813
Publicity and unpublished results S!R,—Your correspondence about publicity raises important issues that have wider relevance. Both your contributors (Feb 29, p 556) accept that considerable anxiety can be caused to patients if the results of research are reported in sensational terms by the press and on television before publication in medical journals. However, the media have as keen an appetite for "could have been saved" stories as for "major breakthrough" stories. There is no easier way for those seeking publicity or extra funding to draw attention to a cause than to approach the general press directly stating that a patient has died because a particular resource was not available-and at least four such instances have been widely reported this year. The real story is that anxiety and distress will be caused to patients with similar medical conditions or who attend the same hospitals or unit. Individual doctors who present clinical research or draw funding difficulties to public attention can make a useful contribution to the debate of important issues. However, the media is not the forum for the careful evaluation of research data nor necessarily for balanced argument about resource priorities. Furthermore, public confidence could be diminished if these practices were to become the norm. The Royal Colleges and editors of medical journals are well placed to guide the profession. Under what circumstances should the results of multicentre trials first be presented to the general press? Should there be a minimum number of signatories if serious allegations about lack of resources are to be made to the general media? At present there are no guidelines: recent widespread publicity indicates that there probably now need to be. Barnet and Edgware Hospitals, London EN5
ROBERT WINTER
3DJ, UK
Finnish survey of public opinion about
public expenditure SIR,-Malcolm Dean (Dec 14, p 1511) compares results of public (NHS). He points out the difficulty of posing the right questions. The theme was continued by Dr Richardson and Dr Chamy (Jan 18, p 184), who discuss economic constraints and possible reallocation of public surveys about the UK National Health Service
spending. a long period of steady economic growth and of development welfare and health has ended. The gross domestic product increase in 1990 was 0-4% and in 1991 it was 6-2%. Tax revenues have failed to meet earlier estimates and a fiscal crisis in the public sector is a reality. The issues are no longer what to spend on and how much more money is needed, but how to limit the growth of the public sector and how to make the best use of present
In
Finland,
resources.
In August, 1991, the National Agency for Welfare and Health asked a representative sample of the Finnish population how the public economy ought to be balanced. Of 998 people interviewed, 80% chose to cut expenditure. Other alternatives were supported RESULTS OF PUBLIC SURVEY OF SPENDING CUTS IN PUBLIC SECTOR
only by some respondents: raising taxes (3%), borrowing money (6%), and raising client’s fees (7%). When asked where savings could be made the result was very similar to that of the Cardiff Health Survey (table).1,2 The Cardiff Health Survey has found the right approach by introducing comparisons. In our survey, to note, for example, that 23% of the population sees no possibility of saving in defence expenditure is meaningless, but when compared with the respective figure of 75 % for health care it becomes of value. Answers to survey questions have no natural scale, and therefore comparative reference points are needed. We can then safely conclude that the welfare state is closer to the heart of the Finnish population than defence or agricultural support. National Agency for Welfare and Health, PO Box 220, 00531 Helsinki, Finland
HANNU UUSITALO TUIRE SIHVO
1.
Charny MC, Lewis PA. Does health knowledge affect eating habits? Health Educ J
2.
Charny MC, Farrow SC, Lewis PA. Who is using cervical cancer screening services?
1987; 4: 172-76. Health Trends 1987; 19: 3-5.
Serious intercurrent disease in healthy volunteers in clinical pharmacological research SIR,-Dr Kroon and Dr Cohen (Feb 22, p 504) provide a valuable reminder that screening healthy volunteers for a research study may occasionally yield some distressing surprises. Vazquez and P reported a parallel experience in which three young and
apparently healthy medical students who had volunteered for research studies were found to have previously unsuspected HIV infection, chronic persistent hepatitis, and a focal lesion in the brain, respectively. The serious difficulty we encountered was the emotional stress for the volunteer and the investigator. Both experienced a sudden change in role. The volunteer was transformed from a healthy student with bright prospects into a frightened patient with a potentially life-threatening illness. The researcher was transformed from an objective investigator into an involved counsellor with no experience or guidelines for coping with this unfamiliar and emotionally charged problem. All the volunteers with abnormal findings were eventually referred for specialist care and follow-up. Clinical researchers who recruit healthy controls would be well advised to plan for similar unpleasant surprises. For example, institutional committees that oversee human research might draft guidelines for the management of these sporadic occurrences, with emphasis on prompt counselling and appropriate care for the affected volunteer, and protection of their confidentiality. Informed consent forms might even warn research volunteers that the screening process could reveal some previously unsuspected abnormality. Department of Medicine, New York Medical College, Staten Island, New York 10310, USA 1.
