- Email: [email protected]
MASS STRATEGIES OF PREVENTION-THE SWINGS AND ROUNDABOUTS
1256
that many patients were middle class and so at relatively low risk. It would be tragic if self-selection by way of prior information, via informed consent or earlier, were to cloud the interpretation of the results of the new trial. It is a last chance, and the omens are not good. In a general practitioners’ newspaperl2 a professor of nutrition is reported to believe that it might almost be medical negligence to withhold vitamins from at-risk mothers; and the Belfast intervention study (unpublished) is claimed to have revealed a seven-fold advantage for supplementation. All concerned may live to regret the dithering that has preceded this potentially important trial. All the same, nothing in the past three years has altered the scientific case-and, therefore, the ethical case-for a trial such as the one the M.R.C. proposes; so, when the full Council meets on Tuesday, it should stick to its guns.
THE LITHOTRIPTER RENAL stones can now be pulverised by externally applied waves. The apparatus, known as the lithotripter, was developed by the Dornier Company in association with Prof. Ch. Chaussy and Prof. E. Schmiedt with a team from the Institute for Surgical Research, Ludwig-Maximillian University of Munich. Under continuous epidural anaesthesia the patient is lowered into a water-bath and positioned, under radiological control, so that the stone in the renal pelvis lies at the focal point ofa shock-wave generator in the bath beneath the patient. The shock-waves are produced by a high-voltage condenser spark discharge, each pulse lasting one microsecond. The spark electrode lies within an ellipsoidal reflector which focuses the wave form. 500-1000 single shock wave exposures are needed to disintegrate a stone 2 cm in diameter, and this takes some 45 min. To date, over 100 patients with renal pelvis stones have been treated and none required open operation. Only about 15% had some degree of renal colic during passage of the resulting particles which generally measure about 2 mm. Mild haematuria results and is monitored with continuous bladder catheter
shock
drainage. Shock-waves
are generated when a mass moves in a medium with a higher velocity than that of sound particular for the same medium. Each single impulse is of very high amplitude and very short duration. The spark at the electrode produces an immediate explosive evaporation of surrounding water with generation of shock-waves which are transmitted to the patient. A report like a pistol shot rings through the laboratory with each spark discharge and staff and patient have to wear earplugs. Preliminary resultshave now been confirmed and there is no doubt that extracorporeal shock-wave lithotripsy (ESWL) is a major advance in the management of kidney stones. Although the basic principle is simple, the equipment is currently very expensive, costing about as much as a CT scanner. The electrode has to be replaced after about 500 shocks and this too is expensive. On the other hand, patients leave hospital in 48 hours so that considerable financial
12. Mason I. Controvesial neural tube defect trials to go ahead. Pulse, Nov. 27, 1982: 3. 1 Chaussy Ch, Brendel W, Schmiedt E. Extracorporeally induced destruction of kidney stones by shock-waves. Lancet 1980; ii: 1265-68. 2. Chaussy Ch, Schmiedt E, Jocham D, Brendel W, Forsmann B, Walther V. First clinical
experience with extracorporeally induced destruction of kidney waves. J Urol 1982; 127: 417-20.
stones
by
shock-
savings result there. To date, patients with urinary-tract infection and ureteric obstruction have been excluded.With increasing experience, patients in these categories will probably be suitable for management by this new technique. Apart from the mild haematuria lithotripsy seems to be remarkably free from complications. Bone damage and local pulmonary infarction have been produced in laboratory animals, but this has not occurred in man. Careful radiological control with crossed image intensifier beams is important in this regard and to maximise the effect of the focused shock waves on the stone. The development of ESWL comes at a time when urologists and interventional radiologists have devised methods for removing stones from the renal pelvis by way ofaa percutaneous nephrostomy avoiding open operation. Various instruments, including wire baskets and forceps of different designs, have been used under radiological or endoscopic control. Marberger3has described a nephroscope which includes an ultrasonic lithotrite to fragment stones under vision. The resulting particles are flushed to the exterior by continuous irrigation. Of 20 patients 19 had a complete clearance after percutaneous nephrostomy, although more than one session In the Federal stone
required in a few cases. Republic of Germany some 22 000 kidney operations were performed in 1979 and these figures was
could be matched in many other countries. The prospects are now bright for removal of many stones without open surgery. The apparatus for ESWL is costly but the absence of surgical intervention is a great advantage.
