Title: Impact of Diagnostic Delay to the Clinical Presentation and Associated Factors in
Pediatric Inflammatory Bowel Disease: A Retrospective Study
Version: 2 Date: 01 Jun 2021
Reviewer's report:
E Sulkanen and colleagues present factors associated with time to referral prior to diagnosis of
inflammatory bowel disease.  They identify abdominal pain as a factor associated with delayed
diagnosis, hematochezia as a symptom associated with a shorter delay, and ulcerative colitis
with less delay compared to Crohn's disease.   While these could be significant findings, I have
several concerns I would recommend that the author's address
Major Concerns:
1. As they mention in their discussion, time to referral may change over time.  Therefore, the
authors should indicate in their methods over what time frame these patients presented for
referral.
2. We know fecal calprotectin's sensitivity/specificity/positive predictive value is dependent
upon what quantitate cutoff is used.  The author's should provide reference for their value of
<100 microgram/g (which seems lower than what most other literature would suggest is used).
3. As their median delay was 5 months, would recommend additional groups for delay rather
than >6 or <6 by separating less than 6 into less than 3 and 3-6 months
4. Since the authors found the majority of delay is prior to referral, would recommend the author's
use a non-IBD diagnosis as a control group.  In addition, do the authors have data on time of
symptoms onset to presentation to their primary care provider?
4. Table 1 and Table 2 are missing any statistical analysis.  While their abstract provides a p-
value for CD vs UC, this is not apparent in their text nor table/figures
5. Table 3 is missing diagnosis as a variable.  Since symptoms may vary among diagnosis, would
recommend multiple regression to determine if symptoms or diagnosis is driving the difference.
6. Would recommend looking at initial disease activity score (PUCAI and either PCDAI or the
short PCDAI) to determine if this varied based upon time to diagnosis.  Related, authors could
determine if disease location was a factor associated with diagnostic delay.
7. The manuscript's title refers to the impact of diagnostic delay.  To answer this question,
the author's should provide some follow-up data to determine the impact on disease control
particularly since table 4 fails to identify any complication/co-morbidity present at the time of
diagnosis.
Minor concerns:
1. The first sentence in the abstract is a bit awkward and more declarative than would be
recommended (this should be the point the manuscript is trying to conclude?)
2. The  first sentence within the introduction is very broad knowledge and is well known so does
not need to be included.
3. Figure 1 does not seem to add much to the manuscript and likely could be removed.  If there
was difference in time to diagnosis associated with disease location, then this could become
more relevant.
Title: Impact of Diagnostic Delay to the Clinical Presentation and Associated Factors in
Pediatric Inflammatory Bowel Disease: A Retrospective Study
Version: 2 Date: 01 Jun 2021
Reviewer's report:
E Sulkanen and colleagues present factors associated with time to referral prior to diagnosis of
inflammatory bowel disease.  They identify abdominal pain as a factor associated with delayed
diagnosis, hematochezia as a symptom associated with a shorter delay, and ulcerative colitis
with less delay compared to Crohn's disease.   While these could be significant findings, I have
several concerns I would recommend that the author's address
Major Concerns:
1. As they mention in their discussion, time to referral may change over time.  Therefore, the
authors should indicate in their methods over what time frame these patients presented for
referral.
2. We know fecal calprotectin's sensitivity/specificity/positive predictive value is dependent
upon what quantitate cutoff is used.  The author's should provide reference for their value of
<100 microgram/g (which seems lower than what most other literature would suggest is used).
3. As their median delay was 5 months, would recommend additional groups for delay rather
than >6 or <6 by separating less than 6 into less than 3 and 3-6 months
4. Since the authors found the majority of delay is prior to referral, would recommend the author's
use a non-IBD diagnosis as a control group.  In addition, do the authors have data on time of
symptoms onset to presentation to their primary care provider?
4. Table 1 and Table 2 are missing any statistical analysis.  While their abstract provides a p-
value for CD vs UC, this is not apparent in their text nor table/figures
5. Table 3 is missing diagnosis as a variable.  Since symptoms may vary among diagnosis, would
recommend multiple regression to determine if symptoms or diagnosis is driving the difference.
6. Would recommend looking at initial disease activity score (PUCAI and either PCDAI or the
short PCDAI) to determine if this varied based upon time to diagnosis.  Related, authors could
determine if disease location was a factor associated with diagnostic delay.
7. The manuscript's title refers to the impact of diagnostic delay.  To answer this question,
the author's should provide some follow-up data to determine the impact on disease control
particularly since table 4 fails to identify any complication/co-morbidity present at the time of
diagnosis.
Minor concerns:
1. The first sentence in the abstract is a bit awkward and more declarative than would be
recommended (this should be the point the manuscript is trying to conclude?)
2. The  first sentence within the introduction is very broad knowledge and is well known so does
not need to be included.
3. Figure 1 does not seem to add much to the manuscript and likely could be removed.  If there
was difference in time to diagnosis associated with disease location, then this could become
more relevant.
Please review this paper.
user
Title: Impact of Diagnostic Delay to the Clinical Presentation and Associated Factors in
Pediatric Inflammatory Bowel Disease: A Retrospective Study
Version: 2 Date: 01 Jun 2021
Reviewer's report:
E Sulkanen and colleagues present factors associated with time to referral prior to diagnosis of
inflammatory bowel disease.  They identify abdominal pain as a factor associated with delayed
diagnosis, hematochezia as a symptom associated with a shorter delay, and ulcerative colitis
with less delay compared to Crohn's disease.   While these could be significant findings, I have
several concerns I would recommend that the author's address
Major Concerns:
1. As they mention in their discussion, time to referral may change over time.  Therefore, the
authors should indicate in their methods over what time frame these patients presented for
referral.
2. We know fecal calprotectin's sensitivity/specificity/positive predictive value is dependent
upon what quantitate cutoff is used.  The author's should provide reference for their value of
<100 microgram/g (which seems lower than what most other literature would suggest is used).
3. As their median delay was 5 months, would recommend additional groups for delay rather
than >6 or <6 by separating less than 6 into less than 3 and 3-6 months
4. Since the authors found the majority of delay is prior to referral, would recommend the author's
use a non-IBD diagnosis as a control group.  In addition, do the authors have data on time of
symptoms onset to presentation to their primary care provider?
4. Table 1 and Table 2 are missing any statistical analysis.  While their abstract provides a p-
value for CD vs UC, this is not apparent in their text nor table/figures
5. Table 3 is missing diagnosis as a variable.  Since symptoms may vary among diagnosis, would
recommend multiple regression to determine if symptoms or diagnosis is driving the difference.
6. Would recommend looking at initial disease activity score (PUCAI and either PCDAI or the
short PCDAI) to determine if this varied based upon time to diagnosis.  Related, authors could
determine if disease location was a factor associated with diagnostic delay.
7. The manuscript's title refers to the impact of diagnostic delay.  To answer this question,
the author's should provide some follow-up data to determine the impact on disease control
particularly since table 4 fails to identify any complication/co-morbidity present at the time of
diagnosis.
Minor concerns:
1. The first sentence in the abstract is a bit awkward and more declarative than would be
recommended (this should be the point the manuscript is trying to conclude?)
2. The  first sentence within the introduction is very broad knowledge and is well known so does
not need to be included.
3. Figure 1 does not seem to add much to the manuscript and likely could be removed.  If there
was difference in time to diagnosis associated with disease location, then this could become
more relevant.
assistant