Vlassov[1] detected something wrong in my short piece.[2] I
would like to thank him very much. The correct lines 2 and 3 of paragraph
2 are: DALYs=(0.33)x(50y)+(1.0)x(80y-50y)=46.5y.
However, this is the minor, I think: the reader can easily understand
or infer that printer's devil has replaced a 5 with a 3.
The major is that a mistake in the title escaped detection: the unit
of m...
Vlassov[1] detected something wrong in my short piece.[2] I
would like to thank him very much. The correct lines 2 and 3 of paragraph
2 are: DALYs=(0.33)x(50y)+(1.0)x(80y-50y)=46.5y.
However, this is the minor, I think: the reader can easily understand
or infer that printer's devil has replaced a 5 with a 3.
The major is that a mistake in the title escaped detection: the unit
of measurement should be in lower case (qy), as in line 4 of the last but
one paragraph – NOT in upper case (QY).
Both mistakes are mine. I apologize.
References
1. Vlassov VV. More accurately? [electronic response to Dimoliatis I D K. Qualia years (QY)—not years—should be the unit of measurement of QALYs, DALYs, life expectancy, and life] jech.com 2004 URL direct link to eLetter
2. Dimoliatis I D K. Qualia years (QY)—not years—should be the unit of measurement of QALYs, DALYs, life expectancy, and life. J Epidemiol Community Health 2004; 58: 1054-a-1055-a.
I read the article by Jefferson[1] with interest. Although they are rare, vaccine reactions do occur and are suspected
of having severe consequences.[2-4] It is here suggested that it is
mainly those infants who already have somewhat depleted vitamin C stores,
who are affected most. We now know that even modest ascorbate depletion is
associated with very high blood histamine levels,[5], as shown in figu...
I read the article by Jefferson[1] with interest. Although they are rare, vaccine reactions do occur and are suspected
of having severe consequences.[2-4] It is here suggested that it is
mainly those infants who already have somewhat depleted vitamin C stores,
who are affected most. We now know that even modest ascorbate depletion is
associated with very high blood histamine levels,[5], as shown in figure
1; so any additional histamine due to infection or vaccinations can cause
a toxic histaminaemia leading to capillary fragility.
Figure 1. Results of plasma ascorbic acid (reduced form) and whole
blood histamine concentrations in the same blood samples from 437
volunteers in Brooklyn, NY (4). A highly significant increase in the blood
histamine level was evident when the plasma ascorbic acid level fell below
0.7 mg/100 mL. This comprised 150 of the 437 (34 percent) men and women.
Data from Clemetson 1980.
A very simple remedy is suggested. There is no doubt that a vitamin C
supplement can be used to prevent the adverse vaccine reactions brought on
by increased blood histamine levels, both in animals and in man. We know
that vitamin C acts to remove histamine from the blood by converting it to
hydantoin-5-acetic acid.
We also know that a dose of vitamin C appropriate for this purpose
may be much greater than the usually recommended dietary allowance.
Ascorbic acid has been shown to be life-saving when given with vaccines,
even in rats, mice, and rabbits, which make their own ascorbic acid in the
liver and do not normally need it in their diet. It seems that even these
animals do not always make enough ascorbic acid for their own needs.
As for human infants, the appropriate dose of vitamin C to be given
with vaccines -- and the best method of administering it -- still need to
be determined. Ascorbic acid is not toxic, so I have suggested 500 mg to
be given to infants in fruit juice on the day of vaccination. Some
authorities may decide to give sodium ascorbate intramuscularly, already
prepared with the vaccine.
Much has been written on the specific toxicity of individual
vaccines, but histamine toxicity is a general effect. Now that infants
receive as many as six vaccines together at eight weeks of age, we have to
think of the cumulative histamine increase as a general toxicity.
Excellent work on vitamin C and vaccine reactions was done many years ago
and was summarized in 1999.[6] The results of all the experiments were
consistent and showed that ascorbic acid reduces both the morbidity and
the mortality due to all the bacterial antigens studied, and in all the
different animals tested.
The observation that borderline ascorbic acid deficiency increases
the morbidity and mortality from diphtheria antigen in guinea pigs goes
back to work by Harde[7] in 1934 and by King and Menten[8] in 1935, not
long after the isolation of ascorbic acid by Svirbely and Szent-Gyorgyi[9] and by King and Waugh[10] in 1932. King and Menten observed that
there is a wide zone of vitamin C depletion, without the appearance of
scurvy, wherein physiological processes are subnormal and an animal is
more sensitive to bacterial toxins.
In addition to providing protection against diphtheria toxoid,
vitamin C is also protective against the toxoids of four different
varieties of gas gangrene bacteria in mice, as shown by Buller-Souto and
Lima[11] in Table 1, and against tetanus toxoid in rats, as shown by Dey[12] in Table 2.
Table 1
Protective activity of L-ascorbic acid 10mg daily, given intramuscularly to mice for 3 days
preceding both a single and a double LD50 dose of four different gas gangrene toxins. Note
the unsurprisingly good protective activity of ascorbic acid even in mice, which make their
own ascorbic acid
LD50 dose>
of Toxin of
Clostridium
AA treated
Controls
Percentage
Survival of
Controls
Percentage
Survival of
AA-treated Mice
n
dead at
48 hrs
n
dead at
48 hrs
welchii
55
14
26
13
50
75
septicum
30
7
10
5
50
77
oedematiens
22
3
11
5
55
86
histolyticum
18
3
15
6
60
83
2 LD50 dose
welchii
57
38
30
30
0
33
septicum
31
15
12
10
17
52
oedematiens
24
9
11
8
27
63
histolyticum
18
16
15
15
0
11
AA=L-ascorbic acid; n=number of animals
An LD50 dose of toxin is that previously found to kill 50 percent of the animals
2 LD50 is twice that dose
From Büller-Souto and Lima.[11]. Translated and summarised by Clemetson,[6] reproduced with permission from the
Journal of Orthomolecular Medicine
Table
2. Efficiency of vitamin C in counteracting the toxicity of tetanus antigen in
adult rats
Treatment
No. of Rats
Symptoms
Survival
2 MLD tetanus toxin i.m.
5
All convulsed and died within 47-65 hrs
None
2 MLD tetanus toxin i.m. with 1g AA (per body weight) i.p.
and 1g AA/kg b.i.d. for 3 days i.p.
