Title: Epidemiology and Outcomes of Choledocholithiasis and Cholangitis in the United States:
Trends and Urban-Rural Variations
Version: 1 Date: 27 Apr 2023
Reviewer's report:
Li et al attempt to describe the urban vs. rural hospital experience for cholangitis and
choledocholithiasis.  While an interesting topic, I have several major concerns around
methodology and results interpretation that should be addressed prior to consideration for
publication.
Methods/Results:
Why not limit to quarter 4 2015-2019 to provide ICD10 based timely estimates?
Why only look in the primary diagnosis? What about those cholangitis in the secondary position
because sepsis or bacteremia are in the primary position or choledocholithiasis and pancreatitis
in the primary position?
“The Charlson enhanced comorbidity index was used to measure the overall burden of comorbid
conditions. Separate sensitivity analysis was additionally conducted utilizing the Elixhauser
comorbidity index.” How were these defined? Where are the sensitivity analysis results in the
manuscript? Elixhauser is a more accepted comorbidity index for large administrative datasets
compared to Charlson and would suggest authors use ECI.
Fig 2 - I don’t see the urban and rural breakdown, only 2 panels which are both labeled "all
hospitalizations"
Table 2 - What is each model adjusted for? There is an “*” after adjusted OR but no reference
text to discuss what covariates were included in the models. In addition, for the analysis for
complications or mortality, ie post-operative mortality, was only the population that underwent
surgery included? The details of analysis are significantly lacking and should be included in
the Methods section as well as foot notes in the tables. This is absolutely necessary before
the statement in the discussion can be validated (“There were, however, significant differences
between urban and rural regions in terms of use of procedural interventions and post-intervention
AEs. “)
Rates of procedures/surgery by location are only in the text and not in any tables and should
be added to a table.
Predictors or Inpatient mortality: This section should precede analysis of mortality (overall and
post-procedure) as this analysis presumably informed how those models were adjusted.
Where is the data to support this statement: “Lastly, in-hospital mortality had a significant
decrease per year over the study period for both patients with choledocholithiasis (aOR 0.91,
95% CI 0.88 to 0.93) and cholangitis (aOR 0.93, 95% CI 0.89 to 0.97).” I did not see in Table 3.
Table 3 - again no clarification that the OR is comparing urban vs. rural (I assumed this is the
case but it should be stated). What was included in each model.?The row “Rural” is not needed.
Why did the authors only analyze predictors of mortality. What are predictors of post-
intervention adverse events and complications? This should have been done to inform the models
created for Table 2.
Additional analyses that would strengthen the impact:
As above, disappointing that authors did not include more recent years of the NIS. These trends
are 10 years old and not really relevant any longer.
How about complications for those who did not receive any interventions - given rural location
is associated with lower intervention rates, are the complication rates higher?
Why are unweighted counts provided - why not national estimates which is what NIS really
should be used for and would substantiate the paragraph in the discussion about national burden
of these conditions and reasons for trends seen.
Authors postulate that one reason for higher rates of endoscopic interventions in urban centers
are due to lack of access to ERCP at rural  centers leading to transfer. NIS is able to flag
discharges that were from a transfer and this would be worth adding to the analysis.
Discussion is over-inflating the rate surgical interventions at rural hospitals, in the end the
aOR was not different than 1 when comparing to urban (as stated in results “The likelihood
of performing surgical interventions did not differ between rural and urban centers for both
choledocholithiasis and cholangitis.”)  Therefore, there are no more surgical interventions at
rural hospitals compared to urban hospitals.
Other limitations:
“Our results were not separately adjusted based on other covariables such as hospital size and
teaching status, although rurality has clear associations with both these factors” - this is a major
limitation - it would be relatively straightforward to adjust for hospital volumes for each of
these conditions or each type of intervention in the relevant models and. highly relevant to the
interpretation of the results.
Title: Epidemiology and Outcomes of Choledocholithiasis and Cholangitis in the United States:
Trends and Urban-Rural Variations
Version: 1 Date: 27 Apr 2023
Reviewer's report:
Li et al attempt to describe the urban vs. rural hospital experience for cholangitis and
choledocholithiasis.  While an interesting topic, I have several major concerns around
methodology and results interpretation that should be addressed prior to consideration for
publication.
Methods/Results:
Why not limit to quarter 4 2015-2019 to provide ICD10 based timely estimates?
Why only look in the primary diagnosis? What about those cholangitis in the secondary position
because sepsis or bacteremia are in the primary position or choledocholithiasis and pancreatitis
in the primary position?
“The Charlson enhanced comorbidity index was used to measure the overall burden of comorbid
conditions. Separate sensitivity analysis was additionally conducted utilizing the Elixhauser
comorbidity index.” How were these defined? Where are the sensitivity analysis results in the
manuscript? Elixhauser is a more accepted comorbidity index for large administrative datasets
compared to Charlson and would suggest authors use ECI.
Fig 2 - I don’t see the urban and rural breakdown, only 2 panels which are both labeled "all
hospitalizations"
Table 2 - What is each model adjusted for? There is an “*” after adjusted OR but no reference
text to discuss what covariates were included in the models. In addition, for the analysis for
complications or mortality, ie post-operative mortality, was only the population that underwent
surgery included? The details of analysis are significantly lacking and should be included in
the Methods section as well as foot notes in the tables. This is absolutely necessary before
the statement in the discussion can be validated (“There were, however, significant differences
between urban and rural regions in terms of use of procedural interventions and post-intervention
AEs. “)
Rates of procedures/surgery by location are only in the text and not in any tables and should
be added to a table.
Predictors or Inpatient mortality: This section should precede analysis of mortality (overall and
post-procedure) as this analysis presumably informed how those models were adjusted.
