Title: A nationwide cohort study suggests clarithromycin-based therapy for Helicobacter pylori
eradication is safe in patients with stable coronary heart disease and subsequent peptic ulcer
disease
Version: 1 Date: 13 Jun 2022
Reviewer:  Abdullah Ozgur Yeniova
Reviewer's report:
The manuscript titled “A nationwide cohort study suggests clarithromycin-based therapy for
Helicobacter pylori eradication is safe in patients with stable coronary heart disease and
subsequent peptic ulcer disease” was reviewed for publication on BMC Gastroenterology. I
think manuscript needs major revision. Comments for the manuscript were listed below
I think this manuscript has an important problem. Although clarithromycin based therapy
has been used for eradication of Helicobacter pylori for decades, it is not recommended by
guidelines due to its resistance. Although every state or health care authority can choose its
own H.pylori eradication program according to its local antibiotic resistance, clarithromycin
resistance has been a major problem for almost every country for all over the world.  Authors
stated that clarithromycin is an essential antibiotic for H.pylori eradication but there are many
eradication regimens that do not include clarithromycin. Authors must clarify why do they
choose clarithromycin for H.pylori eradication in Taiwan. They stated that they do not use
amoxicillin and metronidazole with clarithromycin so what kind of first line treatment was  given
for H.pylori eradication in Taiwan
Another problem is authors did not mention about the eradication success. As they mentioned
in their manuscript H.pylori infection may be linked to cardiovascular mortality so ongoing
H.pylori infection may be a confounding factor
Did all the patients were diagnosed with peptic ulcer disease? I think the ratio is very high
because 44664 of 298417 patient has PUD. This means approximately one of six patients has
been diagnosed with PUD I think some these patients are not PUD but may be diagnosed with
H.pylori gastritis during their endoscopy performed because of their dyspeptic complaints. As
it was known that H.pylori has different virulence factors that may effect the pathogenity of
bacteria. Some of the H.pylori variants for example CagA positive types are more virulent and
may cause cardiovascular mortality more than other variants.
Authors must explain why did they exclude patients not diagnosed with PUD in the 3 years after
CHD inception date. Why did they choose three years as a cut off value and why did they want
to exclude these patients
There is a confusion about stable coronary artery disease and unstable heart conditions. How
can a patient is diagnosed with coronary artery disease otherwise he or she is not underwent
coronary bypass, percutaneous angioplasty. Readers may be confused about stable and unstable
coronary artery disease discrimination. Authors must clarify these issues clearly.
Authors should explain why clarithromycin may increase mortality.  What can be the mechanism
for this clarithromycin related mortality.
Otherwise I think the methodology and statistics is appropriate for study and can be published
after major revision after corrections according to the comments
Title: A nationwide cohort study suggests clarithromycin-based therapy for Helicobacter pylori
eradication is safe in patients with stable coronary heart disease and subsequent peptic ulcer
disease
Version: 1 Date: 13 Jun 2022
Reviewer:  Abdullah Ozgur Yeniova
Reviewer's report:
The manuscript titled “A nationwide cohort study suggests clarithromycin-based therapy for
Helicobacter pylori eradication is safe in patients with stable coronary heart disease and
subsequent peptic ulcer disease” was reviewed for publication on BMC Gastroenterology. I
think manuscript needs major revision. Comments for the manuscript were listed below
I think this manuscript has an important problem. Although clarithromycin based therapy
has been used for eradication of Helicobacter pylori for decades, it is not recommended by
guidelines due to its resistance. Although every state or health care authority can choose its
own H.pylori eradication program according to its local antibiotic resistance, clarithromycin
resistance has been a major problem for almost every country for all over the world.  Authors
stated that clarithromycin is an essential antibiotic for H.pylori eradication but there are many
eradication regimens that do not include clarithromycin. Authors must clarify why do they
choose clarithromycin for H.pylori eradication in Taiwan. They stated that they do not use
amoxicillin and metronidazole with clarithromycin so what kind of first line treatment was  given
for H.pylori eradication in Taiwan
Another problem is authors did not mention about the eradication success. As they mentioned
in their manuscript H.pylori infection may be linked to cardiovascular mortality so ongoing
H.pylori infection may be a confounding factor
Did all the patients were diagnosed with peptic ulcer disease? I think the ratio is very high
because 44664 of 298417 patient has PUD. This means approximately one of six patients has
been diagnosed with PUD I think some these patients are not PUD but may be diagnosed with
H.pylori gastritis during their endoscopy performed because of their dyspeptic complaints. As
it was known that H.pylori has different virulence factors that may effect the pathogenity of
bacteria. Some of the H.pylori variants for example CagA positive types are more virulent and
may cause cardiovascular mortality more than other variants.