MASS STRATEGIES OF PREVENTION-THE SWINGS AND ROUNDABOUTS THE major causes of ill-health and death among the middleaged in developed countries appear to be a consequence of people’s lifestyles. There is reason to believe that many of the cancers4 and much ischaemic heart disease and hypertension may be preventable. There can be no doubt that prevention of these diseases would provide a far more satisfactory and costeffective solution than expansion of therapeutic services alone. There are two main strategies of prevention. The first is to identify symptomless individuals who are at high risk of the disease and to offer them advice and support in changing those aspects of their lifestyles which put them at risk. This approach may not be satisfactory in circumstances where risk is related to a lifetime of ‘ ‘bodily abuse". By the time high-risk individuals are identified it may be too late for any behavioural change usefully to lower subsequent risk. The second strategy is to change the habits of the community as a whole.6 It is predicated upon the assumption that nearly everyone has some small risk of the disease but some people have greater risk than others. That is, individual risk is distributed in the population around some common average risk. A second assumption is that there is some identifiable aspect of lifestyle-e.g., smoking habit-such that risk progressively increases with the degree of indulgence in the 3. Alken P, Hutschenreiter G, Günther R, Marberger M. Percutaneous stone manipulation. J Urol 1981; 125: 463-66. 4. Doll R, Peto R. The causes of cancer. Oxford: Oxford University Press, 1981. 5. Joint working party of the Royal College of Physicians of London and the British Cardiac Society Prevention of coronary heart disease. J Roy Coll Phys 1976; 10: 3. 6. Rose G. Strategy of prevention: lessons from cardiovascular disease. Br Med J 1981; 282: 1847-51.
1257 habit. No assumptions need be made about so-called thresholds of risk. The intervention is aimed at persuading or
forcing the population
to decrease harmful behaviour or increase beneficial behaviour so that the population average risk is shifted downwards. A shift of the average need not imply that every individual has responded to the intervention. Nevertheless a small change in average risk may lead to considerable reduction in the manifestation of the disease in the population and these benefits may be far greater than could be attained by concentrating effort on some subsection of the population arbitrarily defined as being at high risk. The mass strategy is attractive in principle and has been gaining acceptance. Indeed an expert committee of the World Health Organisation has recommended that we are justified in advising populations to alter their dietary habits so as to reduce average serum cholesterol below 200 mg/dl. However, there are grounds to question the wisdom of this recommendation. It is not proven that the association between serum cholesterol level and ischaemic heart disease risk reflects cause and effect.8 Also there is debate9 as to where the optimum level lies. But most worrying is the statistical association 10 between low levels of serum cholesterol and risk of cancer. This risk seems to be small but it must be weighed against the supposed benefits of the mass strategy. It may be that mass strategies are less justified than appears at first sight. Should one not, until proven otherwise, always assume that one man’s reduction in risk may be another man’s increase in risk for a different disease? Might it not be that both extremes of the distribution of many kinds of behaviour and physiological variables are associated with raised risk? There is evidence for an optimum level of alcohol consumption.II-14 High intakes of alcohol lead to a danger of alcoholism and cirrhosis. Moderate intake may protect against ischaemic heart disease. Similarly the extremes of the haemoglobin distribution in people not known to be ill are associated with a small excess mortality.15 In circumstances such as these, mass prevention should aim to reduce the scatter around the population average risk rather than reduce the average itself. However this may hardly be feasible. A distinction6 may be drawn between preventive strategies which seek to remove an unnatural factor and thereby restore "biological normality" and those which seek to add an unnatural factor in the hope of conferring protection. The former might include encouraging people to reduce consumption of saturated fats whereas the latter might be to encourage greatly increased consumption of polyunsaturates. However, it is not always clear what is biologically normal and, if both strategies lead to lowering of serum cholesterol and increase cancer risk, then the distinction ceases to be useful.
7. W.H.O.
Expert Committee. Prevention of coronary heart disease.
WHO TechRepSer
no. 678, 1982.
