581 gest that metronidazole may be domembranous colitis.
a
Gastroenterology Unit, Hotel Dieu, 86021 Poitiers, France
treatment
of choice in pseu-
*,t*This letter has been shown
C. MATUCHANSKY J. ARIES P. MAIRE
SIR,-Nobody would disagree with Dr Seltzer’s point that the presence of statistical association neither proves causality nor demonstrates a preventive effect from lowering the level of exposure to a risk factor. We certainly made no claim that it did. However, our data, together with those of the other workers cited, support a causal relationship between cigarette smoking and C.H.D. as being the most reasonable interpretation of this consistently observed association. Our data were used to suggest a possible level of benefit that a preventive effect of lowering cigarette consumption might achieve. Although our study cannot address directly the preventive effect of lowering cigarette consumption, we did refer to previous work documenting such an effect,1 and other similar data have been reported.2 Most of Seltzer’s queries about our study methods and the possibility of bias are considered, as we indicated, in our 1976 paper. A few of his remarks merit comment. A case-control pair was eliminated if data collected on any variable were not recorded for either member of the pair, and we have no reason to believe that such missing information has introduced bias; age was included in the logit function to control for any residual confounding within age strata, and its inclusion did not alter the estimated association between cigarette smoking and coronary death. Finally, we referred only to the data presented in the paper by Miettinen et al.,4 not to their own conclusions.
STOPPING SMOKING AND CORONARY HEART-DISEASE
al. reported case-control data revealing a positive dose-response association between cigarette consumption and coronary heart-disease (C.H.D.) deaths and concluded that their "data strongly support the benefits of stopping smoking completely" and that people who smoke more than one pack of cigarettes per day "would reduce their risk of dying from C.H.D. by 50%" if they would reduce their smoking by half. The accuracy and reliability of these data are impossible to assess because so many important methodological features have been unreported or ignored:
SIR,-Bain
et
(1) What were the geographical and medical sources of the study population? (2) How were the c.H.D. cases selected, and what proportion of those cases had been admitted to hospital? (3) What "missing data" eliminated 81 potential cases from the 649 patients who died from c.H.D.? (4) What were the patients’ smoking habits for the period earlier than three months before interrogation? (5) How were smoking habits classified? Does the "none" for cigarette smokers include ex-smokers, pipe smokers, or cigar smokers as well as "never" smokers? (6) How was a person classified as to smoking habit when his wife reported that her husband had smoked for two months and quit for one month? How was such a person classified as to amount of smoking
to
Dr
Hennekens, whose reply
follows.-ED. L.
Channing Laboratory, Harvard Medical School and Peter Bent Brigham Hospital, Boston, Massachusetts 02115, U.S.A.
C. BAIN C. H. HENNEKENS* B. ROSNER F. E. SPEIZER
National Institutes of Health,
M.
Bethesda, Maryland
J. JESSE
per day?
(7) What further" as and C.H.D.? Bain
et
regarding
were
the "additional variables" that were "explored factors for the association between smoking
controlling
al. also made no comment or apparent analyses the impact of the following potential sources of bias
in their study:
(1) How was the case group biased by the exclusion of 12% (81/649) of the possible members who were eliminated because of "missing data"? (2) The age-matching of cases and controls was done by decade, although the risk between a 50-year-old control and a 59-year-old case might differ by as much as 400 deaths per 100 000. Did this coarse matching produce biases in age? (3) Only 55‘0 of the eligible wives of cases responded. What bias may have been introduced by this low response-rate? Were the wives of cases likely to overestimate smoking habits and the wives of controls likely to underestimate them? In commenting on the alleged dose-response relationship between smoking and C.H.D. Bain et al. state that "all data strongly support the benefits of stopping smoking completely, but these results and those of Miettinen suggest comparable advantages may be attained by reducing consumption to below one pack a day, with intermediate benefits from reductions to a point above this level". This statement is unwarranted for two reasons. First, Bain et al. have distorted Miettinen’s own conclusion2 which was that "the residual association between may not be cigarette-smoking and [myocardial infarction] interpretable in causal terms". Second, neither published studies nor these workers’ own data show what happens when people stop smoking. The presence of an association is neither proof of causality nor a demonstration that the reversal of a risk factor will prevent the occurrence of a disease. ...
Harvard University, 11 Divinity Avenue, Cambridge, Massachusetts
02138,
U.S.A.
CARL C. SELTZER
*Present address: Department of Regius Professor of Medicine, Radcliffe Infirmary, Oxford OX2 6HE.