5
Only very mild local tetanus after 48 hrs
All
AA 1g/kg b.i.d. for 3 days then 2 MLD tetanus toxin + AA
1g/kg b.i.d. for 3 days
5
No signs of toxicity
All
2 MLD tetanus toxin, AA 1g/kg i.p. only when convulsions
began after 16 to 26 hrs and continued b.i.d. for 3 days
5
Convulsions arrested
All
2 MLD tetanus toxin. Animals anaesthetized after 40 to 47
hours when general tetanic convulsion occurred - then AA 300mg give IV
10
All
AA=L-ascorbic acid; MLD=minimum lethal dose; 2 MLD=twice minimum lethal
dose; i.m.=intramuscular injection; i.p.=intraperitoneal injection.
Data from Dey.[12] Table reproduced with permission from the Journal of
Orthomolecular Medicine.[6]
Fukada and Koyama[13] demonstrated that pretreatment with ascorbic
acid (500 mg/day), mixed in a soybean curd diet, protected their rabbits
against the toxic effects of Salmonella typhi endotoxin. Ascorbic acid
saturation markedly ameliorated the depletion of liver glycogen after
endotoxin, both in intact and in adrenalectomised rabbits, and completely
prevented the attendant hypoglycaemia.
The seminal studies of Kalokerinos[14] showed that supplementary
vitamin C was uniformly effective in preventing infant deaths following
vaccination in Aborigine children in Australia.
In view of all these most important and encouraging findings, one
wonders why ascorbic acid has not yet been widely recommended for routine
use with vaccinations. This reticence may have been due to a sense that
such an anti-toxic action could possibly vitiate the purpose of a vaccine.
However, now that we know that the anti-toxic effect of vitamin C is due
to its role in the removal of histamine and does not affect the antigen,
we can recommend it freely. Ascorbic acid acts as a co-enzyme in the
elimination of histamine by converting it to hydantoin-5-acetic acid, and
on to aspartic acid in vivo.[15] We can recommend vitamin C for general
use with all vaccines, without any fear that the vaccine will lose its
intended potency as a stimulant of immunity.
The vaccine-ascorbate studies cited here are very old, and many, from
abroad. It would be reassuring to hear of any new studies -- not that they
would necessarily be any more reliable, but that plasma ascorbic acid and
whole blood histamine studies could now be included.
References
1. Real or perceived adverse effects of vaccines and the media - a tale of our times. Jefferson T. J Epidemiol Community Health 2000; 54: 402-403
2. Clemetson CAB. Elevated blood histamine caused by vaccinations and
vitamin C deficiency may mimic the shaken baby syndrome. Medical
Hypotheses 2004; 62:533-536.
3. Clemetson CAB. Capillary fragility as a cause of subdural
hemorrhage in infants. Medical Hypotheses and Research 2004; 1:121-129.
4. Clemetson CAB. Is it "shaken baby," or Barlow's disease variant?
Journal of American Physicians and Surgeons 2004; 9:78-80.
5. Clemetson CAB. Histamine and ascorbic acid in human blood. Journal
of Nutrition 1980; 110:662-668.
6. Clemetson CAB. Vaccinations, inoculations and ascorbic acid.
Journal of Orthomolecular Medicine 1999; 14:137-142.
7. Harde E. Acide ascorbique (vitamin C) et intoxications. Comptes
Rendus de l'Academie des Sciences Paris 1934; 119:618-620.
8. King CG, Menten ML. The influence of vitamin C level upon
resistance to diphtheria toxin. Journal of Nutrition 1935; 10:129-140.
9. Svirbely JL,Szent-Gyorgyi A. The chemical nature of vitamin C.
Biochemical Journal 1932; 27:279-285.
10. King CG, Waugh WA. The chemical nature of vitamin C. Science 1932;
75:357-358.
11. Buller-Souto A, Lima C. Activity of L-ascorbic acid on the toxins
of gas gangrene. Memorias do instituto Butantan, Sao Paulo, Brasil, 1939;
12:265-295, in Portuguese; 297-311, in French (same data).
12. Dey PK. Efficiency of vitamin C in counteracting tetanus toxin
toxicity. Naturwissenschaften 1966; 53:310.
13. Fukada T, Koyama T. Prevention by ascorbic acid of liver glycogen
depletion in endotoxin intoxication. Nature (London) 1963; 200:1327.
14. Kalokerinos A. Every Second Child. Thomas Nelson (Australia) Ltd.
1974. Now reprinted by Falconi O, Box 3345, Saratoga, CA 95070.
15. Chatterjee IB, Majumder AK, Nandi BK, Subramanian N. Synthesis
and some major functions of vitamin C in animals. Annals of New York
Academy of Sciences 1975; 258:24-47
I suggest the findings of Gouveia et al[1] may be due to increased
testosterone. It is my hypothesis that increased maternal testosterone
causes prematurity and low birth weight.
In rats, nitrogen dioxide increases maternal testosterone
specifically.[2] It may be
that increased exposure to nitrogen dioxide may increase prematurity and
low birth weight because of increased maternal te...
I suggest the findings of Gouveia et al[1] may be due to increased
testosterone. It is my hypothesis that increased maternal testosterone
causes prematurity and low birth weight.
In rats, nitrogen dioxide increases maternal testosterone
specifically.[2] It may be
that increased exposure to nitrogen dioxide may increase prematurity and
low birth weight because of increased maternal testosterone stimulated by
nitrogen dioxide.
References
1. Gouveia N, Bremner S A, Novaes H M D. Association between ambient air pollution and birth weight in São Paulo, Brazil. J Epidemiol Community Health 2004; 58: 11-17.
2. Watanabe N, Kurita M. The Masculinization of the Fetus During Pregnancy Due to Inhalation of Diesel Exhaust. Environ Health Perspect. 2001 Feb;109(2):111-9.
We read the Letter by Dimoliatis with interest.[1] However, "0.33x50+1.0x(80–50) = 46.5", more accurately, we had to put QALYs = (0.67)x(50y) = 33.5y and DALYs =
(0.33)x(50y)+(1.0)x(80y–30y) = 46.5y.
