Summaries of Product Characteristics (SmPCs) are a cornerstone of the
EU medicines licensing process, and could be a valuable information
resource for doctors and other health professionals. We welcome the paper
by Vromans et al, looking at how SmPCs could better support physicians,
and are pleased to say that their findings with German doctors, are
consistent with the findings from UK doctors which we published
contempo...
Summaries of Product Characteristics (SmPCs) are a cornerstone of the
EU medicines licensing process, and could be a valuable information
resource for doctors and other health professionals. We welcome the paper
by Vromans et al, looking at how SmPCs could better support physicians,
and are pleased to say that their findings with German doctors, are
consistent with the findings from UK doctors which we published
contemporaneously (1). As in Germany, we found that UK doctors did not
value nor use SmPCs in their day-to-day practice.
Our methods similarly used both quantitative and qualitative methods,
under the umbrella of 'user testing', the process widely used in the EU to
test whether the information supplied as patient information leaflets
(PILs) is clear and easy to use (these leaflets are based on the
information in the SmPC, but should be written in a manner understandable
to the public). This performance-based method of testing first determines
whether people can find and understand key pieces of information. It then
includes a short semi-structured interview to determine participants'
general views on the document. Good practice in information writing and
design is then used to improve the document and then it is tested again.
It was recently used to test the European Public Assessment Report (EPAR)
Summary produced by the European Medicines Agency to explain to the public
how decisions to grant a licence for a medicine are made (2).
Our UK study of two SmPCs utilised this iterative 'user testing'
approach to develop a revised format and content which, like the German
study, included a 'synopsis' or 'key information summary at the beginning.
Both studies will form part of the evidence used in the assessment report
from the European Commission on the shortcomings of SmPCs and PILs and
recommendations for improvement.
(1)Raynor DK, De Veene, P, Bryant D. The effectiveness of the SmPC
and recommendations for improvement. Therapeutic Innovation and Regulatory
Science 2013.
DOI: 10.1177/2168479013501311
http://dij.sagepub.com/content/early/2013/09/23/2168479013501311.abstract
(2)Raynor DK, Bryant D. European Public Assessment Report (EPAR)
summaries for the public: are they fit for purpose? A user-testing study.
BMJ Open 2013.
DOI: 10.1136/bmjopen-2013-003185
http://bmjopen.bmj.com/content/3/9/e003185.abstract
Conflict of Interest:
DKR is co-founder and academic advisor to Luto Research, which develops, refines and tests health information materials
I have with interest read the article: Suicide risk in relation to
air pollen counts: a study based on data from Danish registers. As the
data producer and data owner I have identified a number of incorrect
statements in this study, that I would like to see corrected or added. Due
to these errors, the study is unacceptable both with respect to scientific
practice as well as wi...
I have with interest read the article: Suicide risk in relation to
air pollen counts: a study based on data from Danish registers. As the
data producer and data owner I have identified a number of incorrect
statements in this study, that I would like to see corrected or added. Due
to these errors, the study is unacceptable both with respect to scientific
practice as well as with respect to correctness of a number of statements.
It is however straightforward to correct and I try to be as constructive
as possible in this process.
The pollen data that has been used in the article is alone measured
and produced by the Danish Asthma and Allergy Association. All use of the
data must include proper credit to the data owner and producer: Danish
Asthma and Allergy Association. We collaborate with DMI - the Danish
Meteorological Institute. The pollen data is owned by both organizations
and this should be addressed in the article; e.g. in the section on
methods, data and acknowledgments. But it is not. I know that Professor
Ping Qin has received pollen data from DMI, and that she has been given
the information about data copyright in the correspondence with Alix
Rasmussen (DMI) from May, 2008, where Professor Ping Qin discussed data
format and received pollen data according to her wishes.
The phrase in the mail goes:
"Following standard conditions on the use of data shall be followed:
Please note that the Danish Asthma and Allergy Association (AAF) and the
Danish Meteorological Institute (DMI) cannot be held responsible for the
use of incorrect data or the interpretation and use of data in general.
The data are property of AAF and DMI, and may not be sold, copied or
handed over to third party. If data are published AAF and DMI has to be
referred to as source of information".
I am aware that Professor Ping Qin also had a general contract with
DMI on climate and weather data. Climate and weather data are solitary
DMIs property. How this should be handled is reflected by the contract.
And despite the formulation in the contract, then DMI can give access to
pollen data too and these data can be used in scientific publications, if
the authors follow the guideline for referencing and ownership.
Reading the article you could get the impression that Danish pollen
data was only available in the format used in the study: Grand total and
"daily counts". This is incorrect. Pollen concentrations in the air have
been measured in Copenhagen from 1977- and from Viborg since 1980-.
