1123
amine. In the multicentre trial4 three-quarters of the patients on penicillamine had falls in the plateletcount ; but, strangely, so did 45% of the controls. In only 2 of 52 patients was the fall in platelets D-Penicillamine in Rheumatoid judged great enough to require abandonment of Arthritis treatment; both became profoundly thrombocytoIN Wilson’s disease, cystinuria, and lead-poisoning penic in the second 6 months of treatment, but a established is treatment. firmly subsequent experience has shown that this type of penicillamine reaction can also occur during the early weeks. These are menacing conditions and the threat of adverse effects is offset by the benefits. But in Fortunately, the platelet-count falls progressively and sudden catastrophic thrombocytopenia, such as rheumatoid arthritis the position of penicillamine is may occur with other drugs, is uncommon. The very different: the disease is extremely common, it seldom threatens life, and only a minority of patients policy adopted in one rheumatology centre is to disabled. a balance count platelets weekly for the first 4 weeks of treatbecome severely Clearly different ment and thereafter monthly. has to be struck between dangers and benefits. If the count falls to of below counts are reinstituted; administration Furthermore, 100,000, weekly penicillamine well the dose below 70,000 of penicillamine is reduced or much larger numbers of patients may unveil hitherto unrecognised adverse effects. the drug temporarily withdrawn. Thrombocytopenia There is is always reversible if treatment is stopped in time. evidence too that adverse effects encountered in one disease may not be closely mirrored in another. Provided the count has not fallen below 50,000 it The first tentative use of penicillamine in rheumais justifiable to reintroduce the drug, or to increase toid arthritis dates back to 1960 1,2 and evidence the dose cautiously, once the count has returned to supporting its efficacy was published in 1964. But normal. Neutropenia or aplasia are less common, more extensive use of the compound in rheumatoid though fatal blood dyscrasias have occurred in the arthritis has stemmed from later work, including the U.K. during treatment with higher doses of pencill4 multicentre controlled trial reported in 1973.4 This amine than are now customary. Proteinuria was also established that was effective. Howa complication of the second 6 months of the multithe drug firmly in a third the of centre trial and subsequent investigations have conever, patients given penicillamine, treatment had to be stopped because of adverse firmed that it is usually a late development; light and effects. Many readers of this report concluded that transient proteinuria may come on earlier and is not the cost was too high or that responsibility for using serious. As for thrombocytopenia, the threshold of this form of treatment should be accepted only by danger is arbitrary. A protein loss not in excess of 1 g. per 24 hours is probably acceptable and 2 g. not centres familiar with its problems and able to watch It for effects. is true that troublesome unduly alarming-indeed, some clinicians retreat closely clinicians taking part in this trial were wary of a drug only when the level reaches 5 g. When protein is detected in dip-tests it is essential to arrange for a which was unfamiliar to them and that extended result fewer withdrawals in quantitative estimation in a 24-hour specimen. These experience would now in a similar trial. Furthermore, amended dosages and very much larger protein losses resolve on withdrawal of penicillamine but may take up to 2 hold some promise of lessening adverse effects. On the other hand, some hitherto unrecognised reactions years to clear completely. If microscopic hxmaturia is also present, penicillamine treatment should have emerged from wider use of penicillamine. It is useful to separate adverse effects which are a nuisance, probably be abandoned. There is good evidence that those which are hazardous and may necessitate proteinuria indicates an immune-complex nephroabandonment of treatment, and those which are so pathy.5The incidence of permanent renal damage is that to treatment hard to ascertain but is certainly low. It is essential their relation can infrequent only be suspected. Of the first group vagaries of taste, or to keep in mind that both thrombocytopenia and loss of taste, combined with anorexia are commonest. proteinuria may be long delayed and that the watch resolve of treatfor both must never be relaxed. Severe rashes have without They usually interruption ment. Nausea, which is less frequent, may get better occasionally forced abandonment of treatment. with temporary reduction in dosage, and some rashes; The doses of penicillamine used in the controlled can be countered in the same way. Of the more: trial were predetermined, though they could be Later hazardous effects, thrombocytopenia and proteinuria1 modified if adverse reactions developed. are most important, though some rashes prove e experience suggests that more widely spaced increto a in dose reduction and 3 ments and a lower maximum dose decrease the refractory temporary incidence of adverse effects. 6,7 Experience in one withdrawal of force ultimately permanent penicill-
THE LANCET
.
