Reviewer's report
Title:High mortality of pneumonia in cirrhotic patients with ascites
Version: 1Date:17 October 2012
Reviewer: Tony Bruns
Reviewer's report:
The retrospective cohort study by Hung et al. aimed at analyzing the impact of
bacterial infections on mortality in patients with cirrhosis. For this purpose, they
studied the Taiwan
National Health Insurance research database and identified all patient discharges
in Taiwan. They found the highest mortality among 100 patients with
decompensated cirrhosis and pneumonia.
Bacteraemia, SBP and pneumonia have recently identified as major contributors
to death in patients with cirrhosis in a meta-analysis by Arvani et al.
(Gastroenterology. 2010;139:1246-1256). Although the large patient cohort is
impressive, the study design is associated with some methodological problems
that need to be addressed.
Major Compulsory Revisions
1. Mortality:
a) It is not clear how mortality was assessed: Does the database only assess
death during hospitalization or are all deaths after discharge also documented to
ensure that 30-day and 90-day mortality are adequately assessed? How many
patients were lost-to-follow-up before the end of the 90-day period? Was liver
transplantation during follow-up assessed? If yes, were patients undergoing liver
transplantation censored on the day of transplantation?
b) The authors do not provide a mechanistic explanation for the high mortality of
pneumonia: Please provide Kaplan-Meier curves for the different infections to
estimate patients at risk and to assess whether major mortality occurred within
days after infection (suggesting septic shock) or later (suggesting
acute-on-cirrhosis liver failure triggered by infection). Are the causes of death
available to the authors? How many patients were patients on ICU with
ventilator-associated pneumonia?
2. Confounders and definitions:
a) Adjustment for age, gender, and comorbidity disorders in multivariate Cox
regression analysis was performed by the authors. The most important
prognostic parameter ist he MELD score. Did patients with pneumonia have a
higher MELD score than patients with other bacterial infections? Please adjust
for the MELD score in the multivariate model.
b) The authors state that “The patients were classified into infectious and
non-infection group according the baseline presence of infectious diseases or
not“. What does „baseline“ mean in this context: time of hospitalization or time of
diagnosis of infection? Studies suggest a higher mortality in patients with
hospital-acquired infections due to multi-resistant bacteria or secondary
infections. Please provide whether the mode of acquisition (hospital-acquired,
community-acquired, healthcare-associated) was a prognostic factor for different
infections.
c) SWSF is poorly defined using a retrospective ICD-based study design. How
are patients with spontaneous or secondary catheter-associated bacteraemia or
abdominal infection, such as cholangitis, treated? Although the authors state that
“such as necrotizing fasciitis, meningitis, infective endocarditis “ are less relevant
– bacteremia and cholangitis are clearly not.
c) SIRS itself has been identified as a risk factor for mortality in cirrhosis
(Cazzaniga et al. J Hepatol. 2009 Sep;51(3):475-82). How many patients with
infections had SIRS, i.e. sepsis, coded in the database?
3. Interpretation: The authors state that “there were limited studies for identifying
the mortality of bacterial infections other than SBP in cirrhotic patients” and cite
Kim et al. They state further “While this is true for UTI and skin infections, it is
certainly not true for bacteraemia and pneumonia as shown in the meta-analysis
by Arvaniti et al. They state further “The high mortality of pneumonia in cirrhotic
patients were identified in one recent study. In that study, the overall mortality
rates were 14.4% in cirrhotic patients with pneumonia.” Arvaniti et al. extracted
pneumonia-associated mortality from seven studies (46 deaths/123 patients;
37.4%) showing a much higher mortality than that stated by the authors.
Minor Essential Revisions
1. There are some spelling mistakes and grammatical errors throughout the
manuscript, e.g. „Patient who was admitted“ „The mortalities of both groups were
showed”, “with the large case numbers enrolled from short duration“, „Clinical
doctor should notice the high mortality in such patients“
2. The authors state that „Alcoholism was negatively correlated with 30-day and
90-day mortalities of cirrhotic patients with ascites.“ Does this mean that patients
with alcoholism had lower mortality?
3. Was the study really powered to detect “differences in risk of each kind of
major infectious disease”? The authors compared the mortality risk of certain
infections but not differences in mortality between different infections. Please
clarify.
Discretionary Revisions
1. Do the authors have data whether the use of classical pneumonia severity
scores (CRB65 etc.) are valid in patients with cirrhosis. It would be beneficial for
the manuscript if the authors could assess patient charts of the 100 patients with
pneumonia.
Level of interest: An article whose findings are important to those with closely
related research interests
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 declare that I have no competing interests apart from similar research interests
on the impact of infections on mortality in cirrhosis.