If substitute (80-50) by (80-30) result must be different.
I believe that something is wrong in this short piece intended to add
clarity!
We read the Letter by Dimoliatis with interest.[1] However, "0.33x50+1.0x(80–50) = 46.5", more accurately, we had to put QALYs = (0.67)x(50y) = 33.5y and DALYs =
(0.33)x(50y)+(1.0)x(80y–30y) = 46.5y.
If substitute (80-50) by (80-30) result must be different.
I believe that something is wrong in this short piece intended to add
clarity!
Reference
1. Dimoliatis I D K. Qualia years (QY)—not years—should be the unit of measurement of QALYs, DALYs, life expectancy, and life. J Epidemiol Community Health 2004; 58: 1054-1055.
I congratulate the Tatemichi et al on an interesting study.[1] However, as this
paper has been widely sited in the general press, I would like to point
out that this study does not show that heavy computer use causes glaucoma
as suggested by the international press agencies.
The prevalence of open angle glaucoma is well known from various
epidemiological studies and ranges from 1-3% in...
I congratulate the Tatemichi et al on an interesting study.[1] However, as this
paper has been widely sited in the general press, I would like to point
out that this study does not show that heavy computer use causes glaucoma
as suggested by the international press agencies.
The prevalence of open angle glaucoma is well known from various
epidemiological studies and ranges from 1-3% in white populations to 10%
in African Americans and up to 15% in African Caribbeans.[2-12]
In this cohort of 9124 (8602+522) Japanese workers, only 315 of
workers with abnormal visual fields consented to ophthalmological
examination and 210 (66.67%) of those were felt to have suspect
glaucomatous discs. If this percentage were to be taken as the same for
the 207 workers excluded, that would give a total of 348 (210 + 138). This
would give an incidence of glaucoma of 3.8% in this group of workers!
Even if the entire excluded group were taken as positive, this still
gives an incidence of glaucoma of 4.6% (210+207/9124 x %) for this group.
In addition, this study shows that not all the workers with suspect
glaucomatous optic discs had glaucoma suggesting an incidence of glaucoma
in this population of approximately 3%, which corresponds to the incidence
in a general white population!
Furthermore, myopia is thought to be a significant risk factor for the
development of glaucoma[13-15] and 96.4% of the “glaucoma” group in this
study were found to have a myopic prescription.
References
1. Tatemichi M, Nakano T, Tanaka K, Hayashi T, Nawa T, Miyamoto T, Hiro H, Sugita M. Possible association between heavy computer users and glaucomatous visual field abnormalities: a cross sectional study in Japanese workers. J Epidemiol Community Health 2004; 58: 1021-1027
2. Kahn HA, Milton RC. Alternative definitions of open-angle
glaucoma: effect on prevalence and associations in the Framingham Eye
Study. Arch Ophthalmol. 1980;98:2172-2177.
3. Bengtsson B. The prevalence of glaucoma. Br J Ophthalmol.
1981;65:46-49.
4. Tielsch JM, Sommer A, Katz J, Royall RM, Quigley HA, Javitt J.
Racial variations in the prevalence of primary open-angle glaucoma: the
Baltimore Eye Survey. JAMA. 1991;266:369-374.
5. Ringvold A, Blika S, Elsas T, et al. The Middle-Norway eye-
screening study, II: prevalence of simple and capsular glaucoma. Acta
Ophthalmol (Copenh). 1991;69:273-280
6. Klein B, Klein R, Sponsel WE, et al. Prevalence of glaucoma: the
Beaver Dam Eye Study. Ophthalmology. 1992;99:1499-1504.
7. Dielemans I, Vingerling JR, Wolfs RCW, Hofman A, Grobbee DE, de
Jong PT. The prevalence of primary open-angle glaucoma in a population-
based study in the Netherlands. Ophthalmology. 1994;101:1851-1855.
8. Leske MC, Connell AMS, Schachat AP, Hyman L for the Barbados Eye
Study Group. The Barbados Eye Study: prevalence of open-angle glaucoma.
Arch Ophthalmol. 1994;112:821-829
9. Mitchell P, Smith W, Attebo K, Healey PR. Prevalence of open-angle
glaucoma in Australia: the Blue Mountains Eye Study. Ophthalmology.
1996;103:1661-1669.
10. Leske MC, Ederer F, Podgor M. Estimating incidence from age-
specific prevalence in glaucoma. Am J Epidemiol. 1981;113:606-613
11. Podgor MJ, Leske MC, Ederer F. Incidence estimates for lens
changes, macular changes, open-angle glaucoma, and diabetic retinopathy.
Am J Epidemiol. 1983;118:206-212
12. Quigley HA, Vitale S. Models of open-angle glaucoma prevalence
and incidence in the United States. Invest Ophthalmol Vis Sci. 1997;38:83-
91.
13. Ponte F, Giuffre G, Giammanco R, Dardononi G. Risk factors of
ocular hypertension and glaucoma: the Casteldaccia Eye Study. Doc
Ophthalmol. 1994;85:203-210.
14. Mitchell P, Hourihan F, Sandbach J, Wang JJ. The relationship
between glaucoma and myopia: the Blue Mountains Eye Study. Ophthalmology.
1999;106:2010-2015.
15. Perkins ES, Phelps CD. Open angle glaucoma, ocular hypertension,
low-tension glaucoma, and refraction. Arch Ophthalmol. 1982;100:1464-1467
“The further back you look, the further forward you can see”. These
words of Winston Churchill are the compelling reason for backing Berridge
and Gorsky’s,[1] and Scally and Womack’s[2] calls for more attention to
public health history.
The lessons I have learnt from history are that my work is part of a
long tradition, that many others have struggled with the same type of
challenges th...
“The further back you look, the further forward you can see”. These
words of Winston Churchill are the compelling reason for backing Berridge
and Gorsky’s,[1] and Scally and Womack’s[2] calls for more attention to
public health history.
