dealing with the presence or absence of some factor and whether this factor is injurious or protective is not known and, indeed, there is still the possibility that the reported association may not be causally related to the problem. We certainly do not have enough evidence to conclude, as Dr Keilin does, that one of the trace elements is the real culprit, despite the interesting work with cadmium in
we are
rats.
There are several studies, including those referred to by Dr Keilin, that do not conform with the general relationship demonstrated between water hardness and cardiovascular mortality. Considering the complex nature of coronary heart disease this is not surprising, and the second paragraph of my article stressed that the well-established risk factors for coronary heart disease remain of the utmost importance. The possible role played by the "water factor" can only be a contributory one, and even within a limited geographic situation such as the United Kingdom, we are able to locate many towns that do not fit the general pattern of this associa¬ tion between water hardness and car¬ diovascular mortality. I have drawn no "strong conclu¬ sions" and was careful to emphasize that the situation regarding artifi¬ cially softened water had not been closely studied. There can be no argu¬ ment against the use of artificially softened water for domestic appli¬ ances and other household uses; the question of whether soft water, whether naturally or artificially soft¬ ened, is detrimental to health, re¬ mains completely open at the present. There is considerable interest in the
problem
on the part of both water and health authorities, and many use¬ ful research programs are under way at present. There will be no quick an¬ swer to this problem as it is clearly a complex one requiring the combined efforts of a wide field of specialists. Andrew G. Shaper, FRCP London
Emergency Medical Systems Act Of 1973
To the Editor.\p=m-\DrEliastam (232:135, 1975) criticized Dr Harvey's description of the Emergency Medical Systems (EMS) Act (230:1139, 1974) as being idealistic and unrealistic. This latter word was perhaps not used, but I think it adequately describes the content of his communication. It seemed to be his point that there
would be no guarantee of Utopia under the Act and that there are doubts regarding the effect of the Act thus far, if and to what extent it will further be funded; and, finally, the ultimate product of the Act. All of these doubts and reservations are valid and are shared by many of us who work in the field of emergency care. The doubt is not, however, specific for emergency care, but extends into all activities of human endeavor, since very little is assured by virtue of either legislation or funding. There was a dearth of substance, however, in Dr Eliastam's communication that would offer the reader a reason to share his concern as to the success of such legis¬ lation. The EMS Act is very definitely af¬ fecting emergency care on all sides of Palo Alto, Calif, as for example, in Santa Clara County and in San Fran¬ cisco and surrounding counties. The Act and efforts made independently via the Department of Transporta¬ tion, Robert Wood Johnson, the Na¬ tional Registry, and state and local tax monies have radically changed
emergency care availability, quality, and outcomes over a large part of the urban United States. In the rural set¬ ting there are interesting develop¬ ments as a result of the Robert Wood Johnson funding that was distributed to 44 grantees, many of whom do not represent urban populations. At the midpoint of this grant effort, it ap¬ pears to be achieving some limited success in areas where the population is sparse, the miles many, and re¬ sources proportionately few. I would refer Dr Eliastam to Redding, Calif; Hermiston, Oregon; the state of Idaho; San Bernadino, Calif; and the Navajo Nation territory (Window
Rock, Ariz) specifically.
is written of the there is little to suggest systems operation in our present hospital, doctor, allied health personnel, third-party payor, or legis¬ lation confederation. There is much more that suggests systems operation in the emergency care field where many diffuse elements must be coor¬ dinated and combined to provide even a modicum of care in this environ¬
Although much system,"1
"health
ment.
The emergency
is rela¬ in exis¬ tence less than ten years in any strongly organized and publicly vis¬ ible state. Considering the meanderings of the rest of medicine, I would suggest that emergency care
tively
young,
care arena
having been
Downloaded From: http://jama.jamanetwork.com/ by a Simon Fraser University User on 05/31/2015
has made notable achievements on limited resources and without scan¬ dalous waste or embarrassment thus far. I hope that the rest of the medi¬ cal profession may be supportive and critical at the same time in the proper balance. Just being critical may satisfy one's immediate needs, but should be balanced by long-term con¬ structive ideas. I, for one, believe that Dr Harvey's accounting of the EMS Act is both idealistic and realistic in the proper balance. Eugene L. Nagel, MD Commission on Emergency Medical Services Torrance, Calif 1.
Jangled semantics, editorial.
Oral
JAMA 231:1371, 1975.
