Professor Cantani's[1] experience is very similar to what we found
in our review[2] - that egg allergic children do not appear to be at any
greater risk to severe allergic reactions with MMR vaccine.
In our review, we do not advocate hospitalisation of children with
egg allergy for MMR immunisation; on the contrary we suggest that all
children (including
children with egg allergy) can be immu...
Professor Cantani's[1] experience is very similar to what we found
in our review[2] - that egg allergic children do not appear to be at any
greater risk to severe allergic reactions with MMR vaccine.
In our review, we do not advocate hospitalisation of children with
egg allergy for MMR immunisation; on the contrary we suggest that all
children (including
children with egg allergy) can be immunised with MMR vaccine in the
community.
Since anaphylaxis is an extremely rare and unpredictable
consequence of any vaccination, we suggested in our review that all
children (not just children with egg allergy) must receive all
vaccinations (not just MMR) in a place which is equipped to deal with
anaphylaxis- by this we did not mean a hospital - and they must be
observed for sufficient time after the injection to make sure they are
well.
As Professor Cantani mentions, many of the reactions to the MMR may be
due to the gelatin or neomycin. It is generally agreed that MMR vaccine
is contraindicated
in children who have had severe systemic reactions to either gelatin or
neomycin.
References
1. Cantani A, Serra A, Arcese G, Lucenti P. Allergic reactions to MMR
vaccines in egg- and not-egg-sensitive children: a continuing
controversy. Pediatr Asthma Allergy Immunol 1995;9:7-14.
2 Lakshman R, Finn A. MMR vaccine and allergy. Arch Dis Child
2000;82:93-5
Zar et al[1] found that lung deposition of aerolised
technetium-99DTPA inhaled via modified 500 ml plastic bottle was higher
compared to a Babyhaler in both young and other children. There was no
difference in lung deposition when a mask was used. Though other workers[2] have recommended the attachment of facemasks to treat patients of all
ages.
In another study[3] children aged 5 to 13 years...
Zar et al[1] found that lung deposition of aerolised
technetium-99DTPA inhaled via modified 500 ml plastic bottle was higher
compared to a Babyhaler in both young and other children. There was no
difference in lung deposition when a mask was used. Though other workers[2] have recommended the attachment of facemasks to treat patients of all
ages.
In another study[3] children aged 5 to 13 years
with acute asthma were studied and it was concluded that a conventional spacer and sealed
500 ml plastic bottle produced similar bronchodilatation, an unsealed
bottle gave intermediate improvement in lung function, and a polystyrene
cup was least effective as a spacer for children with moderate to severe
airways obstruction.
A metered-dose inhaler (MDI) with spacer is the best way to deliver
inhalation therapy for the treatment of acute asthma. In India,
commercially produced spacers are available but most of the patients find
it too costly and are thus unable to purchase. These patients, then take
the prescribed inhalers directly without any attachment. We know that
inhalers if taken directly are generally ineffective as medicine fails to
reach the lungs. Thus, use of bottle spacers should be incorporated into
the guidelines for asthma management in developing countries. However,
owing to their size, the bottle spacers are inconvenient to carry and in
these patients dry powder inhalers should be recommended as the next best
thing.
Children with asthma can lead relatively normal lives, just like
their non-asthmatic friends. Diligent monitoring and adherence to a
management plan can make all the difference.
References
1. Zar HJ, Weinberg EG, Binns HJ, Gallie F, Mann MD. Lung deposition of aerosol - a comparison of different spacers. Arch Dis Child 2000;82:495-8.
2. O’Callighan C, Milner AD, Swarbrick. Spacer device with facemask attachment for giving bronchodilators to infants with asthma. BMJ 1989;298:160-1.
3. Zar HJ, Brown G, Donson H, Brathwarte N, Manna MD, Weinberg EG. Home-made spacers for bronchodilator therapy in children with acute asthma: a randomised trial. Lancet 1999;354:979-82.