MICHAEL PHILLIPS
Phillips M, Vazquez AJ. Abnormal findings in "normal" research
volunteers.
Controlled Clin Trials 1987; 8: 338-42.
Day care and
pregnancy hypertension SIR,-Dr Tuffnell and colleagues (Jan 25, p 224) report that the introduction of a daycare unit for hypertension in pregnancy reduces the need for and length of antenatal admissions and did not adversely affect outcomes. Our comparison of a daycare system in Glasgow with an inpatient-based system in Aberdeen has revealed
*eg, day-care, homehelp, residential care teg, pensions, sickness, unemployment secunt’
similar effects.’ The degree to which the reduction in inpatient care will lead to savings for the hospital depends on how the inpatient resources freed are used and on the additional outpatient resource use. We found that, for patients similar to those studied by Tuffnell et al, costs are lower for patients managed by day care but not significantly so. We too found that women are prepared to come to a daycare unit frequently to avoid admission. Most daycare attenders
814
and
inpatients were prepared to come to day care 5 times per week. Only 1 woman, who had a poor obstetric history, was not prepared to come to day care. Since outcomes are not adversely affected and patients prefer day care, such care should be encouraged. However the costs savings may be small unless the inpatient beds no longer needed are closed and staff numbers reduced. Department of Public Health, Glasgow Royal Maternity Hospital, Glasgow G4 ONA, UK
SARA TWADDLE
Department of Obstetrics and Gynaecology, University of Aberdeen,
VALERIE HARPER
Aberdeen 1. Twaddle
S, Harper V. An economic evaluation of daycare for hypertension in Br J Obstet Gynaecol (in press).
pregnancy.
Worldwide
worsening wheezing—is the cure
the cause?
StR,—Ten years ago a second epidemic of asthma mortality was first reported in New Zealand.! Since then several countries have reported more gradual increases in mortality, significant increases in admission rates for asthma, and evidence suggesting an increased prevalence of asthma and wheezing. These trends continue to be the subject of speculation, controversy, and concern. Changes in mortality are the most clear-cut and extensively studied. Two patterns have emerged. Epidemic increases were associated with the introduction and widespread use of two high-dose beta-agonists. In the 1960s, epidemics were noted in six countries where high-dose inhaled isoprenaline aerosol was available2 and in the 1970s a second epidemic, confined to New Zealand, was associated with fenoterol. The mechanism for the increased risks associated with these agents is unknown. In contrast to these epidemics, several countries, including the UK and USA, have reported gradual but significant increases in asthma mortality over the past 15-20 years, and increases in admission rates and prevalence.’ The suggestion from these changes is that asthma is becoming more prevalent and severe in different environments around the world. Possible explanations include diagnostic transfer, changes in the delivery of health care, and increased awareness amongst patients and physicians leading to greater self-reporting of asthma. In 1989 Mitchell suggested that beta-agonists might be responsible for increasing asthma mortality and morbidity, referring to evidence of increased bronchial hyperresponsiveness after short periods of regular treatment with beta-agonists. Sears et al6 have reported an increase in clinical asthma severity when fenoterol was added regularly to an on-demand drug regimenand Van Schayck et aF have reported greater reduction in baseline lung function when either salbutamol or ipratropium bromide were given regularly rather than on demand. The implications are that beta-agonists or bronchodilators in general can cause deteriorations in lung function and increases in asthma severity when used regularly. These findings support an association between bronchodilator use and increasing hospital admissions and asthma mortality.6 These effects of bronchodilators may also account for the reported increases in prevalence, we suggest. A child presenting with an episode of wheezing is now more likely to receive a diagnosis of asthma and be given treatment with bronchodilators than a diagnosis of wheezy bronchitis and treatment with antibiotics. Potentially this could lead to a deterioration in symptoms, prolongation of the episode, and the requirement for yet more bronchodilator therapy. In this situation the event is both more likely to be labelled as asthma and more likely to be recalled by the patient or parent in the survey setting. Thus by shifting the "curve" of asthma symptom severity in the community to the left, the possibility arises that the reported prevalence of hospital admissions for, and mortality from, asthma are increased by the regular and widespread use of bronchodilators, principally beta-agonists. We must not overinterpret associations between drug sales/use and trends in asthma prevalence, mortality, and morbidity, especially over long periods. Nevertheless the possibility of an asociation between bronchodilators and these trends must be seriously entertained. Should the association prove to be causal it
