1200 it had been in force for years and it should now be brought up to date. He did not want to return to the multiplicity of small nursing-homes which existed in London and elsewhere before the 1939-45 war. But he saw as quite another matter a complex licensing system aimed at controlling the size of the private sector and blocking the growth and development of its hospitals and clinics. This would give the Government and local health authorities a stranglehold on the private sector. Lord Hill of Luton, a past Secretary of the B.M.A., speaking on the N.H.S. for the first time in Parliament for 25 years, thought the temptation was far too great for a Minister to use the licensing power to make the Service without comparison by destroying its competition. He and other speakers appealed for the pay-beds issue to be referred to the Royal Commission. Others were stronger and directed their criticism straight at Mrs Castle. Lord Cottesloe said a new Minister "would change the whole complexion of the Service overnight". The briefest intervention came from Lord Halsbury, former chairman of the Review Body on doctors’ and dentists’ pay. Although he said he had not intended to
extent
speak, a sudden "quite non-controversial analogy" came to him. "One can buy a first-class or a second-class train ticket, but the first-class passengers do not jump the queue if passengers are queueing to get in the station. It is entirely an option of the customer whether he buys a first-class or a second-class ticket. There are no politics malice about this at all. If one has a short journey and is in good physical health, one probably saves the money and travels second-class." Not all speakers were hostile to the Government. Baroness Gaitskell described the fears of consultants about the abolition of private medicine as "almost paranoid". But, she added, the Government had been somewhat perverse. She did not think that a small percentage of private beds would pose a threat to the N.H.S. and she agreed it would have been a good thing if Mrs Castle had insisted on referring the issue to the Royal Commission. The man with the job of confronting the criticism was Lord Wells-Pestell, a junior all-purpose Government Minister. He said the Government was anxious to introduce its pay-beds policy in a planned and reasonable way which would help the patient to have access to private treatment outside the N.H.S. if he or she preferred and which would recognise consultants’ anxieties. The proposed licensing system was a means to encourage the fairest possible distribution of private practice throughout the country to give the maximum freedom of choice. The Government was already aware of several proposals for large-scale developments in the private field which could do enormous damage to the N.H.S. These were the sort of problems they wanted to discuss with the profession "without preconditions of any kind", and if the profession could convince the Government that the way proposed was wrong and damaging the Government would be pleased to consider other ways. As to how he thought 4100 private beds could make any difference to the situation, he pointed out that only 3000 were fully occupied in the course of a year. A bed could be occupied by between 20 and 23 people during one year, the average stay in hospital normally being about thirteen days. So if these 3000 beds passed into N.H.S. use another 40 000 to 50 000 people could be taken off the waiting-list, which now stood at over 500 000.
of envy
or
Letters
to
the Editor
SURVIVAL IN ACUTE MYELOID LEUKÆMIA
SIR,-We should be wary of drawing general conclusions from the experience of single centres (especially those at teaching hospitals) in the treatment of leukaemia. The report from University College Hospital (Oct. 4, p. 621) presents survival figures for patients admitted to that hospital over the past six years which are compared with survival figures from recent M.R.C. trials,’ to the disadvantage of the latter. The comparison is of doubtful validity. The M.R.C. leukaemia trials were done in a network of cooperating hospitals many of which draw their patients directly from the immediate vicinity, whereas
teaching hospitals commonly provide regional
ser-
vices, taking many patients from a wider area. This introduces a risk of selection; the most seriously ill patients tend not to be referred. Major "reference" hospitals especially are affected by this bias; so are the M.R.C. trials, but to a lesser extent. Addenbrooke’s Hospital admits patients with acute leukgemias from Cambridge and its immediate surroundings, but it also takes in referrals from smaller hospitals in a wider area. In 1970-74, 64 patients with acute myeloid leukaemia were admitted and treated in the leukaemia unit with aggressive therapeutic regimens, mostly in accord with current M.R.C. trial protocols. The median survivals in weeks of patients in the various age-groups are given in the table, and compared with M.R.C. and U.C.H. figures. 12 patients died within a week of admission-3 before starting and 9 before completing one course of cytotoxic treatment and before aplasia had been induced by therapy. These were severely ill patients, and were virtually doomed by intractable haemorrhagic or septicsemic states at the time of admission. Such patients would be unlikely to be referred from outside hospitals. If these patients are excluded (as the U.C.H. report excluded 5 untreated patients) survival figures improve (see table). By reference to the Cambridge Cancer Registration Bureau, we were able to look at records of patients admitted to neighbouring hospitals from which leukaemic patients are usually referred to Addenbrooke’s,who were not in fact transferred. In the period under review there were 58 such patients. 