The lessons I have learnt from history are that my work is part of a
long tradition, that many others have struggled with the same type of
challenges that I confront, and that change requires luck, tenacity,
patience and belief. While Hippocrates’ contributions to public health
are well known, those of Indian physicians are not. My Indian
predecessors Caraka (1st century AD) who said that "concord is health,
discord is disease" and Susruta (4th century AD) whose purpose was to
prolong life and prevent disease are also worth studying.
The University of Edinburgh has a tradition of public health to be
proud of but the story is largely unknown and seldom told. Academics are
well placed to be the champions of public health history, and they can
take such opportunities as inaugural lectures where the contextual legacy
is welcomed.[3]
In the book Concepts of Epidemiology[4] I wrote a section entitled
Building on an Epidemiological Education: Role of Historical Landmarks
(pp 291-293). The study of the classics,[5] or in Thomas Kuhn’s
terminology exemplars,[6] provides inspiration as well as instruction.[4] In my book, I chose Lind and scurvy, Jenner and smallpox and Snow
and cholera as my exemplars. Even in the well known stories there are new
slants that matter in the modern era. For example, John Snow’s book On
the Mode of Communication of Cholera cost him £200 to publish and sold 56
copies in three years, making him £3 and 12 shilling (60p). Learned
committees and many of his peers rejected his findings. This year marks
the 150th anniversary of the Broad Street epidemic of cholera, and Snow’s
famous removal of the pump handle. Those enmeshed in the web of the UK
Research Assessment Exercise would do well to reflect on the limitations
of peer review and indicators of popularity and attention as a judge of
quality in research.
In 2002, Edinburgh University celebrated the 100th anniversary of the
founding of its academic department of public health, the Usher Institute
of Public Health. Our conference examined the past, present and future of
public health, and the proceedings will be published shortly.[7] The
celebrants crossed at least three generations of public health
practitioners and academics. As part of the centenary events we created a
public health walk of Edinburgh. This event centred on public health
history, connected the living and now global public health community of
Edinburgh students and staff to our deceased, illustrious predecessors to
whom we paid respect. I cannot imagine another conference theme that would
have such a broad appeal.
JECH’s support of public health and epidemiological history deserves
acclaim.
References
1. Berridge V, Gorsky M. The importance of the past in public
health. JECH 2004; 258: 728-729
2. Scally G, Womack J. The importance of the past in public health. JECH 2004; 258: 751-755
3. Bhopal R S. Generating health from the pattern of disease. Proc R Coll
Physicians Edinburgh 2001; 31:293-298
4. Bhopal R S. Concepts of Epidemiology. Oxford, Oxford University Press,
2002
5. Buck C, Llopis A, Najera E, Terris M. The Challenge of Epidemiology.
Issues and Selected Readings. Washington DC: Pan American Health
Organization, 1988
6. Kuhn TS. The Structure of Scientific Revolutions. Third ed. Chicago:
The University of Chicago Press, 1996
7. Bhopal R, Last J. Public health: past, present and future. London,
Nuffield Trust 2004 (in press)
Jousilahti and Salomaa appear unhappy with our response to their
paper on the social patterning of serum inflammatory markers.
First they feel that we have misinterpreted their findings and
conclusions. We fail to see how. They found (as others have) that social
disadvantage was associated with increased inflammation – as indexed by
markers such as higher fibrinogen - and that this association...
Jousilahti and Salomaa appear unhappy with our response to their
paper on the social patterning of serum inflammatory markers.
First they feel that we have misinterpreted their findings and
conclusions. We fail to see how. They found (as others have) that social
disadvantage was associated with increased inflammation – as indexed by
markers such as higher fibrinogen - and that this association was only
partly attenuated by adjustment for smoking, obesity and diagnosed
disease. They concluded that “Systemic inflammation is a potential mediator, especially among
young and middle aged men, for the association between socioeconomic
status and cardiovascular disease.”[1]
For inflammation (as indexed by fibrinogen for example) to mediate an
association between social position and heart disease it would have to be
causally related to heart disease risk. Jousilahti and colleagues assume
such a causal relation and explicitly state that “Fibrinogen increases the risk of an acute coronary event through its
prothrombotic and rheological effects, and may also play a part in
atherosclerosis formation.”
The alternative explanation is that the association between
fibrinogen and heart disease is not causal. First, reverse causation
probably contributes. Atherosclerosis is an inflammatory condition
therefore established (including sub-clinical) disease would be associated
with increased inflammatory markers. But these markers do not cause
atherosclerosis any more than chest pain causes myocardial ischaemia.
Second, the association is likely to be confounded. Smoking, being obese
and being poor are all associated with increased fibrinogen and
independently with increased risk of heart disease. Within the non-causal
model, fibrinogen is essentially no more than a marker. A marker of
established disease, a marker of health damaging factors and, because
established disease and health damaging factors are socially patterned, a
marker of social position. If fibrinogen is merely a marker its social
patterning gives us no new insights into the social patterning of heart
disease.
Untangling competing theories of this nature is the bread and butter
of epidemiology and as epidemiologists we have an interest in any strategy
that might be helpful. Experimental studies are of course the mainstay
here. Random allocation of individuals to a condition of higher or lower
fibrinogen should ensure that any effects of fibrinogen subsequently seen
are not the result of confounding or reverse causation. Randomised trials
of manipulation of fibrinogen have not shown any important effects on
heart disease.[2] We think this is an important clue that the fibrinogen-
heart disease link is non-causal. Jousilahti and colleagues dismiss such
evidence on the basis that it is “scarce”. This is not the case: there are
a large number of trials of fibrates, which lower fibrinogen levels, and
the effects of these on coronary heart disease (CHD) have been
disappointing. There is some difficulty in interpretation, since the
fibrates also lower cholesterol levels and should produce reductions in
CHD risk through this effect. However, the fact that any observed
reduction in CHD risk is small, and certainly no greater than would be
anticipated by the cholesterol lowering effect, argues against a causal
role for fibrinogen.
Jousilahti and Salomaa appear to base their support for fibrinogen’s
causal candidacy on consistency of the observational evidence of
associations between higher serum fibrinogen and increased risk of heart
disease. Confounding and reverse causation of the type discussed above
would, of course, predict consistent associations in observational data
(because the associations that lead to the introduction of these biases
are often themselves consistent).
