Reviewer’s report
Title: 
Eradication of Helicobacter pylori may improve dyspepsia in the elderly
for the long term
Version: 
0 
Date: 
30 Apr 2021
Reviewer's report:
The topic explored by the authors is interesting, but some sentences and
conclusion could be not completely supported. Dyspepsia in Helicobacter pylori
infected subjects is frequent and Maasticht and Kyoto reccomendations are in
favour of H.p. eradication to improve dyspepsia. For elderly people, no specific
recomendation are present in literature. The relationship beetwen Hp infection
and upper GI diseases in elderly has been recognized in the past in several
papers: 
A Pilotto 1, M Franceschi, G Leandro, M Rassu, L Bozzola, G Valerio, F Di
Mario Influence of Helicobacter pylori infection on severity of oesophagitis and
response to therapy in the elderly 
Dig Liver Dis . 2002 May;34(5):328-31.
Aliment Pharmacol Ther
A Pilotto 1, M Franceschi, G Leandro, L Bozzola, M Rassu, G Soffiati, F Di
Mario, G Valerio Cure of Helicobacter pylori infection in elderly patients:
comparison of low versus high doses of clarithromycin in combination with
amoxicillin and pantoprazole 2001 Jul;15(7):1031-6. 
Aliment Pharmacol Ther
A Pilotto 1, F Di Mario, M Franceschi, G Leandro, G Battaglia, B Germanà, R
Marin, G Valerio Pantoprazole versus one-week Helicobacter pylori eradication
therapy for the prevention of acute NSAID-related gastroduodenal damage in
elderly subjects. Aliment Pharmacol Ther
. 2000 Aug;14(8):1077-82.
.A Pilotto, M Franceschi, G Valerio, F Di Mario, G Leandro Helicobacter pylori
infection in elderly patients with peptic ulcer Age Ageing, 1999 Jul;28(4):412-4. 
A Pilotto 1, F Rumor, M Franceschi, G Leandro, R Novello, G Soffiati, M
Scagnelli, F Di Mario, G Valerio Lack of association between Helicobacter
pylori infection and extracardiac atherosclerosis in dyspeptic elderly subjects
PMID: 10459790 DOI: 10.1093/ageing/28.4.367
J Gastroenterol Hepatol
A Pilotto 1, M Franceschi, G Leandro, L Bozzola, A Fortunato, M Rassu, S Meli,
G Soffiati, M Scagnelli, F Di Mario, G Valerio . Efficacy of 7 day lansoprazole-
based triple therapy for Helicobacter pylori infection in elderly patients 
1999
May;14(5):468-75. doi: 10.1046/j.1440-1746.1999.01893.x.
A Pilotto 1, M Franceschi, F Di Mario, G Leandro, L Bozzola, G Valerio The
long-term clinical outcome of elderly patients with Helicobacter pylori-
associated peptic ulcer disease. 1998;44(3):153-8. doi: 10.1159/000022000.
J Clin Gastroenterol
A Pilotto 1, M Rassu, L Bozzola, G Leandro, M Franceschi, F Furlan, S Meli, M
Scagnelli, F Di Mario, G Valerio Cytotoxin-associated gene A-positive
Helicobacter pylori infection in the elderly. Association with gastric atrophy and
intestinal metaplasia . 1998 Jan;26(1):18-22. doi: 10.1097/00004836-199801000-
00006.
The effect of Helicobacter pylori infection on NSAID-related gastroduodenal
damage in the elderly. Eur J Gastroenterol Hepatol . 1997 Oct;9(10):951-6. doi:
10.1097/00042737-199710000-00006.
A Pilotto 1, M Franceschi, G Leandro, F Di Mario, G Valerio
A Pilotto 1, M Franceschi, G Leandro, F Di Mario, G Valerio The effect of
Helicobacter pylori infection on NSAID-related gastroduodenal damage in the
elderly Eur J Gastroenterol Hepatol . 1997 Oct;9(10):951-6.
A Pilotto 1, F Di Mario, M Franceschi, G Leandro, G Soffiati, M Scagnelli, L
Bozzola, G Valerio Cure of Helicobacter pylori infection in the elderly: effects of
eradication on gastritis and serological markers. Aliment Pharmacol Ther . 1996
Dec;10(6):1021-7.