Following their studies of whole gut lavage fluid Smyth
et al have suggested that a non-idiopathic intestinal
inflammation occurs constituitively in CF patients, as a
consequence of a proinflammatory effect of the
patient's CFTR mutations.[1] They reported marginally
elevated excretion of IgG, IgM, IL-1 , neutrophil
elastase and eosinophil cationic protein, and much more
significant increase in excreti...
Following their studies of whole gut lavage fluid Smyth
et al have suggested that a non-idiopathic intestinal
inflammation occurs constituitively in CF patients, as a
consequence of a proinflammatory effect of the
patient's CFTR mutations.[1] They reported marginally
elevated excretion of IgG, IgM, IL-1 , neutrophil
elastase and eosinophil cationic protein, and much more
significant increase in excretion of IL-8 and albumin,
but no increase in excretion of alpha 1-antitrypsin or IgA.
In this study where lavage fluid was administered
continuously, and intestinal effluent was collected in
discrete samples, pooling of the effluent before
analysis would have allowed small differences in
calculated inflammatory marker outputs to be
interpreted as representative of gastroentestinal
output. Of all the inflammatory markers presented only
interleukin-8 shows a range of cytokine outputs in CF
patients with or without fibrosing colonopathy that
does not extend into the range seen in controls, in
these non parametric datasets. The author's evidence
for intestinal inflammation therefore relies heavily on
the validity of their IL-8 Quantikine assay (R&D
Minneapolis) protocol.
I have explored the validity of this assay for use in
supernatants of faecal homogenates in children with
cystic fibrosis and found it wanting. Recovery of a
500 pg/ml spike of IL-8 progressively increased from 41%
in samples which were a 12-fold dilution of faeces to
189% in samples which were a 120,000-fold dilution of
faeces, when used according to manufacturers
instructions. Pre-diluting the samples 50:50 in newborn
calf serum, and using calf serum for further dilutions
gave this assay (R&D catalogue no D8000) mean (sd)
spike recovery of 92.1 (12.5)% and coefficients of
variation of 3.46% (intra assay) and 6.85% (inter
assay).[2]
Without knowledge of Smyth et al's IL-8 ELISA
validation data, I assume that this assay returns
similarly spuriously high IL-8 concentrations in
polyethylene glycol based wholegut lavage fluid to my
120,000-fold dilution faecal supernatant. The absence
of a significant difference between CF patients and
controls in their alpha 1-antitrypsin outputs suggests that
intestinal inflammation was not presentin the CF
patients. Overestimation of the WGLF IL-8 concentration
would explain the apparently implausably large volumes
of swallowed sputum that the authors estimate would be
required to account for their results. In this study
which could not turn off the mucociliary escalator, but
did dramatically increase the rate of intestinal
transit and exclude exogenous pancreatic enzymes,
swallowed sputum is the most likely explanation for the results.
References
1. Smyth RL, Croft NM, O'Hea U, Marshall T G,
Ferguson A. Intestinal inflammation in cystic fibrosis. Arch Dis Child
2000;82:394-9.
2. Briars GL, Shepherd RW. Faecal interleukin-8 and TNF ELISA: The
first validated assay protocol. Immunology and Cell Biology
1997;suppl 1:A114
According to our studies 1803 children allergic to egg have
been safely received the MMR vaccine. Systemic reactions
were present only in 0.1% of cases and untoward reactions
only in 1.7% cases (p = 0.0001).[1] No child vaccinated by
us has manifested immediate reactions.[1] According to
Sampson et al[2] the MMR vaccine is safe in such children,
evaluating on the basis of confidence intervals (95%) t...