Denmark has a long, unique detailed 2-hour data base of pollen
concentrations for 23 individual pollen taxa and one fungal spore taxon:
Alternaria. Cladosporium data is also available, but only as a daily mean
values. These data can all be aggregated to daily, weekly or annual
totals. It is the authors that selected an atypical aggregation. It is not
a limitation of the data. A number of studies on the same data set that
have been published since 2007 have shown this very clearly. A more
thorough literature review on studies that use this data set would easily
have revealed this inconsistency. A recent study on the data from
Copenhagen was recently published in Atmospheric Chemistry and Physics and
later in February 2013 highlighted by the European Commission as one of
the most important studies in relation to air quality, health and policy.
The newsletter and the paper are both freely available and I will suggest
that the authors use this as a starting point (e.g.
http://ec.europa.eu/environment/integration/research/newsalert/pdf/317na4.pdf)
for their literature review as they provides a good description of
observational methods and links to related literature.
Concerning the methods, then the authors use "todays daily pollen
count" and not the daily mean concentration. "Todays daily pollen count"
is the average concentration in numbers of pollen grains per m3 of air
from specific taxa measured from 1 p.m. the previous day to 1 p.m today
for Copenhagen. For Viborg this is from 9 a.m. to 9a.m. These numbers are
only used for forecasting and dissemination studies. These numbers have
never been used in scientific research. All previous clinical and
aerobiological studies on the Danish data set have used daily mean
concentrations or similar. It will mean that a part of this study is not
directly comparable to previous clinical studies on this data set. This
issue is not discussed in either the methods or the discussion of the
results. In aerobiological studies it is common to use bi-hourly data,
daily mean (00 a.m. to 24 p.m.) or annual totals. Moreover pollen data and
season expresses large variations from year to year. If annual data or
seasonality is studied, especially in statistical studies, then data gabs
must be taken into account. This is not done here.
A minor flaw is that the article states that ragweed is common
allergenic pollen in Denmark. It is not. Ragweed is an invasive species
that can become a problem over time. I assume that you mean mugwort =
Artemisia vulgaris L. in Latin. Ragweed is Ambrosia artemisiifolia L. It
should also be corrected. I will strongly recommend using Latin names in
this article with respect to botany in order to avoid such
misunderstandings.
Kind regards
Janne Sommer
Aerobiologist at the Danish Asthma-Allergy Association. Head of pollen
monitoring in Denmark from 2004 to October, 2013.
Referred reference:
C. A. Skj?th, J. Sommer, L. Frederiksen, and U. Gosewinkel Karlson. Crop
harvest in Denmark and Central Europe contributes to the local load of
airborne Alternaria spore concentrations in Copenhagen. Atmos. Chem.
Phys., 12, 11107-11123, 2012.
Language in and of itself has no meaning . Only people have meaning.
For example:
Through the Looking Glass, by Lewis Carroll
'I don't know what you mean by "glory",' Alice said.
Humpty Dumpty smiled contemptuously. 'Of course you don't --till I
tell you. I meant "there's a nice knock-down argument for you!"'
'But "glory" doesn't mean "a nice knock-down argument",' Alice
objected.
'When I use a word,' Humpty Dumpty said, in rather a scornful tone,
it means just what I choose it to mean -neither more nor less.'
'The question is,' said Alice, 'whether you can make words mean so
many different things.'
'The question is,' said Humpty Dumpty, 'which is to be master --
that's all.'
******************************
With that in mind , and amending 'Dr.' to 'Mr.', the opening
paragraph of the authors' response reads as follows :
Dr. O'Hagan's suggestion that SIDS may be due to maternal vitamin C
deficiency seems unlikely because baby formula milk includes vitamin C
supplement. We would therefore expect on his hypothesis that bottle fed
babies would, if anything, be at lower risk than breast fed infants, which
is not the case(1,2).
Comment: The above statement advisedly merits re- examination by its
author(s) with a view to either its deletion or by their acknowledgement
that what it concludes is totally in the realm of the non sequitur... and
that's putting it mildly !
The Vennemann et al study (1) was structured to compare the two
types of infant feeding and the totals of the diagnoses of SIDS
respectively. However, neither it nor Dr. Carpenter's report (2), can be
cited to support such an entirely erroneously based and thoroughly
misleading
conclusion.
Note that the implied objective of the response was to refute the "
...suggestion that SIDS may be due to maternal vitamin C deficiency ...".
Accordingly, and inasmuch as the terms 'breast fed infants' and 'bottle
fed babies' have been employed absent further qualification, they
ambiguusly ... and need it be said , most conveniently... provide complete
disregard of the the requirement of distinguishing between their
employment in (1) and (2), and similarly nourished infants/ babies,
who from the moment of their births are deficient in vitamin C.
In other words, Carpenter et al would have been well-advised to
'measure twice prior to cutting once'. Paradoxically, the direct opposite
is what they should 'expect' if they were to give a ittle more thought
to it ; namely, that vitamin C deficient "... bottle fed babies would,
if anything, be at lower risk than breast fed infants ".