A Pilotto 1, R Fabrello, M Franceschi, M Scagnelli, F Soffiati, F Di Mario, A
Fortunato, G Valerio Helicobacter pylori infection in asymptomatic elderly
subjects living at home or in a nursing home: effects on gastric function and
nutritional status. Age Ageing . 1996 May;25(3):245-9. 
We suggest to include in bibliography some on these papers. In particular, the
sentence opening the discussion: "This is the first report....." appears inadeguate.
I suggest to include in both background and discussion papers related with Hp
eradication schedules in elderly as well as Hp infection and dyspepsia and Hp
eradication and dyspepsia.
Dyspepsia is closely influenced by fluttuation lasting the time and this is true
also for the relationship beetwen Hp eradication and improvement of dyspepsia,
as reported in this paper: Francesco di Mario 1, Nicoletta Stefani, Nadia Dal Bò,
Massimo Rugge, Alberto Pilotto, Giulia Martina Cavestro, Lucas Giovanni
Cavallaro, Angelo Franzé, Gioacchino Leandro Natural course of functional
dyspepsia after Helicobacter pylori eradication: a seven-year survey. Dig Dis Sci
. 2005 Dec;50(12):2286-95.
The study lasting a period of 7 years after Hp eradication showed a fluttuation in
dyspeptic symptoms after Hp eradication.
On this subject, the authors reported that in a subgroup of elderly patients the
answers to the questionaire have been obtained after 54.8 months, but aonly
results after one year were reported in the paper. I suggest to clarify.
Other comments and suggestion
We suggest to detail which symptoms improved and possible related
mechanisms 
In elderly, atrophic gastritis is increasing. We suggest to report data on the
frequency of atrophic gastritis in studied population beside the autoimmune
gastritis correctly mentioned.
We believe that the control group (N) is not appropriate for the aims of the study.
A proper control group, to me, could be an elderly Hp positive population not
treated and with an adeguate follow-up. At present the study is consistent only
with the demonstartion that younger people have a better response to eradication
teraphy in comparison with elderly.
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 I agree for my report to be made available
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) if this manuscript is accepted for
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do not
 publish my name
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Is the study design appropriate to answer the research question (including the use
of appropriate controls), and are the conclusions supported by the evidence
presented?
Yes
Are the methods sufficiently described to allow the study to be repeated?
Yes
Is the use of statistics and treatment of uncertainties appropriate?
Yes
Is the presentation of the work clear?
No
Are the images in this manuscript (including electrophoretic gels and blots) free
from apparent manipulation?
Yes
Reviewer’s report
Title: 
Eradication of Helicobacter pylori may improve dyspepsia in the elderly
for the long term
Version: 
0 
Date: 
30 Apr 2021
Reviewer's report:
The topic explored by the authors is interesting, but some sentences and
conclusion could be not completely supported. Dyspepsia in Helicobacter pylori
infected subjects is frequent and Maasticht and Kyoto reccomendations are in
favour of H.p. eradication to improve dyspepsia. For elderly people, no specific
recomendation are present in literature. The relationship beetwen Hp infection
and upper GI diseases in elderly has been recognized in the past in several
papers: 
A Pilotto 1, M Franceschi, G Leandro, M Rassu, L Bozzola, G Valerio, F Di
Mario Influence of Helicobacter pylori infection on severity of oesophagitis and
response to therapy in the elderly 
Dig Liver Dis . 2002 May;34(5):328-31.
Aliment Pharmacol Ther
A Pilotto 1, M Franceschi, G Leandro, L Bozzola, M Rassu, G Soffiati, F Di
Mario, G Valerio Cure of Helicobacter pylori infection in elderly patients:
comparison of low versus high doses of clarithromycin in combination with
amoxicillin and pantoprazole 2001 Jul;15(7):1031-6. 
Aliment Pharmacol Ther
A Pilotto 1, F Di Mario, M Franceschi, G Leandro, G Battaglia, B Germanà, R
Marin, G Valerio Pantoprazole versus one-week Helicobacter pylori eradication
therapy for the prevention of acute NSAID-related gastroduodenal damage in
elderly subjects. Aliment Pharmacol Ther
. 2000 Aug;14(8):1077-82.
