Review for 10.1186/1471-230X-14-91 (2014)

Reviewer's report
Title:Acid Suppress Agents and Risk of Mycobacterium Tuberculosis: A
Population-Based, Case-Control Study
Version: 1Date:8 May 2013
Reviewer: Puja Myles
Reviewer's report:
The potential health risks associated with acid suppressant therapy is an
important research question to investigate given their increasing use within
primary care over the years. The findings are very interesting and if this is a truly
causal relationship, they suggest caution when prescribing acid suppressants to
relieve symptoms without concomitant investigation and treatment of the
underlying cause. However, this makes it all the more important to be very clear
with respect to the methods and definitions used in this study. My
recommendations for revisions largely relate to clarity on methodological aspects
of the study.
Major compulsory revisions
1. Abstract (conclusion): The conclusion is a bit strong and implies causality. It is
more accurate to say that a statistically significant association was observed
between acid suppressant agents and increased tuberculosis
incidence/activation.
2. Introduction: The biological plausibility of acid suppression agents being
associated with an increased risk of infection is generally accepted. However, it
would be worth briefly commenting on the biological plausibility of tuberculosis
infection and reactivation with the use of acid suppressants.
3. Methods (TB cases and controls): The following sentence is not clear,
“According the index date of each TB case, we randomly selected the persons
who received medical service within one week…”
Do you mean that controls had to have a medical consultation within one week of
the index date of the matched TB case? If yes, why was this important for
inclusion?
4. Methods (Exposure ascertainment, definition and categorisation):
a) Are acid suppressive agents available as ‘over the counter’ medication or does
the NHI database have access to complete records of all prescriptions of these
drugs within Taiwan?
b) Please briefly outline your approach to calculating the defined daily dosage
(DDD) in your methods.
c) Exposure categories (prescription of acid suppressive therapy 6 months, 12
months and 24 months prior to TB index date): Are these exposure categories
mutually exclusive or could a person counted as having an acid suppressive
therapy prescription 6 months prior to the TB index data, be also included in the
category relating to prescriptions 12 months prior to the index date if they had
been on long-term medication?
d) Have you tried to separate long-term acid suppressant therapy use from
short-term or one-off prescriptions? Was there a difference between patients on
long-term and short-term acid suppressant therapy in terms of clinical and
socio-demographic characteristics?
e) What is the average length of prescription for acid suppressant therapy in
Taiwan? Are all repeat prescriptions recorded in the database?
5. Methods (Statistical analysis): Please briefly outline your model building
strategy for the multivariable model.
6. Discussion (conclusion): The conclusion as follows seems incomplete: “In the
society where Mycobacterium tuberculosis was prevalent, evaluation of
pulmonary TB before prescription of PPI or H2RA is warranted”. How and why
will this help?
Minor essential revisions
• The manuscript will benefit from general language editing (grammar and
spelling checks)
• Title: Use suppressive /suppressant/suppressor instead of ‘suppress’ in ‘acid
suppress agents’
• Replace ‘correlation’ with ‘association’ throughout the manuscript to avoid
confusion with the statistical meaning of the former term
• In the results section of the abstract please include 95%CI
• Table 2: Please review the formatting as some of the symbols are not showing
properly; please be consistent with the use of decimal places.
• Tables 3 and 4: Please present percentages of cases and controls in each
exposure category.
Level of interest: An article of importance in its field
Quality of written English: Needs some language corrections before being
published
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
I have received an unrestricted educational grant from F.Hoffman-La Roche for
research in the area of pandemic influenza. This is not related in any way to the
content of the paper I have reviewed.