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GENERALISED VACCINIA IN THE HUMAN FŒTUS
169 when the true difference is amount-shall be assumed ?
as
great
or
greater than the
important
As we read the results of the Glasgow trial there is no indication of the magnitude of increase in mortality which Professor Hutchison and his colleagues wished to detect. The observed mortality among the intubation group (15/111) indicates a mortality, associated with this standard treatment, of 14%. If the pretrial agreement were to conduct a fixed-sample-size trial that would be sensitive to, let us say, a doubling of mortality (from the standard rate of 14% to 28%) in the pressure chamber, the total number of infants required to be enrolled in the trial would be about 360, divided equally between treatments, to control both of the risks of error mentioned above at the 500 level, or roughly twice as many to control both types of error at the 1 % level. If less than a doubling of mortality were to be expected in the pressure chamber, a significant experiment would occur less often, unless the number of infants enrolled were further increased. It appears to us that in concluding from the reported experi" ence, no significant difference ", Professor Hutchison and his colleagues cannot exclude the possibility that the true difference may not be zero, and that the increase in mortality in the pressure chamber could attain a size which many physicians might consider important. Indeed, the true difference might be quite large, and the decision " no significant difference " might have been reached in the trial because of an inappropriately small sample size. Departments of Pediatrics and Biostatistics, WILLIAM A. SILVERMAN College of Physicians and JOHN C. SINCLAIR Surgeons of Columbia University, New York, New York 10032. JOHN W. FERTIG.
his
This letter has been shown to Professor Hutchison and follows.-ED. L.
colleagues, whose reply
SIR,-We would admit that a larger sample size would have been desirable, although it would have had to be a very large size indeed to exclude the possibility that the true difference in mortality between intubation and hyperbaric oxygen may not be zero. The sample size in the two hospitals (100 days and 80 days) was chosen in relation to the length of time likely to be required to complete the trial, and the availability of trained staff night and day throughout this period. It was obvious that the intubations had to be performed only by experienced and skilled people if the comparison between this technique and
hyperbaric oxygenation was to be a fair one.
Dr. Silverman as clinician will be well aware of the enormous effort which a of staff. trial, even of this size, demands from the members " In the term " no significant difference we used the word significantin its statistical sense (i.e., no greater than would be expected reasonably often in repeated trials of this size, solely as the result of random variation) rather than in its everyday interpretation. We must agree that our trial results have not excluded the possibility of a true difference in the mortality between intubation and the pressure chamber-only that they failed to reveal such a difference. We think that even more important than the mortality figures is the fact that the postmortem examinations performed in 31 of the 34 infants who died failed to show severe pathology other than uncomplicated asphyxia in only 3 instances. In 2 of these intubation was the resuscitatory method employed. J. H. HUTCHISON MARGARET M. KERR JOHN A. INALL ROBERT A. SHANKS. a
"
GENERALISED VACCINIA IN THE HUMAN FŒTUS SIR,—The article by Dr. Green and his colleagues1 emphasises once more the hazards of smallpox vaccination at any time 1.
during pregnancy. During the smallpox outbreaks in
Green, D. M., Reid, S. M., Rhaney, K. Lancet, 1966, i, 1296.
South Wales in 1962, Waddington and his colleagues2 recorded examples of foetal vaccinia among 242 cases of cutaneous complications of vaccination. The 2nd fcetus survived not only the hazards of premature birth but also the vaccinial virasmia, and is now normally developed but marked with large foveated scars on head, face, and bodv. Welsh National School of Medicine,
2
Department of Child Health, Llandough Hospital, Penarth, Glam.
