Title: VALIDATION OF DIAGNOSES OF LIVER DISORDERS IN USERS OF SYSTEMIC
ANTIFUNGAL MEDICATION IN SWEDEN
Version: 1 Date: 06 Oct 2023
Reviewer's report:
This is a well written and well conducted validation study. Patients treated with systemic anti
fugal drugs were identified through the Swedish Prescribed Drug Register and subsequent
diagnosis of toxic liver disease in the National Patient Register. The diagnoses were thoroughly
validated using predefined criteria based on information in the medical journals (including
biochemical data, pathology and imaging).
I only have a few minor comments
1) Line 72: Instead of "secondary databases" - I would suggest "Routinely collected clinical data
such as discharge diagnoses"
2) Lines 77-82 beginning with "Mislassification can occur......using positive predictive values."
This sound a bit like text book material. I would delete this or shorten and move to the discussion.
3) Did the authors have any information on azoles administered during hospital admissions?
4) I was considering whether you could apply algorithms to obtain higher PPVs for subgroups
of patients. a) Could there be a dose-dependent effect with higher PPV for those who received
higher doses and longer treatment? b) Could there be a difference according to cancer? You
could explore this and calculate PPVS for patients with active cancer and those with prior cancer/
no cancer.
5) Are you in Sweden allowed to present table cells with less than 5 cases (GDPR etc.)?
6) In table 2 I would suggest to combine n (%) in one column, so you will have only 3 columns
with liver diseases to improve readability.
7) Figure 1. The flow chart is not entirely self explanatory in the current version.  In order to
really understand the flow you need the text in the manuscript. I think it would benefit from a
revision to improve readability.
Title: VALIDATION OF DIAGNOSES OF LIVER DISORDERS IN USERS OF SYSTEMIC
ANTIFUNGAL MEDICATION IN SWEDEN
Version: 1 Date: 06 Oct 2023
Reviewer's report:
This is a well written and well conducted validation study. Patients treated with systemic anti
fugal drugs were identified through the Swedish Prescribed Drug Register and subsequent
diagnosis of toxic liver disease in the National Patient Register. The diagnoses were thoroughly
validated using predefined criteria based on information in the medical journals (including
biochemical data, pathology and imaging).
I only have a few minor comments
1) Line 72: Instead of "secondary databases" - I would suggest "Routinely collected clinical data
such as discharge diagnoses"
2) Lines 77-82 beginning with "Mislassification can occur......using positive predictive values."
This sound a bit like text book material. I would delete this or shorten and move to the discussion.
3) Did the authors have any information on azoles administered during hospital admissions?
4) I was considering whether you could apply algorithms to obtain higher PPVs for subgroups
of patients. a) Could there be a dose-dependent effect with higher PPV for those who received
higher doses and longer treatment? b) Could there be a difference according to cancer? You
could explore this and calculate PPVS for patients with active cancer and those with prior cancer/
no cancer.
5) Are you in Sweden allowed to present table cells with less than 5 cases (GDPR etc.)?
6) In table 2 I would suggest to combine n (%) in one column, so you will have only 3 columns
with liver diseases to improve readability.
7) Figure 1. The flow chart is not entirely self explanatory in the current version.  In order to
really understand the flow you need the text in the manuscript. I think it would benefit from a
revision to improve readability.
Please review this paper.
user
Title: VALIDATION OF DIAGNOSES OF LIVER DISORDERS IN USERS OF SYSTEMIC
ANTIFUNGAL MEDICATION IN SWEDEN
Version: 1 Date: 06 Oct 2023
Reviewer's report:
This is a well written and well conducted validation study. Patients treated with systemic anti
fugal drugs were identified through the Swedish Prescribed Drug Register and subsequent
diagnosis of toxic liver disease in the National Patient Register. The diagnoses were thoroughly
validated using predefined criteria based on information in the medical journals (including
biochemical data, pathology and imaging).
I only have a few minor comments
1) Line 72: Instead of "secondary databases" - I would suggest "Routinely collected clinical data
such as discharge diagnoses"
2) Lines 77-82 beginning with "Mislassification can occur......using positive predictive values."
This sound a bit like text book material. I would delete this or shorten and move to the discussion.
3) Did the authors have any information on azoles administered during hospital admissions?
4) I was considering whether you could apply algorithms to obtain higher PPVs for subgroups
of patients. a) Could there be a dose-dependent effect with higher PPV for those who received
higher doses and longer treatment? b) Could there be a difference according to cancer? You
could explore this and calculate PPVS for patients with active cancer and those with prior cancer/
no cancer.
5) Are you in Sweden allowed to present table cells with less than 5 cases (GDPR etc.)?
6) In table 2 I would suggest to combine n (%) in one column, so you will have only 3 columns
with liver diseases to improve readability.
7) Figure 1. The flow chart is not entirely self explanatory in the current version.  In order to
really understand the flow you need the text in the manuscript. I think it would benefit from a
revision to improve readability.
assistant