Reviewer's report
Title:High mortality of pneumonia in cirrhotic patients with ascites
Version: 1Date:17 October 2012
Reviewer: Tony Bruns
Reviewer's report:
The retrospective cohort study by Hung et al. aimed at analyzing the impact of
bacterial infections on mortality in patients with cirrhosis. For this purpose, they
studied the Taiwan
National Health Insurance research database and identified all patient discharges
in Taiwan. They found the highest mortality among 100 patients with
decompensated cirrhosis and pneumonia.
Bacteraemia, SBP and pneumonia have recently identified as major contributors
to death in patients with cirrhosis in a meta-analysis by Arvani et al.
(Gastroenterology. 2010;139:1246-1256). Although the large patient cohort is
impressive, the study design is associated with some methodological problems
that need to be addressed.
Major Compulsory Revisions
1. Mortality:
a) It is not clear how mortality was assessed: Does the database only assess
death during hospitalization or are all deaths after discharge also documented to
ensure that 30-day and 90-day mortality are adequately assessed? How many
patients were lost-to-follow-up before the end of the 90-day period? Was liver
transplantation during follow-up assessed? If yes, were patients undergoing liver
transplantation censored on the day of transplantation?
b) The authors do not provide a mechanistic explanation for the high mortality of
pneumonia: Please provide Kaplan-Meier curves for the different infections to
estimate patients at risk and to assess whether major mortality occurred within
days after infection (suggesting septic shock) or later (suggesting
acute-on-cirrhosis liver failure triggered by infection). Are the causes of death
available to the authors? How many patients were patients on ICU with
ventilator-associated pneumonia?
2. Confounders and definitions:
a) Adjustment for age, gender, and comorbidity disorders in multivariate Cox
regression analysis was performed by the authors. The most important
prognostic parameter ist he MELD score. Did patients with pneumonia have a
higher MELD score than patients with other bacterial infections? Please adjust
for the MELD score in the multivariate model.
b) The authors state that “The patients were classified into infectious and
non-infection group according the baseline presence of infectious diseases or
not“. What does „baseline“ mean in this context: time of hospitalization or time of
diagnosis of infection? Studies suggest a higher mortality in patients with
hospital-acquired infections due to multi-resistant bacteria or secondary
infections. Please provide whether the mode of acquisition (hospital-acquired,
community-acquired, healthcare-associated) was a prognostic factor for different
infections.
c) SWSF is poorly defined using a retrospective ICD-based study design. How
are patients with spontaneous or secondary catheter-associated bacteraemia or
abdominal infection, such as cholangitis, treated? Although the authors state that
“such as necrotizing fasciitis, meningitis, infective endocarditis “ are less relevant
– bacteremia and cholangitis are clearly not.
c) SIRS itself has been identified as a risk factor for mortality in cirrhosis
(Cazzaniga et al. J Hepatol. 2009 Sep;51(3):475-82). How many patients with
infections had SIRS, i.e. sepsis, coded in the database?
3. Interpretation: The authors state that “there were limited studies for identifying
the mortality of bacterial infections other than SBP in cirrhotic patients” and cite
Kim et al. They state further “While this is true for UTI and skin infections, it is
certainly not true for bacteraemia and pneumonia as shown in the meta-analysis
by Arvaniti et al. They state further “The high mortality of pneumonia in cirrhotic
patients were identified in one recent study. In that study, the overall mortality
rates were 14.4% in cirrhotic patients with pneumonia.” Arvaniti et al. extracted
pneumonia-associated mortality from seven studies (46 deaths/123 patients;
37.4%) showing a much higher mortality than that stated by the authors.
Minor Essential Revisions
1. There are some spelling mistakes and grammatical errors throughout the
manuscript, e.g. „Patient who was admitted“ „The mortalities of both groups were
showed”, “with the large case numbers enrolled from short duration“, „Clinical
doctor should notice the high mortality in such patients“
2. The authors state that „Alcoholism was negatively correlated with 30-day and
90-day mortalities of cirrhotic patients with ascites.“ Does this mean that patients
with alcoholism had lower mortality?
3. Was the study really powered to detect “differences in risk of each kind of
major infectious disease”? The authors compared the mortality risk of certain
infections but not differences in mortality between different infections. Please
clarify.
Discretionary Revisions
1. Do the authors have data whether the use of classical pneumonia severity
scores (CRB65 etc.) are valid in patients with cirrhosis. It would be beneficial for
the manuscript if the authors could assess patient charts of the 100 patients with
pneumonia.
Level of interest: An article whose findings are important to those with closely
related research interests
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 declare that I have no competing interests apart from similar research interests
on the impact of infections on mortality in cirrhosis.