According to our studies 1803 children allergic to egg have
been safely received the MMR vaccine. Systemic reactions
were present only in 0.1% of cases and untoward reactions
only in 1.7% cases (p = 0.0001).[1] No child vaccinated by
us has manifested immediate reactions.[1] According to
Sampson et al[2] the MMR vaccine is safe in such children,
evaluating on the basis of confidence intervals (95%) that
97.5% of children can be safely vaccinated. The reactions
reported by various authors were provoked by the gelatin
present in plasma-expanders, which provokes reactions in
0.07-0.2% of cases and neomycin of which MMR vaccine
contains 25 mg.[1]
In 47 non egg-allergic children a case
of anaphylactic shock was due to gelatin, while the skin
reactions to neomycin are more frequent, thus explaining the
prevalence of urticarial manifestations in the vaccinated
children. However the risk of untoward reactions in non
egg-allergic children, is almost non existent, being =
0.00005%.[1] Two recent works increase the confusion,
because one[3] suggests to perform MMR vaccinations in all
children under controlled conditions in hospital, and the
other[4] restrict these precautions to children with
cardiorespiratory responses to egg and/or chronic asthma.
No
one gives suggestions about possible reactions to gelatin
and/or neomycin.
We judge these conclusions[3, 4]
allarmistic, and suggest that no guideline should prevent
MMR vaccination in children. Obviously we recommend to
vaccinate in the hospital all the children who have
manifested severe, life-threatening reactions to egg. The
door remains open for children who have had anaphylactic
reactions to gelatin or neomycin: give MMR vaccine in
hospital. Adrenaline at hand could be a useful addition.
References
1. Cantani A, Serra A, Arcese G, Lucenti P. Allergic
reactions to MMR vaccines in egg- and not-egg-sensitive
children: a continuing controversy. Pediatr Asthma Allergy
Immunol 1995;9:7-14.
2. James JM, Burks AW, Roberson PK, Sampson HA. Safe
administration of the measles vaccine to children allergic
to eggs. N Engl J Med 1995;332:1262-6.
3. Lakshman R, Finn A. MMR vaccine and allergy. Arch Dis
Child 2000;82:93-5
4. Khakoo GA, Lack G. Recommendations for using MMR vaccine
in children allergic to eggs. BMJ 2000;320:929-32.
The demonstration by Blair et al[1] of an association between poor postnatal
growth and an increased risk of SIDS, is a useful addition to our
understanding of the aetiology of this condition. It is unfortunate that
the conclusion in the abstract that "Poor postnatal weight gain was
independently associated with an increased risk of SIDS and could be
identified at the routine six week assessment" (italics added...
The demonstration by Blair et al[1] of an association between poor postnatal
growth and an increased risk of SIDS, is a useful addition to our
understanding of the aetiology of this condition. It is unfortunate that
the conclusion in the abstract that "Poor postnatal weight gain was
independently associated with an increased risk of SIDS and could be
identified at the routine six week assessment" (italics added) goes beyond
the data presented.
It can be estimated from the data in this study that the overall risk
of SIDS was 0.77/1000 livebirths. The risk in babies with birthweights
>15th centile, the group in whom the relationship with postnatal growth
was detected, was 0.68/1000. Given the reported odds ratio of 1.75
associated with being in the slowest growing 16% who might be identified
at by six weeks, the data suggest that the absolute risk of SIDS among
this group would be about 1.1/1000. Even a programme targeted at infants
below the 2nd centile for growth at six weeks, would identify a group
whose absolute risk of SIDS was about 4.2/1000, i.e. for every infant who
might benefit from the intervention, there would be 240 who wouldn't. Even
if it were accepted that this level of risk was sufficient to trigger an
intervention, the nature of the intervention remains unclear.
To the best
of our knowledge, with the exception of the 'Back to Sleep' campaign,
there is no convincing evidence of the effectiveness of any intervention
aimed at preventing SIDS. None of the intervention programmes described
in the accompanying commentary[2] have been evaluated in appropriately
controlled studies.
The discussion in the paper is rather more circumspect than the
conclusion in the abstract, but it is the latter which, reinforced by the
accompanying commentary, is likely to have disproportionate impact on
those readers who do not read the whole paper. In the commentary Dr
Carpenter acknowledges that the low rates of SIDS make such interventions
difficult to justify but then suggests that "Targeting such infants for
weight monitoring at home….. will also identify numerous other problems at
a remedial stage." This is a suggestion for which there is currently
little evidence.
There are clear dangers in recommending population interventions on
the basis of relative risks without taking account of absolute risks or of
the need for interventions to be of proven effectiveness.