40 of these were over sixty. The patients not transferred were mostly treated with supportive measures and mild cytotoxic therapy in a manner not unlike that recommended by the U.C.H. group, and with palliative rather than radical aims. The survival figures for these unreferred patients are given in the table. Although the numbers of patients, except those derived from the M.R.C. report, are small, certain similarities and differences emerge. The survival figures for the full Addenbrooke’s series generally resemble those of the M.R.C. series; those for the Addenbrooke’s series excluding very early deaths resemble the U.C.H. figures; survivals in the group of patients not referred to the centre but treated along conservative lines are much worse than those of any other series. In the Cambridge area as a whole, 55% of the 122 patients were over the age of sixty; this probably represents fairly well the age incidence of the disease. Older patients are less likely to be referred to specialised units than are younger ones, as our referral pattern shows. The low percentage of elderly patients in the M.R.C. trials indicates that it is probably true in most areas, and suggests that further selection against including older patients in trials may be operating. Comparisons of survival or remission rates in different series are of little value unless the age-distributions are allowed for, since advancing age carries a worsening prognosis. The M.R.C. Working Party takes care to emphasise age patterns, but not everyone doesand even when they do their survival figures or remission rates are often cited without qualification and compared as if dif1. M.R.C.
Working Party Br. J. Hœmat. 1974, 27,
373.
1201 MEDIAN SURVIVAL IN DIFFERENT SERIES OF PATIENTS WITH ACUTE MYELOID LEUKAEMIA
ferences between them were attributable solely to the kinds of treatment used. A second factor of major importance in comparing survival figures is the clinical condition of the patients. Severely ill patients are much less likely to be transferred to specialised centres than are less ill patients. The risks and delays of transfer are judged to outweigh the possible benefits of more "expert" care. The poor duration of survival in the untransferred cases in the Cambridge area is probably attributable in part to this practice. The heterogeneity in remission-rates and duration of survival between centres participating in multicentre trials is largely due to differences in initial death-rates, which have been attributed to variation in the quality of supportive care.’ This attribution may be partly correct, but centres providing the best supportive care are often specialist centres, and many of the most severely ill leuksmic patients in their usual catchment areas may not reach them because they are too ill to be transferred. If this supposition is true, as the Cambridge figures and much anecdotal experience suggest, it provides a mechanism of case selection which is much more difficult to assess and compensate for than the age factor, but one which may be of almost equal importance. I suspect that selection has been at work in any series of acute myeloid leukaemia without 10-20% of deaths within the first week, and with less than 40% of patients over the age of sixty. University Department of Hæmatological Medicine, Hills Road,
Cambridge CB2 2QL.
F. G.
J. HAYHOE
from this study and a separate study of mortality from appendicitis and appendicectomy2 suggest that the avoidable mortality (death after removal of a normal appendix or after non-removal of an abnormal appendix) was low and equal for the two approaches. Addition of the estimated death-rate from perforation of the appendix would not have altered this balance. The higher operation-rate appeared to be associated with a lower incidence of morbidity (which included the later readmission for observation or operation) and a higher incidence of relief of symptoms. In Britain, where operative mortality seems to have fallen to a point which will be difficult to reduce and where the already low incidence of perforation is rarely due to unreasonable delay in hospital, future attempts to reduce mortality from appendicitis might usefully concentrate on the 11% of appendicitis deaths in patients who have had an episode of possible appendicitis at some time before the fatal illness. Of a group of 71 such patients, 24 had previously been observed in hospital without operation, 14 had been seen at hospital but not admitted for observation, and 29 had attended their general practitioner without being referred to hospital.3 Although appendicitis is a common reason for admission to hospital, patients with possible appendicitis represent no more than 0.2% of the work of general practice.4 Progress towards reducing mortality and morbidity from this important disorder clearly requires complementary consideration of the very different problems posed by this condition in the hospital and in the community. Department of General Practice, University Medical Buildings, Foresterhill, Aberdeen AB9 2ZD.