-
-
1.
Griffin, S. W., Ulloa, A., Henry, M., Johnston, M. L., Holley, H. L. Clin. Res. 1960, 8, 87.
Dresner, E., Trombly, P. ibid. p. 16. 3. Jaffe, I. A. Ann. intern. Med. 1964, 61, 556. 4. Multicentre Trial Group. Lancet, 1973, i, 275.
2.
Tribe, C. R., Mackenzie, J. C., Bacon, P. A. Penicillamine— International Symposium. Royal Society of Medicine, Oct. 25 and 26, 1974 (abstr.). 6. Hill, H. F. H. Curr. med. Res. Opin. 1974, 2, 573. 7. Day, A. T. ibid. p. 581.
5.
1124
rheumatology centre has shown that when increments of 250 mg. (in terms of base) are made at monthly intervals to a maximum daily intake of 750 mg. the incidence of
"
nuisance " adverse reactions is much
reduced, thrombocytopenia is probably less frequent, but proteinuria remains as big a problem as with the earlier schedule of fortnightly increments to 1500 mg. (exceeding 2 g. in 24 hours in about 15% of patients, irrespective of which of the two schedules is followed). When the drug is used even more cautiously 7,8 still fewer patients experienced adverse effects. Clearly more work must be done before authoritative guidance can be given about dosage in terms both of efficacy and of adverse reactions. Earlier this year a group of 20 clinicians who had used penicillamine variously in Wilson’s disease,
cystinuria, morphoea, keloid, systemic sclerosis, and rheumatoid
arthritis, with a few experts in other spheres, gathered at St. Bartholomew’s Hospital to pool their experience of adverse reactions to the drug,
1000 patients. It was agreed that taste of 9 could not be prevented by supplevagaries ments of copper or zinc.1o Oddly enough, this effect is commoner in rheumatoid arthritis than in Wilson’s disease and is absent or unnoticed in children. Treatment was impossible because of vomiting, irrespective of dose, in a small group of patients, some of whom and a few others reacted with prompt hyperpyrexia. Blood dyscrasias, too, were more prominent in rheumatoid arthritis than in Wilson’s disease or cystinuria. For a drug effective in rheumatoid arthritis, penicillamine can behave in a wayward fashion: at the St. Bartholomew’s Hospital meeting Dr J. M. WALSHE described a form of polyarthritis induced by penicillamine in patients with Wilson’s disease, sometimes with positive tests for rheumatoid factor and distinct from the systemic-lupus-like reaction which he had also encountered. There is potential confusion if penicillamine proves capable of inducing arthralgia in rheumatoid arthritis. Buccal or lingual ulceration may occur after several months oftreatment and may accompany a pemphigoid eruption. Other rashes include the early morbilliform type, a characteristic late eruption, and a rather different type of lesion-elastosis perforans serpiginosa.ll Other reactions were reported, but in many the link with penicillamine remains speculative. They include a myasthenia-like condition, 12 Goodpasture’s syndrome, mammary gigantism, diarrhoea, alopecia, hirsutism, hasmolytic anasmia, altered liver-function tests, haemoptysis, dermatomyositis, and creaking joints. There were only two reports of peptic-ulcer among
some
Golding, J. R., Lee, P. N., Butterworth, D. Br. med. J. 1974, i, 180. Henkin, R. I., Keiser, H. R., Jaffe, I. A., Sternlieb, I., Scheinberg, I. H. Lancet, 1967, ii, 1268. Lyle, W. H. ibid. 1974, ii, 1140. Pass, D., Goldfischer, S., Sternlieb, I., Scheinberg, I. H. Archs Derm. 1973, 108, 713. Bucknall, R. C., Dixon, A. St. J., Glick, E. N., Woodland, J., Zutshi, D. W. Br. med. J. 1975, i, 600.