.A Pilotto, M Franceschi, G Valerio, F Di Mario, G Leandro Helicobacter pylori
infection in elderly patients with peptic ulcer Age Ageing, 1999 Jul;28(4):412-4. 
A Pilotto 1, F Rumor, M Franceschi, G Leandro, R Novello, G Soffiati, M
Scagnelli, F Di Mario, G Valerio Lack of association between Helicobacter
pylori infection and extracardiac atherosclerosis in dyspeptic elderly subjects
PMID: 10459790 DOI: 10.1093/ageing/28.4.367
J Gastroenterol Hepatol
A Pilotto 1, M Franceschi, G Leandro, L Bozzola, A Fortunato, M Rassu, S Meli,
G Soffiati, M Scagnelli, F Di Mario, G Valerio . Efficacy of 7 day lansoprazole-
based triple therapy for Helicobacter pylori infection in elderly patients 
1999
May;14(5):468-75. doi: 10.1046/j.1440-1746.1999.01893.x.
A Pilotto 1, M Franceschi, F Di Mario, G Leandro, L Bozzola, G Valerio The
long-term clinical outcome of elderly patients with Helicobacter pylori-
associated peptic ulcer disease. 1998;44(3):153-8. doi: 10.1159/000022000.
J Clin Gastroenterol
A Pilotto 1, M Rassu, L Bozzola, G Leandro, M Franceschi, F Furlan, S Meli, M
Scagnelli, F Di Mario, G Valerio Cytotoxin-associated gene A-positive
Helicobacter pylori infection in the elderly. Association with gastric atrophy and
intestinal metaplasia . 1998 Jan;26(1):18-22. doi: 10.1097/00004836-199801000-
00006.
The effect of Helicobacter pylori infection on NSAID-related gastroduodenal
damage in the elderly. Eur J Gastroenterol Hepatol . 1997 Oct;9(10):951-6. doi:
10.1097/00042737-199710000-00006.
A Pilotto 1, M Franceschi, G Leandro, F Di Mario, G Valerio
A Pilotto 1, M Franceschi, G Leandro, F Di Mario, G Valerio The effect of
Helicobacter pylori infection on NSAID-related gastroduodenal damage in the
elderly Eur J Gastroenterol Hepatol . 1997 Oct;9(10):951-6.
A Pilotto 1, F Di Mario, M Franceschi, G Leandro, G Soffiati, M Scagnelli, L
Bozzola, G Valerio Cure of Helicobacter pylori infection in the elderly: effects of
eradication on gastritis and serological markers. Aliment Pharmacol Ther . 1996
Dec;10(6):1021-7.
A Pilotto 1, R Fabrello, M Franceschi, M Scagnelli, F Soffiati, F Di Mario, A
Fortunato, G Valerio Helicobacter pylori infection in asymptomatic elderly
subjects living at home or in a nursing home: effects on gastric function and
nutritional status. Age Ageing . 1996 May;25(3):245-9. 
We suggest to include in bibliography some on these papers. In particular, the
sentence opening the discussion: "This is the first report....." appears inadeguate.
I suggest to include in both background and discussion papers related with Hp
eradication schedules in elderly as well as Hp infection and dyspepsia and Hp
eradication and dyspepsia.
Dyspepsia is closely influenced by fluttuation lasting the time and this is true
also for the relationship beetwen Hp eradication and improvement of dyspepsia,
as reported in this paper: Francesco di Mario 1, Nicoletta Stefani, Nadia Dal Bò,
Massimo Rugge, Alberto Pilotto, Giulia Martina Cavestro, Lucas Giovanni
Cavallaro, Angelo Franzé, Gioacchino Leandro Natural course of functional
dyspepsia after Helicobacter pylori eradication: a seven-year survey. Dig Dis Sci
. 2005 Dec;50(12):2286-95.
The study lasting a period of 7 years after Hp eradication showed a fluttuation in
dyspeptic symptoms after Hp eradication.
On this subject, the authors reported that in a subgroup of elderly patients the
answers to the questionaire have been obtained after 54.8 months, but aonly
results after one year were reported in the paper. I suggest to clarify.
