640
Journal of the Royal Society of Medicine Volume 84 November 1991
treatment such as the HELP-System'4, originally designed to remove LDL from the plasma. At present this therapy is expensive and offers only an intermittent solution. Lowering fibrinogen may turn out to be the most valuable means to enhance the flow properties of blood. What then are the hard facts about haemorheological therapy? PAOD can be treated successfully by rheological means. It is still controversial whether this is true also for the management of ischaemia of the brain. Haemorheological treatment of coronary heart disease is but a hope for the future. One should, of course, also advocate simple common sense and the adoption of healthy lifestyles which have been shown to gently but safely normalize blood rheology in individuals at high risks2 - no cigarettes, more exercise, less stress, more fish in the daily diet and weight loss in the obese. This strategy may be the best in terms ofprevention, yet for treatment of ischaemic states it will usually be too weak. We need to rely on the pharmacological approaches outlined above and to encourage the research which will ultimately produce the ideal solution. E Ernst University of Vienna Allgemeines Krankenhaus Department of Physical Medicine Rehabilitation Wahringer Gurtel 18-20 A-1097 Vienna References 1 Goslinga H. Blood viscosity and shock. Berlin: Springer, 1984
What is the best dosage schedule for patients? Non-compliance by patients with the advice and treatment which they receive from their doctors is not a new discovery. Earlier this century Stephen Leacock wrote: 'In the old fashioned days when a man got sick he went to the family doctor and said he was sick. The doctor gave him a bottle of medicine. He took it home and drank it and got well. On the bottle was written, "Three times a day in water". The man drank it three times a day the first day, twice the second day, and once the third day. On the fourth day he forgot it. But that didn't matter. He was well by that time . . .'.
But it was only about 20 years ago that compliance was formally identified as an important factor in therapeutic evaluation'. The proportion of patients failing to follow protracted courses of treatment is thought to be greater than 50%2 and is considered to be associated with unnecessary morbidity and mortality in such chronic diseases as hypertension, asthma, diabetes and mental illness. A whole range of measures has been
2 Chien S, Dormandy J, Ernst E, Matrai A. Clinical hemorheology. Dordrecht: M. Nijhoff, 1987 3 Ernst E, Matrai A, Kollar L. Haemodilution in peripheral vascular disease, a placebo-controlled, double blind trial. Lancet 1987;ii:1449-51 4 Ernst E, Kollar L, Matrai A. A double-blind trial of Dextran haemodilution vs. placebo in claudicants. Int J Med 1990;227:19-24 5 Haal A. Hamorheologische Therapie, Stand und Perspektiven. Nervenarzt 1989;60:528-39 6 Back T, Kummer R. Blutverdunnung bei zerebraler Ischamie. Dtsch Med Wochenschr 1989;114:350-6 7 Goslinga H, Eijzenbach E. Importance ofblood viscosity in low flow states. Tijdschrift 1990;15:103-6 8 Gyton AC, Richardson TQ. Effect of hematocrit on venous return. Circ Res 1961;9:157-64 9 Ward A, Clissold SP. Pentoxifylline. Drugs 1987;34: 50-97 10 Lindgarde F. Conservative drug treatment in patients with moderately severe chronic occlusive peripheral arterial disease. Circulation 1989;80:1549-56 11 Ernst E, Kollar L, Resch KL, Bergmann H. Arterial occlusive disease. Comparison between Pentoxifylline and exercise vs. exercise alone in patients with stage II of disease. Munch Med Wochenschr 1990;132: 456-8 12 Ernst E. Plasma fibrinogen - an independent cardiovascular risk factor. J Intern Med 1990;227:36572 13 Ernst E. Therapeutic defibrinogenation in peripheral vascular disease. Int Angiol 1985;4:373-7 14 Schuff-Werner P, Schutz E, Seyde WC, et al. Improved haemorheology associated with a reduction in plasma fibrinogen and LDL in patients being treated by heparin - induced extracorporal LDL precipitation (HELP). Eur J Clin Invest 1989;19:30-7
suggested to improve patient compliance3 and some quite elaborate attempts have been made to measure compliance4. One of the factors that has been studied is the frequency of daily dosing, on the assumption that the fewer times a day a medicine has to be used, the closer the adherence to a treatment regimen. On this basis, once-daily dosing has been regarded as the target of perfection. However, the evidence for the superiority of once-daily dosing is equivocal and, in view of the many factors involved in patient compliance, it is questionable whether emphasis on this single factor is actually helpful to patients in improving the outcome of their recommended treatments. In diabetic patients, compliance with twice-daily oral dosing was similar to that of a once-daily regimen but both were superior to three-times-daily medication5. Furthermore, in a review of 57 publications on the relationship between patient compliance and medication dosing6, the rate of compliance with once-a-day dosing (73%) was similar to that of twicea-day dosing (70%) and significantly better than threetimes-daily (52%) and four-times-daily (42%) dosing. Other factors which impinge on the frequency of dosing are the importance of the interval between doses and the loss of therapeutic effect from missed doses. These aspects are especially important for medicines with a narrow therapeutic range and for those with a relatively short elimination half-life.