Coronary heart disease, cancer, lipoproteins, and the effects of clofibrate: Is enzyme induction a common link and are lipoproteins red herrings? Lancet 1981; ii: 1258-59. 9. Kannel WB, Gordon T. The search for an optimum serum cholesterol. Lancet 1982; ii: 374-75. See also correspondence pp. 655, 656, 815, 816. 10. Oliver MF. Serum cholesterol-the knave of hearts and the joker. Lancet 1981; ii: 1090-95. 11. Editorial. Need pleasure be harmful. Lancet 1980; i: 350. 12. Dyer AR, et al. Alcohol, cardiovascular risk factors and mortality. The Chicago experience. Circulation 1981; 64 (suppl. 3): 1, 20-27. 13. Kagan A, et al. Alcohol and cardiovascular disease: the Hawaiian experience. Circulation 1981; 64 (suppl. 3): 27-31. 14. Marmot MG, Rose G, Shipley MJ, Thomas BJ. Alcohol and mortality: a U-shaped curve. Lancet 1981; i: 580-83. 15 Elwood PC, Waters WE, Benjamin IT, Sweetnam PM. Mortality and anaemia in women.Lancet 1974; i: 891-94. 8. Heller RF.
Even when there are no doubts that a change in habit can alter average risk without incidentally harming anybody, it is a long step to justifying such a change as the basis of a mass strategy. For example, it is one thing to show that increasing dietary potassium intake in twenty healthy volunteers reduces their average blood-pressurel6 and quite another to claim that this action forms the basis of a mass strategy. The authors of,this and other similar small studies are acting perfectly properly when they point out the practical potential of their results in a larger context, but it would be unwise for others to latch onto such findings and dive straight into a mass intervention. Findings from small studies must first be replicated on a much larger sample of people more representative of the community as a whole. Strategies of mass prevention may well be the way forward in controlling many chronic diseases. However, if the public and policy makers are to have confidence in the recommendations of the medical profession then we should ensure that we base them on sound evidence. Furthermore we must be clear that the benefits outweigh the risks. The chronic diseases have been with us for some time and perhaps a little delay whilst we sort out the ethics of our proposals would do less harm than premature action.
THE INFLUENCE OF DRUG ADVERTISEMENTS
DRUG advertising by the pharmaceutical industry has come under renewed criticism. Grahame-Smith is reportedl as deploring the poor standard of advertisements and putting the blame on the medical profession: if doctors did not respond to these advertisements, he argues, industry would not spend money on them. The extent to which prescribing is influenced by advertisements is uncertain. Most advertisements do not give enough information to assist a practitioner to make a decision on prescribing;2 and although research by the Medical Sociology Research Centre, Swansea,3 showed that more than 60% of general practitioners found them helpful in notifying the existence of a
drug, only
17%
thought they provided adequate
information on usefulness-a hopeful distinction. In support of this view, the editor of the British Journal of Hospital Medicine (which depends almost wholly on pharmaceutical company advertising) claimed that only a "deranged few" could be influenced by such advertisements.4 Nevertheless, other studies from the Swansea group5 showed that, among various therapeutic classes, distributions of prescriptions and journal advertisements were similar and apparently related. Further evidence for the influence, albeit unrecognised, of advertisements, comes from an analysis of the prescribing behaviour of 85 physicians in Boston, U.S.A.6 Answering questionnaires, 68% of them claimed that drug advertisements had "minimal" importance in influencing their prescribing habits, 28% moderate importance, and only KT, Thom S. Randomised double-blind cross-over trial of potassium on blood in normal subjects. Lancet 1982; ii: 1127-29. 1 Anonymous. "Doctors to blame for poor standard of industry advertising". Pharm J 1982; 229: 517. 2. Stimson GV Information contained in drug advertisements. Br Med J 1975; iv:
16. Khaw
pressure
508-09.