8. Day, A. T., 9. 10. 11. 12.
reactivation with bleeding; and there was general scepticism about any effect on wound healing. Altogether, 19 patients are known to have died while taking penicillamine for various conditions. In 6 the drug was probably not responsible (deaths from cerebrovascular accidents, hypertensive heart-disease, postoperative embolism, coronary thrombosis). In 7 the drug was almost certainly the cause of death: 3 American patients with Wilson’s disease died of Goodpasture’s syndrome and 4 died of agranulocytosis or aplastic anxmia. The role of penicillamine This was debatable in the remaining 6 deaths. of adverse is as reactions not catalogue daunting as its length suggests. For most clinicians the important obstacles to successful treatment with penicillamine
thrombocytopenia, proteinuria, and rashes. Many patients can be encouraged to weather the nuisance are
effects. The final place of penicillamine in rheumatoid arthritis will rest not only on its proved efficacy in a substantial proportion of patients and the incidence and seriousness of adverse reactions but also on a comparison with the virtues and defects of other agents. For the moment, penicillamine will rarely be prescribed in early rheumatoid arthritis when the chances of a spontaneous remission are good and
simple analgesic/anti-inflammatory drugs, splints, and rest exert a sufficient measure of control-though the position would change if it could be shown to retard or stop the natural evolution of the disease. Most clinicians will probably think about using penicillamine when their patient’s arthritis shows signs of pursuing an aggressive course, and the alternatives will be gold, chloroquine, or an immunosuppressive drug. Chloroquine is less effective than gold, and for many penicillamine will seem less menacing than the immunosuppressive drugs, though the efficacy of the last two will certainly be compared. The results of a multicentre trial comparing gold with penicillamine 13 have already been published. There was little to choose between the efficacy of the twoboth were highly effective in about 4 patients out of 5 and there was no significant difference between them. Adverse effects were commoner with penicillamine, but withdrawal of treatment was more frequent when gold was given (mainly because of rashes). In patients with an early rash, penicillamine could often be re-started, whereas rashes with gold always recurred if treatment was resumed. In this trial penicillamine won by a short head because treatment less often had to be abandoned permanently. Like all such trials this one could not aspire to the stringent conditions of the ultimate test of widespread use. The relative incidence of rare but serious blood dyscrasias cannot be compared in clinical trials with groups of patients of manageable size. 13. Huskisson, E. C., Gibson, T. J., Balme, H. W., Berry, H., Burry, H. C., Grahame, R., Hart, F. D., Henderson, D. R. F., Wojtulewski, J. A. Ann. rheum. Dis. 1974, 33, 532.