Other comments and suggestion
We suggest to detail which symptoms improved and possible related
mechanisms 
In elderly, atrophic gastritis is increasing. We suggest to report data on the
frequency of atrophic gastritis in studied population beside the autoimmune
gastritis correctly mentioned.
We believe that the control group (N) is not appropriate for the aims of the study.
A proper control group, to me, could be an elderly Hp positive population not
treated and with an adeguate follow-up. At present the study is consistent only
with the demonstartion that younger people have a better response to eradication
teraphy in comparison with elderly.
Publons Reviewer Recognition
. Springer Nature can send verification of this
review directly to Publons (a subsidiary of Clarivate Analytics). If you would
like to take advantage of this service, please click on the “Yes” option below.
Your name, email address, title of the reviewed manuscript, name of the journal,
and date of your review submission (the “Review Data”) will then be transmitted
to Publons after the final decision on the manuscript has been made. If you have
already registered at Publons, they will notify you of the receipt of this review
and update your profile 
as per your settings and their policy. If you are not
registered with Publons, you will receive an email from them asking you to
register in order for them to be able to recognize your review on your new
profile page. Publons may use the Review Data to generate derivative metadata
for the benefit of Publons and you as a reviewer, carefully considering the
sensitivity of such information. For example, Publons may verify your record as
a reviewer by updating your profile published on its webservice if you have
registered for such service or help editors to identify candidate reviewers. Please
find the details of processing in Publons’ privacy policy
https://publons.com/about/terms
Yes
Declaration of competing interests
Please complete a declaration of competing
interests, considering the following questions:
1
. 
Have you in the past five years received reimbursements, fees, funding, or
salary from an organisation that may in any way gain or lose financially
from the publication of this manuscript, either now or in the future?
2
. 
Do you hold any stocks or shares in an organisation that may in any way
gain or lose financially from the publication of this manuscript, either now
or in the future?
3
. 
Do you hold or are you currently applying for any patents relating to the
content of the manuscript?
4
. 
Have you received reimbursements, fees, funding, or salary from an
organization that holds or has applied for patents relating to the content of
the manuscript?
5
. 
Do you have any other financial competing interests?
6
. 
Do you have any non-financial competing interests in relation to this
paper?
If you can answer no to all of the above, write 'I declare that I have no competing
interests' below. If your reply is yes to any, please give details below.
No declaration
Reviewer Publication Consent.
 I agree for my report to be made available
under an Open Access Creative Commons CC-BY License (
http://creativecommons.org/licenses/by/4.0
) if this manuscript is accepted for
publication. Any comments that I do not wish to be included in the published
report have been included as confidential comments to the editor, which will not
be published.
If you are not happy for us to publish this report, please contact the
editorial office before completing the review.
If you wish, you can include your
name in your published report. Please note you must decide whether to include
your name at the start of the process and confirm this decision whenever
prompted. If you change your decision later, we will not be able to publish your
name.
I agree to the terms of the CC-BY 4.0 license; please 
do not
 publish my name
with my report. (default)
Is the study design appropriate to answer the research question (including the use
of appropriate controls), and are the conclusions supported by the evidence
presented?
Yes
Are the methods sufficiently described to allow the study to be repeated?
Yes
Is the use of statistics and treatment of uncertainties appropriate?
Yes
Is the presentation of the work clear?
No
Are the images in this manuscript (including electrophoretic gels and blots) free
from apparent manipulation?
Yes
Please review this paper.
user
Reviewer’s report
Title: 
Eradication of Helicobacter pylori may improve dyspepsia in the elderly
for the long term
Version: 
0 
Date: 
30 Apr 2021
Reviewer's report:
The topic explored by the authors is interesting, but some sentences and
conclusion could be not completely supported. Dyspepsia in Helicobacter pylori
infected subjects is frequent and Maasticht and Kyoto reccomendations are in
favour of H.p. eradication to improve dyspepsia. For elderly people, no specific
recomendation are present in literature. The relationship beetwen Hp infection
and upper GI diseases in elderly has been recognized in the past in several
papers: 
A Pilotto 1, M Franceschi, G Leandro, M Rassu, L Bozzola, G Valerio, F Di
Mario Influence of Helicobacter pylori infection on severity of oesophagitis and
response to therapy in the elderly 
Dig Liver Dis . 2002 May;34(5):328-31.
