Title: Effect of clinical vs. administrative data definitions on the epidemiology of C. difficile
among hospitalized individuals with IBD: A population-based cohort study
Version: 1 Date: 07 Dec 2021
Reviewer's report:
Shaffer-CDI in ICD codes vs lab tests
The authors have used linked datasets from Manitoba 2005-2014 to compare CDI rates among
hospitalized patients when CDI is classified based on discharge ICD-10 codes versus when CDI
is classified based on lab testing.  They looked at this question for patients with IBD (Crohn’s
and UC) and for matched controls without IBD.  They found that the ICD-10 codes were (to my
surprise) not bad at classifying CDI with a sensitivity of 70-80% and near perfect specificity.
The sensitivity was slightly worse among those with IBD than among the matched controls
without IBD, which also was surprising.  In general, this paper is professionally assembled and
it is a useful addition to those working in epidemiology related to CDI.  While not entirely novel,
it adds incrementally to their own prior work (reference 11) and that of others (e.g., ref 27).
My most important comment is related to their emphasis which often seems to wander away from
the question of interest (which is comparing CDI classified by ICD-10 codes vs CDI classified
by labs).  To be specific, take Table 1.  This table emphasizes the comparison of those with IBD
vs matched controls without IBD.  This is not the comparison of interest!  Rather, the columns
should be rearranged so that they are comparing risk factors when CDI is classified via ICD-10
vs when CDI is classified via labs.  E.g., 5-ASA use for CDI by ICD-10 vs 5-ASA use for CDI
by labs, etc.  They could do this first for IBD and then for non-IBD.  Elsewhere in the manuscript
similar changes of emphasis could be made and the manuscript would be improved.
Less important:
1. Discussion - Although the authors recognize the problem of CDI colonization in the
limitations section, they should further tone down their statement in the Discussion (end of
first page) about this, which diminishes this very important problem that plagues CDI research.
Although I agree that a positive C. diff is invariably treated in IBD patients, this doesn’t mean
that these are true CDI cases.  A large proportion of these patients are colonized and treating
C. diff makes no difference.  Ultimately, the true diagnosis of CDI is clinical and cannot be
ascertained retrospectively.
2. Methods - The final sentence before the “Study Measures” section implies that have linked
individual patients within the datasets—i.e., that each patient is a single row of data.  This is a
very important point and, assuming this is the case, it should be stated even more explicitly.  If
I somehow misunderstood and this is not the case, it’s a major problem.
3. The most recent data is from 2014 making the study data a minimum of 8 years old and a
maximum of 16 years old.  The fact that the data is relatively stale should be recognized as a
limitation.
Title: Effect of clinical vs. administrative data definitions on the epidemiology of C. difficile
among hospitalized individuals with IBD: A population-based cohort study
Version: 1 Date: 07 Dec 2021
Reviewer's report:
Shaffer-CDI in ICD codes vs lab tests
The authors have used linked datasets from Manitoba 2005-2014 to compare CDI rates among
hospitalized patients when CDI is classified based on discharge ICD-10 codes versus when CDI
is classified based on lab testing.  They looked at this question for patients with IBD (Crohn’s
and UC) and for matched controls without IBD.  They found that the ICD-10 codes were (to my
surprise) not bad at classifying CDI with a sensitivity of 70-80% and near perfect specificity.
The sensitivity was slightly worse among those with IBD than among the matched controls
without IBD, which also was surprising.  In general, this paper is professionally assembled and
it is a useful addition to those working in epidemiology related to CDI.  While not entirely novel,
it adds incrementally to their own prior work (reference 11) and that of others (e.g., ref 27).