Sociology. Research Centre, University College of Swansea, Wales. Prescribing in general practice. J Roy Coil Gen Pract 1976; 26 (suppl. 1): 58-64. 4. Editorial rejoinder Br J Hosp Med 1981; 25: 309. 5. Medical Sociology Research Centre, University College of Swansea, Wales. Prescribing in general practJ Roy Coll Gen Practit 1976; 26 (suppl. 1): 69-76. 6. Avon J, Chen M, Hartley R Scientific versus commercial sources of influence on the prescribing behaviour of physicians. AmJ Med 1982; 73: 4-8. 3 Medical
that many patients were middle class and so at relatively low risk. It would be tragic if self-selection by way of prior information, via informed consent or earlier, were to cloud the interpretation of the results of the new trial. It is a last chance, and the omens are not good. In a general practitioners’ newspaperl2 a professor of nutrition is reported to believe that it might almost be medical negligence to withhold vitamins from at-risk mothers; and the Belfast intervention study (unpublished) is claimed to have revealed a seven-fold advantage for supplementation. All concerned may live to regret the dithering that has preceded this potentially important trial. All the same, nothing in the past three years has altered the scientific case-and, therefore, the ethical case-for a trial such as the one the M.R.C. proposes; so, when the full Council meets on Tuesday, it should stick to its guns.
THE LITHOTRIPTER RENAL stones can now be pulverised by externally applied waves. The apparatus, known as the lithotripter, was developed by the Dornier Company in association with Prof. Ch. Chaussy and Prof. E. Schmiedt with a team from the Institute for Surgical Research, Ludwig-Maximillian University of Munich. Under continuous epidural anaesthesia the patient is lowered into a water-bath and positioned, under radiological control, so that the stone in the renal pelvis lies at the focal point ofa shock-wave generator in the bath beneath the patient. The shock-waves are produced by a high-voltage condenser spark discharge, each pulse lasting one microsecond. The spark electrode lies within an ellipsoidal reflector which focuses the wave form. 500-1000 single shock wave exposures are needed to disintegrate a stone 2 cm in diameter, and this takes some 45 min. To date, over 100 patients with renal pelvis stones have been treated and none required open operation. Only about 15% had some degree of renal colic during passage of the resulting particles which generally measure about 2 mm. Mild haematuria results and is monitored with continuous bladder catheter
shock
drainage. Shock-waves
are generated when a mass moves in a medium with a higher velocity than that of sound particular for the same medium. Each single impulse is of very high amplitude and very short duration. The spark at the electrode produces an immediate explosive evaporation of surrounding water with generation of shock-waves which are transmitted to the patient. A report like a pistol shot rings through the laboratory with each spark discharge and staff and patient have to wear earplugs. Preliminary resultshave now been confirmed and there is no doubt that extracorporeal shock-wave lithotripsy (ESWL) is a major advance in the management of kidney stones. Although the basic principle is simple, the equipment is currently very expensive, costing about as much as a CT scanner. The electrode has to be replaced after about 500 shocks and this too is expensive. On the other hand, patients leave hospital in 48 hours so that considerable financial
12. Mason I. Controvesial neural tube defect trials to go ahead. Pulse, Nov. 27, 1982: 3. 1 Chaussy Ch, Brendel W, Schmiedt E. Extracorporeally induced destruction of kidney stones by shock-waves. Lancet 1980; ii: 1265-68. 2. Chaussy Ch, Schmiedt E, Jocham D, Brendel W, Forsmann B, Walther V. First clinical
experience with extracorporeally induced destruction of kidney waves. J Urol 1982; 127: 417-20.
stones
by
shock-
savings result there. To date, patients with urinary-tract infection and ureteric obstruction have been excluded.With increasing experience, patients in these categories will probably be suitable for management by this new technique. Apart from the mild haematuria lithotripsy seems to be remarkably free from complications. Bone damage and local pulmonary infarction have been produced in laboratory animals, but this has not occurred in man. Careful radiological control with crossed image intensifier beams is important in this regard and to maximise the effect of the focused shock waves on the stone. The development of ESWL comes at a time when urologists and interventional radiologists have devised methods for removing stones from the renal pelvis by way ofaa percutaneous nephrostomy avoiding open operation. Various instruments, including wire baskets and forceps of different designs, have been used under radiological or endoscopic control. Marberger3has described a nephroscope which includes an ultrasonic lithotrite to fragment stones under vision. The resulting particles are flushed to the exterior by continuous irrigation. Of 20 patients 19 had a complete clearance after percutaneous nephrostomy, although more than one session In the Federal stone
required in a few cases. Republic of Germany some 22 000 kidney operations were performed in 1979 and these figures was
could be matched in many other countries. The prospects are now bright for removal of many stones without open surgery. The apparatus for ESWL is costly but the absence of surgical intervention is a great advantage.