Aliment Pharmacol Ther
A Pilotto 1, M Franceschi, G Leandro, L Bozzola, M Rassu, G Soffiati, F Di
Mario, G Valerio Cure of Helicobacter pylori infection in elderly patients:
comparison of low versus high doses of clarithromycin in combination with
amoxicillin and pantoprazole 2001 Jul;15(7):1031-6. 
Aliment Pharmacol Ther
A Pilotto 1, F Di Mario, M Franceschi, G Leandro, G Battaglia, B Germanà, R
Marin, G Valerio Pantoprazole versus one-week Helicobacter pylori eradication
therapy for the prevention of acute NSAID-related gastroduodenal damage in
elderly subjects. Aliment Pharmacol Ther
. 2000 Aug;14(8):1077-82.
.A Pilotto, M Franceschi, G Valerio, F Di Mario, G Leandro Helicobacter pylori
infection in elderly patients with peptic ulcer Age Ageing, 1999 Jul;28(4):412-4. 
A Pilotto 1, F Rumor, M Franceschi, G Leandro, R Novello, G Soffiati, M
Scagnelli, F Di Mario, G Valerio Lack of association between Helicobacter
pylori infection and extracardiac atherosclerosis in dyspeptic elderly subjects
PMID: 10459790 DOI: 10.1093/ageing/28.4.367
J Gastroenterol Hepatol
A Pilotto 1, M Franceschi, G Leandro, L Bozzola, A Fortunato, M Rassu, S Meli,
G Soffiati, M Scagnelli, F Di Mario, G Valerio . Efficacy of 7 day lansoprazole-
based triple therapy for Helicobacter pylori infection in elderly patients 
1999
May;14(5):468-75. doi: 10.1046/j.1440-1746.1999.01893.x.
A Pilotto 1, M Franceschi, F Di Mario, G Leandro, L Bozzola, G Valerio The
long-term clinical outcome of elderly patients with Helicobacter pylori-
associated peptic ulcer disease. 1998;44(3):153-8. doi: 10.1159/000022000.
J Clin Gastroenterol
A Pilotto 1, M Rassu, L Bozzola, G Leandro, M Franceschi, F Furlan, S Meli, M
Scagnelli, F Di Mario, G Valerio Cytotoxin-associated gene A-positive
Helicobacter pylori infection in the elderly. Association with gastric atrophy and
intestinal metaplasia . 1998 Jan;26(1):18-22. doi: 10.1097/00004836-199801000-
00006.
The effect of Helicobacter pylori infection on NSAID-related gastroduodenal
damage in the elderly. Eur J Gastroenterol Hepatol . 1997 Oct;9(10):951-6. doi:
10.1097/00042737-199710000-00006.
A Pilotto 1, M Franceschi, G Leandro, F Di Mario, G Valerio
A Pilotto 1, M Franceschi, G Leandro, F Di Mario, G Valerio The effect of
Helicobacter pylori infection on NSAID-related gastroduodenal damage in the
elderly Eur J Gastroenterol Hepatol . 1997 Oct;9(10):951-6.
A Pilotto 1, F Di Mario, M Franceschi, G Leandro, G Soffiati, M Scagnelli, L
Bozzola, G Valerio Cure of Helicobacter pylori infection in the elderly: effects of
eradication on gastritis and serological markers. Aliment Pharmacol Ther . 1996
Dec;10(6):1021-7.
A Pilotto 1, R Fabrello, M Franceschi, M Scagnelli, F Soffiati, F Di Mario, A
Fortunato, G Valerio Helicobacter pylori infection in asymptomatic elderly
subjects living at home or in a nursing home: effects on gastric function and
nutritional status. Age Ageing . 1996 May;25(3):245-9. 
We suggest to include in bibliography some on these papers. In particular, the
sentence opening the discussion: "This is the first report....." appears inadeguate.
I suggest to include in both background and discussion papers related with Hp
eradication schedules in elderly as well as Hp infection and dyspepsia and Hp
eradication and dyspepsia.