The European Medicines Agency (EMA) welcomes the research on the
usability of the summaries of the European Public Assessment reports (EPAR
summaries) by Professor David K Raynor and David Bryant recently published
on the BMJ Open website.
The EMA had first become aware of the results of this user-testing
study in 2011 while the Agency was already consulting stakeholders on
improving the EPAR summaries, aiming a...
The European Medicines Agency (EMA) welcomes the research on the
usability of the summaries of the European Public Assessment reports (EPAR
summaries) by Professor David K Raynor and David Bryant recently published
on the BMJ Open website.
The EMA had first become aware of the results of this user-testing
study in 2011 while the Agency was already consulting stakeholders on
improving the EPAR summaries, aiming at making them easier to read by a
lay audience. Although the limitations of the study pointed out by the
peer reviewers (such as the suitability of the questions, the
representativeness of the participants and the fact that only one summary
was user tested) reduced its applicability, the EMA included the results
as input to this process.
Using feedback from various stakeholders, but particularly patients
and healthcare professionals, the format and content of EPAR summaries
were updated in 2012 and this standard is now being used for all new
summaries and to gradually update old summaries on the EMA website. The
study by Raynor and Bryant used an EPAR summary prepared in 2009, which
precedes these extensive changes. Although the changes introduced during
the update in 2012 went beyond the scope of the authors' user-testing, the
EMA believes that the results of the study are addressed by the current
EPAR summary template.
The EMA continues to encourage research in the area of public
communication, particularly on the use of lay-language documents, and
thanks the authors for conducting this important research.
Conflict of Interest:
The European Medicines Agency is the owner of the EPAR summary documents
Many thanks to the College of Podiatry and the Society of
Chiropodists and Podiatrists for your response to our systematic review
examining the published evidence for the effect of contact with a
podiatrist on the occurrence of a lower extremity amputation in people
with diabetes. We agree wholeheartedly that this review does not provide
proof that podiatric intervention has no effect on amputation rates.
Rather, it hig...
Many thanks to the College of Podiatry and the Society of
Chiropodists and Podiatrists for your response to our systematic review
examining the published evidence for the effect of contact with a
podiatrist on the occurrence of a lower extremity amputation in people
with diabetes. We agree wholeheartedly that this review does not provide
proof that podiatric intervention has no effect on amputation rates.
Rather, it highlights the paucity of research in this area.
At the time of designing this study, a question regarding the
contribution of podiatrists (as health professionals) to amputation
prevention in patients with diabetes had been raised in order to try and
inform a policy decision about employing more podiatrists in the Irish
healthcare system. Given that teams already existed and had already
undertaken some footcare work we were, initially, keen to see if the
specific contribution of podiatry could be identified (albeit isolated
from other effects on foot health of other members of a footcare team).
In the event, it was apparent that the literature did now allow us to
answer this question.
Now having reviewed the literature, we recognise that the literature
may never be able to answer this question because it is no longer possible
to envisage foot care teams without a podiatrist where teams with one have
been shown to be effective. As mentioned in your response, many centres
have demonstrated reduced amputation risk in people with diabetes
coinciding with the introduction of multidisciplinary footcare teams [1-
5]. As you also correctly highlight 'podiatrists do not work in isolation
and always seek to work as part of a multidisciplinary team for those
patients who are at risk of amputation'. Thus, we concluded that looking
at one service in isolation could be flawed as services are seldom
delivered in isolation and recommended a systematic review of the
literature looking at the effectiveness of multidisciplinary teams which
include contact with a podiatrist.
It was most definitely not our intention to 'give the impression that
podiatry has at best a benign effect upon those with diabetes'. We wished
to highlight this as an area worthy of further research. As you accurately
state 'research has not been undertaken to show that a podiatrist working
in isolation can influence amputation rates.' However, research has been
conducted showing that a podiatrist working as part of a multidisciplinary
footcare team can influence amputation rates. This is where future
research should be focused.
Thank You.
1. Canavan RJ, Unwin NC, Kelly WF, Connolly VM. Diabetes- and
Nondiabetes-Related Lower Extremity Amputation Incidence Before and After
the Introduction of Better Organized Diabetes Foot Care. Diabetes Care
2008;31(3):459-63
2. Krishnan S, Nash F, Baker N, Fowler D, Rayman G. Reduction in
Diabetic Amputations Over 11 Years in a Defined U.K. Population. Diabetes
Care 2008;31(1):99-101
3. Driver VR, Madsen J, Goodman RA. Reducing Amputation Rates in
Patients With Diabetes at a Military Medical Center. Diabetes Care
2005;28(2):248-53
4. Larsson J, Apelqvist J, Agardh CD, Stenstrom A. Decreasing
incidence of major amputation in diabetic patients: a consequence of a
multidisciplinary foot care team approach? Diabet Med 1995;12(9):770-6
5. Meltzer DD, Pels S, Payne WG, et al. Decreasing amputation rates
in patients with diabetes mellitus. An outcome study. Journal of the
American Podiatric Medical Association 2002;92(8):425-28
Roy,
If we saw worse mortality in this group, we would have a problem. We
don't, we see the 'healthy soldier' effect. This probably means that the
Maori men in our sample were as healthy as anyone else.