1125
N.H.S. hospitals. All this comes at a time of such economic peril that any hopes of raising or even maintaining N.H.S. standards (to offset the attractions of private practice for patients and doctors) are vain. So, if it were done, then ’twere well it were done slowly; and the unions which are urging on the Government to rapid phasing-out must pause and contemplate again what damage they may do to the N.H.S. in its present delicate state. What Aneurin Bevan really thought about private practice is, as David McKie records on p. 1134, now a subject for quotation and counter-quotation. Our view is that he would have preferred private practice to lie entirely outside the N.H.S.-and so would we. has shown the need for a low initial dose and small But that was a long time back. Now that the shortages increments at long intervals. Yet this has happened, of money and everything else needed to sustain the and it would be sad if a promising method of treatService are dire, the pressure on the phasing-out ment fell into disrepute because of misuse or inaccelerator must be delicately applied. We are not adequate safeguards. opposed to the Government’s plans: we simply fear the consequences of advancing them hastily. Finally, the real wormwood for those who wish to A TANGLED PATH see an extension of private practice outside the N.H.S. POLITICIANS, once they are in office, are not spring from the coming events, or those who fear its renowned for pursuing exactly those courses which total elimination, lay in Mrs Castle’s references to they advocated before the election. On the issue of stricter licensing of private hospitals and nursingprivate practice in N.H.S. hospitals, however, Britain’s homes. Consultations are again promised; and, as David McKie remarks (p. 1134), fears of a direct present Government has undoubtedly so far escaped that gibe by setting out to do what it declared it would threat to private practice will dominate the attitude of the consultants. Again, too precipitate Government do-phase-out pay-beds from N.H.S. hospitals. The statement by the Secretary of State for Social Services, action may bring on " the rash of nursing-homes " in Mrs Barbara Castle, the House of Commons on (signs of the eruption are already very evident); and May 51 was the next logical step in a path which she to seek to control it, and the consequent loss of sees as the only way to eliminate injustices in the doctors, nurses, and other skilled staff from the N.H.S., distribution of health care; and which plenty of by licensing criteria other than those of quality would others see as a " monumental irrelevance " 2to the cause a fierce exacerbation of the conflict between real problems of the N.H.S. and as a doctrinaire Government and consultants. It is a tangled cliff edge Service by misjudgment which will damage along which the Government and Mrs Castle are depriving it of skilled manpower. Whoever is right, treading: if they can slowly reach a surer foothold, consultations on the phasing-out programme are to they will have achieved a valuable reform in health It is not one that The Lancet would begin at once; and legislation to effect it will be care in Britain. introduced as soon as Parliament has time. place at the top of today’s list of N.H.S. priorities; Mrs Castle bases her case largely on the argument but we do not condemn the Government on that that " the whole fabric of the National Health Service account. would rot away if the principle of treatment on the basis of medical priority only were ever to be seriously DRUGS FOR ARRHYTHMIAS undermined ". There she is absolutely right. The CARDIAC arrhythmias, particularly ventricular ectopic injustices, those situations in which the patient’s are important clinical events. In symptomless beats, to medical to be and not is seen ability pay, priority, individuals and in patients with myocardial infarction the determining consideration, lie almost entirely in they signify an increased risk of sudden death; but it the area of non-urgent surgery. A common N.H.S. is still not possible to say whether arrhythmias represent as has been the reasonable waiting-list widely proposed an independent risk factor, or whether the association eliminator of queue-jumping. The profession has is indirect owing to their prevalence in patients with never leapt at the idea, but its negotiators will no underlying heart-disease.1 No single treatment is doubt apply their minds to it again in the forthcoming consistently effective, hence the wide variety of antidiscussions. And the prompt provision of more arrhythmic drugs now available. The pathophysiology N.H.S. amenity beds, which might be physically none of arrhythmias is still largely unknown (which is too easy to achieve, would supply some of the privacy hardly surprising in view of the complexity of the it is is that most all want. which, said, private patients neural and chemical control of the heart and vascular The danger of too enthusiastic phasing-out is that system 2-4), but the newer techniques for recording it will aggravate inequalities by transfusing more national and medical resources into the private sector, 1. Kuller, L. H., Perper, J. A., Cooper, M. C. in Modern Trends in leaving an all too common (and longer) waiting-list in Cardiology 3 (edited by M. F. OLIVER); p. 292. London: Butter-
Any clinician who believes that his patient would benefit from penicillamine has the right to prescribe it. But he has a duty to acquaint himself of the hazards, to draw on the experience of others for guidance about dosage and supervision, and to ensure not only that blood and urine tests are done but also that he sees the results promptly and compares them with previous results. If he is in any doubt as to his ability to protect his -patient in this way he should invoke the help of a centre familiar with the drug. There is no justification for prescribing the drug in full doses from the start when hard-won experience
the
1. See Lancet, May 10, 2. See Br. med. J. May
1975, p. 1095. 10, 1975, p. 300.
2. 3.