ORAL CONTRACEPTIVES, SMOKING, AND FOOD ALERGY
SIR,-Dr Petitti and Mr Wingerd (July 29, p. 234) report that the risk of women developing subarachnoid haemorrhage is increased S-77 times in cigarette smokers, 6-35 times in oral contraceptive (o.c.) users, and 22 times in women who both smoked and used o.c. compared with non-users. They found that hypertension and migraine headaches were no more common in the subarachnoid haemorrhage cases than in the controls. Curiously, however, many of the controls appeared to smoke, or to use or have previously used o.c., both factors known to affect the incidence of migraine and hypertension. In an analysis of patients attending Charing Cross migraine clinic, 22patients were referred from other clinicians and 111 patients were self-referred for the emergency treatment of one or more migraine attacks.5 The self-referred women were 61% of those using o.c. and smoking, 46% of those using o.c. 36% of those smoking, and 22% of non-users. The self-referred men were 35% of smokers and 20% of non-smokers. Self-referred men and women were twice as likely to be taking regular ergotamine as referred cases. In a follow-up study, the average monthly incidence of headache and migraine in three groups of patients before and after discontinuing o.c., smoking, and ergotamine has now been assessed and compared with a group of non-users. Before discontinuation there were four times more migraine attacks in 1.
Wilhelmsson, C., Vedin, J. A., Elmfeldt, D., Tibblin, G., Wilhelmsen, L. Lancet, 1975,i,415. 2. Gordon, T., Kannel, W. B., McGee, D., Dawber, T. R. ibid. 1974, ii, 1345. 3. Hennekens, C. H., Drolette, M. E., Jesse, M. J., Davies, J E., Hutchison, G. B. New Engl.J. Med.
1. Bain,
C., Hennekens, C. H., Rosner, B., Speizer, F. E., Jesse, M. J. Lancet, 1978,i, 1007 2. Miettinen, O S.,Neff,R. K., Jick, H. Am.J. Epidem. 1976,103, 30.
MIGRAINE,
1976, 294, 633.
4.
Miettinen,O.S.,Neff, R.K., Jick, H. Am. J. Epidem. 1976, 103, 30.
5.
Grant, E. C. G., Albuquerque, M., Steiner, T. J., Clifford, R. F. Current Concepts in Migraine Research (edited by R. Green); p. 97. New York, 1978.
582 CHANGE IN MONTHLY HEADACHE INCIDENCE
* Improvement was a reduction in number of migraines and headaches. Significance assessed by t test on paired values. I
group and three times more migraine attacks group compared with the non-user group (see table). Most "tension" headaches occurred in the smoking group. The average age for o.c. users was 29 years, o.c. pastusers 35 years, and for women who had never used o.c. was 41 years. The average duration of o.c. use was 3 years but the average duration of smoking was 20 years for both sexes. All patients were advised to discontinue the three major factors and, in addition, cheese, chocolate, citrus fruit, and alcohol. There was a highly significant improvement in all groups but most patients continued to get migraine attacks or headaches. A food-allergy exclusion diet 7,8 avoiding 1-20 common foods was then carried out faithfully by a group of 30 patients. The monthly incidence of migraines dropped from 187 to 0 in and the incidence of headaches from 284 to 14 (P
a
Gastroenterology Unit, Hotel Dieu, 86021 Poitiers, France
treatment
of choice in pseu-
*,t*This letter has been shown
C. MATUCHANSKY J. ARIES P. MAIRE
SIR,-Nobody would disagree with Dr Seltzer’s point that the presence of statistical association neither proves causality nor demonstrates a preventive effect from lowering the level of exposure to a risk factor. We certainly made no claim that it did. However, our data, together with those of the other workers cited, support a causal relationship between cigarette smoking and C.H.D. as being the most reasonable interpretation of this consistently observed association. Our data were used to suggest a possible level of benefit that a preventive effect of lowering cigarette consumption might achieve. Although our study cannot address directly the preventive effect of lowering cigarette consumption, we did refer to previous work documenting such an effect,1 and other similar data have been reported.2 Most of Seltzer’s queries about our study methods and the possibility of bias are considered, as we indicated, in our 1976 paper. A few of his remarks merit comment. A case-control pair was eliminated if data collected on any variable were not recorded for either member of the pair, and we have no reason to believe that such missing information has introduced bias; age was included in the logit function to control for any residual confounding within age strata, and its inclusion did not alter the estimated association between cigarette smoking and coronary death. Finally, we referred only to the data presented in the paper by Miettinen et al.,4 not to their own conclusions.
STOPPING SMOKING AND CORONARY HEART-DISEASE
al. reported case-control data revealing a positive dose-response association between cigarette consumption and coronary heart-disease (C.H.D.) deaths and concluded that their "data strongly support the benefits of stopping smoking completely" and that people who smoke more than one pack of cigarettes per day "would reduce their risk of dying from C.H.D. by 50%" if they would reduce their smoking by half. The accuracy and reliability of these data are impossible to assess because so many important methodological features have been unreported or ignored:
SIR,-Bain
et
(1) What were the geographical and medical sources of the study population? (2) How were the c.H.D. cases selected, and what proportion of those cases had been admitted to hospital? (3) What "missing data" eliminated 81 potential cases from the 649 patients who died from c.H.D.? (4) What were the patients’ smoking habits for the period earlier than three months before interrogation? (5) How were smoking habits classified? Does the "none" for cigarette smokers include ex-smokers, pipe smokers, or cigar smokers as well as "never" smokers? (6) How was a person classified as to smoking habit when his wife reported that her husband had smoked for two months and quit for one month? How was such a person classified as to amount of smoking
to
Dr
Hennekens, whose reply
follows.-ED. L.