But if experimental evidence is difficult to interpret, and
conventional observational evidence consistently compromised by concerns
over reverse causation and confounding, how else can we progress our
understanding? One potential approach is Mendelian randomisation.[3] This
is not a panacea, but many epidemiologists have recognised and are excited
by its potential contribution.[4-11] Mendelian randomisation refers to
the random assortment of genes from parents to offspring that occurs
during gamete formation and conception. This leads to a distribution of
genotype in populations that is not, generally, confounded by lifestyle or
socioeconomic factors, unlike measured phenotypes such as fibrinogen
levels. The association between risk of a disease and a genetic variant
that mimics the biological link between a proposed exposure and disease is
not generally susceptible to the reverse causation or confounding that may
distort interpretations of conventional observational studies. Several
examples where the phenotypic effects of polymorphisms are well documented
provide encouraging evidence of the potential of Mendelian randomisation.[3,12]
Youngman and colleagues, through their work on fibrinogen and heart
disease, recently exemplified this contribution.[13] In their
observational study, fibrinogen was associated with heart disease in the
usual way – a 0.12g/l increase conferring a relative risk of CHD of 1.20
(1.13-1.26). However serum fibrinogen is also influenced by a polymorphism
in the beta fibrinogen gene, presence of the T allele being associated
with a 0.12g/l increase in serum levels in this population. Presence or
absence of the T allele will not (apart from in very unusual
circumstances) be associated with any of the behavioural or environmental
correlates of fibrinogen that may confound associations with heart
disease, because genotype is randomly assigned at meiosis. Therefore
estimates of effects of this allele on CHD risks are in effect,
unconfounded, “intention to treat” estimates of the effect of the higher
fibrinogen levels associated with presence of the allele. This is the
principle of Mendelian randomisation. In their study, Youngman and
colleagues found that the relative risk of CHD associated with presence of
the T allele (i.e. the unconfounded effect of a 0.12g/l increase in
fibrinogen) was 1.03 (0.96-1.10). They interpreted this as strong evidence
increased fibrinogen did not cause increased risk of heart disease.
Jousilahti and Salomaa apparently disagree, both in relation to the
specific example of fibrinogen and with regard to the general usefulness
of the Mendelian randomisation principle. With respect, we found their
arguments difficult to follow and felt they suggested some
misunderstanding of the issues involved. For example they point out that a
number of genetic and environmental factors influence fibrinogen levels.
Well so they do, but this fact is irrelevant in the present context.
Presence of the beta fibrinogen T allele was probably not the most
important determinant of serum fibrinogen in the Youngman study
population. However it was an identifiable trait consistently associated
with higher fibrinogen levels. Consider another example. Within a
population the use of anti-hypertensive medicines (even if these are
widely and appropriately prescribed) will only make a small contribution
to variance in blood pressure. However this doesn’t mean that anti-
hypertensive drugs will not have a major influence on the sequelae of
elevated blood pressure in this population. The fact that there are many
other environmental and genetic factors contributing to blood pressure
other than anti-hypertensive drugs is irrelevant, as is the wide range of
factors contributing to variance in fibrinogen levels. Indeed, it is the
fact that fibrinogen levels are associated with so many environmental
factors that makes the association with coronary heart disease difficult
to study, due to the considerable potential confounding that can arise.
Jousilahti and Salomaa then appear to confuse arguments around the
shortcomings of association studies in identifying genetic determinants of
complex disease with arguments around the usefulness of Mendelian
randomisation. We have discussed the former (including the specific issues
of replicability and low population attributable risk of any single
factor) at length elsewhere. However these arguments do not apply in the
present context.[14] We [3,12] and others [6-8, 15] have also discussed
the potential limitations of Mendelian randomisation in what we feel is a
coherent way. With regard to understanding the causal role of fibrinogen
the large sample sizes required is probably the major issue.[16]
What is now termed Mendelian randomisation was first advanced as an
approach to clarifying issues of confounding and reverse causation 20
years ago.[17] As epidemiologists, predominantly working with
observational data we are well aware of these problems and are therefore
interested in the exploration of possible solutions. Others seem to share
this interest, and seem prepared to discuss the potential, and the
potential pitfalls, of this methodology coherently and constructively.
References
1. Jousilahtil P, Salomaa V, Rasi V, Vahtera E and Palosuo T. Association of markers of systemic inflammation, C reactive protein, serum amyloid A, and fibrinogen, with socioeconomic status. J Epidemiol Community Health 2003;57:730-733.
2. Meade T, Zuhrie R, Cook C, Cooper J. Bezafibrate in men with lower
extremity arterial disease: randomised controlled trial. BMJ 2002;325:1139
-41
3. Davey Smith G, Ebrahim S. “Mendelian randomisation”: can genetic
epidemiology contribute to understanding environmental determinants of
disease? Int J Epidemiol 2003;32:1-22.
4. Katan MB. Commentary: Mendelian randomization, 18 years on. Int J
Epidemiol 2004;33:10–11.
5. Wheatley K, Gray R. Commentary: Mendelian randomization—an update
on its use to evaluate allogenic stem cell transplantation in leukaemia.
Int J Epidemiol 2004;33:15–17.
6. Brennan P. Commentary: Mendelian randomization and
gene–environment interaction. Int J Epidemiol 2004;33:17–21.
7. Thomas DC, Conti DV. Commentary: The concept of ‘Mendelian
Randomization’. Int J Epidemiol 2004;33:21–25.
8. Tobin MD, Minelli C, Burton PR, Thompson JR. Commentary:
Development of Mendelian randomization: from hypothesis test to ‘Mendelian
deconfounding’. Int J Epidemiol 2004;33:26–29.
9. Keavney B. Commentary: Katan's remarkable foresight: genes and
causality 18 years on. Int J Epidemiol 2004;33:11–14.
10. Clayton D, McKeigue PM. Epidemiological methods for studying genes
and environmental factors in comples diseases. Lancet 2001;358:1356-60.
11. Keavney B. Genetic epidemiological studies of coronary heart
disease. Int J Epidemiol 2002;31:730-6
12. Davey Smith G, Ebrahim S. Mendelian randomisation: prospects,
potentials and limitations. Int J Epidemiol. 2004;33:30-42.