4.
worths. 1975. £11. Sleight, P. ibid. p. 1. Barrett, A. M., Einstein, R. ibid. p. 44. Horton, E. W., Ungar, A. ibid. p. 67.
amine. In the multicentre trial4 three-quarters of the patients on penicillamine had falls in the plateletcount ; but, strangely, so did 45% of the controls. In only 2 of 52 patients was the fall in platelets D-Penicillamine in Rheumatoid judged great enough to require abandonment of Arthritis treatment; both became profoundly thrombocytoIN Wilson’s disease, cystinuria, and lead-poisoning penic in the second 6 months of treatment, but a established is treatment. firmly subsequent experience has shown that this type of penicillamine reaction can also occur during the early weeks. These are menacing conditions and the threat of adverse effects is offset by the benefits. But in Fortunately, the platelet-count falls progressively and sudden catastrophic thrombocytopenia, such as rheumatoid arthritis the position of penicillamine is may occur with other drugs, is uncommon. The very different: the disease is extremely common, it seldom threatens life, and only a minority of patients policy adopted in one rheumatology centre is to disabled. a balance count platelets weekly for the first 4 weeks of treatbecome severely Clearly different ment and thereafter monthly. has to be struck between dangers and benefits. If the count falls to of below counts are reinstituted; administration Furthermore, 100,000, weekly penicillamine well the dose below 70,000 of penicillamine is reduced or much larger numbers of patients may unveil hitherto unrecognised adverse effects. the drug temporarily withdrawn. Thrombocytopenia There is is always reversible if treatment is stopped in time. evidence too that adverse effects encountered in one disease may not be closely mirrored in another. Provided the count has not fallen below 50,000 it The first tentative use of penicillamine in rheumais justifiable to reintroduce the drug, or to increase toid arthritis dates back to 1960 1,2 and evidence the dose cautiously, once the count has returned to supporting its efficacy was published in 1964. But normal. Neutropenia or aplasia are less common, more extensive use of the compound in rheumatoid though fatal blood dyscrasias have occurred in the arthritis has stemmed from later work, including the U.K. during treatment with higher doses of pencill4 multicentre controlled trial reported in 1973.4 This amine than are now customary. Proteinuria was also established that was effective. Howa complication of the second 6 months of the multithe drug firmly in a third the of centre trial and subsequent investigations have conever, patients given penicillamine, treatment had to be stopped because of adverse firmed that it is usually a late development; light and effects. Many readers of this report concluded that transient proteinuria may come on earlier and is not the cost was too high or that responsibility for using serious. As for thrombocytopenia, the threshold of this form of treatment should be accepted only by danger is arbitrary. A protein loss not in excess of 1 g. per 24 hours is probably acceptable and 2 g. not centres familiar with its problems and able to watch It for effects. is true that troublesome unduly alarming-indeed, some clinicians retreat closely clinicians taking part in this trial were wary of a drug only when the level reaches 5 g. When protein is detected in dip-tests it is essential to arrange for a which was unfamiliar to them and that extended result fewer withdrawals in quantitative estimation in a 24-hour specimen. These experience would now in a similar trial. Furthermore, amended dosages and very much larger protein losses resolve on withdrawal of penicillamine but may take up to 2 hold some promise of lessening adverse effects. On the other hand, some hitherto unrecognised reactions years to clear completely. If microscopic hxmaturia is also present, penicillamine treatment should have emerged from wider use of penicillamine. It is useful to separate adverse effects which are a nuisance, probably be abandoned. There is good evidence that those which are hazardous and may necessitate proteinuria indicates an immune-complex nephroabandonment of treatment, and those which are so pathy.5The incidence of permanent renal damage is that to treatment hard to ascertain but is certainly low. It is essential their relation can infrequent only be suspected. Of the first group vagaries of taste, or to keep in mind that both thrombocytopenia and loss of taste, combined with anorexia are commonest. proteinuria may be long delayed and that the watch resolve of treatfor both must never be relaxed. Severe rashes have without They usually interruption ment. Nausea, which is less frequent, may get better occasionally forced abandonment of treatment. with temporary reduction in dosage, and some rashes; The doses of penicillamine used in the controlled can be countered in the same way. Of the more: trial were predetermined, though they could be Later hazardous effects, thrombocytopenia and proteinuria1 modified if adverse reactions developed. are most important, though some rashes prove e experience suggests that more widely spaced increto a in dose reduction and 3 ments and a lower maximum dose decrease the refractory temporary incidence of adverse effects. 6,7 Experience in one withdrawal of force ultimately permanent penicill-
THE LANCET
.