J. G.
R. HOWIE
MANAGEMENT OF POSSIBLE APPENDICITIS
S:R,—Dr Jacob and his colleagues (Nov. 22, p. 1032) believe that removal of "some 25% of innocent appendices is bound to lower the rates of perforation and consequently the mortality" from appendicitis. It would indeed be surprising if perforation-rates and mortality were not closely linked, but to suggest relating error-rates to perforation-rates is of doubtful validity. A high incidence of perforated appendices is more likely to reflect delay by the patient or referring doctor than delay by the surgeon, and similarly a low error-rate may reflect the cross-section of patients referred as well as the surgeon’s acumen or policy. To examine their interesting hypothesis Dr Jacob’s team should calculate error-rates, perforation-rates, and mortality using a denominator of more epidemiological relevance than the number of operations carried out. Few opportunities exist to compare mortality, morbidity, and relief of symptoms in a single population served by surgeons with recognisably different approaches to the use of operation in managing patients with possible appendicitis. In this context, my own findings may be relevant.’ I studied 533 consecutive patients aged 12-29 admitted during one year to the care of two groups of surgeons. The groups of surgeons operated on 82% and 60% of the patients referred to them and had "error-rates" of 40% and 30%, respectively. Projections 1. Howie,
J. G. R. Lancet, 1968, i, 1365.
HOW DO DOCTORS LEARN ABOUT DRUGS?
SiR,—The correspondence following your editorial (Aug. 9,
emphasised the importance of pharmacist-based drug-information services-particularly in the use of compup.
268)
has
ter-based retrieval systems. We have no doubt that information pharmacists have had a useful role to play in providing basic information about drugs, as well as expert advice on pharmaceutical problems. However, pharmacists have little training in clinical medicine, and therefore they are unable to offer expert advice on interactions between drugs and disease. For this reason, we have recently established a clinical drug information service to doctors in hospital and general practice in the Northern Region. The service is provided on a voluntary basis by medically qualified pharmacologists and clinical pharmacologists who are on call from their place of work during the day, and from their homes by night. Inquiries are made through the telephone exchange at the Royal Victoria Infirmary, Newcastle upon Tyne (Newcastle 25131). The aim of the service is to provide rapid communication between doctors in the region and 2. Howie, J. G. R. ibid. 1966, ii, 1334. 3. Howie, J. G. R.J. R. Coll. gen. Practit. 1972, 22, 265. 4. Morbidity Statistics from General Practice (Stud. med. H. M. Stationery Office, 1974.
Popul. Subj. no. 26).
extent
speak, a sudden "quite non-controversial analogy" came to him. "One can buy a first-class or a second-class train ticket, but the first-class passengers do not jump the queue if passengers are queueing to get in the station. It is entirely an option of the customer whether he buys a first-class or a second-class ticket. There are no politics malice about this at all. If one has a short journey and is in good physical health, one probably saves the money and travels second-class." Not all speakers were hostile to the Government. Baroness Gaitskell described the fears of consultants about the abolition of private medicine as "almost paranoid". But, she added, the Government had been somewhat perverse. She did not think that a small percentage of private beds would pose a threat to the N.H.S. and she agreed it would have been a good thing if Mrs Castle had insisted on referring the issue to the Royal Commission. The man with the job of confronting the criticism was Lord Wells-Pestell, a junior all-purpose Government Minister. He said the Government was anxious to introduce its pay-beds policy in a planned and reasonable way which would help the patient to have access to private treatment outside the N.H.S. if he or she preferred and which would recognise consultants’ anxieties. The proposed licensing system was a means to encourage the fairest possible distribution of private practice throughout the country to give the maximum freedom of choice. The Government was already aware of several proposals for large-scale developments in the private field which could do enormous damage to the N.H.S. These were the sort of problems they wanted to discuss with the profession "without preconditions of any kind", and if the profession could convince the Government that the way proposed was wrong and damaging the Government would be pleased to consider other ways. As to how he thought 4100 private beds could make any difference to the situation, he pointed out that only 3000 were fully occupied in the course of a year. A bed could be occupied by between 20 and 23 people during one year, the average stay in hospital normally being about thirteen days. So if these 3000 beds passed into N.H.S. use another 40 000 to 50 000 people could be taken off the waiting-list, which now stood at over 500 000.