Contraceptives, Serum
Folate, and Hematologic Status To the Editor.\p=m-\Authorsof BRIEF REPORT
(231:731, 1975)
recent must be
a
commended for their simple and clear data presentation. I have, however, a few observations that should be taken into account, as their data enter the growing list of publications on the topic of the impact of contraceptive hormones on micronutrient metabolism. While I am eager to accept their conclusion that "the incidence of subnormal serum folate values was no greater in the group using oral contraceptives than in the control group .," their data do not reinforce this propositon. Incidence is not studied, since only one measurement series was obtained and no changes were investigated; ie, the study was cross\x=req-\ sectional, not prospective. There was no control group, only a group of patients self-selected into the category of "any contraceptive method other than birth control pills," whose inclusion permits comparison but not control. Of most interest, however, is the fact that their data reveal a notable difference in the distributions of se¬ rum folate values using the Lactobacillus casei assay (their Fig 1), with a gradient unfavorable to the hormone .
.
users.
The latter problem in data analysis is, in some ways, a minor one but de¬ serves
attention: the arithmetic
mean
provides the best measure of central tendency in a normal distribution, but it appears that serum folate val¬ are not normally distributed. Without actually working over the raw data, my guess is that the data are log-normally distributed, which would suggest the use of the geomet¬ ric mean; at the very least, the meues
dian yields a better estimate of cen¬ tral tendency. The authors' figures enable the reader to calculate the lat¬ ter. The medians appear to be about 6.3 and 5.3, respectively, for "others" and "pill users," a difference of per¬ haps 15%. Is this "significant"? Their Fig 3 (radioassay for serum folate) appears to show more comparable dis¬ tributions and medians, though the percentage difference, because of the smaller absolute values, may also ap¬ proach 15%. Among those using the pill, dura¬ tion of use does not seem to depress the mean, nor the median, folate lev¬ els, and this argues well for the con¬ tention that nutrient metabolism of folate is not adversely affected by continuing use. But, again, no base¬ lines are provided prior to use for pur¬ poses of comparison. Finally, I'm not sure what is gained by the introduction of inferential sta¬ tistics, in this case the analysis of variance, to compare the two "treat¬ ment" groups. At best, it indicates what would be the case if distribu¬ tions were normal and randomization had occurred, neither of which is true. Multivariate descriptive tech¬ niques would have provided the reader more information. Despite these criticisms, I found the publication of the distributions to be refreshing and thoughtful. Would that more investigators adopted such an open approach to their measure¬ ment and analysis. I only fear now that several previous reports on fo¬ late level depression among oral con¬ traceptive users are liable to similar
réévaluations, thereby intensifying
the notion that there is a "problem." In fact, of course, no one has yet pro¬ vided relevant clinical or health ob¬ servations. We do not even have su¬ perficial indications that the minor subjective side effects of the pill in some users bear any relation to their baseline values of serum folate.
Something more than laboratory sé¬ rologie findings must be focused on this issue soon, to
it should be allowed into the archives.
or
lapse quietly
Gary Merritt, PhD
Population and Humanitarian Assistance
Bureau for
Washington, DC
In Reply.\p=m-\We would like to thank Dr Merritt for the generally complimentary remarks in reference to our paper. We accept his criticism of the semantic impropriety of the terms "incidence" and "control." In relation to his second question, we believe that
Dr Merritt is correct in his assessment that the L casei serum folate values are log-normally distributed. We have computed the geometric means for the L casei serum folate for the group taking oral contraceptives and the group not taking oral contraceptives. For the group not taking oral contraceptives, the geometric mean is 6.2 ng/ml; for the group taking oral contaceptives, the geometric mean is 5.83 ng/ml. This is a difference of only 6% and is not sta-
tistically significant (P>.5).
We believe that this statistical mahas reinforced our original contentions, and we continue to believe that our data demonstrate no significant difference in serum folate values by L casei or radioassay for women taking oral contraceptives vs those not taking them. neuver
Charles J. Paine, MD Louisiana State University Medical Center
Shreveport
Chlamydial
Infections
To the Editor.\p=m-\Ina recent article (231:1252, 1975), Schachter et al discussed the high prevalence of chlamydial infections in nonvenereal disease clinics under the title, "Are Chlamydial Infections the Most Prevalent Venereal Disease?" Nowhere in their paper did they deal with the question of mode of transmission to the infection seen. If they believe that they have evidence to indicate that the chlamydial infections observed were sexually transmitted, such data should have been presented within the paper. If such data do not exist, their title is clearly
inappropriate.