Stuart Logan*
Helen Bedford*
David Elliman#
*Department of Paediatric Epidemiology,
Institute of Child Health,
30 Guilford Street, London WC1N 1EH, UK
#St Georges Hospital,
Blackshaw Road, London SW17 0QT, UK
References
1. Blair PS, Nadin P, Cole TJ, Fleming PJ, Smith IJ, Platt MW, Berry PJ, Golding J. Weight gain and the sudden infant death syndrome: change in weight z scores may identify infants at increased risk. Arch
Dis Child 2000;82:462-9.
We agree with the letter from Professor
Koletzko suggesting that more studies in this field are
necessary (Arch Dis Child Rapid Response 6 June 2000). However, Table 4 of my study detailed all the
data of the "other authors" and tried to make a mean among
all such data. Since Sampson et al documented a 0%
prevelence of sensitisation to soy, we concluded that about
"80-100%" of children.
We agree with the letter from Professor
Koletzko suggesting that more studies in this field are
necessary (Arch Dis Child Rapid Response 6 June 2000). However, Table 4 of my study detailed all the
data of the "other authors" and tried to make a mean among
all such data. Since Sampson et al documented a 0%
prevelence of sensitisation to soy, we concluded that about
"80-100%" of children.
Professor Koletzko fails to consider the 243 reactions to
hydrolysate formulae documented by us. When both papers are published we shall gladly send him reprints.
The American Academy of Pediatrics distinguish between IgE and not
IgE mediated reactions. However, we refer to the paper by
Burks et al (J Pediatr Gastroenterol Nutr 1989;8:195-203) who demonstrated that most reactions to soy are
not IgE mediated.
Returning to the data analysed in Table 4: we concluded that a proportion of children with colitis/enterocolitiis do not tolerate soy formulae and therefore are better fed the Rezza's diet, that is a home made, meat-based formula.
I believe that Dr Narchi's worries about Chong et al's paper are
unjustified.
The t test is known to be in the technical sense robust to non-
Normality, meaning that unless the departure from Normality is severe the
t table p values are very close to the correct ones. From general
experience the variables studied in the paper are likely to have
distributions that are close to Normality.
I believe that Dr Narchi's worries about Chong et al's paper are
unjustified.
The t test is known to be in the technical sense robust to non-
Normality, meaning that unless the departure from Normality is severe the
t table p values are very close to the correct ones. From general
experience the variables studied in the paper are likely to have
distributions that are close to Normality.
Choing et al state that "statistical comparisons were made by the
Student's t test"; not specifying whether paired or unpaired. Internal
evidence suggests that the paired version was used - for example, using
the figures in table 1, the value of unpaired t for systolic blood
pressure is 1.43, which does not give p <0.05.
Dr Wiersma and colleagues suggest that the yield from a single sputum
induction should be compared only with the results of those children who
had 3 consecutive gastric lavages (Arch Dis Child Rapid Response 2 June
2000). Only 26 of our patients had 3 gastric lavages; amongst this subset
however, 4 children were culture positive on sputum while only 3 were
positive on gastric...
Dr Wiersma and colleagues suggest that the yield from a single sputum
induction should be compared only with the results of those children who
had 3 consecutive gastric lavages (Arch Dis Child Rapid Response 2 June
2000). Only 26 of our patients had 3 gastric lavages; amongst this subset
however, 4 children were culture positive on sputum while only 3 were
positive on gastric lavage.
Although the yield from gastric lavage is improved with increasing
number of specimens, it is frequently not feasible to perform this
procedure on 3 consecutive days, particularly in developing countries with
limited resources. Moreover, performing 3 repeated gastric lavages may be
very unpleasant both to the child and the health worker. In practice, even
in tertiary institutions such as those in which our study was performed,
obtaining 3 sequential gastric lavages is rarely feasible.
