shown by this technique when they are unrecognised or invisible by CT scanning.4 In specialist epilepsy centres the frequency of such lesions is probably 20-25%.5 Unfortunately, the Taggart DP, Reece IJ, Wheatley DJ. Cerebral deficit after elective cardiac surgery. Lancet 1987; i: 47. 1. Daumas-Duport C, Scheithauer BW, Chodkiewicz JP, Laws ER, Vedrenne C. Dysembryoplastic neuroepithelial tumor: a surgically curable tumor of young patients with intractable partial seizures. Neurosurgery 1988; 23: 545-56. 2. Gastaut H, Gastaut HL. Computerised transverse axial tomography in epilepsy Epilepsia 1976, 17: 325-36. 3 Yang PJ, Berger PE, Cohen ME, Duffner PK. Computed tomography and childhood seizure disorders. Neurology 1979; 29: 1084-88. 4. Sperling MR, Wilson G, Engel J, Babb TL, Phelps M, Bradley W. Magnetic resonance imaging in intractable partial epilepsy: correlative studies. Ann Neurol 1986; 20: 57-62 5. Adams CBT, Anslow OWP, Molyneux A, Oxbury J Radiological detection of surgically treatable lesions. In: Engel J, ed Surgical treatment of the epilepsies. New York: Raven, 1987: 213-33.
23.
367
provision of MRI facilities, or funding for access to them, is often inadequate. Treatment of drug-resistant epilepsy by surgery has been carried out for over a hundred years and there are about fifty centres
in the western world where such skills
are
available.
Morbidity, both physical and intellectual, and mortality are commendably low for these procedures. Mortality overall is now less than 1 % and for anterior temporal lobectomy is less than 0-5%. Likewise, overall morbidity is less than 5% and serious morbidity less than 2%.6 The results for seizure control are also good overall--even if we exclude hemispherectomy, which is better. Resective surgery renders 50% of patients seizure free. In patients with tumours such as those described above, or with other benign tumours, complete freedom from seizures is achieved in 70% or more.5,7,8 About 45% of patients with partial complex seizures are poorly controlled.9 If the Paris figures are representative, then at least 7-5% of them have a remediable lesion that can be demonstrated by non-invasive brain imaging.
INFORMING PATIENTS ABOUT CLINICAL DISAGREEMENT THE public are not generally aware of the extent of variation and disagreement in clinical practice. Patients may witness medical debate around the bedside and accept that their doctor may have to try several treatments to get the best result, but there is widespread belief that most clinical decisions are uniform and made with certainty. Many patients would therefore be surprised to fmd that, if admitted for elective surgery, their chances of having a preoperative chest radiograph could vary from 10 to 50% depending on the surgical unit;10 that general practitioners may vary four-fold in their decisions to refer patients with the same diagnosis to hospital;" and that age and sex standardised haemorrhoidectomy rates could be about five times higher in one district than another within the same regional health authority.12 Such variations in practice within small areas are more likely to be due to differences between doctors in diagnostic style and therapeutic beliefs than in supply and organisation of services. 13 In the USA, Brook and colleagues have been examining how clinical disagreement might explain geographical variations in the use of common medical procedures.14,15
6. Van Buren
J Complications of surgical procedures in the diagnosis and treatment of epilepsy. In Engel J, ed. Surgical treatment of the epilepsies. New York: Raven, 1987: 465-76.
Polkey CE. Neurosurgery. Chap 13. In: Laidlaw J, Richens A, Oxley J, eds. A textbook of epilepsy Edinburgh: Churchill-Livingstone, 1988 484-510. 8. Wieser HG ’Selective amygdalo-hippocampectomy’: indications, investigative technique and results. In: Symon L, ed. Advances and technical standards in neurosurgery. Vol 13. Vienna: Springer Verlag, 1986: 39-133. 9. Dreifuss FE. Goals of surgery for epilepsy. In: Engel J, ed. Surgical treatment of the epilepsies. New York: Raven, 1987: 31-50. 10. National Study by the Royal College of Radiologists. Preoperative chest radiology. Lancet 1979; ii 83-86. 11. Wilkin D, Smith A. Variation in general practitioners’ referrals to consultants. J R Coll 7.