The study by Bouwmans and colleagues seems to be well designed and
thoroughly executed [1], but the primary results are surprising regarding
both the transcranial sonography (TCS) and dopamine transporters - single-
photon emission computed tomography (DAT-SPECT) results. According to
large scale prospective studies, DAT-SPECT should have a specificity close
to 100% in differentiating neurodegenerative parkinsonian syndrom...
The study by Bouwmans and colleagues seems to be well designed and
thoroughly executed [1], but the primary results are surprising regarding
both the transcranial sonography (TCS) and dopamine transporters - single-
photon emission computed tomography (DAT-SPECT) results. According to
large scale prospective studies, DAT-SPECT should have a specificity close
to 100% in differentiating neurodegenerative parkinsonian syndromes such
as Parkinson's disease (PD) and atypical parkinsonian disorders (APD)
based on the underlying nigrostriatal dopaminergic depletion versus other
conditions without nigrostriatal denervation [2,3]. In this study
specificity for PD was 68% and if merging the conditions which should not
be associated with nigrostriatal denervation (i.e. the groups essential
tremor, vascular parkinsonism, drug induced parkinsonism, and no
parkinsonism) it still was only 84%. Sensitivity of DAT-SPECT to diagnose
neurodegenerative parkinsonism was 88% for PD and 84% for
neurodegenerative parkinsonism (i.e. merging the groups PD, multiple
system atrophy, progressive supranuclear palsy, dementia with Lewy bodies,
and corticobasal degeneration) which is the range of the reported
sensitivity in literature. However, considering that DAT-SPECT should
detect neurodegenerative parkinsonian disorders in general, the negative
predictive value was only 74% due the high false negative rate
misclassifying subjects with a neurodegenerative process as having one of
the other conditions. Such diagnostic accuracy data suggest not to use DAT
-SPECT in the diagnostic work-up of patients presenting with a
parkinsonian syndrome of recent onset which is against current
recommendations [4,5]. Similarly, the TCS data in this study have
determined suboptimal diagnostic accuracy in detecting PD. Up to now
several independent studies by various groups have detected substantia
nigra (SN) hyperechogenicity in 80-90% of patients with PD [6-13].
Depending on the cut-off, approximately 10% of healthy adult controls and
patients with APDs and a slightly higher number of patients with ET have
been reported to show SN hyperechogenicity [6,14-17].
It is unclear, why both the TCS and DAT-SPECT results in this study were
surprisingly disappointing. Regarding the TCS data, one has to consider
that insufficient technical equipment may have played a role; the authors
used the Sonos 5500 Philips machine, which they had judged to be
insufficient to display SN- hyperechogenicity in an earlier analysis of
the baseline data ("Fourthly, the quality of the ultrasound system is a
non-neglectable variable, since in our pilot examinations, we found that
the newest ultrasound systems will reveal hyperechointensity of the SN in
more patients...") [18]. However, the Sonos 5500 Philips machine has also
been used by other groups, yielding useful images suitable for further
statistical analysis. It is well known that the way settings are adjusted
do play a major role for the visibility of structures under investigation.
It cannot be estimated why the authors had more problems in scanning with
this machine than other groups. Still, it needs to be acknowledged, that
they realized themselves, that they would have done better with another
device [18].
The main reason given by the authors for their discrepant results to the
literature is that they postulate that their study is the second
prospective after the study by Gaenslen et al. [20]. However, there are
several other prospective studies in this field, showing the diagnostic
utility of TCS in PD, APDs and essential tremor [6,17,22-24]and in the
assessment of PD risk in rapid eye movement sleep behaviour disorder
patients[25] as well as the general population [26]. Also recent
guidelines from the EFNS/MDS-ES recommend TCS for the differential
diagnosis of PD from APS and secondary parkinsonian syndromes, for the
early diagnosis of PD, and for the detection of subjects at risk for PD
[27]. As DAT-SPECT data are not in accordance with the clinical data,
clinical classification of the patients might have been suboptimal. Other
studies used DAT-imaging in addition to the clinical information to reach
a final diagnosis and it would be interesting to know the diagnostic
accuracy of TCS in the subjects, whose final clinical diagnosis was also
supported by their DAT-Scan.
Taken together, this study proves the importance of a good gold standard
for diagnosis of all disease entities investigated in studies trying to
validate other diagnostic instruments. Moreover, careful consideration
should be given to the devices used and to the way methods are applied and
data are analysed.