Channing Laboratory, Harvard Medical School and Peter Bent Brigham Hospital, Boston, Massachusetts 02115, U.S.A.
C. BAIN C. H. HENNEKENS* B. ROSNER F. E. SPEIZER
National Institutes of Health,
M.
Bethesda, Maryland
J. JESSE
per day?
(7) What further" as and C.H.D.? Bain
et
regarding
were
the "additional variables" that were "explored factors for the association between smoking
controlling
al. also made no comment or apparent analyses the impact of the following potential sources of bias
in their study:
(1) How was the case group biased by the exclusion of 12% (81/649) of the possible members who were eliminated because of "missing data"? (2) The age-matching of cases and controls was done by decade, although the risk between a 50-year-old control and a 59-year-old case might differ by as much as 400 deaths per 100 000. Did this coarse matching produce biases in age? (3) Only 55‘0 of the eligible wives of cases responded. What bias may have been introduced by this low response-rate? Were the wives of cases likely to overestimate smoking habits and the wives of controls likely to underestimate them? In commenting on the alleged dose-response relationship between smoking and C.H.D. Bain et al. state that "all data strongly support the benefits of stopping smoking completely, but these results and those of Miettinen suggest comparable advantages may be attained by reducing consumption to below one pack a day, with intermediate benefits from reductions to a point above this level". This statement is unwarranted for two reasons. First, Bain et al. have distorted Miettinen’s own conclusion2 which was that "the residual association between may not be cigarette-smoking and [myocardial infarction] interpretable in causal terms". Second, neither published studies nor these workers’ own data show what happens when people stop smoking. The presence of an association is neither proof of causality nor a demonstration that the reversal of a risk factor will prevent the occurrence of a disease. ...
Harvard University, 11 Divinity Avenue, Cambridge, Massachusetts
02138,
U.S.A.
CARL C. SELTZER
*Present address: Department of Regius Professor of Medicine, Radcliffe Infirmary, Oxford OX2 6HE.
ORAL CONTRACEPTIVES, SMOKING, AND FOOD ALERGY
SIR,-Dr Petitti and Mr Wingerd (July 29, p. 234) report that the risk of women developing subarachnoid haemorrhage is increased S-77 times in cigarette smokers, 6-35 times in oral contraceptive (o.c.) users, and 22 times in women who both smoked and used o.c. compared with non-users. They found that hypertension and migraine headaches were no more common in the subarachnoid haemorrhage cases than in the controls. Curiously, however, many of the controls appeared to smoke, or to use or have previously used o.c., both factors known to affect the incidence of migraine and hypertension. In an analysis of patients attending Charing Cross migraine clinic, 22patients were referred from other clinicians and 111 patients were self-referred for the emergency treatment of one or more migraine attacks.5 The self-referred women were 61% of those using o.c. and smoking, 46% of those using o.c. 36% of those smoking, and 22% of non-users. The self-referred men were 35% of smokers and 20% of non-smokers. Self-referred men and women were twice as likely to be taking regular ergotamine as referred cases. In a follow-up study, the average monthly incidence of headache and migraine in three groups of patients before and after discontinuing o.c., smoking, and ergotamine has now been assessed and compared with a group of non-users. Before discontinuation there were four times more migraine attacks in 1.
Wilhelmsson, C., Vedin, J. A., Elmfeldt, D., Tibblin, G., Wilhelmsen, L. Lancet, 1975,i,415. 2. Gordon, T., Kannel, W. B., McGee, D., Dawber, T. R. ibid. 1974, ii, 1345. 3. Hennekens, C. H., Drolette, M. E., Jesse, M. J., Davies, J E., Hutchison, G. B. New Engl.J. Med.
1. Bain,
C., Hennekens, C. H., Rosner, B., Speizer, F. E., Jesse, M. J. Lancet, 1978,i, 1007 2. Miettinen, O S.,Neff,R. K., Jick, H. Am.J. Epidem. 1976,103, 30.
MIGRAINE,
1976, 294, 633.
4.
Miettinen,O.S.,Neff, R.K., Jick, H. Am. J. Epidem. 1976, 103, 30.
5.
Grant, E. C. G., Albuquerque, M., Steiner, T. J., Clifford, R. F. Current Concepts in Migraine Research (edited by R. Green); p. 97. New York, 1978.
582 CHANGE IN MONTHLY HEADACHE INCIDENCE
* Improvement was a reduction in number of migraines and headaches. Significance assessed by t test on paired values. I
group and three times more migraine attacks group compared with the non-user group (see table). Most "tension" headaches occurred in the smoking group. The average age for o.c. users was 29 years, o.c. pastusers 35 years, and for women who had never used o.c. was 41 years. The average duration of o.c. use was 3 years but the average duration of smoking was 20 years for both sexes. All patients were advised to discontinue the three major factors and, in addition, cheese, chocolate, citrus fruit, and alcohol. There was a highly significant improvement in all groups but most patients continued to get migraine attacks or headaches. A food-allergy exclusion diet 7,8 avoiding 1-20 common foods was then carried out faithfully by a group of 30 patients. The monthly incidence of migraines dropped from 187 to 0 in and the incidence of headaches from 284 to 14 (P