Gen Pract 1987; 37: 350-53. 12 McPherson K, Wennberg JE, Hovind OB, Clifford P. Small area variations in the use of common surgical procedures: an international comparison of New England, England, and Norway. N Engl J Med 1982; 307: 1310-14. 13. Wennberg JE, Gittlesohn A. Variations in medical care among small areas. Sci Am 1982, 246: 120-34. 14 Park RE, Fink A, Brook RH, et al Physician ratings of appropnate indications for six medical and surgical procedures Am J Publ Health 1986; 76: 766-72. 15 Chassin MR, Kosecoff J, Park RE, et al. Does inappropnate use explain geographic variations in the use of health services? A study of three procedures JAMA 1987; 258: 2533-37.
They found considerable dissent among clinical experts on the indications for coronary
angiography, coronary artery bypass graft surgery (CABG), cholecystectomy, upper gastrointestinal endoscopy, colonoscopy, and carotid endarterectomy.14 There was even more discord on the indications for coronary angiography and CABG among a panel of doctors in the UK.’6 Moreover, in a survey of several thousand patients who had had at least one of these procedures, Chassin et al found that many of the indications were those open to considerable disagreement. 15 So, this work confirms previous suspicions-whether patients have major diagnostic and therapeutic procedures often depends on whom they consult. Brook’s group have lately suggested that when a doctor plans a procedure under circumstances without firm scientific justification, then the patient has a right to know that other doctors might disagree.l’ Informing patients about clinical variability and disagreement may become more relevant in the UK because Working for Patients18 implies that substantial differences may be created in clinical practice. Thus, self-governing hospitals will be able to provide some services and not others, thereby creating discrepancies in supply locally. General practice budgets will encourage doctors to consider more carefully the financial implications of their decisions, so introducing another element into the decision-making process and promoting greater discord. At the same time, patients are to be encouraged to shop around to register with the doctor who best suits their needs. We hope that doctors will provide more information about the services on offer—eg, well-women clinics and blood pressure screening. But to what extent should doctors inform patients that they carry out certain procedures and others do not? When a surgeon is advocating cholecystectomy for symptomless gallstones, should the patient be told that another surgeon in the same hospital probably would not operate under the circumstances? Greater participation by patients in clinical decisionmaking is laudable in many respects; involvement of patients in mapping out their own destiny with less abrogation of this task to the medical profession must surely encourage greater self-responsibility for health. And people should know about the risks and benefits of medical procedures to which they might be subjected. However, there are limitations in providing such information. Disagreement is so rife throughout medicine that explanations to patients may be time consuming and in many cases complex and confusing. Randomised controlled trials have multiplied, but "firm scientific" evidence often remains inconclusive. It is often impossible to discuss the nuances of the evidence, and emphasising controversy may instil unnecessary alarm. Members of the general public usually seek medical care because they recognise the knowledge and skill of doctors. On the whole, patients trust doctors’ judgments. The extent to which patients are involved in clinical decisions should obviously depend on medical circumstances and on the patient’s desires and capabilities. To inform someone about clinical disagreement when he is not in a position to make a rational choice seems same
foolhardy. RH, Kosecoff JB, Park RE, et al. Diagnosis and treatment of coronary disease: comparison of doctors’ attitudes in the USA and the UK. Lancet 1988; i: 750-53. 17. Park RE, Fink A, Brook RH, et al. Physician ratings of appropriate indications for three procedures: theoretical indications vs indications used in practice. Am J Publ Health 1989; 79: 445-47. 18 Working for Patients (Cm 555). London: HM Stationery Office, 1989. 16. Brook