Title: Frequency, outcomes, and need for intervention in stricturing gastrointestinal
tuberculosis: A systematic review and meta-analysis
Version: 3 Date: 02 Dec 2022
Reviewer's report:
The authors have made a valiant attempt to extract data from the literature regarding the
frequency and outcomes of gastrointestinal TB.
From a clinical point of view, the analysis might be able to answer a patient who wonders
whether drug treatment for TB is likely to be sufficient to manage their symptoms.
PICO analysis.
In the analysis, the population is variously defined as those with gastro-intestinal TB (limited to
peritoneal or bowel involvement and excluding liver TB or abdominal lymph node TB), those
with clinical symptoms or radiological evidence of narrowing of the bowel, and those who
had an intervention for stricturing.  Most included studies were retrospective (70%: 23/33), 9
(27%) were prospective and one was unspecified.  The denominator is therefore unclear and,
in consequence, the frequency of “stricturing” is likely an over-estimate.  The authors note the
selection bias was inevitable in the case series that contributed to the meta-analysis.
The interventions included a) endoscopic dilatation or b) surgery and c) drug treatment for TB.
The decision for the first two procedures was at the discretion of the medical personnel and
no definition or standard is suggested.  The regimens of TB treatment were mostly not those
accepted as standard by the international community.  Six (18%) studies could have included
the standard 6-month course of treatment.
There is a retrospective comparator of those who did or did not have a surgical/endoscopic
intervention.  The reader is left to assume that the control group were those who received only
medical treatment for TB, but some may not have received any specific treatment.
The outcomes are also varied. They include endoscopic or surgery before and during treatment,
resolution of symptoms and resolution of bowel narrowing (presumably radiological or
endoscopic).  One included paper appears to imply that clinical improvement was made “without
needing therapy” (Alvares JF et al, 2005; Supplemental Table 3)!  The need for surgical
intervention in 12 studies showed significant heterogeneity but was more consistent for rates
of endoscopic dilatation.
Misuse of a Baujat plot.
• The y-axis of such a plot compares the squared-difference difference between those with and
without the intervention plotted against the x-axis where a chi-squared estimate of the study
squared difference from the mean trial effect is adjusted by the variance of the study.  The
assumption is that the intervention or treatment is standard.
• A dotted line indicating the x-axis value 3.84 should be used to indicate those studies which
contributed significantly to heterogeneity
• Table 1 shows that the treatment regimens were inconsistent and the majority not of
internationally accepted regimens.  There was no clear definition of when surgical or endoscopic
intervention was required – this should be evidence of intermittent (defined by number of
episodes and their duration) or complete bowel obstruction.
• The purpose of a Baujat plot is to identify outliers and then look back at why these studies
contributed most to the heterogeneity.  Three of the larger studies are noted to have contributed
most to heterogeneity of prevalence of stricturing.  However, there is no explanation as to why
they were important, nor how removal of these studies affected the heterogeneity score.  With
regard to treatment response, again heterogeneity is high but no Baujat plot was used to identify
individual outlier studies – the authors note that these five studies had different definitions for
stricture response and different modalities for the measurement.
Quality assessment (Newcastle-Ottawa) assessment.
• The authors should carefully distinguish between the cross-sectional cohort elements of the
study.
• Supplementary Table 4 starring of cohort studies shows that only 8 did not have the outcome
of interest present at the start of the study and were therefore eligible for a cohort study.
• All cohorts were not comparable on the basis of the design or analysis controlled for
confounders, deeming all the selected studies as POOR quality.
• In terms of cross-sectional elements, the coding for this justifies the use of the “total” column,
12 of the chosen studies were deemed “unsatisfactory” with a score of 4 or less.  Fifteen were
satisfactory (5-6 points) and six were “good”.  The use of the cohort study terminology in the
cross-sectional scoring is confusing.
• The authors should justify the inclusion of “poor” or “unsatisfactory” studies.
The conclusions (abstract and text) should therefore state that heterogeneity prevented an
estimate of the prevalence of stricture formation and response to antituberculosis treatment, but
that endoscopic intervention might be required in 14% (95% CI 9-21%) in those presenting with
clinical evidence of intrinsic intestinal obstruction.
The authors could suggest how to limit heterogeneity in future studies.