of envy
or
Letters
to
the Editor
SURVIVAL IN ACUTE MYELOID LEUKÆMIA
SIR,-We should be wary of drawing general conclusions from the experience of single centres (especially those at teaching hospitals) in the treatment of leukaemia. The report from University College Hospital (Oct. 4, p. 621) presents survival figures for patients admitted to that hospital over the past six years which are compared with survival figures from recent M.R.C. trials,’ to the disadvantage of the latter. The comparison is of doubtful validity. The M.R.C. leukaemia trials were done in a network of cooperating hospitals many of which draw their patients directly from the immediate vicinity, whereas
teaching hospitals commonly provide regional
ser-
vices, taking many patients from a wider area. This introduces a risk of selection; the most seriously ill patients tend not to be referred. Major "reference" hospitals especially are affected by this bias; so are the M.R.C. trials, but to a lesser extent. Addenbrooke’s Hospital admits patients with acute leukgemias from Cambridge and its immediate surroundings, but it also takes in referrals from smaller hospitals in a wider area. In 1970-74, 64 patients with acute myeloid leukaemia were admitted and treated in the leukaemia unit with aggressive therapeutic regimens, mostly in accord with current M.R.C. trial protocols. The median survivals in weeks of patients in the various age-groups are given in the table, and compared with M.R.C. and U.C.H. figures. 12 patients died within a week of admission-3 before starting and 9 before completing one course of cytotoxic treatment and before aplasia had been induced by therapy. These were severely ill patients, and were virtually doomed by intractable haemorrhagic or septicsemic states at the time of admission. Such patients would be unlikely to be referred from outside hospitals. If these patients are excluded (as the U.C.H. report excluded 5 untreated patients) survival figures improve (see table). By reference to the Cambridge Cancer Registration Bureau, we were able to look at records of patients admitted to neighbouring hospitals from which leukaemic patients are usually referred to Addenbrooke’s,who were not in fact transferred. In the period under review there were 58 such patients. 40 of these were over sixty. The patients not transferred were mostly treated with supportive measures and mild cytotoxic therapy in a manner not unlike that recommended by the U.C.H. group, and with palliative rather than radical aims. The survival figures for these unreferred patients are given in the table. Although the numbers of patients, except those derived from the M.R.C. report, are small, certain similarities and differences emerge. The survival figures for the full Addenbrooke’s series generally resemble those of the M.R.C. series; those for the Addenbrooke’s series excluding very early deaths resemble the U.C.H. figures; survivals in the group of patients not referred to the centre but treated along conservative lines are much worse than those of any other series. In the Cambridge area as a whole, 55% of the 122 patients were over the age of sixty; this probably represents fairly well the age incidence of the disease. Older patients are less likely to be referred to specialised units than are younger ones, as our referral pattern shows. The low percentage of elderly patients in the M.R.C. trials indicates that it is probably true in most areas, and suggests that further selection against including older patients in trials may be operating. Comparisons of survival or remission rates in different series are of little value unless the age-distributions are allowed for, since advancing age carries a worsening prognosis. The M.R.C. Working Party takes care to emphasise age patterns, but not everyone doesand even when they do their survival figures or remission rates are often cited without qualification and compared as if dif1. M.R.C.
Working Party Br. J. Hœmat. 1974, 27,
373.
1201 MEDIAN SURVIVAL IN DIFFERENT SERIES OF PATIENTS WITH ACUTE MYELOID LEUKAEMIA
ferences between them were attributable solely to the kinds of treatment used. A second factor of major importance in comparing survival figures is the clinical condition of the patients. Severely ill patients are much less likely to be transferred to specialised centres than are less ill patients. The risks and delays of transfer are judged to outweigh the possible benefits of more "expert" care. The poor duration of survival in the untransferred cases in the Cambridge area is probably attributable in part to this practice. The heterogeneity in remission-rates and duration of survival between centres participating in multicentre trials is largely due to differences in initial death-rates, which have been attributed to variation in the quality of supportive care.’ This attribution may be partly correct, but centres providing the best supportive care are often specialist centres, and many of the most severely ill leuksmic patients in their usual catchment areas may not reach them because they are too ill to be transferred. If this supposition is true, as the Cambridge figures and much anecdotal experience suggest, it provides a mechanism of case selection which is much more difficult to assess and compensate for than the age factor, but one which may be of almost equal importance. I suspect that selection has been at work in any series of acute myeloid leukaemia without 10-20% of deaths within the first week, and with less than 40% of patients over the age of sixty. University Department of Hæmatological Medicine, Hills Road,
Cambridge CB2 2QL.