would be important to find out whether this applied to bronchodilators in general and the extent to which the effects are specific to individual beta-agonists or the class as a whole. For the individual with wheezing the implications would be profound. To avoid worsening asthma in the longer term a rethink of asthma management strategies would be required, with patients taking bronchodilators solely to relieve airway obstruction, rather than regularly. The widely promoted concept of asthma selfmanagement would be even more important, requiring patients to adjust bronchodilator therapy to a minimum based on a regular and educated interpretation of lung function. JULIAN CRANE Wellington Asthma Research Group, NEIL PEARCE Department of Medicine, RICHARD BEASLEY School of Medicine, CARL BURGESS Wellington, New Zealand Jackson RT, Beaglehole R, Rea HH, Sutherland DC. Mortality from asthma: a new epidemic in New Zealand Br Med J 1982; 285: 771-74. 2. Stolley PD, Schinnar R. Association between asthma mortality and isoproterenol. a review. Prev Med 1978; 7: 519-38. 3. Grainger J, Woodman K, Pearce N, et al. Prescribed fenoterol and death from asthma in New Zealand, 1981-1987: a further case control study. Thorax 1991; 46: 105-11. 4. Buist AS, Vollmer WM Reflections on the rise in asthma morbidity and mortality. JAMA 1990, 264: 1719-28. 5. Mitchell EA. Is current treatment increasing asthma mortality and morbidity? Thorax 1989; 44: 81-84. 6 Sears MR, Taylor DR, Print CG, et al. Regular inhaled beta-agonist treatment m bronchial asthma. Lancet 1990; 336: 1391-96. 7. Van Schayck CP, Dompelmg E, van Herwaarden LA, et al. Bronchodilator treatment 1.
moderate asthma randomised controlled m
or
chronic bronchitis continuous Br Med J 1991; 303: 1426-31.
or on
demand? A
study.
Dependence and oestrogen replacement SIR,-We are interested in the responses (Feb 22, p 505) from menopause experts to our idea (Feb 1, p 290) that drug dependence might occur with oestrogen prescribed as hormone replacement
therapy (HRT). This possible side-effect has not yet been sought. The little, though highly suggestive, evidence is the combination of psychoactivity, reports of shorter intervals between clinic visits, and the development of supraphysiological levels in a minority. To respond that many women use HRT safely, that some doctors in the past prescribed high doses, that symptoms are relieved, or that women have "dependence on good health" is irrelevant: that does not prove the absence of drug dependence. The comparison of postmenopausal oestrogen with insulin is misleading. Diabetes is not a disease that spontaneously recedes, unlike many climacteric symptoms, and its definition relates to absolute high levels of glucose. The analogy ignores the central prescribing problem. Are the postmenopausal years a state of disease, namely "oestrogen deficiency"? If so, are symptom-free women also diseased? Or does the menopause mark the (sometimes painful) transition from one normal level of oestrogen to another (as with menarche and pregnancy). Or is it more complex still, with some symptoms related to absolute, and others to changing levels? As Mr Studd points out, symptoms that return 4-8 months after implants despite normal oestradiol levels (for the reproductive years), are related to falling, not absolute, levels. If the menopause causes symptoms due to falling levels of oestrogen, it is inevitable that the wellbeing induced by oestrogen as levels rise will be followed by suffering as levels fall and thus produce a need to continue taking the drug (even without an added effect if it is dependence-inducing). Also the rational treatment might be a tailored, slowly reducing dose over a fixed period, not a constant and limitless supply of replacement. However, if postmenopausal oestrogen does prolong life and health, there is a completely different indication for preventive prescribing, without defining all older women as having a deficiency disease, and dependence could then be welcomed for compliance. Women may feel better because the drug relieves symptoms and/or because it is a euphoriant. The two effects have not been distinguished, and it is the second which should be the cause for concern. If dependence were shown to exist, even in a small number of women on implants, it would be likely to be a property of the drug and the dose and not just the route of administration. Oral codeine and intravenous morphine can both cause dependence, to different