P. T. BRAY.
CORONARY ANGIOGRAPHY SIR Your leading article3 refers to Sones’ technique of selective coronary arteriography as an aid to diagnosis in ischaemic heart-disease which offers little that cannot be obtained by good history-taking and electrocardiography. I am afraid that this initial statement will find little support among people who are cognisant of the value of this technique. Dr. William L. Proudfit’s article in the current issue of Circulation (June, 1966) deals with a thousand patients who were investigated in this clinic for ischasmic heart-disease; the range of diagnostic error for the cardiologist was 17%, and for the referring physician 37%. If these figures attest to the value of good history-taking and electrocardiography, then I would suggest that coin-flipping be considered for the " does he have it or doesn’t he have it " type of case. You refer to " the fact that only 4 operations were performed " in the first 1500 patients studied by selective coronary arteriography at the Cleveland Clinic. This information was obtained from our first paper dealing with coronary endarterectomy. At the time of writing Sones and his colleagues have performed studies in 6200 patients of this group. 96 have had direct coronary-artery surgery, and 64 have been operated upon for ventricular aneurysm, 15 for correction of coronary arteriovenous fistula, and 436 for internal-mammary implant procedures. The misconception created by the " 4 out of 1500 patients " concerns me less than does the suggestion that a diagnostic procedure should in any way be judged by surgical
yield. lour
leading
arucie
goes
on IO siaie:
coronary
anen-
ography is hardly necessary for other kinds of operation aimed at revascularising the heart from outside sources ..." This statement
needs clarification. Selection of the candidate for
revascularising procedure requires an accurate assessment of the individual patient’s needs. In other words, for an internalmammary implant procedure to succeed one must demonstrate, firstly, functional demand in the myocardium and, secondly, the specific area of demand. What better method of demonstrating physiological need for blood is available than that which will demonstrate a major arterial occlusion and the presence of established collaterals
to
the
area
involved ?
Until 1962,
applied in a hit-or-miss fashion and the results were unimpressive. At the time of writing the candidate for an implant procedure is selected by coronary arteriography (in addition to good history-taking and electrocardiography), and, as important, revaluated by angiography which includes opacification of the implanted systemic vessel. Analysis of our first 73 patients studied one year after operation shows 90-3% functioning implants. Without arteriography this operation would not be performed in the Cleveland Clinic Hospital. mammary
implant procedures
were
Your leader concludes with the statement that the clinical of arteriography " so far does not justify the wider establishment of the elaborate facilities needed for its safe and proper performance ". Nothing can be farther from the truth. In both the United States and Great Britain the interest in this diagnostic adjunct increases daily, and existing facilities to provide coronary arteriography will multiply many times over within the next year or two. As a surgeon, I am impressed by the reaction of many cardiologists to a relatively new diagnostic procedure. The
application
2.
Waddington, E., Bray, P. T., Evans, A. D., Richards, St. John’s Hosp. derm. Soc., Lond. 1964, 50, 22. 3. Lancet, 1966, i, 1084.
I. D. G Trans.
as
great
or
greater than the
important
As we read the results of the Glasgow trial there is no indication of the magnitude of increase in mortality which Professor Hutchison and his colleagues wished to detect. The observed mortality among the intubation group (15/111) indicates a mortality, associated with this standard treatment, of 14%. If the pretrial agreement were to conduct a fixed-sample-size trial that would be sensitive to, let us say, a doubling of mortality (from the standard rate of 14% to 28%) in the pressure chamber, the total number of infants required to be enrolled in the trial would be about 360, divided equally between treatments, to control both of the risks of error mentioned above at the 500 level, or roughly twice as many to control both types of error at the 1 % level. If less than a doubling of mortality were to be expected in the pressure chamber, a significant experiment would occur less often, unless the number of infants enrolled were further increased. It appears to us that in concluding from the reported experi" ence, no significant difference ", Professor Hutchison and his colleagues cannot exclude the possibility that the true difference may not be zero, and that the increase in mortality in the pressure chamber could attain a size which many physicians might consider important. Indeed, the true difference might be quite large, and the decision " no significant difference " might have been reached in the trial because of an inappropriately small sample size. Departments of Pediatrics and Biostatistics, WILLIAM A. SILVERMAN College of Physicians and JOHN C. SINCLAIR Surgeons of Columbia University, New York, New York 10032. JOHN W. FERTIG.
his
This letter has been shown to Professor Hutchison and follows.-ED. L.
colleagues, whose reply
SIR,-We would admit that a larger sample size would have been desirable, although it would have had to be a very large size indeed to exclude the possibility that the true difference in mortality between intubation and hyperbaric oxygen may not be zero. The sample size in the two hospitals (100 days and 80 days) was chosen in relation to the length of time likely to be required to complete the trial, and the availability of trained staff night and day throughout this period. It was obvious that the intubations had to be performed only by experienced and skilled people if the comparison between this technique and
hyperbaric oxygenation was to be a fair one.