-
-
1.
Griffin, S. W., Ulloa, A., Henry, M., Johnston, M. L., Holley, H. L. Clin. Res. 1960, 8, 87.
Dresner, E., Trombly, P. ibid. p. 16. 3. Jaffe, I. A. Ann. intern. Med. 1964, 61, 556. 4. Multicentre Trial Group. Lancet, 1973, i, 275.
2.
Tribe, C. R., Mackenzie, J. C., Bacon, P. A. Penicillamine— International Symposium. Royal Society of Medicine, Oct. 25 and 26, 1974 (abstr.). 6. Hill, H. F. H. Curr. med. Res. Opin. 1974, 2, 573. 7. Day, A. T. ibid. p. 581.
5.
1124
rheumatology centre has shown that when increments of 250 mg. (in terms of base) are made at monthly intervals to a maximum daily intake of 750 mg. the incidence of
"
nuisance " adverse reactions is much
reduced, thrombocytopenia is probably less frequent, but proteinuria remains as big a problem as with the earlier schedule of fortnightly increments to 1500 mg. (exceeding 2 g. in 24 hours in about 15% of patients, irrespective of which of the two schedules is followed). When the drug is used even more cautiously 7,8 still fewer patients experienced adverse effects. Clearly more work must be done before authoritative guidance can be given about dosage in terms both of efficacy and of adverse reactions. Earlier this year a group of 20 clinicians who had used penicillamine variously in Wilson’s disease,
cystinuria, morphoea, keloid, systemic sclerosis, and rheumatoid
arthritis, with a few experts in other spheres, gathered at St. Bartholomew’s Hospital to pool their experience of adverse reactions to the drug,
1000 patients. It was agreed that taste of 9 could not be prevented by supplevagaries ments of copper or zinc.1o Oddly enough, this effect is commoner in rheumatoid arthritis than in Wilson’s disease and is absent or unnoticed in children. Treatment was impossible because of vomiting, irrespective of dose, in a small group of patients, some of whom and a few others reacted with prompt hyperpyrexia. Blood dyscrasias, too, were more prominent in rheumatoid arthritis than in Wilson’s disease or cystinuria. For a drug effective in rheumatoid arthritis, penicillamine can behave in a wayward fashion: at the St. Bartholomew’s Hospital meeting Dr J. M. WALSHE described a form of polyarthritis induced by penicillamine in patients with Wilson’s disease, sometimes with positive tests for rheumatoid factor and distinct from the systemic-lupus-like reaction which he had also encountered. There is potential confusion if penicillamine proves capable of inducing arthralgia in rheumatoid arthritis. Buccal or lingual ulceration may occur after several months oftreatment and may accompany a pemphigoid eruption. Other rashes include the early morbilliform type, a characteristic late eruption, and a rather different type of lesion-elastosis perforans serpiginosa.ll Other reactions were reported, but in many the link with penicillamine remains speculative. They include a myasthenia-like condition, 12 Goodpasture’s syndrome, mammary gigantism, diarrhoea, alopecia, hirsutism, hasmolytic anasmia, altered liver-function tests, haemoptysis, dermatomyositis, and creaking joints. There were only two reports of peptic-ulcer among
some
Golding, J. R., Lee, P. N., Butterworth, D. Br. med. J. 1974, i, 180. Henkin, R. I., Keiser, H. R., Jaffe, I. A., Sternlieb, I., Scheinberg, I. H. Lancet, 1967, ii, 1268. Lyle, W. H. ibid. 1974, ii, 1140. Pass, D., Goldfischer, S., Sternlieb, I., Scheinberg, I. H. Archs Derm. 1973, 108, 713. Bucknall, R. C., Dixon, A. St. J., Glick, E. N., Woodland, J., Zutshi, D. W. Br. med. J. 1975, i, 600.