Publicity and unpublished results S!R,—Your correspondence about publicity raises important issues that have wider relevance. Both your contributors (Feb 29, p 556) accept that considerable anxiety can be caused to patients if the results of research are reported in sensational terms by the press and on television before publication in medical journals. However, the media have as keen an appetite for "could have been saved" stories as for "major breakthrough" stories. There is no easier way for those seeking publicity or extra funding to draw attention to a cause than to approach the general press directly stating that a patient has died because a particular resource was not available-and at least four such instances have been widely reported this year. The real story is that anxiety and distress will be caused to patients with similar medical conditions or who attend the same hospitals or unit. Individual doctors who present clinical research or draw funding difficulties to public attention can make a useful contribution to the debate of important issues. However, the media is not the forum for the careful evaluation of research data nor necessarily for balanced argument about resource priorities. Furthermore, public confidence could be diminished if these practices were to become the norm. The Royal Colleges and editors of medical journals are well placed to guide the profession. Under what circumstances should the results of multicentre trials first be presented to the general press? Should there be a minimum number of signatories if serious allegations about lack of resources are to be made to the general media? At present there are no guidelines: recent widespread publicity indicates that there probably now need to be. Barnet and Edgware Hospitals, London EN5
ROBERT WINTER
3DJ, UK
Finnish survey of public opinion about
public expenditure SIR,-Malcolm Dean (Dec 14, p 1511) compares results of public (NHS). He points out the difficulty of posing the right questions. The theme was continued by Dr Richardson and Dr Chamy (Jan 18, p 184), who discuss economic constraints and possible reallocation of public surveys about the UK National Health Service
spending. a long period of steady economic growth and of development welfare and health has ended. The gross domestic product increase in 1990 was 0-4% and in 1991 it was 6-2%. Tax revenues have failed to meet earlier estimates and a fiscal crisis in the public sector is a reality. The issues are no longer what to spend on and how much more money is needed, but how to limit the growth of the public sector and how to make the best use of present
In
Finland,
resources.
In August, 1991, the National Agency for Welfare and Health asked a representative sample of the Finnish population how the public economy ought to be balanced. Of 998 people interviewed, 80% chose to cut expenditure. Other alternatives were supported RESULTS OF PUBLIC SURVEY OF SPENDING CUTS IN PUBLIC SECTOR
only by some respondents: raising taxes (3%), borrowing money (6%), and raising client’s fees (7%). When asked where savings could be made the result was very similar to that of the Cardiff Health Survey (table).1,2 The Cardiff Health Survey has found the right approach by introducing comparisons. In our survey, to note, for example, that 23% of the population sees no possibility of saving in defence expenditure is meaningless, but when compared with the respective figure of 75 % for health care it becomes of value. Answers to survey questions have no natural scale, and therefore comparative reference points are needed. We can then safely conclude that the welfare state is closer to the heart of the Finnish population than defence or agricultural support. National Agency for Welfare and Health, PO Box 220, 00531 Helsinki, Finland
HANNU UUSITALO TUIRE SIHVO
1.
Charny MC, Lewis PA. Does health knowledge affect eating habits? Health Educ J
2.
Charny MC, Farrow SC, Lewis PA. Who is using cervical cancer screening services?
1987; 4: 172-76. Health Trends 1987; 19: 3-5.
Serious intercurrent disease in healthy volunteers in clinical pharmacological research SIR,-Dr Kroon and Dr Cohen (Feb 22, p 504) provide a valuable reminder that screening healthy volunteers for a research study may occasionally yield some distressing surprises. Vazquez and P reported a parallel experience in which three young and
apparently healthy medical students who had volunteered for research studies were found to have previously unsuspected HIV infection, chronic persistent hepatitis, and a focal lesion in the brain, respectively. The serious difficulty we encountered was the emotional stress for the volunteer and the investigator. Both experienced a sudden change in role. The volunteer was transformed from a healthy student with bright prospects into a frightened patient with a potentially life-threatening illness. The researcher was transformed from an objective investigator into an involved counsellor with no experience or guidelines for coping with this unfamiliar and emotionally charged problem. All the volunteers with abnormal findings were eventually referred for specialist care and follow-up. Clinical researchers who recruit healthy controls would be well advised to plan for similar unpleasant surprises. For example, institutional committees that oversee human research might draft guidelines for the management of these sporadic occurrences, with emphasis on prompt counselling and appropriate care for the affected volunteer, and protection of their confidentiality. Informed consent forms might even warn research volunteers that the screening process could reveal some previously unsuspected abnormality. Department of Medicine, New York Medical College, Staten Island, New York 10310, USA 1.