Title: Frequency, outcomes, and need for intervention in stricturing gastrointestinal
tuberculosis: A systematic review and meta-analysis
Version: 3 Date: 02 Dec 2022
Reviewer's report:
The authors have made a valiant attempt to extract data from the literature regarding the
frequency and outcomes of gastrointestinal TB.
From a clinical point of view, the analysis might be able to answer a patient who wonders
whether drug treatment for TB is likely to be sufficient to manage their symptoms.
PICO analysis.
In the analysis, the population is variously defined as those with gastro-intestinal TB (limited to
peritoneal or bowel involvement and excluding liver TB or abdominal lymph node TB), those
with clinical symptoms or radiological evidence of narrowing of the bowel, and those who
had an intervention for stricturing.  Most included studies were retrospective (70%: 23/33), 9
(27%) were prospective and one was unspecified.  The denominator is therefore unclear and,
in consequence, the frequency of “stricturing” is likely an over-estimate.  The authors note the
selection bias was inevitable in the case series that contributed to the meta-analysis.
The interventions included a) endoscopic dilatation or b) surgery and c) drug treatment for TB.
The decision for the first two procedures was at the discretion of the medical personnel and
no definition or standard is suggested.  The regimens of TB treatment were mostly not those
accepted as standard by the international community.  Six (18%) studies could have included
the standard 6-month course of treatment.
There is a retrospective comparator of those who did or did not have a surgical/endoscopic
intervention.  The reader is left to assume that the control group were those who received only
medical treatment for TB, but some may not have received any specific treatment.
The outcomes are also varied. They include endoscopic or surgery before and during treatment,
resolution of symptoms and resolution of bowel narrowing (presumably radiological or
endoscopic).  One included paper appears to imply that clinical improvement was made “without
needing therapy” (Alvares JF et al, 2005; Supplemental Table 3)!  The need for surgical
intervention in 12 studies showed significant heterogeneity but was more consistent for rates
of endoscopic dilatation.
Misuse of a Baujat plot.
• The y-axis of such a plot compares the squared-difference difference between those with and
without the intervention plotted against the x-axis where a chi-squared estimate of the study
squared difference from the mean trial effect is adjusted by the variance of the study.  The
assumption is that the intervention or treatment is standard.
• A dotted line indicating the x-axis value 3.84 should be used to indicate those studies which
contributed significantly to heterogeneity
• Table 1 shows that the treatment regimens were inconsistent and the majority not of
internationally accepted regimens.  There was no clear definition of when surgical or endoscopic
intervention was required – this should be evidence of intermittent (defined by number of
episodes and their duration) or complete bowel obstruction.
• The purpose of a Baujat plot is to identify outliers and then look back at why these studies
contributed most to the heterogeneity.  Three of the larger studies are noted to have contributed
most to heterogeneity of prevalence of stricturing.  However, there is no explanation as to why
they were important, nor how removal of these studies affected the heterogeneity score.  With
regard to treatment response, again heterogeneity is high but no Baujat plot was used to identify
individual outlier studies – the authors note that these five studies had different definitions for
stricture response and different modalities for the measurement.
Quality assessment (Newcastle-Ottawa) assessment.
• The authors should carefully distinguish between the cross-sectional cohort elements of the
study.
• Supplementary Table 4 starring of cohort studies shows that only 8 did not have the outcome
of interest present at the start of the study and were therefore eligible for a cohort study.
• All cohorts were not comparable on the basis of the design or analysis controlled for
confounders, deeming all the selected studies as POOR quality.
• In terms of cross-sectional elements, the coding for this justifies the use of the “total” column,
12 of the chosen studies were deemed “unsatisfactory” with a score of 4 or less.  Fifteen were
satisfactory (5-6 points) and six were “good”.  The use of the cohort study terminology in the
cross-sectional scoring is confusing.
• The authors should justify the inclusion of “poor” or “unsatisfactory” studies.
The conclusions (abstract and text) should therefore state that heterogeneity prevented an
estimate of the prevalence of stricture formation and response to antituberculosis treatment, but
that endoscopic intervention might be required in 14% (95% CI 9-21%) in those presenting with
clinical evidence of intrinsic intestinal obstruction.
The authors could suggest how to limit heterogeneity in future studies.