Where is the data to support this statement: “Lastly, in-hospital mortality had a significant
decrease per year over the study period for both patients with choledocholithiasis (aOR 0.91,
95% CI 0.88 to 0.93) and cholangitis (aOR 0.93, 95% CI 0.89 to 0.97).” I did not see in Table 3.
Table 3 - again no clarification that the OR is comparing urban vs. rural (I assumed this is the
case but it should be stated). What was included in each model.?The row “Rural” is not needed.
Why did the authors only analyze predictors of mortality. What are predictors of post-
intervention adverse events and complications? This should have been done to inform the models
created for Table 2.
Additional analyses that would strengthen the impact:
As above, disappointing that authors did not include more recent years of the NIS. These trends
are 10 years old and not really relevant any longer.
How about complications for those who did not receive any interventions - given rural location
is associated with lower intervention rates, are the complication rates higher?
Why are unweighted counts provided - why not national estimates which is what NIS really
should be used for and would substantiate the paragraph in the discussion about national burden
of these conditions and reasons for trends seen.
Authors postulate that one reason for higher rates of endoscopic interventions in urban centers
are due to lack of access to ERCP at rural  centers leading to transfer. NIS is able to flag
discharges that were from a transfer and this would be worth adding to the analysis.
Discussion is over-inflating the rate surgical interventions at rural hospitals, in the end the
aOR was not different than 1 when comparing to urban (as stated in results “The likelihood
of performing surgical interventions did not differ between rural and urban centers for both
choledocholithiasis and cholangitis.”)  Therefore, there are no more surgical interventions at
rural hospitals compared to urban hospitals.
Other limitations:
“Our results were not separately adjusted based on other covariables such as hospital size and
teaching status, although rurality has clear associations with both these factors” - this is a major
limitation - it would be relatively straightforward to adjust for hospital volumes for each of
these conditions or each type of intervention in the relevant models and. highly relevant to the
interpretation of the results.
Please review this paper.
user
Title: Epidemiology and Outcomes of Choledocholithiasis and Cholangitis in the United States:
Trends and Urban-Rural Variations
Version: 1 Date: 27 Apr 2023
Reviewer's report:
Li et al attempt to describe the urban vs. rural hospital experience for cholangitis and
choledocholithiasis.  While an interesting topic, I have several major concerns around
methodology and results interpretation that should be addressed prior to consideration for
publication.
Methods/Results:
Why not limit to quarter 4 2015-2019 to provide ICD10 based timely estimates?
Why only look in the primary diagnosis? What about those cholangitis in the secondary position
because sepsis or bacteremia are in the primary position or choledocholithiasis and pancreatitis
in the primary position?
“The Charlson enhanced comorbidity index was used to measure the overall burden of comorbid
conditions. Separate sensitivity analysis was additionally conducted utilizing the Elixhauser
comorbidity index.” How were these defined? Where are the sensitivity analysis results in the
manuscript? Elixhauser is a more accepted comorbidity index for large administrative datasets
compared to Charlson and would suggest authors use ECI.
Fig 2 - I don’t see the urban and rural breakdown, only 2 panels which are both labeled "all
hospitalizations"
Table 2 - What is each model adjusted for? There is an “*” after adjusted OR but no reference
text to discuss what covariates were included in the models. In addition, for the analysis for
complications or mortality, ie post-operative mortality, was only the population that underwent
surgery included? The details of analysis are significantly lacking and should be included in
the Methods section as well as foot notes in the tables. This is absolutely necessary before
the statement in the discussion can be validated (“There were, however, significant differences
between urban and rural regions in terms of use of procedural interventions and post-intervention
AEs. “)
Rates of procedures/surgery by location are only in the text and not in any tables and should
be added to a table.
Predictors or Inpatient mortality: This section should precede analysis of mortality (overall and
post-procedure) as this analysis presumably informed how those models were adjusted.
Where is the data to support this statement: “Lastly, in-hospital mortality had a significant
decrease per year over the study period for both patients with choledocholithiasis (aOR 0.91,
95% CI 0.88 to 0.93) and cholangitis (aOR 0.93, 95% CI 0.89 to 0.97).” I did not see in Table 3.
Table 3 - again no clarification that the OR is comparing urban vs. rural (I assumed this is the
case but it should be stated). What was included in each model.?The row “Rural” is not needed.
Why did the authors only analyze predictors of mortality. What are predictors of post-
intervention adverse events and complications? This should have been done to inform the models
created for Table 2.
Additional analyses that would strengthen the impact:
As above, disappointing that authors did not include more recent years of the NIS. These trends
are 10 years old and not really relevant any longer.
How about complications for those who did not receive any interventions - given rural location
is associated with lower intervention rates, are the complication rates higher?
Why are unweighted counts provided - why not national estimates which is what NIS really
should be used for and would substantiate the paragraph in the discussion about national burden
of these conditions and reasons for trends seen.
Authors postulate that one reason for higher rates of endoscopic interventions in urban centers
are due to lack of access to ERCP at rural  centers leading to transfer. NIS is able to flag
discharges that were from a transfer and this would be worth adding to the analysis.
Discussion is over-inflating the rate surgical interventions at rural hospitals, in the end the
aOR was not different than 1 when comparing to urban (as stated in results “The likelihood
of performing surgical interventions did not differ between rural and urban centers for both
choledocholithiasis and cholangitis.”)  Therefore, there are no more surgical interventions at
rural hospitals compared to urban hospitals.
Other limitations:
“Our results were not separately adjusted based on other covariables such as hospital size and
teaching status, although rurality has clear associations with both these factors” - this is a major
limitation - it would be relatively straightforward to adjust for hospital volumes for each of
these conditions or each type of intervention in the relevant models and. highly relevant to the
interpretation of the results.
assistant