0140-0768/91/ 110640-02/$02.00/0 © 1991 The Royal Society of Medicine
Journal of the Royal Society of Medicine Volume 84 November 1991
The spacing of doses is more even with twice-daily treatment regimens than with three-times-daily dosing7 and a missed dose is likely to result in a greater loss of therapeutic effect with a once-daily regimen than with more frequent dosing. In the compulsion to attain a perceived marketing advantage, the frequency of missed and mistimed doses has been overlooked and their impact on the therapeutic effect has been ignored. In fact compliance with twice-daily dosing has been shown to be similar to that with once-a-day treatment but the former regimen may actually be better in terms of therapeutic effect because it has greater toleration of irregularities in the dosing schedule and consequently may be a better option for the patient. Peter J Keen Editorial Representative Library (Scientific Research) Section Royal Society of Medicine 1 Wimpole Street, London WIM 8AE
Some recent books Health care Audio Services for Children. Recommended Practice. The National Deaf Children's Society (pp 36 £5.00) Care of Old People: A Framework for Progress (Occasional paper 45). Royal College of General Practitioners (pp 23 £7.00). ISBN 0-85084-151-8, London: Royal College of General Practitioners 1991
Deprivation and Health in Scotland. Vera Carstairs and Russell Morris (pp 348 £19.95). ISBN 0-08-037979-6, Aberdeen: Aberdeen University Press 1991 Empowering the Elderly: Direct Consumer Funding ofCare Services CThe IEA Health and Welfare Unit Choice in Welfare Series No. 6). William Laing (pp 50). ISBN 0-255-362684, London: IEA Health and Welfare Unit, 1991
Interprofessional Collaboration in Primary Health Care Organizations (Occasional Paper 52). Bara A Gregson, Ann Cartlidge and John Bond (pp 52 £6.50). ISBN 0-85084-158-5, London: The Royal College of General Practitioners, 1991
References 1 Sackett D, Haynes RB, Taylor DW, Compliance in health care. Baltimore, Maryland: The Johns Hopkins University Press, 1979 2 Haskitt RL. Patient compliance: tapping into a billiondollar drug market. Pharmaceutical Executive July 1989;46-52 3 Peck CL, King NJ. Increasing patient compliance with prescriptions. JAMA 1982;248:2874-7 4 Pullar T, Feely M. Problems of compliance with drug treatment: new solutions? Pharm J 1990;245: 213-15 5 Pullar T, Birtwell AJ, Wiles PG, Hay A, Feely MP. Use of pharmacologic indicator to compare compliance with tablets prescribed to be taken once, twice, or three times daily. Clin Pharmacol Ther 1988;44:540-5 6 Greenberg RN. Overview of patient compliance with medication dosing: a literature review. Clin Ther 1984; 6:592-9 7 Alfriedsson LS, Norell SE. Spacing between doses on a thrice-daily regimen. BMJ 1981;282:1036
Medical Statistics on Microcomputers. R A Brown and J Swanson Beck (pp 103 £8.95). ISBN 0-7279-0290-3, London: British Medical Association, 1991
Other People's Tobacco Smoke. A K Armitage (pp 192 £12.95/US$25.00). ISBN 0-9508726-1-X, Yorkshire: Galen Press, 1991 Patient Information in Medicine. R D Mann (pp 199 £19.95). ISBN 1-85070-367-1, Carnforth: Parthenon Publishing, 1991
Primary Care for People with a Mental Handicap. Royal College of General Practitioners (pp 50 £7.50). ISBN 0-850-841-56-9, London: Royal College of General Practitioners, 1991. Testing People. A Practical Guide to Psychometrics. John R Beech and Leonora Harding (pp 164). ISBN 0-7005-1256-X, Berkshire: NFER-Nelson, 1990 Textbook ofAdverse Drug Reactions 4/e. D M Davies (£95.00). ISBN 0-19-262045-2, Oxford: Oxford University Press, 1991 The Childhood Environment and Adult Disease (Ciba Foundation Symposium No. 156). Ciba Foundation (pp 243 £39.50). ISBN 0-47-192957-3, Chichester: John Wiley & Sons Limited, 1991
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Journal of the Royal Society of Medicine Volume 84 November 1991
treatment such as the HELP-System'4, originally designed to remove LDL from the plasma. At present this therapy is expensive and offers only an intermittent solution. Lowering fibrinogen may turn out to be the most valuable means to enhance the flow properties of blood. What then are the hard facts about haemorheological therapy? PAOD can be treated successfully by rheological means. It is still controversial whether this is true also for the management of ischaemia of the brain. Haemorheological treatment of coronary heart disease is but a hope for the future. One should, of course, also advocate simple common sense and the adoption of healthy lifestyles which have been shown to gently but safely normalize blood rheology in individuals at high risks2 - no cigarettes, more exercise, less stress, more fish in the daily diet and weight loss in the obese. This strategy may be the best in terms ofprevention, yet for treatment of ischaemic states it will usually be too weak. We need to rely on the pharmacological approaches outlined above and to encourage the research which will ultimately produce the ideal solution. E Ernst University of Vienna Allgemeines Krankenhaus Department of Physical Medicine Rehabilitation Wahringer Gurtel 18-20 A-1097 Vienna References 1 Goslinga H. Blood viscosity and shock. Berlin: Springer, 1984