Please review this paper.
user
Title: Frequency, outcomes, and need for intervention in stricturing gastrointestinal
tuberculosis: A systematic review and meta-analysis
Version: 3 Date: 02 Dec 2022
Reviewer's report:
The authors have made a valiant attempt to extract data from the literature regarding the
frequency and outcomes of gastrointestinal TB.
From a clinical point of view, the analysis might be able to answer a patient who wonders
whether drug treatment for TB is likely to be sufficient to manage their symptoms.
PICO analysis.
In the analysis, the population is variously defined as those with gastro-intestinal TB (limited to
peritoneal or bowel involvement and excluding liver TB or abdominal lymph node TB), those
with clinical symptoms or radiological evidence of narrowing of the bowel, and those who
had an intervention for stricturing.  Most included studies were retrospective (70%: 23/33), 9
(27%) were prospective and one was unspecified.  The denominator is therefore unclear and,
in consequence, the frequency of “stricturing” is likely an over-estimate.  The authors note the
selection bias was inevitable in the case series that contributed to the meta-analysis.
The interventions included a) endoscopic dilatation or b) surgery and c) drug treatment for TB.
The decision for the first two procedures was at the discretion of the medical personnel and
no definition or standard is suggested.  The regimens of TB treatment were mostly not those
accepted as standard by the international community.  Six (18%) studies could have included
the standard 6-month course of treatment.
There is a retrospective comparator of those who did or did not have a surgical/endoscopic
intervention.  The reader is left to assume that the control group were those who received only
medical treatment for TB, but some may not have received any specific treatment.
The outcomes are also varied. They include endoscopic or surgery before and during treatment,
resolution of symptoms and resolution of bowel narrowing (presumably radiological or
endoscopic).  One included paper appears to imply that clinical improvement was made “without
needing therapy” (Alvares JF et al, 2005; Supplemental Table 3)!  The need for surgical
intervention in 12 studies showed significant heterogeneity but was more consistent for rates
of endoscopic dilatation.
Misuse of a Baujat plot.
• The y-axis of such a plot compares the squared-difference difference between those with and
without the intervention plotted against the x-axis where a chi-squared estimate of the study
squared difference from the mean trial effect is adjusted by the variance of the study.  The
assumption is that the intervention or treatment is standard.
• A dotted line indicating the x-axis value 3.84 should be used to indicate those studies which
contributed significantly to heterogeneity
• Table 1 shows that the treatment regimens were inconsistent and the majority not of
internationally accepted regimens.  There was no clear definition of when surgical or endoscopic
intervention was required – this should be evidence of intermittent (defined by number of
episodes and their duration) or complete bowel obstruction.
• The purpose of a Baujat plot is to identify outliers and then look back at why these studies
contributed most to the heterogeneity.  Three of the larger studies are noted to have contributed
most to heterogeneity of prevalence of stricturing.  However, there is no explanation as to why
they were important, nor how removal of these studies affected the heterogeneity score.  With
regard to treatment response, again heterogeneity is high but no Baujat plot was used to identify
individual outlier studies – the authors note that these five studies had different definitions for
stricture response and different modalities for the measurement.
Quality assessment (Newcastle-Ottawa) assessment.
• The authors should carefully distinguish between the cross-sectional cohort elements of the
study.
• Supplementary Table 4 starring of cohort studies shows that only 8 did not have the outcome
of interest present at the start of the study and were therefore eligible for a cohort study.
• All cohorts were not comparable on the basis of the design or analysis controlled for
confounders, deeming all the selected studies as POOR quality.
• In terms of cross-sectional elements, the coding for this justifies the use of the “total” column,
12 of the chosen studies were deemed “unsatisfactory” with a score of 4 or less.  Fifteen were
satisfactory (5-6 points) and six were “good”.  The use of the cohort study terminology in the
cross-sectional scoring is confusing.
• The authors should justify the inclusion of “poor” or “unsatisfactory” studies.
The conclusions (abstract and text) should therefore state that heterogeneity prevented an
estimate of the prevalence of stricture formation and response to antituberculosis treatment, but
that endoscopic intervention might be required in 14% (95% CI 9-21%) in those presenting with
clinical evidence of intrinsic intestinal obstruction.
The authors could suggest how to limit heterogeneity in future studies.
assistant