Dr. Silverman as clinician will be well aware of the enormous effort which a of staff. trial, even of this size, demands from the members " In the term " no significant difference we used the word significantin its statistical sense (i.e., no greater than would be expected reasonably often in repeated trials of this size, solely as the result of random variation) rather than in its everyday interpretation. We must agree that our trial results have not excluded the possibility of a true difference in the mortality between intubation and the pressure chamber-only that they failed to reveal such a difference. We think that even more important than the mortality figures is the fact that the postmortem examinations performed in 31 of the 34 infants who died failed to show severe pathology other than uncomplicated asphyxia in only 3 instances. In 2 of these intubation was the resuscitatory method employed. J. H. HUTCHISON MARGARET M. KERR JOHN A. INALL ROBERT A. SHANKS. a
"
GENERALISED VACCINIA IN THE HUMAN FŒTUS SIR,—The article by Dr. Green and his colleagues1 emphasises once more the hazards of smallpox vaccination at any time 1.
during pregnancy. During the smallpox outbreaks in
Green, D. M., Reid, S. M., Rhaney, K. Lancet, 1966, i, 1296.
South Wales in 1962, Waddington and his colleagues2 recorded examples of foetal vaccinia among 242 cases of cutaneous complications of vaccination. The 2nd fcetus survived not only the hazards of premature birth but also the vaccinial virasmia, and is now normally developed but marked with large foveated scars on head, face, and bodv. Welsh National School of Medicine,
2
Department of Child Health, Llandough Hospital, Penarth, Glam.
P. T. BRAY.
CORONARY ANGIOGRAPHY SIR Your leading article3 refers to Sones’ technique of selective coronary arteriography as an aid to diagnosis in ischaemic heart-disease which offers little that cannot be obtained by good history-taking and electrocardiography. I am afraid that this initial statement will find little support among people who are cognisant of the value of this technique. Dr. William L. Proudfit’s article in the current issue of Circulation (June, 1966) deals with a thousand patients who were investigated in this clinic for ischasmic heart-disease; the range of diagnostic error for the cardiologist was 17%, and for the referring physician 37%. If these figures attest to the value of good history-taking and electrocardiography, then I would suggest that coin-flipping be considered for the " does he have it or doesn’t he have it " type of case. You refer to " the fact that only 4 operations were performed " in the first 1500 patients studied by selective coronary arteriography at the Cleveland Clinic. This information was obtained from our first paper dealing with coronary endarterectomy. At the time of writing Sones and his colleagues have performed studies in 6200 patients of this group. 96 have had direct coronary-artery surgery, and 64 have been operated upon for ventricular aneurysm, 15 for correction of coronary arteriovenous fistula, and 436 for internal-mammary implant procedures. The misconception created by the " 4 out of 1500 patients " concerns me less than does the suggestion that a diagnostic procedure should in any way be judged by surgical
yield. lour
leading
arucie
goes
on IO siaie:
coronary
anen-
ography is hardly necessary for other kinds of operation aimed at revascularising the heart from outside sources ..." This statement
needs clarification. Selection of the candidate for
revascularising procedure requires an accurate assessment of the individual patient’s needs. In other words, for an internalmammary implant procedure to succeed one must demonstrate, firstly, functional demand in the myocardium and, secondly, the specific area of demand. What better method of demonstrating physiological need for blood is available than that which will demonstrate a major arterial occlusion and the presence of established collaterals
to
the
area
involved ?
Until 1962,
applied in a hit-or-miss fashion and the results were unimpressive. At the time of writing the candidate for an implant procedure is selected by coronary arteriography (in addition to good history-taking and electrocardiography), and, as important, revaluated by angiography which includes opacification of the implanted systemic vessel. Analysis of our first 73 patients studied one year after operation shows 90-3% functioning implants. Without arteriography this operation would not be performed in the Cleveland Clinic Hospital. mammary
implant procedures
were
Your leader concludes with the statement that the clinical of arteriography " so far does not justify the wider establishment of the elaborate facilities needed for its safe and proper performance ". Nothing can be farther from the truth. In both the United States and Great Britain the interest in this diagnostic adjunct increases daily, and existing facilities to provide coronary arteriography will multiply many times over within the next year or two. As a surgeon, I am impressed by the reaction of many cardiologists to a relatively new diagnostic procedure. The
application
2.
Waddington, E., Bray, P. T., Evans, A. D., Richards, St. John’s Hosp. derm. Soc., Lond. 1964, 50, 22. 3. Lancet, 1966, i, 1084.
I. D. G Trans.