Joel L. Nitzkin, MD Dade
County Department of Public Health
Miami, Fla
Reply.\p=m-\Theepidemiology of incluconjunctivitis (for this is the chlamydial agent of concern here)
In
sion
elucidated in the first decade of this century; for example, see the review (!) by Lindner (Arch Ophthalmol 78:345-380, 1911). The agent is found in the male urethra and the female cervix and produces eye disease when infective genital tract discharges reach the conjunctiva. This has been amply confirmed by the cytologic studies of Thygeson and Stone (Arch Ophthalmol 27:91-122, 1942) and by agent isolation in many studies by Jones and Dunlop and colleagues in England and our group in San Francisco. Clear-cut cases of sexual transwas
Downloaded From: http://jama.jamanetwork.com/ by a Simon Fraser University User on 05/31/2015
mission have been described (Am J Epidemiol 85:445-452, 1967). To the best of my knowledge, volunteer studies of experimental infection and
transmission have not been performed. Dr Nitzkin appears to be concerned that our study was performed in clinics other than those devoted to venereal disease (VD). There have been many studies of chlamydial infection in VD populations (several cited in our paper). For many reasons, most venereal disease clinics treat only gonorrhea and syphilis. Unfortu¬ nately, these two represent only a portion of the sexually transmitted infections. We intended to emphasize that there are other very common sexually transmitted diseases that
being seen in hospital outpatient clinics, as well as in VD clinics. It is clear that nongonococcal urethritis is becoming a venereal disease of in¬ creasing importance. Chlamydiae rep¬ resent a major cause of this condition, which is commonly seen in both VD and hospital clinics. are
Julius Schachter, PhD University of California San Francisco
Per TRENDS
Minute IN
Omitted. In
the article titled Patient: An Al-
THERAPY
Hypertensive gorithm for Treatment," published in the Sept 1 issue (233:990-992, 1975), an error occurred on page 990. "The
The first complete sentence in col2 should read "The dose of hydralazine hydrochloride is 0.1 to 0.4 mg/min given in a non-glucose-containing fluid." The time element ("/min") was omitted from the published sentence. umn
Dosage
Errors. Erroneous
dosage
forms for two oral contraceptives were given in a QUESTION AND ANSWER, "Hirsutism With Hyperthyroidism in Young Woman," published in the Sept 8 issue (233:1109-1110, 1975). The last line of the second paragraph of the question should state that the dosage form of norethynodrel and mestranol (Enovid E) was 0.1 mg, not 1 mg; and in the last sentence of the third paragraph of the question, the dosage form of norgestrel and ethinyl estradiol (Ovral) is 0.05 mg, not 0.5 mg as given. The first error is repeated in the answer as well.
we are
rats.
There are several studies, including those referred to by Dr Keilin, that do not conform with the general relationship demonstrated between water hardness and cardiovascular mortality. Considering the complex nature of coronary heart disease this is not surprising, and the second paragraph of my article stressed that the well-established risk factors for coronary heart disease remain of the utmost importance. The possible role played by the "water factor" can only be a contributory one, and even within a limited geographic situation such as the United Kingdom, we are able to locate many towns that do not fit the general pattern of this associa¬ tion between water hardness and car¬ diovascular mortality. I have drawn no "strong conclu¬ sions" and was careful to emphasize that the situation regarding artifi¬ cially softened water had not been closely studied. There can be no argu¬ ment against the use of artificially softened water for domestic appli¬ ances and other household uses; the question of whether soft water, whether naturally or artificially soft¬ ened, is detrimental to health, re¬ mains completely open at the present. There is considerable interest in the
problem
on the part of both water and health authorities, and many use¬ ful research programs are under way at present. There will be no quick an¬ swer to this problem as it is clearly a complex one requiring the combined efforts of a wide field of specialists. Andrew G. Shaper, FRCP London
Emergency Medical Systems Act Of 1973
To the Editor.\p=m-\DrEliastam (232:135, 1975) criticized Dr Harvey's description of the Emergency Medical Systems (EMS) Act (230:1139, 1974) as being idealistic and unrealistic. This latter word was perhaps not used, but I think it adequately describes the content of his communication. It seemed to be his point that there
would be no guarantee of Utopia under the Act and that there are doubts regarding the effect of the Act thus far, if and to what extent it will further be funded; and, finally, the ultimate product of the Act. All of these doubts and reservations are valid and are shared by many of us who work in the field of emergency care. The doubt is not, however, specific for emergency care, but extends into all activities of human endeavor, since very little is assured by virtue of either legislation or funding. There was a dearth of substance, however, in Dr Eliastam's communication that would offer the reader a reason to share his concern as to the success of such legis¬ lation. The EMS Act is very definitely af¬ fecting emergency care on all sides of Palo Alto, Calif, as for example, in Santa Clara County and in San Fran¬ cisco and surrounding counties. The Act and efforts made independently via the Department of Transporta¬ tion, Robert Wood Johnson, the Na¬ tional Registry, and state and local tax monies have radically changed
emergency care availability, quality, and outcomes over a large part of the urban United States. In the rural set¬ ting there are interesting develop¬ ments as a result of the Robert Wood Johnson funding that was distributed to 44 grantees, many of whom do not represent urban populations. At the midpoint of this grant effort, it ap¬ pears to be achieving some limited success in areas where the population is sparse, the miles many, and re¬ sources proportionately few. I would refer Dr Eliastam to Redding, Calif; Hermiston, Oregon; the state of Idaho; San Bernadino, Calif; and the Navajo Nation territory (Window
Rock, Ariz) specifically.