My most important comment is related to their emphasis which often seems to wander away from
the question of interest (which is comparing CDI classified by ICD-10 codes vs CDI classified
by labs).  To be specific, take Table 1.  This table emphasizes the comparison of those with IBD
vs matched controls without IBD.  This is not the comparison of interest!  Rather, the columns
should be rearranged so that they are comparing risk factors when CDI is classified via ICD-10
vs when CDI is classified via labs.  E.g., 5-ASA use for CDI by ICD-10 vs 5-ASA use for CDI
by labs, etc.  They could do this first for IBD and then for non-IBD.  Elsewhere in the manuscript
similar changes of emphasis could be made and the manuscript would be improved.
Less important:
1. Discussion - Although the authors recognize the problem of CDI colonization in the
limitations section, they should further tone down their statement in the Discussion (end of
first page) about this, which diminishes this very important problem that plagues CDI research.
Although I agree that a positive C. diff is invariably treated in IBD patients, this doesn’t mean
that these are true CDI cases.  A large proportion of these patients are colonized and treating
C. diff makes no difference.  Ultimately, the true diagnosis of CDI is clinical and cannot be
ascertained retrospectively.
2. Methods - The final sentence before the “Study Measures” section implies that have linked
individual patients within the datasets—i.e., that each patient is a single row of data.  This is a
very important point and, assuming this is the case, it should be stated even more explicitly.  If
I somehow misunderstood and this is not the case, it’s a major problem.
3. The most recent data is from 2014 making the study data a minimum of 8 years old and a
maximum of 16 years old.  The fact that the data is relatively stale should be recognized as a
limitation.
Please review this paper.
user
Title: Effect of clinical vs. administrative data definitions on the epidemiology of C. difficile
among hospitalized individuals with IBD: A population-based cohort study
Version: 1 Date: 07 Dec 2021
Reviewer's report:
Shaffer-CDI in ICD codes vs lab tests
The authors have used linked datasets from Manitoba 2005-2014 to compare CDI rates among
hospitalized patients when CDI is classified based on discharge ICD-10 codes versus when CDI
is classified based on lab testing.  They looked at this question for patients with IBD (Crohn’s
and UC) and for matched controls without IBD.  They found that the ICD-10 codes were (to my
surprise) not bad at classifying CDI with a sensitivity of 70-80% and near perfect specificity.
The sensitivity was slightly worse among those with IBD than among the matched controls
without IBD, which also was surprising.  In general, this paper is professionally assembled and
it is a useful addition to those working in epidemiology related to CDI.  While not entirely novel,
it adds incrementally to their own prior work (reference 11) and that of others (e.g., ref 27).
My most important comment is related to their emphasis which often seems to wander away from
the question of interest (which is comparing CDI classified by ICD-10 codes vs CDI classified
by labs).  To be specific, take Table 1.  This table emphasizes the comparison of those with IBD
vs matched controls without IBD.  This is not the comparison of interest!  Rather, the columns
should be rearranged so that they are comparing risk factors when CDI is classified via ICD-10
vs when CDI is classified via labs.  E.g., 5-ASA use for CDI by ICD-10 vs 5-ASA use for CDI
by labs, etc.  They could do this first for IBD and then for non-IBD.  Elsewhere in the manuscript
similar changes of emphasis could be made and the manuscript would be improved.
Less important:
1. Discussion - Although the authors recognize the problem of CDI colonization in the
limitations section, they should further tone down their statement in the Discussion (end of
first page) about this, which diminishes this very important problem that plagues CDI research.
Although I agree that a positive C. diff is invariably treated in IBD patients, this doesn’t mean
that these are true CDI cases.  A large proportion of these patients are colonized and treating
C. diff makes no difference.  Ultimately, the true diagnosis of CDI is clinical and cannot be
ascertained retrospectively.
2. Methods - The final sentence before the “Study Measures” section implies that have linked
individual patients within the datasets—i.e., that each patient is a single row of data.  This is a
very important point and, assuming this is the case, it should be stated even more explicitly.  If
I somehow misunderstood and this is not the case, it’s a major problem.
3. The most recent data is from 2014 making the study data a minimum of 8 years old and a
maximum of 16 years old.  The fact that the data is relatively stale should be recognized as a
limitation.
assistant