13. Youngman LD, Keavney BD, Palmer A et al. Plasma fibrinogen and
fibrinogen genotypes in 4685 cases of myocardial infarction and in 6002
controls: test of causality by “Mendelian randomisation”. Circulation
2000;102(suppl II):31-32.
14. Colhoun HM, McKeigue P M, Davey Smith G. Problems of reporting
genetic associations with complex outcomes. Lancet 2003;361:865-72.
15. Little J, Khoury MJ. Mendelian randomisation, a new spin or real
progress? Lancet 2003;362:930- 31.
16. Davey Smith G, Harbord R, Ebrahim S. Fibrinogen, C-reactive
protein and coronary heart disease: does Mendelian randomization suggest
the associations are non-causal? Q J Med 2004;97:163-166.
17. Katan MB. Apolipoprotein E isoforms, serum cholesterol, and
cancer. Lancet 1986;i:507–08. Reprinted Int J Epidemiol 2004;33:9.
After a journey to Asia during the SARS outbreak, Syed et al
suggested that "the public health significance of such potent symbols as
the face mask may be considered in strategies to tackle other emerging
infections" [1]. Nevertheless, like other unsolved puzzles of the SARS
emergence, the exact impact and lesson learned from this collective and
profound symbol of masks wearing is still controversia...
After a journey to Asia during the SARS outbreak, Syed et al
suggested that "the public health significance of such potent symbols as
the face mask may be considered in strategies to tackle other emerging
infections" [1]. Nevertheless, like other unsolved puzzles of the SARS
emergence, the exact impact and lesson learned from this collective and
profound symbol of masks wearing is still controversial.
Face mask for SARS prevention - a significant public health strategy?
The dramatic, somehow fearful image of people collectively wearing
masks has indeed become a mighty symbol of the SARS epidemic. Syed et al
indicated that "though of uncertain protective benefit, the wearing of
masks may have contributed to the awareness of the collective and personal
responsibility in combating infectious disease". However, firsthand
experiences of SARS in affected areas seem to provide a quite different
scenario. Already
at the beginning of the SARS outbreak, WHO spokesman Dick Thompson warned
against making the public wear face masks. He said "people buying them so
they feel comfortable riding the subway doesn't make a lot of sense,
we're just not going to encourage silliness because we don't want to see
a shortage of masks" [2].
In addition to competing to obtain masks with medical workers who
really needed them during the crisis, having the people collectively wear
masks in all kinds of non-nosocomial environments delivered a strong but
exaggerated impression of the SARS risk to the public.
This behavior was interpreted in a lay epidemiological perspective -
the chance of getting infected with SARS was virtually everywhere
otherwise why would random people wear masks while going to school or
work, riding the metro, or leaving home for simply grocery shopping.
The truth was that before the "mask-terror" started, fair
epidemiological investigation showed that it was adequate to advise the
public to keep their routines as normal as possible because people's
routine life wouldn't increase the risk of SARS transmission.
For example, in the early stage of the endemic, WHO epidemiologists
maintained the view that asymptomatic transmission doesn't appear to
occur [3]. People wouldn't just sit there and release SARS bugs. Canadian
health officials also indicated that the chance of contracting SARS in
places like Chinatowns was virtually nil [4] and urged the public to stop
buying masks in fear of a possible shortage of masks in health care
facilities [5].
The risk of SARS infection was definitely limited to the close
contacts with SARS symptomatic patients. The close contact, by WHO's
definition, was having cared for, lived with, or had direct contact with
respiratory secretions or body fluids of a suspected or probable case of
SARS [6]. Therefore, the need to wear mask by the general public to reduce
the risk was by all means an epidemiological misunderstanding that created
enormous fear an
d hysteria in Asians countries. In comparison to its counterpart Asian
cities, where a mask was considered a must-have and eventually become a
symbol of public horror and panic, the Canadian¡¦s transparent and
epidemiology-based risk communication assessment probably made Toronto a
less panic-stricken city considering that not many people were wearing
masks on the streets.
The thought "risk-is-everywhere" best portrayed by mass mask
wearing fired up an extreme public panic and impaired disease control
efforts in several ways.
Forced to response to the widespread public panic induced by this
dramatic and visual "mask-terror" on TV on an hourly base, every public
health jurisdiction in SARS affected areas was overwhelmed with
unthinkable and cumbersome tasks triggered by the infectious "mask
panic". These included finding millions of facial mask in a very short
period of time, calling off regular social and economic activities, mass
resignation of health workers [
7, 8], preventing the rejection of seasonal fever patients by some medical
institutions in fear of SARS infection or of losing general patients who
refused to visit hospitals where SARS patients had previously been found
[9].
The epidemiology of fear 'V the unlearned lesson of the SARS outbreak
The importance of the public's reaction to an unknown outbreak or a
comparable bio-terrorism attack is critical, especially because it risks
creating chaos and widespread mass panic, thus crippling effective
responses to the situation. The epidemiology of fear is arguably the most
under-learned lesson of last years SARS crisis. Indeed, while a sudden
outbreak or a bio-terrorist attack unfolds, in addition to possible
biological agents, there is always another equally dreadful infectious phenomenon in the shadows
- public panic. The lessons from SARS prove again that unmanaged public
panic may be as alarming as the disease itself.
Two lessons learned from Taipei, one of the epicenters of the SARS
outbreak last year, reveal some of the possible mechanisms of public panic
escalation and how this can be avoided.
The leader's example effect - Taipei's costly lesson
In a crisis, decision makers are tempted to implement draconian
measures even in the absence of substantial evidence. Taipei, the last
city to be removed from WHO's list of SARS affected area, exemplifies the
costly lesson of risk communication within the public. When a patient who
had recently visited China was reported ill and further diagnosed as a
SARS probable case, leaders of the Taipei city government, including the
mayor and the hea
d of the health department, started wearing masks at SARS press
conferences. They believed that they were thus showing their determination
to combat this disease.
Nevertheless, this political posturing of a lineup of well-known
leaders wearing face masks in the city hall created an alarming image.