Affiliations:
Department of Neurology, Innsbruck Medical University (Philipp Mahlknecht
and Klaus Seppi)
Center of Neurology, Department of Neurodegeneration and Hertie Institute
for Clinical Brain Research, University of Tuebingen, Tuebingen, Germany;
German Center for Neurodegenerative Diseases, University of Tuebingen,
Tuebingen, Germany (Daniela Berg)
References
1. Bouwmans AE, Vlaar AM, Mess WH, Kessels A, Weber WE. Specificity and
sensitivity of transcranial sonography of the substantia nigra in the
diagnosis of Parkinson's disease: prospective cohort study in 196
patients. BMJ Open 2013;3. doi:pii: e002613. 10.1136/bmjopen-2013-002613.
2. Marshall VL, Reininger CB, Marquardt M. Parkinson's disease is
overdiagnosed clinically at baseline in diagnostically uncertain cases: a
3-year European multicenter study with repeat [123I]FP-CIT SPECT. Mov
Disord 2009;24:500-8.
3. Jennings DL, Seibyl JP, Oakes D, Eberly S, Murphy J, Marek K. (123I)
beta-CIT and single-photon emission computed tomographic imaging vs
clinical evaluation in Parkinsonian syndrome: unmasking an early
diagnosis. Arch Neurol 2004;61:1224-9.
4. Suchowersky O, Reich S, Perlmutter J, Zesiewicz T, Gronseth G, Weiner
WJ. Practice parameter: diagnosis and prognosis of new onset Parkinson
disease (an evidence-based review): report of the Quality Standards
Subcommittee of the American Academy of Neurology. Neurology 2006;66:968-
75.
5. Pahwa R, Lyons KE. Early diagnosis of Parkinson's disease:
recommendations from diagnostic clinical guidelines. Am J Manag Care
2010;16 Suppl:94-9.
6. Stockner H, Sojer M, Seppi K. Midbrain sonography in patients with
essential tremor. Mov Disord 2007;22:414-7.
7. Ressner P, Skoloudik D, Hlustik P, Kanovsky P. Hyperechogenicity of the
substantia nigra in Parkinson's disease. J Neuroimaging 2007;17:164-7.
8. Huang YW, Jeng JS, Tsai CF, Chen LL, Wu RM.Transcranial imaging of
substantia nigra hyperechogenicity in a Taiwanese cohort of Parkinson's
disease. Mov Disord 2007;22:550-5.
9. Walter U, Wittstock M, Benecke R, Dressler D. Substantia nigra
echogenicity is normal in non-extrapyramidal cerebral disorders but
increased in Parkinson's disease. J Neural Transm 2002;109:191-6.
10. Berg D, Siefker C, Becker G. Echogenicity of the substantia nigra in
Parkinson's disease and its relation to clinical findings. J Neurol
2001;248:684-9.
11. Kolevski G, Petrov I, Petrova V. Transcranial sonography in the
evaluation of Parkinson disease. J Ultrasound Med 2007;26:509-12.
12. Kim JY, Kim ST, Jeon SH, Lee WY. Midbrain transcranial sonography in
Korean patients with Parkinson's disease. Mov Disord 2007;22:1922-6.
13. Okawa M, Miwa H, Kajimoto Y, et al. Transcranial sonography of the
substantia nigra in Japanese patients with Parkinson's disease or atypical
parkinsonism: clinical potential and limitations. Intern Med 2007;46:1527-
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14. Berg D, Becker G, Zeiler B, et al. Vulnerability of the nigrostriatal
system as detected by transcranial ultrasound. Neurology 1999;53:1026-31.
15. Berg D, Behnke S, Walter U. Application of transcranial sonography in
extrapyramidal disorders: updated recommendations. Ultraschall Med
2006;27:12-9.
16. Berg D. Transcranial sonography in the early and differential
diagnosis of Parkinson's disease. J Neural Transm Suppl 2006;249-54.
17. Mahlknecht P, Seppi K, Stockner H. Substantia Nigra Hyperechogenicity
as a Marker for Parkinson's Disease: A Population-Based Study.
Neurodegener Dis 2013;18. [Epub ahead of print]
18. Vlaar AM, de Nijs T, van Kroonenburgh MJ et al. The predictive value
of transcranial duplex sonography for the clinical diagnosis in
undiagnosed parkinsonian syndromes: comparison with SPECT scans. BMC
Neurol 2008;8:42.
19. Hagenah J, K?nig IR, Sperner J et al. Life-long increase of substantia
nigra hyperechogenicity in transcranial sonography. Neuroimage 2010;51:28-
32.
20. Mehnert S, Reuter I, Schepp K et al. Transcranial sonography for
diagnosis of Parkinson's disease. BMC Neurol 2010;10:9.
21. Gaenslen A, Unmuth B, Godau J, et al. The specificity and sensitivity
of transcranial ultrasound in the differential diagnosis of Parkinson's
disease: a prospective blinded study. Lancet Neurol 2008;7:417-24.