MASS STRATEGIES OF PREVENTION-THE SWINGS AND ROUNDABOUTS THE major causes of ill-health and death among the middleaged in developed countries appear to be a consequence of people’s lifestyles. There is reason to believe that many of the cancers4 and much ischaemic heart disease and hypertension may be preventable. There can be no doubt that prevention of these diseases would provide a far more satisfactory and costeffective solution than expansion of therapeutic services alone. There are two main strategies of prevention. The first is to identify symptomless individuals who are at high risk of the disease and to offer them advice and support in changing those aspects of their lifestyles which put them at risk. This approach may not be satisfactory in circumstances where risk is related to a lifetime of ‘ ‘bodily abuse". By the time high-risk individuals are identified it may be too late for any behavioural change usefully to lower subsequent risk. The second strategy is to change the habits of the community as a whole.6 It is predicated upon the assumption that nearly everyone has some small risk of the disease but some people have greater risk than others. That is, individual risk is distributed in the population around some common average risk. A second assumption is that there is some identifiable aspect of lifestyle-e.g., smoking habit-such that risk progressively increases with the degree of indulgence in the 3. Alken P, Hutschenreiter G, Günther R, Marberger M. Percutaneous stone manipulation. J Urol 1981; 125: 463-66. 4. Doll R, Peto R. The causes of cancer. Oxford: Oxford University Press, 1981. 5. Joint working party of the Royal College of Physicians of London and the British Cardiac Society Prevention of coronary heart disease. J Roy Coll Phys 1976; 10: 3. 6. Rose G. Strategy of prevention: lessons from cardiovascular disease. Br Med J 1981; 282: 1847-51.
1257 habit. No assumptions need be made about so-called thresholds of risk. The intervention is aimed at persuading or
forcing the population
to decrease harmful behaviour or increase beneficial behaviour so that the population average risk is shifted downwards. A shift of the average need not imply that every individual has responded to the intervention. Nevertheless a small change in average risk may lead to considerable reduction in the manifestation of the disease in the population and these benefits may be far greater than could be attained by concentrating effort on some subsection of the population arbitrarily defined as being at high risk. The mass strategy is attractive in principle and has been gaining acceptance. Indeed an expert committee of the World Health Organisation has recommended that we are justified in advising populations to alter their dietary habits so as to reduce average serum cholesterol below 200 mg/dl. However, there are grounds to question the wisdom of this recommendation. It is not proven that the association between serum cholesterol level and ischaemic heart disease risk reflects cause and effect.8 Also there is debate9 as to where the optimum level lies. But most worrying is the statistical association 10 between low levels of serum cholesterol and risk of cancer. This risk seems to be small but it must be weighed against the supposed benefits of the mass strategy. It may be that mass strategies are less justified than appears at first sight. Should one not, until proven otherwise, always assume that one man’s reduction in risk may be another man’s increase in risk for a different disease? Might it not be that both extremes of the distribution of many kinds of behaviour and physiological variables are associated with raised risk? There is evidence for an optimum level of alcohol consumption.II-14 High intakes of alcohol lead to a danger of alcoholism and cirrhosis. Moderate intake may protect against ischaemic heart disease. Similarly the extremes of the haemoglobin distribution in people not known to be ill are associated with a small excess mortality.15 In circumstances such as these, mass prevention should aim to reduce the scatter around the population average risk rather than reduce the average itself. However this may hardly be feasible. A distinction6 may be drawn between preventive strategies which seek to remove an unnatural factor and thereby restore "biological normality" and those which seek to add an unnatural factor in the hope of conferring protection. The former might include encouraging people to reduce consumption of saturated fats whereas the latter might be to encourage greatly increased consumption of polyunsaturates. However, it is not always clear what is biologically normal and, if both strategies lead to lowering of serum cholesterol and increase cancer risk, then the distinction ceases to be useful.
7. W.H.O.
Expert Committee. Prevention of coronary heart disease.
WHO TechRepSer
no. 678, 1982.