8. Day, A. T., 9. 10. 11. 12.
reactivation with bleeding; and there was general scepticism about any effect on wound healing. Altogether, 19 patients are known to have died while taking penicillamine for various conditions. In 6 the drug was probably not responsible (deaths from cerebrovascular accidents, hypertensive heart-disease, postoperative embolism, coronary thrombosis). In 7 the drug was almost certainly the cause of death: 3 American patients with Wilson’s disease died of Goodpasture’s syndrome and 4 died of agranulocytosis or aplastic anxmia. The role of penicillamine This was debatable in the remaining 6 deaths. of adverse is as reactions not catalogue daunting as its length suggests. For most clinicians the important obstacles to successful treatment with penicillamine
thrombocytopenia, proteinuria, and rashes. Many patients can be encouraged to weather the nuisance are
effects. The final place of penicillamine in rheumatoid arthritis will rest not only on its proved efficacy in a substantial proportion of patients and the incidence and seriousness of adverse reactions but also on a comparison with the virtues and defects of other agents. For the moment, penicillamine will rarely be prescribed in early rheumatoid arthritis when the chances of a spontaneous remission are good and
simple analgesic/anti-inflammatory drugs, splints, and rest exert a sufficient measure of control-though the position would change if it could be shown to retard or stop the natural evolution of the disease. Most clinicians will probably think about using penicillamine when their patient’s arthritis shows signs of pursuing an aggressive course, and the alternatives will be gold, chloroquine, or an immunosuppressive drug. Chloroquine is less effective than gold, and for many penicillamine will seem less menacing than the immunosuppressive drugs, though the efficacy of the last two will certainly be compared. The results of a multicentre trial comparing gold with penicillamine 13 have already been published. There was little to choose between the efficacy of the twoboth were highly effective in about 4 patients out of 5 and there was no significant difference between them. Adverse effects were commoner with penicillamine, but withdrawal of treatment was more frequent when gold was given (mainly because of rashes). In patients with an early rash, penicillamine could often be re-started, whereas rashes with gold always recurred if treatment was resumed. In this trial penicillamine won by a short head because treatment less often had to be abandoned permanently. Like all such trials this one could not aspire to the stringent conditions of the ultimate test of widespread use. The relative incidence of rare but serious blood dyscrasias cannot be compared in clinical trials with groups of patients of manageable size. 13. Huskisson, E. C., Gibson, T. J., Balme, H. W., Berry, H., Burry, H. C., Grahame, R., Hart, F. D., Henderson, D. R. F., Wojtulewski, J. A. Ann. rheum. Dis. 1974, 33, 532.