MICHAEL PHILLIPS
Phillips M, Vazquez AJ. Abnormal findings in "normal" research
volunteers.
Controlled Clin Trials 1987; 8: 338-42.
Day care and
pregnancy hypertension SIR,-Dr Tuffnell and colleagues (Jan 25, p 224) report that the introduction of a daycare unit for hypertension in pregnancy reduces the need for and length of antenatal admissions and did not adversely affect outcomes. Our comparison of a daycare system in Glasgow with an inpatient-based system in Aberdeen has revealed
*eg, day-care, homehelp, residential care teg, pensions, sickness, unemployment secunt’
similar effects.’ The degree to which the reduction in inpatient care will lead to savings for the hospital depends on how the inpatient resources freed are used and on the additional outpatient resource use. We found that, for patients similar to those studied by Tuffnell et al, costs are lower for patients managed by day care but not significantly so. We too found that women are prepared to come to a daycare unit frequently to avoid admission. Most daycare attenders
814
and
inpatients were prepared to come to day care 5 times per week. Only 1 woman, who had a poor obstetric history, was not prepared to come to day care. Since outcomes are not adversely affected and patients prefer day care, such care should be encouraged. However the costs savings may be small unless the inpatient beds no longer needed are closed and staff numbers reduced. Department of Public Health, Glasgow Royal Maternity Hospital, Glasgow G4 ONA, UK
SARA TWADDLE
Department of Obstetrics and Gynaecology, University of Aberdeen,
VALERIE HARPER
Aberdeen 1. Twaddle
S, Harper V. An economic evaluation of daycare for hypertension in Br J Obstet Gynaecol (in press).
pregnancy.
Worldwide
worsening wheezing—is the cure
the cause?
StR,—Ten years ago a second epidemic of asthma mortality was first reported in New Zealand.! Since then several countries have reported more gradual increases in mortality, significant increases in admission rates for asthma, and evidence suggesting an increased prevalence of asthma and wheezing. These trends continue to be the subject of speculation, controversy, and concern. Changes in mortality are the most clear-cut and extensively studied. Two patterns have emerged. Epidemic increases were associated with the introduction and widespread use of two high-dose beta-agonists. In the 1960s, epidemics were noted in six countries where high-dose inhaled isoprenaline aerosol was available2 and in the 1970s a second epidemic, confined to New Zealand, was associated with fenoterol. The mechanism for the increased risks associated with these agents is unknown. In contrast to these epidemics, several countries, including the UK and USA, have reported gradual but significant increases in asthma mortality over the past 15-20 years, and increases in admission rates and prevalence.’ The suggestion from these changes is that asthma is becoming more prevalent and severe in different environments around the world. Possible explanations include diagnostic transfer, changes in the delivery of health care, and increased awareness amongst patients and physicians leading to greater self-reporting of asthma. In 1989 Mitchell suggested that beta-agonists might be responsible for increasing asthma mortality and morbidity, referring to evidence of increased bronchial hyperresponsiveness after short periods of regular treatment with beta-agonists. Sears et al6 have reported an increase in clinical asthma severity when fenoterol was added regularly to an on-demand drug regimenand Van Schayck et aF have reported greater reduction in baseline lung function when either salbutamol or ipratropium bromide were given regularly rather than on demand. The implications are that beta-agonists or bronchodilators in general can cause deteriorations in lung function and increases in asthma severity when used regularly. These findings support an association between bronchodilator use and increasing hospital admissions and asthma mortality.6 These effects of bronchodilators may also account for the reported increases in prevalence, we suggest. A child presenting with an episode of wheezing is now more likely to receive a diagnosis of asthma and be given treatment with bronchodilators than a diagnosis of wheezy bronchitis and treatment with antibiotics. Potentially this could lead to a deterioration in symptoms, prolongation of the episode, and the requirement for yet more bronchodilator therapy. In this situation the event is both more likely to be labelled as asthma and more likely to be recalled by the patient or parent in the survey setting. Thus by shifting the "curve" of asthma symptom severity in the community to the left, the possibility arises that the reported prevalence of hospital admissions for, and mortality from, asthma are increased by the regular and widespread use of bronchodilators, principally beta-agonists. We must not overinterpret associations between drug sales/use and trends in asthma prevalence, mortality, and morbidity, especially over long periods. Nevertheless the possibility of an asociation between bronchodilators and these trends must be seriously entertained. Should the association prove to be causal it