This image, once broadcasted through the media, set off an enormous public
panic in Taipei. Residents in Taipei felt that the risk of getting
infected with SARS was literally everywhere. The "mask-panic" developed
when Mayor Ma Ying-jiu ordered every citizen to put on a face mask when
ridding the city metro and visiting city hall.
A shocking proposal to compulsory
quarantine the whole country¡'s 23 millions people for 10 days gained
majority support according to a local poll [10]. This unprecedented
"whole nation quarantine" was formally discussed by local politicians
and influential opinion leaders. Fortunately, the outbreak faded away
almost as promptly as it bloomed. This multi-billion dollar proposal
didn't survive. Still, the exceptional
magnitude of Taiwan's compulsory quarantine overwhelmed its SARS
affected rivals which reflected its unparalleled mass panic rather than
rational reactions. In terms of number of people quarantined per SARS
patient found, Taiwan's 227 people quarantined per SARS case [11] largely
outnumbered Hong-Kong's 2 to 3 people [12], Singapore's 37 people[13]
and Toronto's close contacts oriented, epidemiology-based voluntary
quarantine measure.
Social amplification of the risk
We learned from Taipei's experience that disease control measures
taken by the health authority helped formulate the risk perception of
SARS. The SARS corona virus was invisible, novel and hard to comprehend in
a short period of time. But the initial SARS control measures were obvious
and magnified in the media spotlight, which helped create the first
impressions of SARS, its infection risk, and routes of transmission. The
control measures
implemented by the Taipei city government included spreading disinfectant
on the streets, free distribution of volumes of bleach to nearly one
million households, compulsory quarantine of hundreds of thousands healthy
people who didn't have any known close contact with SARS patients but
simply had visited the hospitals where SARS patients were later found,
encouraging politicians and professional health leaders not clinically
involved in SAR
S patient care to wear masks in public and show this on TV, etc. All of
these non-epidemiology based measures helped greatly enhance the public
panic toward SARS.
These experiences showed how important it is to respond to an
outbreak with prompt epidemiological investigation for both disease
containment as well as ease of the escalating public panic. Public health
history has shown that in order to fail a disease control effort, health
authorities can't do better than stigmatize patients, exaggerate the
threat, and horrify the public with measures that have no scientific
support.
The Experiences from last year tell us that in facing an unknown
outbreak, neither reacting with ignorance like the Chinese authority (SARS
was officially found in Vietnam, three months after the first case had
surfaced in Guangdong, China) nor responding with paranoia (like WHO's
unscientific SARS travel advisory announcements which exaggerated the SARS
risk and literally killed local economies) had helped to conquer SARS. The
assertion "the only thing we have to fear is fear itself" has never been so accurate
as during the SARS crisis. In a word, any outbreak control measure, no
matter how fearsome the disease may seem to be, should be based on
epidemiological evidences, not fear let alone hysteria.
References
1.Syed Q, Sopwith W, M Regan M, Bellis MA. Behind the mask. Journey
through an epidemic: some observations of contrasting public health
responses to SARS. J Epidemiol Community Health, 2003; 57: 855 - 856.
2.Tom Cohen. Most don¡¦t need masks to stave off SARS. Associated
Press. 11 April 2003.
3.WHO. SARS 'V multi-country outbreak - Update 25. Interim report of
the WHO team in China, status of the main SARS outbreaks in different
countries. http://www.who.int/csr/don/2003_04_09/en/ (accessed 11 April
2003).
4.CBC News. SARS deals Toronto economic hit. 03 April 2003;
http://www.cbc.ca/stories/2003/04/03/sars$030403 (accessed 03 April 2003 )
5.CBC British Columbia. SARS clinic ready for opening. Apr 03, 2003;
http://vancouver.cbc.ca/regional/servlet/View?filename=bc_masks20030403
(accessed 10 August 2004)
6.WHO. Case definition for surveillance of Severe Acute Respiratory
Syndrome (SARS). http://www.who.int/csr/sars/casedefinition/en/
7.BBC News UK Edition. Mass resignations of health workers in Taiwan
are bringing extra pressure on the island¡¦s medical system as a record 65
new cases of SARS are reported. 27 May 2003.
8.CBC News. Some Toronto nurses quit over SARS. 26 April 2003.
http://www.cbc.ca/stories/2003/04/26/sarsnurses_030426 (accessed 10 August
2004)
9.Next Magazine Taiwan. Nine SARS tolls undeserved, killed by the lie
of the chief of municipal Ho-Ping hospital. Vol. 102. 8 May 2003. (in
Chinese)
10.Hong Shu-hui. More than 70% of the respondents agree on the
implementation of whole country quarantine, according to a poll. United
Daily News. 16 May 2003.
http://udndata.com/library/
11.Division of Medical and Outberk Respons, Cabitent¡¦s SARS
Committee Taiwan. Report on SARS Contorl in Taiwan (in chinese)
12.Government of the Hong Kong Special Administrative Region. Health,
Welfare and Food Bureau. SARS Bulletin. 23 June 2003
http://www.info.gov.hk/dh/diseases/ap/eng/bulletin0517.pdf
13.Sharmiipal Kaur. $2.8m paid to SARS-hit businesses, quarantine
cases so far. The straits Times. 15 August 2003
http://www.sars.gov.sg/archive/
It was very interesting to go through the article by Lawor.[1]
Since long ago women have been one way or the other victim of male
dominance. In different societies, there exists varieties of myths and
superstition that women should not be as independent as men are. They have
their own status which they should maintain and not compete with the
males, still this sort of speech exists in most part of South Asia....
It was very interesting to go through the article by Lawor.[1]
Since long ago women have been one way or the other victim of male
dominance. In different societies, there exists varieties of myths and
superstition that women should not be as independent as men are. They have
their own status which they should maintain and not compete with the
males, still this sort of speech exists in most part of South Asia. In
this era of civilisation even in the developed and educated socities of
the West where the females scientists and researchers feel that they
should not reveal their names for the fear of discrimination is a greater
blow to the human civilisation of thousands of years. There is no point in
descriminating women in any scientific works when they are as competent as
their male counterparts.