F. G.
J. HAYHOE
from this study and a separate study of mortality from appendicitis and appendicectomy2 suggest that the avoidable mortality (death after removal of a normal appendix or after non-removal of an abnormal appendix) was low and equal for the two approaches. Addition of the estimated death-rate from perforation of the appendix would not have altered this balance. The higher operation-rate appeared to be associated with a lower incidence of morbidity (which included the later readmission for observation or operation) and a higher incidence of relief of symptoms. In Britain, where operative mortality seems to have fallen to a point which will be difficult to reduce and where the already low incidence of perforation is rarely due to unreasonable delay in hospital, future attempts to reduce mortality from appendicitis might usefully concentrate on the 11% of appendicitis deaths in patients who have had an episode of possible appendicitis at some time before the fatal illness. Of a group of 71 such patients, 24 had previously been observed in hospital without operation, 14 had been seen at hospital but not admitted for observation, and 29 had attended their general practitioner without being referred to hospital.3 Although appendicitis is a common reason for admission to hospital, patients with possible appendicitis represent no more than 0.2% of the work of general practice.4 Progress towards reducing mortality and morbidity from this important disorder clearly requires complementary consideration of the very different problems posed by this condition in the hospital and in the community. Department of General Practice, University Medical Buildings, Foresterhill, Aberdeen AB9 2ZD.
J. G.
R. HOWIE
MANAGEMENT OF POSSIBLE APPENDICITIS
S:R,—Dr Jacob and his colleagues (Nov. 22, p. 1032) believe that removal of "some 25% of innocent appendices is bound to lower the rates of perforation and consequently the mortality" from appendicitis. It would indeed be surprising if perforation-rates and mortality were not closely linked, but to suggest relating error-rates to perforation-rates is of doubtful validity. A high incidence of perforated appendices is more likely to reflect delay by the patient or referring doctor than delay by the surgeon, and similarly a low error-rate may reflect the cross-section of patients referred as well as the surgeon’s acumen or policy. To examine their interesting hypothesis Dr Jacob’s team should calculate error-rates, perforation-rates, and mortality using a denominator of more epidemiological relevance than the number of operations carried out. Few opportunities exist to compare mortality, morbidity, and relief of symptoms in a single population served by surgeons with recognisably different approaches to the use of operation in managing patients with possible appendicitis. In this context, my own findings may be relevant.’ I studied 533 consecutive patients aged 12-29 admitted during one year to the care of two groups of surgeons. The groups of surgeons operated on 82% and 60% of the patients referred to them and had "error-rates" of 40% and 30%, respectively. Projections 1. Howie,
J. G. R. Lancet, 1968, i, 1365.
HOW DO DOCTORS LEARN ABOUT DRUGS?
SiR,—The correspondence following your editorial (Aug. 9,
emphasised the importance of pharmacist-based drug-information services-particularly in the use of compup.
268)
has
ter-based retrieval systems. We have no doubt that information pharmacists have had a useful role to play in providing basic information about drugs, as well as expert advice on pharmaceutical problems. However, pharmacists have little training in clinical medicine, and therefore they are unable to offer expert advice on interactions between drugs and disease. For this reason, we have recently established a clinical drug information service to doctors in hospital and general practice in the Northern Region. The service is provided on a voluntary basis by medically qualified pharmacologists and clinical pharmacologists who are on call from their place of work during the day, and from their homes by night. Inquiries are made through the telephone exchange at the Royal Victoria Infirmary, Newcastle upon Tyne (Newcastle 25131). The aim of the service is to provide rapid communication between doctors in the region and 2. Howie, J. G. R. ibid. 1966, ii, 1334. 3. Howie, J. G. R.J. R. Coll. gen. Practit. 1972, 22, 265. 4. Morbidity Statistics from General Practice (Stud. med. H. M. Stationery Office, 1974.
Popul. Subj. no. 26).