is written of the there is little to suggest systems operation in our present hospital, doctor, allied health personnel, third-party payor, or legis¬ lation confederation. There is much more that suggests systems operation in the emergency care field where many diffuse elements must be coor¬ dinated and combined to provide even a modicum of care in this environ¬
Although much system,"1
"health
ment.
The emergency
is rela¬ in exis¬ tence less than ten years in any strongly organized and publicly vis¬ ible state. Considering the meanderings of the rest of medicine, I would suggest that emergency care
tively
young,
care arena
having been
Downloaded From: http://jama.jamanetwork.com/ by a Simon Fraser University User on 05/31/2015
has made notable achievements on limited resources and without scan¬ dalous waste or embarrassment thus far. I hope that the rest of the medi¬ cal profession may be supportive and critical at the same time in the proper balance. Just being critical may satisfy one's immediate needs, but should be balanced by long-term con¬ structive ideas. I, for one, believe that Dr Harvey's accounting of the EMS Act is both idealistic and realistic in the proper balance. Eugene L. Nagel, MD Commission on Emergency Medical Services Torrance, Calif 1.
Jangled semantics, editorial.
Oral
JAMA 231:1371, 1975.
Contraceptives, Serum
Folate, and Hematologic Status To the Editor.\p=m-\Authorsof BRIEF REPORT
(231:731, 1975)
recent must be
a
commended for their simple and clear data presentation. I have, however, a few observations that should be taken into account, as their data enter the growing list of publications on the topic of the impact of contraceptive hormones on micronutrient metabolism. While I am eager to accept their conclusion that "the incidence of subnormal serum folate values was no greater in the group using oral contraceptives than in the control group .," their data do not reinforce this propositon. Incidence is not studied, since only one measurement series was obtained and no changes were investigated; ie, the study was cross\x=req-\ sectional, not prospective. There was no control group, only a group of patients self-selected into the category of "any contraceptive method other than birth control pills," whose inclusion permits comparison but not control. Of most interest, however, is the fact that their data reveal a notable difference in the distributions of se¬ rum folate values using the Lactobacillus casei assay (their Fig 1), with a gradient unfavorable to the hormone .
.
users.
The latter problem in data analysis is, in some ways, a minor one but de¬ serves
attention: the arithmetic
mean
provides the best measure of central tendency in a normal distribution, but it appears that serum folate val¬ are not normally distributed. Without actually working over the raw data, my guess is that the data are log-normally distributed, which would suggest the use of the geomet¬ ric mean; at the very least, the meues
dian yields a better estimate of cen¬ tral tendency. The authors' figures enable the reader to calculate the lat¬ ter. The medians appear to be about 6.3 and 5.3, respectively, for "others" and "pill users," a difference of per¬ haps 15%. Is this "significant"? Their Fig 3 (radioassay for serum folate) appears to show more comparable dis¬ tributions and medians, though the percentage difference, because of the smaller absolute values, may also ap¬ proach 15%. Among those using the pill, dura¬ tion of use does not seem to depress the mean, nor the median, folate lev¬ els, and this argues well for the con¬ tention that nutrient metabolism of folate is not adversely affected by continuing use. But, again, no base¬ lines are provided prior to use for pur¬ poses of comparison. Finally, I'm not sure what is gained by the introduction of inferential sta¬ tistics, in this case the analysis of variance, to compare the two "treat¬ ment" groups. At best, it indicates what would be the case if distribu¬ tions were normal and randomization had occurred, neither of which is true. Multivariate descriptive tech¬ niques would have provided the reader more information. Despite these criticisms, I found the publication of the distributions to be refreshing and thoughtful. Would that more investigators adopted such an open approach to their measure¬ ment and analysis. I only fear now that several previous reports on fo¬ late level depression among oral con¬ traceptive users are liable to similar
réévaluations, thereby intensifying
the notion that there is a "problem." In fact, of course, no one has yet pro¬ vided relevant clinical or health ob¬ servations. We do not even have su¬ perficial indications that the minor subjective side effects of the pill in some users bear any relation to their baseline values of serum folate.