Despite the laws that exist in many countries of the world which
guarantees the equal rights to the women, the prejudice that is rampant in
every part of the world is due to the conservative thinking that is still
deep even in the educated population. Women have proved themselves that
they are not less to men in any task that carry out but the thing that I
found lacking in them is the confidence. When they are succesful and
competent why should they fear any one? Why they are reluctant to write
their full names. It is seen that female medical doctors have out numbered
the males in less than two centuries. They can take better admistrative
position in near future.
As the world is still not that ready to accept female dominance the
women have to teach the world that they are ready to take any positions to
make a better world e.g. scientific world, they are eqally good in
comparison to men. The world would in vey near future see when every
woman irrespective of any field would not hesitate to read her name fully
or write similarly. Its not because they are superior to male but they
deserve equal opportunities and resepect as male.
References
1. Lawlor D A. What's in a name? J Epidemiol Community Health 2004; 58: 726
Boyle [1] raises very interesting points that deserve rigorous
research and debate -see, for example, a recent editorial in BMJ by
Ferries [2] on these and related issues. I believe that the debate over
these issues contributes to increase their visibility for the research and
professional communities, a visibility that hopefully will increase
public, scientific and professional concern for domestic...
Boyle [1] raises very interesting points that deserve rigorous
research and debate -see, for example, a recent editorial in BMJ by
Ferries [2] on these and related issues. I believe that the debate over
these issues contributes to increase their visibility for the research and
professional communities, a visibility that hopefully will increase
public, scientific and professional concern for domestic violence against
women prevention and intervention.
Boyle agrees with the "softer" benefits of routine inquiry for
domestic violence. But I would not underestimate what Boyle calls “softer”
benefits. After all, social movements and grassroots efforts in the 70’s
(which could be include in the “soft” category) are at the origin of
public, scientific and professional concern about violence against women.
Beginning in the 70s and until now, things have changed substantially.
From almost a non-existing social, public health, and human rights issue,
nowadays public and scientific concern and awareness of domestic violence
has increased most notably. I believe, however, that still is needed
another step forward, which is a point that I emphasized in my editorial.
Public and professional concern needs to translate into greater personal
and collective sense of responsibility at all levels, (both as citizens
and as professionals in a variety of fields), as well as in actions
indicative of social intolerance towards domestic violence.
This step forward will almost inevitably involve tensions between
personal and family privacy and the need to expose family violence,
helping the victims, and conducting research [3]. Domestic violence
thrives on secrecy, silence, indifference, tolerance and passivity. The
health sector, as well as other fields (law enforcement, social services,
community organizations…), can help to shape a social environment of
intolerance that can contribute to greater exposure and social control of
domestic violence against women.
(2) Ferries LE. Intimate partner violence. Doctors should offer
referral to existing interventions, while better evidence is awaited. BMJ
2004;328:595–6
(3) American Psychological Association. Report of the American
Psychological Association Task Force on Violence and the Family.
Washington, DC: Author, 1996.
Dear Editor
Vlassov[1] detected something wrong in my short piece.[2] I would like to thank him very much. The correct lines 2 and 3 of paragraph 2 are: DALYs=(0.33)x(50y)+(1.0)x(80y-50y)=46.5y.
However, this is the minor, I think: the reader can easily understand or infer that printer's devil has replaced a 5 with a 3.
The major is that a mistake in the title escaped detection: the unit of m...
Dear Editor
I read the article by Jefferson[1] with interest. Although they are rare, vaccine reactions do occur and are suspected of having severe consequences.[2-4] It is here suggested that it is mainly those infants who already have somewhat depleted vitamin C stores, who are affected most. We now know that even modest ascorbate depletion is associated with very high blood histamine levels,[5], as shown in figu...
Dear Editor
I suggest the findings of Gouveia et al[1] may be due to increased testosterone. It is my hypothesis that increased maternal testosterone causes prematurity and low birth weight.
In rats, nitrogen dioxide increases maternal testosterone specifically.[2] It may be that increased exposure to nitrogen dioxide may increase prematurity and low birth weight because of increased maternal te...
We read the Letter by Dimoliatis with interest.[1] However, "0.33x50+1.0x(80–50) = 46.5", more accurately, we had to put QALYs = (0.67)x(50y) = 33.5y and DALYs = (0.33)x(50y)+(1.0)x(80y–30y) = 46.5y.
If substitute (80-50) by (80-30) result must be different.
I believe that something is wrong in this short piece intended to add clarity!
Reference
1. Dimoliatis I D K. Qual...
Dear Editor
I congratulate the Tatemichi et al on an interesting study.[1] However, as this paper has been widely sited in the general press, I would like to point out that this study does not show that heavy computer use causes glaucoma as suggested by the international press agencies.
The prevalence of open angle glaucoma is well known from various epidemiological studies and ranges from 1-3% in...
Dear Editor
“The further back you look, the further forward you can see”. These words of Winston Churchill are the compelling reason for backing Berridge and Gorsky’s,[1] and Scally and Womack’s[2] calls for more attention to public health history.
The lessons I have learnt from history are that my work is part of a long tradition, that many others have struggled with the same type of challenges th...
Dear Editor
Jousilahti and Salomaa appear unhappy with our response to their paper on the social patterning of serum inflammatory markers.
First they feel that we have misinterpreted their findings and conclusions. We fail to see how. They found (as others have) that social disadvantage was associated with increased inflammation – as indexed by markers such as higher fibrinogen - and that this association...
Dear Editor
After a journey to Asia during the SARS outbreak, Syed et al suggested that "the public health significance of such potent symbols as the face mask may be considered in strategies to tackle other emerging infections" [1]. Nevertheless, like other unsolved puzzles of the SARS emergence, the exact impact and lesson learned from this collective and profound symbol of masks wearing is still controversia...
It was very interesting to go through the article by Lawor.[1] Since long ago women have been one way or the other victim of male dominance. In different societies, there exists varieties of myths and superstition that women should not be as independent as men are. They have their own status which they should maintain and not compete with the males, still this sort of speech exists in most part of South Asia....
Dear Editor
Boyle [1] raises very interesting points that deserve rigorous research and debate -see, for example, a recent editorial in BMJ by Ferries [2] on these and related issues. I believe that the debate over these issues contributes to increase their visibility for the research and professional communities, a visibility that hopefully will increase public, scientific and professional concern for domestic...
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