The yield from sputum induction may also be increased with increasing
number of specimens.[1] Therefore we would submit that the yield from
consecutive gastric lavages should be compared with that of repeated
induced sputa. Data from studies of adult patients using paired specimens
of induced sputum and gastric aspirates have reported a higher yield from
sputa specimens.[2-4] In our study, the findings that a single induced
sputum specimen yielded M tuberculosis more frequently than repeated GLs
(in the majority of children) further strengthens our conclusion.
Heather J Zar
Esta Tannenbaum
Patti Apolles
David Hanslo
Gregory Hussey
References
1. Finch D, Beaty CD. The utility of a single sputum specimen in the
diagnosis of tuberculosis - comparison between HIV-infected and non-HIV-
infected patients. Chest 1997;111:1174-9
2. Elliott RC, Reichel J. The efficacy of sputum specimens obtained
by nebulization versus gastric aspirates in the bacteriological diagnosis
of pulmonary tuberculosis. Am Rev Resp Dis 1963;88:223-7
3. Jones FL. The relative efficacy of spontaneous sputa, aerosol-
induced sputa and gastric aspirates in the bacteriologic diagnosis of
pulmonary tuberculosis. Dis Chest 1966;50:403-8
4. Lillehei JP. Sputum induction with heated aerosol inhalations for
the diagnosis of tuberculosis. Am Rev Resp Dis 1961;84:276-8
Dr Riordan ask which expert opinion to follow. The answer surely
lies in reading the papers carefully, seeking out any key references
quoted and deciding for oneself who has provided the best evidence. This
should be the case for all guidelines, but we know that they are often
absorbed undigested, which is one reason why ADC erects fairly firm
barriers to their publication. Lakshman and Finn's paper was commissioned
b...
Dr Riordan ask which expert opinion to follow. The answer surely
lies in reading the papers carefully, seeking out any key references
quoted and deciding for oneself who has provided the best evidence. This
should be the case for all guidelines, but we know that they are often
absorbed undigested, which is one reason why ADC erects fairly firm
barriers to their publication. Lakshman and Finn's paper was commissioned
by the editors as a leading article because, as practising paediatricians,
we recognised that all of us have problems responding logically to
requests to immunise children in hospital.
When we commissioned this paper we did not know that a college
committee was embarking on an enquiry; we learned this only after our
leading article had been peer reviewed and was set up for publication.
Editors of ADC have long been saddened that many of our readers, including
members and fellows of the RCPCH, prefer first to submit their papers
elsewhere; we realise, of course, that the artificial constraints of the
research assessment exercise result in some authors needing to collect
Brownie points by publishing in journals with a high impact factor even if
their research thereby reaches an inappropriate readership. In this
sense, the BMJ is our competitor not our partner which is why editors do
not tell each other what they have in the pipeline.
I realise that this cannot have been the case in this instance as the
BMJ copied Khakoo and Lack's paper from the specialist journal in which it
originally appeared (which probably has a lower score than ADC and read by
far fewer paediatricians).
Dr Riordan suggests seeking a consensus. Far better would be to
undertake a full literature search of RCTs and subject it to a systematic
review. The days of guidelines by GOBSAT* are over. At this year's
annual scientific meeting of the RCPCH the journal and the college's
quality of practice committee have forged a working relationship that
should leave our readers less confused in future.
We note Riordan's response to our editorial on the issue of MMR
vaccine and allergy[1] and the recommendations put forward by Khakoo and
Lack[2] on this topic. While we agree that conflicting advice creates
confusion, we cannot agree with his proposed "pragmatic approach". This
amounts to a pointless waste of time and resources - greater than that
proposed by anyone else to date - which will simply...
We note Riordan's response to our editorial on the issue of MMR
vaccine and allergy[1] and the recommendations put forward by Khakoo and
Lack[2] on this topic. While we agree that conflicting advice creates
confusion, we cannot agree with his proposed "pragmatic approach". This
amounts to a pointless waste of time and resources - greater than that
proposed by anyone else to date - which will simply stoke up unfounded
concerns about this vaccine while diverting people from the important
necessity to prepare themselves to tackle cases of severe anaphylaxis
which, on the rare occasions that they occur, will continue to do so in
community clinic settings.