Dyspepsia is closely influenced by fluttuation lasting the time and this is true
also for the relationship beetwen Hp eradication and improvement of dyspepsia,
as reported in this paper: Francesco di Mario 1, Nicoletta Stefani, Nadia Dal Bò,
Massimo Rugge, Alberto Pilotto, Giulia Martina Cavestro, Lucas Giovanni
Cavallaro, Angelo Franzé, Gioacchino Leandro Natural course of functional
dyspepsia after Helicobacter pylori eradication: a seven-year survey. Dig Dis Sci
. 2005 Dec;50(12):2286-95.
The study lasting a period of 7 years after Hp eradication showed a fluttuation in
dyspeptic symptoms after Hp eradication.
On this subject, the authors reported that in a subgroup of elderly patients the
answers to the questionaire have been obtained after 54.8 months, but aonly
results after one year were reported in the paper. I suggest to clarify.
Other comments and suggestion
We suggest to detail which symptoms improved and possible related
mechanisms 
In elderly, atrophic gastritis is increasing. We suggest to report data on the
frequency of atrophic gastritis in studied population beside the autoimmune
gastritis correctly mentioned.
We believe that the control group (N) is not appropriate for the aims of the study.
A proper control group, to me, could be an elderly Hp positive population not
treated and with an adeguate follow-up. At present the study is consistent only
with the demonstartion that younger people have a better response to eradication
teraphy in comparison with elderly.
Publons Reviewer Recognition
. Springer Nature can send verification of this
review directly to Publons (a subsidiary of Clarivate Analytics). If you would
like to take advantage of this service, please click on the “Yes” option below.
Your name, email address, title of the reviewed manuscript, name of the journal,
and date of your review submission (the “Review Data”) will then be transmitted
to Publons after the final decision on the manuscript has been made. If you have
already registered at Publons, they will notify you of the receipt of this review
and update your profile 
as per your settings and their policy. If you are not
registered with Publons, you will receive an email from them asking you to
register in order for them to be able to recognize your review on your new
profile page. Publons may use the Review Data to generate derivative metadata
for the benefit of Publons and you as a reviewer, carefully considering the
sensitivity of such information. For example, Publons may verify your record as
a reviewer by updating your profile published on its webservice if you have
registered for such service or help editors to identify candidate reviewers. Please
find the details of processing in Publons’ privacy policy
https://publons.com/about/terms
Yes
Declaration of competing interests
Please complete a declaration of competing
interests, considering the following questions:
1
. 
Have you in the past five years received reimbursements, fees, funding, or
salary from an organisation that may in any way gain or lose financially
from the publication of this manuscript, either now or in the future?
2
. 
Do you hold any stocks or shares in an organisation that may in any way
gain or lose financially from the publication of this manuscript, either now
or in the future?
3
. 
Do you hold or are you currently applying for any patents relating to the
content of the manuscript?
4
. 
Have you received reimbursements, fees, funding, or salary from an
organization that holds or has applied for patents relating to the content of
the manuscript?
5
. 
Do you have any other financial competing interests?
6
. 
Do you have any non-financial competing interests in relation to this
paper?
If you can answer no to all of the above, write 'I declare that I have no competing
interests' below. If your reply is yes to any, please give details below.
No declaration
Reviewer Publication Consent.
 I agree for my report to be made available
under an Open Access Creative Commons CC-BY License (
http://creativecommons.org/licenses/by/4.0
) if this manuscript is accepted for
publication. Any comments that I do not wish to be included in the published
report have been included as confidential comments to the editor, which will not
be published.
If you are not happy for us to publish this report, please contact the
editorial office before completing the review.
If you wish, you can include your
name in your published report. Please note you must decide whether to include
your name at the start of the process and confirm this decision whenever
prompted. If you change your decision later, we will not be able to publish your
name.
I agree to the terms of the CC-BY 4.0 license; please 
do not
 publish my name
with my report. (default)
Is the study design appropriate to answer the research question (including the use
of appropriate controls), and are the conclusions supported by the evidence
presented?
Yes
Are the methods sufficiently described to allow the study to be repeated?
Yes
Is the use of statistics and treatment of uncertainties appropriate?
Yes
Is the presentation of the work clear?
No
Are the images in this manuscript (including electrophoretic gels and blots) free
from apparent manipulation?
Yes
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