22. Walter U, Dressler D, Wolters A, Probst T, Grossmann A, Benecke R.
Sonographic discrimination of corticobasal degeneration vs progressive
supranuclear palsy. Neurology 2004;63:504-9.
23. Walter U, Dressler D, Probst T, et al. Transcranial brain sonography
findings in discriminating between parkinsonism and idiopathic Parkinson
disease. Arch Neurol 2007;64:1635-40.
24. Behnke S, Hellwig D, B?rmann J, et al. Evaluation of transcranial
sonographic findings and MIBG cardiac scintigraphy in the diagnosis of
idiopathic Parkinson's disease. Parkinsonism Relat Disord 2013 Jul 20.
[Epub ahead of print].
25. Iranzo A, Lome?a F, Stockner H, et al. Decreased striatal dopamine
transporter uptake and substantia nigra hyperechogenicity as risk markers
of synucleinopathy in patients with idiopathic rapid-eye-movement sleep
behaviour disorder: a prospective study. Lancet Neurol 2010;9:1070-7.
26. Enlarged substantia nigra hyperechogenicity and risk for Parkinson
disease: a 37-month 3-center study of 1847 older persons. Berg D, Seppi K,
Behnke S, et al. Arch Neurol 2011;68:932-7.
27. Berardelli A, Wenning GK, Antonini A, et al. EFNS/MDS-ES/ENS
[corrected] recommendations for the diagnosis of Parkinson's disease. Eur
J Neurol 2013;20:16-34.
The use of complementary and alternative treatment in asthmatic
patients was very well described by Chen et al. It is indeed a good piece
of research wherein relationship of different types of CAM is done with
asthma severity and treatment by conventional medications. However, it is
also important to estimate the therapeutic-toxicologic safety profile
(risk-benefit ratio) of various CAM interventions for asthma 1. Also,...
The use of complementary and alternative treatment in asthmatic
patients was very well described by Chen et al. It is indeed a good piece
of research wherein relationship of different types of CAM is done with
asthma severity and treatment by conventional medications. However, it is
also important to estimate the therapeutic-toxicologic safety profile
(risk-benefit ratio) of various CAM interventions for asthma 1. Also, a
study done by Blanc et al revealed that there was increase incidence of
hospitalization with the use of herbal medicines, attributed to lack of
control of airway inflammation in herbal medicine 2.Similarly, Mizushima
and Kobayashi published a series of 24 cases of interstitial pneumonitis
induced by herbal remedies 3.Thus, it is important to assess via
questionnaire history of such episodes and the patients must be counseled
about potential benefits and harmful effects of the therapy they use.
Lastly, this study would have been more comprehensive if children were
also included in it.There has been tremendous rise in asthma in children
both in number and severity.This may be due to early exposure, immature
immunity or genetic factors 4. It is seen that many parents are opting for
CAM as a treatment modality for children due to concerns about the long
term treatment with conventional medicines 5.
This study indeed opens avenue for future investigators to look upon the
above mentioned factors for devising a better approach for preventing and
treating asthmatic patients.
REFERENCES:
1. L. Bielory, J. Russin, and G. B. Zuckerman, "Clinical efficacy,
mechanisms of action, and adverse effects of complementary and alternative
medicine therapies for asthma," Allergy and Asthma Proceedings, vol. 25,
no. 5, pp. 283-291, 2004
2. Marino LA, shen, Joannie. Characteristics of complementary and
alternative medicine use among adults with current asthma. Journal of
Asthma : 47;5; 2010: 521-525.
3. Sonibare MA, Gbile ZO. Ethnobotanical survey of anti- asthma plants in
south western Nigeria. Afr. J. trad. CAM 2008:5;340-345.
4. O'Connell EJ. The burden of atopy and asthma in children. Allergy. 2004
Aug;59 Suppl 78:7-11.
5. Helen Kopnina, "Alternative Treatment for Asthma: Case Study of Success
of Traditional Chinese Medicine Treatment of Children from Urban Areas
with Different Levels of Environmental Pollution,"ISRN Allergy, vol. 2012,
Article ID 547534, 6 pages, 2012.
Rossouw et al. addressed only the comparisons of results from
randomized controlled trials (RCTs) and observational studies (OSs). They
did not consider analyses that compared outcomes of participants who had
the same treatment but were in different studies. These analyses found
that adjusting for the WHI risk factors was not sufficient to account for
unmeasured risk differences between subjects in different studies. T...
Rossouw et al. addressed only the comparisons of results from
randomized controlled trials (RCTs) and observational studies (OSs). They
did not consider analyses that compared outcomes of participants who had
the same treatment but were in different studies. These analyses found
that adjusting for the WHI risk factors was not sufficient to account for
unmeasured risk differences between subjects in different studies. The
differences between studies due to unexplained confounding were sometimes
larger then the effects of HT on either MI or stroke in the RCTs. For
example, after adjusting for risk factors measured by the WHI,
participants in the RCT of E-alone had a 37% higher rate of an MI
(p<0.0001) than participants in the WHI OS if both sets of participants
were not taking any HT and a 44% higher rate of an MI (p<0.0001) if
both sets of participants were taking E-alone. Explanations other than
unmeasured confounders are unlikely to account for differences in outcomes
among the studies.