Something more than laboratory sé¬ rologie findings must be focused on this issue soon, to
it should be allowed into the archives.
or
lapse quietly
Gary Merritt, PhD
Population and Humanitarian Assistance
Bureau for
Washington, DC
In Reply.\p=m-\We would like to thank Dr Merritt for the generally complimentary remarks in reference to our paper. We accept his criticism of the semantic impropriety of the terms "incidence" and "control." In relation to his second question, we believe that
Dr Merritt is correct in his assessment that the L casei serum folate values are log-normally distributed. We have computed the geometric means for the L casei serum folate for the group taking oral contraceptives and the group not taking oral contraceptives. For the group not taking oral contraceptives, the geometric mean is 6.2 ng/ml; for the group taking oral contaceptives, the geometric mean is 5.83 ng/ml. This is a difference of only 6% and is not sta-
tistically significant (P>.5).
We believe that this statistical mahas reinforced our original contentions, and we continue to believe that our data demonstrate no significant difference in serum folate values by L casei or radioassay for women taking oral contraceptives vs those not taking them. neuver
Charles J. Paine, MD Louisiana State University Medical Center
Shreveport
Chlamydial
Infections
To the Editor.\p=m-\Ina recent article (231:1252, 1975), Schachter et al discussed the high prevalence of chlamydial infections in nonvenereal disease clinics under the title, "Are Chlamydial Infections the Most Prevalent Venereal Disease?" Nowhere in their paper did they deal with the question of mode of transmission to the infection seen. If they believe that they have evidence to indicate that the chlamydial infections observed were sexually transmitted, such data should have been presented within the paper. If such data do not exist, their title is clearly
inappropriate.
Joel L. Nitzkin, MD Dade
County Department of Public Health
Miami, Fla
Reply.\p=m-\Theepidemiology of incluconjunctivitis (for this is the chlamydial agent of concern here)
In
sion
elucidated in the first decade of this century; for example, see the review (!) by Lindner (Arch Ophthalmol 78:345-380, 1911). The agent is found in the male urethra and the female cervix and produces eye disease when infective genital tract discharges reach the conjunctiva. This has been amply confirmed by the cytologic studies of Thygeson and Stone (Arch Ophthalmol 27:91-122, 1942) and by agent isolation in many studies by Jones and Dunlop and colleagues in England and our group in San Francisco. Clear-cut cases of sexual transwas
Downloaded From: http://jama.jamanetwork.com/ by a Simon Fraser University User on 05/31/2015
mission have been described (Am J Epidemiol 85:445-452, 1967). To the best of my knowledge, volunteer studies of experimental infection and
transmission have not been performed. Dr Nitzkin appears to be concerned that our study was performed in clinics other than those devoted to venereal disease (VD). There have been many studies of chlamydial infection in VD populations (several cited in our paper). For many reasons, most venereal disease clinics treat only gonorrhea and syphilis. Unfortu¬ nately, these two represent only a portion of the sexually transmitted infections. We intended to emphasize that there are other very common sexually transmitted diseases that
being seen in hospital outpatient clinics, as well as in VD clinics. It is clear that nongonococcal urethritis is becoming a venereal disease of in¬ creasing importance. Chlamydiae rep¬ resent a major cause of this condition, which is commonly seen in both VD and hospital clinics. are
Julius Schachter, PhD University of California San Francisco
Per TRENDS
Minute IN
Omitted. In
the article titled Patient: An Al-
THERAPY
Hypertensive gorithm for Treatment," published in the Sept 1 issue (233:990-992, 1975), an error occurred on page 990. "The
The first complete sentence in col2 should read "The dose of hydralazine hydrochloride is 0.1 to 0.4 mg/min given in a non-glucose-containing fluid." The time element ("/min") was omitted from the published sentence. umn
Dosage
Errors. Erroneous
dosage
forms for two oral contraceptives were given in a QUESTION AND ANSWER, "Hirsutism With Hyperthyroidism in Young Woman," published in the Sept 8 issue (233:1109-1110, 1975). The last line of the second paragraph of the question should state that the dosage form of norethynodrel and mestranol (Enovid E) was 0.1 mg, not 1 mg; and in the last sentence of the third paragraph of the question, the dosage form of norgestrel and ethinyl estradiol (Ovral) is 0.05 mg, not 0.5 mg as given. The first error is repeated in the answer as well.