What is the best dosage schedule for patients? Non-compliance by patients with the advice and treatment which they receive from their doctors is not a new discovery. Earlier this century Stephen Leacock wrote: 'In the old fashioned days when a man got sick he went to the family doctor and said he was sick. The doctor gave him a bottle of medicine. He took it home and drank it and got well. On the bottle was written, "Three times a day in water". The man drank it three times a day the first day, twice the second day, and once the third day. On the fourth day he forgot it. But that didn't matter. He was well by that time . . .'.
But it was only about 20 years ago that compliance was formally identified as an important factor in therapeutic evaluation'. The proportion of patients failing to follow protracted courses of treatment is thought to be greater than 50%2 and is considered to be associated with unnecessary morbidity and mortality in such chronic diseases as hypertension, asthma, diabetes and mental illness. A whole range of measures has been
2 Chien S, Dormandy J, Ernst E, Matrai A. Clinical hemorheology. Dordrecht: M. Nijhoff, 1987 3 Ernst E, Matrai A, Kollar L. Haemodilution in peripheral vascular disease, a placebo-controlled, double blind trial. Lancet 1987;ii:1449-51 4 Ernst E, Kollar L, Matrai A. A double-blind trial of Dextran haemodilution vs. placebo in claudicants. Int J Med 1990;227:19-24 5 Haal A. Hamorheologische Therapie, Stand und Perspektiven. Nervenarzt 1989;60:528-39 6 Back T, Kummer R. Blutverdunnung bei zerebraler Ischamie. Dtsch Med Wochenschr 1989;114:350-6 7 Goslinga H, Eijzenbach E. Importance ofblood viscosity in low flow states. Tijdschrift 1990;15:103-6 8 Gyton AC, Richardson TQ. Effect of hematocrit on venous return. Circ Res 1961;9:157-64 9 Ward A, Clissold SP. Pentoxifylline. Drugs 1987;34: 50-97 10 Lindgarde F. Conservative drug treatment in patients with moderately severe chronic occlusive peripheral arterial disease. Circulation 1989;80:1549-56 11 Ernst E, Kollar L, Resch KL, Bergmann H. Arterial occlusive disease. Comparison between Pentoxifylline and exercise vs. exercise alone in patients with stage II of disease. Munch Med Wochenschr 1990;132: 456-8 12 Ernst E. Plasma fibrinogen - an independent cardiovascular risk factor. J Intern Med 1990;227:36572 13 Ernst E. Therapeutic defibrinogenation in peripheral vascular disease. Int Angiol 1985;4:373-7 14 Schuff-Werner P, Schutz E, Seyde WC, et al. Improved haemorheology associated with a reduction in plasma fibrinogen and LDL in patients being treated by heparin - induced extracorporal LDL precipitation (HELP). Eur J Clin Invest 1989;19:30-7
suggested to improve patient compliance3 and some quite elaborate attempts have been made to measure compliance4. One of the factors that has been studied is the frequency of daily dosing, on the assumption that the fewer times a day a medicine has to be used, the closer the adherence to a treatment regimen. On this basis, once-daily dosing has been regarded as the target of perfection. However, the evidence for the superiority of once-daily dosing is equivocal and, in view of the many factors involved in patient compliance, it is questionable whether emphasis on this single factor is actually helpful to patients in improving the outcome of their recommended treatments. In diabetic patients, compliance with twice-daily oral dosing was similar to that of a once-daily regimen but both were superior to three-times-daily medication5. Furthermore, in a review of 57 publications on the relationship between patient compliance and medication dosing6, the rate of compliance with once-a-day dosing (73%) was similar to that of twicea-day dosing (70%) and significantly better than threetimes-daily (52%) and four-times-daily (42%) dosing. Other factors which impinge on the frequency of dosing are the importance of the interval between doses and the loss of therapeutic effect from missed doses. These aspects are especially important for medicines with a narrow therapeutic range and for those with a relatively short elimination half-life.