These findings are important because comparisons of subjects in
different studies are closely related to OS comparisons of subjects on
different treatments. It is therefore likely that unmeasured confounders
may in some cases greatly distort apparent treatment effects in OSs even
after adjusting for WHI variables.
Below we summarized and responded to the Rossouw et al. critiques of
our OS/RCT comparisons.
1. THE DIFFERENCES BETWEEN OBSERVATIONAL STUDIES (OSS) AND RANDOMIZED
CONTROLLED TRIALS (RCTS) IN THE WHI CAN BE EXPLAINED BY TAKING INTO
ACCOUNT TIME SINCE INITIATION OF CURRENT REGIMEN OF HORMONE THERAPY (HT)
AND TIME SINCE MENOPAUSE.
This explanation depends on two beliefs: a) HT increases adverse
outcomes soon after it is initiated, and this effect disappears after two
years of continuing HT; b) HT increases adverse outcomes more for persons
who are older or more years past menopause. If these beliefs are true,
then associations between HT and adverse outcomes will be weaker for OS
participants because they have been on HT for considerable time before the
study and will be stronger for RCT participants who are older at the time
they are put on HT. The first belief was supported by our analysis of
the RCT of estrogen plus progestin (E+P). This analysis found HT
increased the MI rate during the first three years of the study but not
subsequently. However, the following findings from our analysis
challenged these beliefs.
a. In the RCT of estrogen alone (E-alone) there was no evidence that
HT increased the risk of MI either soon after beginning HT or
subsequently.
b. In the RCTs of E+P and of E-alone the associations between HT and
stroke remained constant over time, i.e., there was no effect of time
since initiation of therapy.
c. In the OSs there was a protective effect of HT for MI and no
effect of HT on stroke. Regardless of time since initiation the RCTs
never show a protective effect of HT and always showed an effect of HT on
stroke . In other words, time since initiation does not seem to account
for the differences between the OS and RCTs.
d. OS participants who began HT after the start date of the OS should show
increased risk according to the Rossouw et al. explanation, but instead
there was a statistically significant protective effect of HT.
e. In contrast to the Rossouw et al. analysis, neither years since
menopause nor age at study baseline significantly modulated the effect of
HT on outcome in any of numerous analyses (some reported and most not
reported) in the present study. It is possible that Rossouw et al. had a
particularly fortuitous way of analyzing the data and slight changes in
their analysis might give results that do not show that the HT effect was
significantly altered by effects of age or years since menopause.
2. RESULTS FROM THE PRESENT STUDY WERE INVALID BECAUSE WE USED THE
WRONG FOLLOW-UP MEASURES AND USED MI INSTEAD OF CHD AS AN OUTCOME MEASURE.
We have two responses to this criticism. The first is that it was
irrelevant to our research question, i.e., to determine whether OS results
were reliably valid. It has already been well established that OS and RCT
results can be similar. It makes no difference whether OS and RCT results
are similar for some follow-up times and some outcomes. If OS results are
reliably valid, they should be reliably valid for all modifications of the
research question. Our second response is that all analyses reported were
also performed for different follow-up periods and definitions of CHD as
close as we could make it to the Rossouw definition. These additional
results were not reported, but they were qualitatively the same as those
we did report.
3. THE INCLUSION OF HYSTERECTOMY STATUS WAS UNCLEAR. All of our
analyses were done for three data sets: the RCT of E+P (given only to
participants without a hysterectomy), the RCT of E-alone (given only to
participants with a hysterectomy), and the combined RCT data sets. All
three results were report for MI, but only the combined results were
reported for stroke because E+P and E-alone results were similar for
stroke, the confidence intervals for hazard ratios for stroke were very
wide in the individual RCTS, and the estimate for the combined dataset was
essentially the average of the estimates in the individual RCTs. OS
participants taking HT were also divided into those taking E+P and those
taking E-alone. OS participants not taking HT were not divided into those
who had or didn't have a hysterectomy because hysterectomy status was
unrelated to either subsequent MI or stroke after adjusting for the other
risk factors considered. It is unclear how we could have done a better
job managing hysterectomy status.
4. THE RCT DATA SHOULD HAVE BEEN DICHOTOMIZED BY A 2 YEAR INSTEAD OF
A 3 YEAR PERIOD SINCE ENROLLMENT.
We found no evidence that third year RCT results differed from second
year RCT results, and results based on our dichotomization were similar to
studies that dichotomized at 2 years. In addition, after delaying follow
-up for three years, the RCT results should have looked like the OS
results (i.e., HT should have been protective), but they did not.