Authors must explain why did they exclude patients not diagnosed with PUD in the 3 years after
CHD inception date. Why did they choose three years as a cut off value and why did they want
to exclude these patients
There is a confusion about stable coronary artery disease and unstable heart conditions. How
can a patient is diagnosed with coronary artery disease otherwise he or she is not underwent
coronary bypass, percutaneous angioplasty. Readers may be confused about stable and unstable
coronary artery disease discrimination. Authors must clarify these issues clearly.
Authors should explain why clarithromycin may increase mortality.  What can be the mechanism
for this clarithromycin related mortality.
Otherwise I think the methodology and statistics is appropriate for study and can be published
after major revision after corrections according to the comments
Please review this paper.
user
Title: A nationwide cohort study suggests clarithromycin-based therapy for Helicobacter pylori
eradication is safe in patients with stable coronary heart disease and subsequent peptic ulcer
disease
Version: 1 Date: 13 Jun 2022
Reviewer:  Abdullah Ozgur Yeniova
Reviewer's report:
The manuscript titled “A nationwide cohort study suggests clarithromycin-based therapy for
Helicobacter pylori eradication is safe in patients with stable coronary heart disease and
subsequent peptic ulcer disease” was reviewed for publication on BMC Gastroenterology. I
think manuscript needs major revision. Comments for the manuscript were listed below
I think this manuscript has an important problem. Although clarithromycin based therapy
has been used for eradication of Helicobacter pylori for decades, it is not recommended by
guidelines due to its resistance. Although every state or health care authority can choose its
own H.pylori eradication program according to its local antibiotic resistance, clarithromycin
resistance has been a major problem for almost every country for all over the world.  Authors
stated that clarithromycin is an essential antibiotic for H.pylori eradication but there are many
eradication regimens that do not include clarithromycin. Authors must clarify why do they
choose clarithromycin for H.pylori eradication in Taiwan. They stated that they do not use
amoxicillin and metronidazole with clarithromycin so what kind of first line treatment was  given
for H.pylori eradication in Taiwan
Another problem is authors did not mention about the eradication success. As they mentioned
in their manuscript H.pylori infection may be linked to cardiovascular mortality so ongoing
H.pylori infection may be a confounding factor
Did all the patients were diagnosed with peptic ulcer disease? I think the ratio is very high
because 44664 of 298417 patient has PUD. This means approximately one of six patients has
been diagnosed with PUD I think some these patients are not PUD but may be diagnosed with
H.pylori gastritis during their endoscopy performed because of their dyspeptic complaints. As
it was known that H.pylori has different virulence factors that may effect the pathogenity of
bacteria. Some of the H.pylori variants for example CagA positive types are more virulent and
may cause cardiovascular mortality more than other variants.
Authors must explain why did they exclude patients not diagnosed with PUD in the 3 years after
CHD inception date. Why did they choose three years as a cut off value and why did they want
to exclude these patients
There is a confusion about stable coronary artery disease and unstable heart conditions. How
can a patient is diagnosed with coronary artery disease otherwise he or she is not underwent
coronary bypass, percutaneous angioplasty. Readers may be confused about stable and unstable
coronary artery disease discrimination. Authors must clarify these issues clearly.
Authors should explain why clarithromycin may increase mortality.  What can be the mechanism
for this clarithromycin related mortality.
Otherwise I think the methodology and statistics is appropriate for study and can be published
after major revision after corrections according to the comments
assistant