Coronary heart disease, cancer, lipoproteins, and the effects of clofibrate: Is enzyme induction a common link and are lipoproteins red herrings? Lancet 1981; ii: 1258-59. 9. Kannel WB, Gordon T. The search for an optimum serum cholesterol. Lancet 1982; ii: 374-75. See also correspondence pp. 655, 656, 815, 816. 10. Oliver MF. Serum cholesterol-the knave of hearts and the joker. Lancet 1981; ii: 1090-95. 11. Editorial. Need pleasure be harmful. Lancet 1980; i: 350. 12. Dyer AR, et al. Alcohol, cardiovascular risk factors and mortality. The Chicago experience. Circulation 1981; 64 (suppl. 3): 1, 20-27. 13. Kagan A, et al. Alcohol and cardiovascular disease: the Hawaiian experience. Circulation 1981; 64 (suppl. 3): 27-31. 14. Marmot MG, Rose G, Shipley MJ, Thomas BJ. Alcohol and mortality: a U-shaped curve. Lancet 1981; i: 580-83. 15 Elwood PC, Waters WE, Benjamin IT, Sweetnam PM. Mortality and anaemia in women.Lancet 1974; i: 891-94. 8. Heller RF.
Even when there are no doubts that a change in habit can alter average risk without incidentally harming anybody, it is a long step to justifying such a change as the basis of a mass strategy. For example, it is one thing to show that increasing dietary potassium intake in twenty healthy volunteers reduces their average blood-pressurel6 and quite another to claim that this action forms the basis of a mass strategy. The authors of,this and other similar small studies are acting perfectly properly when they point out the practical potential of their results in a larger context, but it would be unwise for others to latch onto such findings and dive straight into a mass intervention. Findings from small studies must first be replicated on a much larger sample of people more representative of the community as a whole. Strategies of mass prevention may well be the way forward in controlling many chronic diseases. However, if the public and policy makers are to have confidence in the recommendations of the medical profession then we should ensure that we base them on sound evidence. Furthermore we must be clear that the benefits outweigh the risks. The chronic diseases have been with us for some time and perhaps a little delay whilst we sort out the ethics of our proposals would do less harm than premature action.
THE INFLUENCE OF DRUG ADVERTISEMENTS
DRUG advertising by the pharmaceutical industry has come under renewed criticism. Grahame-Smith is reportedl as deploring the poor standard of advertisements and putting the blame on the medical profession: if doctors did not respond to these advertisements, he argues, industry would not spend money on them. The extent to which prescribing is influenced by advertisements is uncertain. Most advertisements do not give enough information to assist a practitioner to make a decision on prescribing;2 and although research by the Medical Sociology Research Centre, Swansea,3 showed that more than 60% of general practitioners found them helpful in notifying the existence of a
drug, only
17%
thought they provided adequate
information on usefulness-a hopeful distinction. In support of this view, the editor of the British Journal of Hospital Medicine (which depends almost wholly on pharmaceutical company advertising) claimed that only a "deranged few" could be influenced by such advertisements.4 Nevertheless, other studies from the Swansea group5 showed that, among various therapeutic classes, distributions of prescriptions and journal advertisements were similar and apparently related. Further evidence for the influence, albeit unrecognised, of advertisements, comes from an analysis of the prescribing behaviour of 85 physicians in Boston, U.S.A.6 Answering questionnaires, 68% of them claimed that drug advertisements had "minimal" importance in influencing their prescribing habits, 28% moderate importance, and only KT, Thom S. Randomised double-blind cross-over trial of potassium on blood in normal subjects. Lancet 1982; ii: 1127-29. 1 Anonymous. "Doctors to blame for poor standard of industry advertising". Pharm J 1982; 229: 517. 2. Stimson GV Information contained in drug advertisements. Br Med J 1975; iv:
16. Khaw
pressure
508-09.
Sociology. Research Centre, University College of Swansea, Wales. Prescribing in general practice. J Roy Coil Gen Pract 1976; 26 (suppl. 1): 58-64. 4. Editorial rejoinder Br J Hosp Med 1981; 25: 309. 5. Medical Sociology Research Centre, University College of Swansea, Wales. Prescribing in general practJ Roy Coll Gen Practit 1976; 26 (suppl. 1): 69-76. 6. Avon J, Chen M, Hartley R Scientific versus commercial sources of influence on the prescribing behaviour of physicians. AmJ Med 1982; 73: 4-8. 3 Medical