0140-0768/91/ 110640-02/$02.00/0 © 1991 The Royal Society of Medicine
Journal of the Royal Society of Medicine Volume 84 November 1991
The spacing of doses is more even with twice-daily treatment regimens than with three-times-daily dosing7 and a missed dose is likely to result in a greater loss of therapeutic effect with a once-daily regimen than with more frequent dosing. In the compulsion to attain a perceived marketing advantage, the frequency of missed and mistimed doses has been overlooked and their impact on the therapeutic effect has been ignored. In fact compliance with twice-daily dosing has been shown to be similar to that with once-a-day treatment but the former regimen may actually be better in terms of therapeutic effect because it has greater toleration of irregularities in the dosing schedule and consequently may be a better option for the patient. Peter J Keen Editorial Representative Library (Scientific Research) Section Royal Society of Medicine 1 Wimpole Street, London WIM 8AE
Some recent books Health care Audio Services for Children. Recommended Practice. The National Deaf Children's Society (pp 36 £5.00) Care of Old People: A Framework for Progress (Occasional paper 45). Royal College of General Practitioners (pp 23 £7.00). ISBN 0-85084-151-8, London: Royal College of General Practitioners 1991
Deprivation and Health in Scotland. Vera Carstairs and Russell Morris (pp 348 £19.95). ISBN 0-08-037979-6, Aberdeen: Aberdeen University Press 1991 Empowering the Elderly: Direct Consumer Funding ofCare Services CThe IEA Health and Welfare Unit Choice in Welfare Series No. 6). William Laing (pp 50). ISBN 0-255-362684, London: IEA Health and Welfare Unit, 1991
Interprofessional Collaboration in Primary Health Care Organizations (Occasional Paper 52). Bara A Gregson, Ann Cartlidge and John Bond (pp 52 £6.50). ISBN 0-85084-158-5, London: The Royal College of General Practitioners, 1991
References 1 Sackett D, Haynes RB, Taylor DW, Compliance in health care. Baltimore, Maryland: The Johns Hopkins University Press, 1979 2 Haskitt RL. Patient compliance: tapping into a billiondollar drug market. Pharmaceutical Executive July 1989;46-52 3 Peck CL, King NJ. Increasing patient compliance with prescriptions. JAMA 1982;248:2874-7 4 Pullar T, Feely M. Problems of compliance with drug treatment: new solutions? Pharm J 1990;245: 213-15 5 Pullar T, Birtwell AJ, Wiles PG, Hay A, Feely MP. Use of pharmacologic indicator to compare compliance with tablets prescribed to be taken once, twice, or three times daily. Clin Pharmacol Ther 1988;44:540-5 6 Greenberg RN. Overview of patient compliance with medication dosing: a literature review. Clin Ther 1984; 6:592-9 7 Alfriedsson LS, Norell SE. Spacing between doses on a thrice-daily regimen. BMJ 1981;282:1036
Medical Statistics on Microcomputers. R A Brown and J Swanson Beck (pp 103 £8.95). ISBN 0-7279-0290-3, London: British Medical Association, 1991
Other People's Tobacco Smoke. A K Armitage (pp 192 £12.95/US$25.00). ISBN 0-9508726-1-X, Yorkshire: Galen Press, 1991 Patient Information in Medicine. R D Mann (pp 199 £19.95). ISBN 1-85070-367-1, Carnforth: Parthenon Publishing, 1991
Primary Care for People with a Mental Handicap. Royal College of General Practitioners (pp 50 £7.50). ISBN 0-850-841-56-9, London: Royal College of General Practitioners, 1991. Testing People. A Practical Guide to Psychometrics. John R Beech and Leonora Harding (pp 164). ISBN 0-7005-1256-X, Berkshire: NFER-Nelson, 1990 Textbook ofAdverse Drug Reactions 4/e. D M Davies (£95.00). ISBN 0-19-262045-2, Oxford: Oxford University Press, 1991 The Childhood Environment and Adult Disease (Ciba Foundation Symposium No. 156). Ciba Foundation (pp 243 £39.50). ISBN 0-47-192957-3, Chichester: John Wiley & Sons Limited, 1991
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