1. Lakshman R, Finn A. MMR Vaccine and Allergy. Arch Dis Child
2000;82:93-95
2. Khakoo GA, Lack G. Recommendations for using MMR vaccine in children
allergic to eggs. BMJ 2000;320:929-932
R Lakshman
Research Fellow
Adam Finn MA PhD FRCPCH FRCP
Senior Lecturer in Immunology and Infectious Diseases
Sheffield Institute for Vaccine Studies
Division of Child Health
University of Sheffield
Dear Editor
Professor Cantani's[1] experience is very similar to what we found in our review[2] - that egg allergic children do not appear to be at any greater risk to severe allergic reactions with MMR vaccine.
In our review, we do not advocate hospitalisation of children with egg allergy for MMR immunisation; on the contrary we suggest that all children (including children with egg allergy) can be immu...
Dear Editor
Zar et al[1] found that lung deposition of aerolised technetium-99DTPA inhaled via modified 500 ml plastic bottle was higher compared to a Babyhaler in both young and other children. There was no difference in lung deposition when a mask was used. Though other workers[2] have recommended the attachment of facemasks to treat patients of all ages.
In another study[3] children aged 5 to 13 years...
Dear Editor
Following their studies of whole gut lavage fluid Smyth et al have suggested that a non-idiopathic intestinal inflammation occurs constituitively in CF patients, as a consequence of a proinflammatory effect of the patient's CFTR mutations.[1] They reported marginally elevated excretion of IgG, IgM, IL-1 , neutrophil elastase and eosinophil cationic protein, and much more significant increase in excreti...
Dear Editor,
According to our studies 1803 children allergic to egg have been safely received the MMR vaccine. Systemic reactions were present only in 0.1% of cases and untoward reactions only in 1.7% cases (p = 0.0001).[1] No child vaccinated by us has manifested immediate reactions.[1] According to Sampson et al[2] the MMR vaccine is safe in such children, evaluating on the basis of confidence intervals (95%) t...
Sir
The demonstration by Blair et al[1] of an association between poor postnatal growth and an increased risk of SIDS, is a useful addition to our understanding of the aetiology of this condition. It is unfortunate that the conclusion in the abstract that "Poor postnatal weight gain was independently associated with an increased risk of SIDS and could be identified at the routine six week assessment" (italics added...
We agree with the letter from Professor Koletzko suggesting that more studies in this field are necessary (Arch Dis Child Rapid Response 6 June 2000). However, Table 4 of my study detailed all the data of the "other authors" and tried to make a mean among all such data. Since Sampson et al documented a 0% prevelence of sensitisation to soy, we concluded that about "80-100%" of children.
Professor...
I believe that Dr Narchi's worries about Chong et al's paper are unjustified.
The t test is known to be in the technical sense robust to non- Normality, meaning that unless the departure from Normality is severe the t table p values are very close to the correct ones. From general experience the variables studied in the paper are likely to have distributions that are close to Normality.
Choing et al st...
Reply to Dr Wiersma and colleagues:
Dr Wiersma and colleagues suggest that the yield from a single sputum induction should be compared only with the results of those children who had 3 consecutive gastric lavages (Arch Dis Child Rapid Response 2 June 2000). Only 26 of our patients had 3 gastric lavages; amongst this subset however, 4 children were culture positive on sputum while only 3 were positive on gastric...
Dr Riordan ask which expert opinion to follow. The answer surely lies in reading the papers carefully, seeking out any key references quoted and deciding for oneself who has provided the best evidence. This should be the case for all guidelines, but we know that they are often absorbed undigested, which is one reason why ADC erects fairly firm barriers to their publication. Lakshman and Finn's paper was commissioned b...
Dear Editor:
We note Riordan's response to our editorial on the issue of MMR vaccine and allergy[1] and the recommendations put forward by Khakoo and Lack[2] on this topic. While we agree that conflicting advice creates confusion, we cannot agree with his proposed "pragmatic approach". This amounts to a pointless waste of time and resources - greater than that proposed by anyone else to date - which will simply...
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