1125
N.H.S. hospitals. All this comes at a time of such economic peril that any hopes of raising or even maintaining N.H.S. standards (to offset the attractions of private practice for patients and doctors) are vain. So, if it were done, then ’twere well it were done slowly; and the unions which are urging on the Government to rapid phasing-out must pause and contemplate again what damage they may do to the N.H.S. in its present delicate state. What Aneurin Bevan really thought about private practice is, as David McKie records on p. 1134, now a subject for quotation and counter-quotation. Our view is that he would have preferred private practice to lie entirely outside the N.H.S.-and so would we. has shown the need for a low initial dose and small But that was a long time back. Now that the shortages increments at long intervals. Yet this has happened, of money and everything else needed to sustain the and it would be sad if a promising method of treatService are dire, the pressure on the phasing-out ment fell into disrepute because of misuse or inaccelerator must be delicately applied. We are not adequate safeguards. opposed to the Government’s plans: we simply fear the consequences of advancing them hastily. Finally, the real wormwood for those who wish to A TANGLED PATH see an extension of private practice outside the N.H.S. POLITICIANS, once they are in office, are not spring from the coming events, or those who fear its renowned for pursuing exactly those courses which total elimination, lay in Mrs Castle’s references to they advocated before the election. On the issue of stricter licensing of private hospitals and nursingprivate practice in N.H.S. hospitals, however, Britain’s homes. Consultations are again promised; and, as David McKie remarks (p. 1134), fears of a direct present Government has undoubtedly so far escaped that gibe by setting out to do what it declared it would threat to private practice will dominate the attitude of the consultants. Again, too precipitate Government do-phase-out pay-beds from N.H.S. hospitals. The statement by the Secretary of State for Social Services, action may bring on " the rash of nursing-homes " in Mrs Barbara Castle, the House of Commons on (signs of the eruption are already very evident); and May 51 was the next logical step in a path which she to seek to control it, and the consequent loss of sees as the only way to eliminate injustices in the doctors, nurses, and other skilled staff from the N.H.S., distribution of health care; and which plenty of by licensing criteria other than those of quality would others see as a " monumental irrelevance " 2to the cause a fierce exacerbation of the conflict between real problems of the N.H.S. and as a doctrinaire Government and consultants. It is a tangled cliff edge Service by misjudgment which will damage along which the Government and Mrs Castle are depriving it of skilled manpower. Whoever is right, treading: if they can slowly reach a surer foothold, consultations on the phasing-out programme are to they will have achieved a valuable reform in health It is not one that The Lancet would begin at once; and legislation to effect it will be care in Britain. introduced as soon as Parliament has time. place at the top of today’s list of N.H.S. priorities; Mrs Castle bases her case largely on the argument but we do not condemn the Government on that that " the whole fabric of the National Health Service account. would rot away if the principle of treatment on the basis of medical priority only were ever to be seriously DRUGS FOR ARRHYTHMIAS undermined ". There she is absolutely right. The CARDIAC arrhythmias, particularly ventricular ectopic injustices, those situations in which the patient’s are important clinical events. In symptomless beats, to medical to be and not is seen ability pay, priority, individuals and in patients with myocardial infarction the determining consideration, lie almost entirely in they signify an increased risk of sudden death; but it the area of non-urgent surgery. A common N.H.S. is still not possible to say whether arrhythmias represent as has been the reasonable waiting-list widely proposed an independent risk factor, or whether the association eliminator of queue-jumping. The profession has is indirect owing to their prevalence in patients with never leapt at the idea, but its negotiators will no underlying heart-disease.1 No single treatment is doubt apply their minds to it again in the forthcoming consistently effective, hence the wide variety of antidiscussions. And the prompt provision of more arrhythmic drugs now available. The pathophysiology N.H.S. amenity beds, which might be physically none of arrhythmias is still largely unknown (which is too easy to achieve, would supply some of the privacy hardly surprising in view of the complexity of the it is is that most all want. which, said, private patients neural and chemical control of the heart and vascular The danger of too enthusiastic phasing-out is that system 2-4), but the newer techniques for recording it will aggravate inequalities by transfusing more national and medical resources into the private sector, 1. Kuller, L. H., Perper, J. A., Cooper, M. C. in Modern Trends in leaving an all too common (and longer) waiting-list in Cardiology 3 (edited by M. F. OLIVER); p. 292. London: Butter-
Any clinician who believes that his patient would benefit from penicillamine has the right to prescribe it. But he has a duty to acquaint himself of the hazards, to draw on the experience of others for guidance about dosage and supervision, and to ensure not only that blood and urine tests are done but also that he sees the results promptly and compares them with previous results. If he is in any doubt as to his ability to protect his -patient in this way he should invoke the help of a centre familiar with the drug. There is no justification for prescribing the drug in full doses from the start when hard-won experience
the
1. See Lancet, May 10, 2. See Br. med. J. May
1975, p. 1095. 10, 1975, p. 300.
2. 3.
4.
worths. 1975. £11. Sleight, P. ibid. p. 1. Barrett, A. M., Einstein, R. ibid. p. 44. Horton, E. W., Ungar, A. ibid. p. 67.