5. WE WOULD HAVE BEEN WISE TO REQUEST THAT THE ANALYTIC PLAN BE
REVIEWED THROUGH THE USUAL WHI PUBLICATIONS PROCESS.
I do not know what the usual WHI publication process is. However,
many requests to WHI investigators and even a Nurses' Study Investigator
to collaborate on manuscripts, review manuscripts, or allow presentations
of this study were declined. I do not know how we could have obtained a
review.
With the currently available evidence it is premature to conclude
that the WHI data set was adequate to remove confounding. This is not a
criticism of the WHI data set, which is universally considered to be
outstanding. It is a criticism of the repeated claims that differences
between OS and RCT results of HT studies have been resolved. I wish this
were the case and that we could be confident of results in well done OSs.
Unfortunately, reliably valid OSs are still awaiting methodological
improvements.
The Maori population of New Zealand was about 12% at the time of the
Vietnam war. The New Zealand Vietnam veterans have a Maori participation
of 30%+ over double the percentage of Maori in the general population.
Statistics NZ tell us that Maori males die at twice the rate of
Caucasians, mainly cancers, diabetes and heart attacks. By their late
fifties Maori male mortality is two and a half time...
The Maori population of New Zealand was about 12% at the time of the
Vietnam war. The New Zealand Vietnam veterans have a Maori participation
of 30%+ over double the percentage of Maori in the general population.
Statistics NZ tell us that Maori males die at twice the rate of
Caucasians, mainly cancers, diabetes and heart attacks. By their late
fifties Maori male mortality is two and a half times that of Caucasians so
using the general population to measure mortality or disease is as futile
as it is pointless.
Summaries of Product Characteristics (SmPCs) are a cornerstone of the EU medicines licensing process, and could be a valuable information resource for doctors and other health professionals. We welcome the paper by Vromans et al, looking at how SmPCs could better support physicians, and are pleased to say that their findings with German doctors, are consistent with the findings from UK doctors which we published contempo...
Dear Professor Ping Qin, Dear Editor
I have with interest read the article: Suicide risk in relation to air pollen counts: a study based on data from Danish registers. As the data producer and data owner I have identified a number of incorrect statements in this study, that I would like to see corrected or added. Due to these errors, the study is unacceptable both with respect to scientific practice as well as wi...
Language in and of itself has no meaning . Only people have meaning. For example:
Through the Looking Glass, by Lewis Carroll
'I don't know what you mean by "glory",' Alice said.
Humpty Dumpty smiled contemptuously. 'Of course you don't --till I tell you. I meant "there's a nice knock-down argument for you!"'
'But "glory" doesn't mean "a nice knock-down argument",' Alice objected....
The European Medicines Agency (EMA) welcomes the research on the usability of the summaries of the European Public Assessment reports (EPAR summaries) by Professor David K Raynor and David Bryant recently published on the BMJ Open website.
The EMA had first become aware of the results of this user-testing study in 2011 while the Agency was already consulting stakeholders on improving the EPAR summaries, aiming a...
Many thanks to the College of Podiatry and the Society of Chiropodists and Podiatrists for your response to our systematic review examining the published evidence for the effect of contact with a podiatrist on the occurrence of a lower extremity amputation in people with diabetes. We agree wholeheartedly that this review does not provide proof that podiatric intervention has no effect on amputation rates. Rather, it hig...
Roy, If we saw worse mortality in this group, we would have a problem. We don't, we see the 'healthy soldier' effect. This probably means that the Maori men in our sample were as healthy as anyone else.
Conflict of Interest:
None declared
The study by Bouwmans and colleagues seems to be well designed and thoroughly executed [1], but the primary results are surprising regarding both the transcranial sonography (TCS) and dopamine transporters - single- photon emission computed tomography (DAT-SPECT) results. According to large scale prospective studies, DAT-SPECT should have a specificity close to 100% in differentiating neurodegenerative parkinsonian syndrom...
The use of complementary and alternative treatment in asthmatic patients was very well described by Chen et al. It is indeed a good piece of research wherein relationship of different types of CAM is done with asthma severity and treatment by conventional medications. However, it is also important to estimate the therapeutic-toxicologic safety profile (risk-benefit ratio) of various CAM interventions for asthma 1. Also,...
Rossouw et al. addressed only the comparisons of results from randomized controlled trials (RCTs) and observational studies (OSs). They did not consider analyses that compared outcomes of participants who had the same treatment but were in different studies. These analyses found that adjusting for the WHI risk factors was not sufficient to account for unmeasured risk differences between subjects in different studies. T...
Sir,
The Maori population of New Zealand was about 12% at the time of the Vietnam war. The New Zealand Vietnam veterans have a Maori participation of 30%+ over double the percentage of Maori in the general population.
Statistics NZ tell us that Maori males die at twice the rate of Caucasians, mainly cancers, diabetes and heart attacks. By their late fifties Maori male mortality is two and a half time...
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