Please review this paper.
user
Reviewer's report
Title:High mortality of pneumonia in cirrhotic patients with ascites
Version: 1Date:17 October 2012
Reviewer: Tony Bruns
Reviewer's report:
The retrospective cohort study by Hung et al. aimed at analyzing the impact of
bacterial infections on mortality in patients with cirrhosis. For this purpose, they
studied the Taiwan
National Health Insurance research database and identified all patient discharges
in Taiwan. They found the highest mortality among 100 patients with
decompensated cirrhosis and pneumonia.
Bacteraemia, SBP and pneumonia have recently identified as major contributors
to death in patients with cirrhosis in a meta-analysis by Arvani et al.
(Gastroenterology. 2010;139:1246-1256). Although the large patient cohort is
impressive, the study design is associated with some methodological problems
that need to be addressed.
Major Compulsory Revisions
1. Mortality:
a) It is not clear how mortality was assessed: Does the database only assess
death during hospitalization or are all deaths after discharge also documented to
ensure that 30-day and 90-day mortality are adequately assessed? How many
patients were lost-to-follow-up before the end of the 90-day period? Was liver
transplantation during follow-up assessed? If yes, were patients undergoing liver
transplantation censored on the day of transplantation?
b) The authors do not provide a mechanistic explanation for the high mortality of
pneumonia: Please provide Kaplan-Meier curves for the different infections to
estimate patients at risk and to assess whether major mortality occurred within
days after infection (suggesting septic shock) or later (suggesting
acute-on-cirrhosis liver failure triggered by infection). Are the causes of death
available to the authors? How many patients were patients on ICU with
ventilator-associated pneumonia?
2. Confounders and definitions:
a) Adjustment for age, gender, and comorbidity disorders in multivariate Cox
regression analysis was performed by the authors. The most important
prognostic parameter ist he MELD score. Did patients with pneumonia have a
higher MELD score than patients with other bacterial infections? Please adjust
for the MELD score in the multivariate model.
b) The authors state that “The patients were classified into infectious and
non-infection group according the baseline presence of infectious diseases or
not“. What does „baseline“ mean in this context: time of hospitalization or time of
diagnosis of infection? Studies suggest a higher mortality in patients with
hospital-acquired infections due to multi-resistant bacteria or secondary
infections. Please provide whether the mode of acquisition (hospital-acquired,
community-acquired, healthcare-associated) was a prognostic factor for different
infections.
c) SWSF is poorly defined using a retrospective ICD-based study design. How
are patients with spontaneous or secondary catheter-associated bacteraemia or
abdominal infection, such as cholangitis, treated? Although the authors state that
“such as necrotizing fasciitis, meningitis, infective endocarditis “ are less relevant
– bacteremia and cholangitis are clearly not.
c) SIRS itself has been identified as a risk factor for mortality in cirrhosis
(Cazzaniga et al. J Hepatol. 2009 Sep;51(3):475-82). How many patients with
infections had SIRS, i.e. sepsis, coded in the database?
3. Interpretation: The authors state that “there were limited studies for identifying
the mortality of bacterial infections other than SBP in cirrhotic patients” and cite
Kim et al. They state further “While this is true for UTI and skin infections, it is
certainly not true for bacteraemia and pneumonia as shown in the meta-analysis
by Arvaniti et al. They state further “The high mortality of pneumonia in cirrhotic
patients were identified in one recent study. In that study, the overall mortality
rates were 14.4% in cirrhotic patients with pneumonia.” Arvaniti et al. extracted
pneumonia-associated mortality from seven studies (46 deaths/123 patients;
37.4%) showing a much higher mortality than that stated by the authors.
Minor Essential Revisions
1. There are some spelling mistakes and grammatical errors throughout the
manuscript, e.g. „Patient who was admitted“ „The mortalities of both groups were
showed”, “with the large case numbers enrolled from short duration“, „Clinical
doctor should notice the high mortality in such patients“
2. The authors state that „Alcoholism was negatively correlated with 30-day and
90-day mortalities of cirrhotic patients with ascites.“ Does this mean that patients
with alcoholism had lower mortality?
3. Was the study really powered to detect “differences in risk of each kind of
major infectious disease”? The authors compared the mortality risk of certain
infections but not differences in mortality between different infections. Please
clarify.
Discretionary Revisions
1. Do the authors have data whether the use of classical pneumonia severity
scores (CRB65 etc.) are valid in patients with cirrhosis. It would be beneficial for
the manuscript if the authors could assess patient charts of the 100 patients with
pneumonia.
Level of interest: An article whose findings are important to those with closely
related research interests
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 declare that I have no competing interests apart from similar research interests
on the impact of infections on mortality in cirrhosis.
assistant