would be important to find out whether this applied to bronchodilators in general and the extent to which the effects are specific to individual beta-agonists or the class as a whole. For the individual with wheezing the implications would be profound. To avoid worsening asthma in the longer term a rethink of asthma management strategies would be required, with patients taking bronchodilators solely to relieve airway obstruction, rather than regularly. The widely promoted concept of asthma selfmanagement would be even more important, requiring patients to adjust bronchodilator therapy to a minimum based on a regular and educated interpretation of lung function. JULIAN CRANE Wellington Asthma Research Group, NEIL PEARCE Department of Medicine, RICHARD BEASLEY School of Medicine, CARL BURGESS Wellington, New Zealand Jackson RT, Beaglehole R, Rea HH, Sutherland DC. Mortality from asthma: a new epidemic in New Zealand Br Med J 1982; 285: 771-74. 2. Stolley PD, Schinnar R. Association between asthma mortality and isoproterenol. a review. Prev Med 1978; 7: 519-38. 3. Grainger J, Woodman K, Pearce N, et al. Prescribed fenoterol and death from asthma in New Zealand, 1981-1987: a further case control study. Thorax 1991; 46: 105-11. 4. Buist AS, Vollmer WM Reflections on the rise in asthma morbidity and mortality. JAMA 1990, 264: 1719-28. 5. Mitchell EA. Is current treatment increasing asthma mortality and morbidity? Thorax 1989; 44: 81-84. 6 Sears MR, Taylor DR, Print CG, et al. Regular inhaled beta-agonist treatment m bronchial asthma. Lancet 1990; 336: 1391-96. 7. Van Schayck CP, Dompelmg E, van Herwaarden LA, et al. Bronchodilator treatment 1.
moderate asthma randomised controlled m
or
chronic bronchitis continuous Br Med J 1991; 303: 1426-31.
or on
demand? A
study.
Dependence and oestrogen replacement SIR,-We are interested in the responses (Feb 22, p 505) from menopause experts to our idea (Feb 1, p 290) that drug dependence might occur with oestrogen prescribed as hormone replacement
therapy (HRT). This possible side-effect has not yet been sought. The little, though highly suggestive, evidence is the combination of psychoactivity, reports of shorter intervals between clinic visits, and the development of supraphysiological levels in a minority. To respond that many women use HRT safely, that some doctors in the past prescribed high doses, that symptoms are relieved, or that women have "dependence on good health" is irrelevant: that does not prove the absence of drug dependence. The comparison of postmenopausal oestrogen with insulin is misleading. Diabetes is not a disease that spontaneously recedes, unlike many climacteric symptoms, and its definition relates to absolute high levels of glucose. The analogy ignores the central prescribing problem. Are the postmenopausal years a state of disease, namely "oestrogen deficiency"? If so, are symptom-free women also diseased? Or does the menopause mark the (sometimes painful) transition from one normal level of oestrogen to another (as with menarche and pregnancy). Or is it more complex still, with some symptoms related to absolute, and others to changing levels? As Mr Studd points out, symptoms that return 4-8 months after implants despite normal oestradiol levels (for the reproductive years), are related to falling, not absolute, levels. If the menopause causes symptoms due to falling levels of oestrogen, it is inevitable that the wellbeing induced by oestrogen as levels rise will be followed by suffering as levels fall and thus produce a need to continue taking the drug (even without an added effect if it is dependence-inducing). Also the rational treatment might be a tailored, slowly reducing dose over a fixed period, not a constant and limitless supply of replacement. However, if postmenopausal oestrogen does prolong life and health, there is a completely different indication for preventive prescribing, without defining all older women as having a deficiency disease, and dependence could then be welcomed for compliance. Women may feel better because the drug relieves symptoms and/or because it is a euphoriant. The two effects have not been distinguished, and it is the second which should be the cause for concern. If dependence were shown to exist, even in a small number of women on implants, it would be likely to be a property of the drug and the dose and not just the route of administration. Oral codeine and intravenous morphine can both cause dependence, to different
