Association between Anemia and New-Onset Atrial Fibrillation in Critically Ill Patients in the Intensive Care Unit: A Retrospective Cohort Analysis
Round 1
Reviewer 1 Report
-) Introduction: Very well written - concise but giving a good overview of the topic!
-) Methods: Inclusion-/exclusion criteria: Please state why you chose these specific criteria for each item, as this is vital for the interpretation of the whole study. For example, why were patients after cardiac surgery excluded and not put into subgroup analysis, etc.
-) Methods: Please cite the guideline you refer to (page 2, line 83). Are these recommendations in line with international guidelines? Transfusion treshholds / triggers have been a widely discussed topic in the recent years.
-) Methods: How were patients screened for the development of AF, and how exactly was AF diagnosed (ECG, how long,...)?
-) Results/methods: Do you think further stratifying the Hb levels into more subgroups than just anemic yes/no would provide us with more detailed information?
-) Results/methods: How many of your patients have been ventilated (invasively/non-invasively)? Details on this would be very interesting.
-) Discussion: Please structure this better, e.g. through subheadings, in order to provide a better reading experience.
-) Discussion: Have you thought about the impact of volume substitution and / or postoperative ventilation settings on AF rates (both have already been published) - they could have impacted on your results and acted as non-identified confounders.
Author Response
REVIEWER 1
Dear Referee,
With reference to your letter, please find enclosed my revised manuscript covering you’re your valuable comments and corrections.
The manuscript has become much better, owing to your comments.
Yours sincerely,
--------------
-) Introduction: Very well written - concise but giving a good overview of the topic!
We appreciate your valuable comments.
-) Methods: Inclusion-/exclusion criteria: Please state why you chose these specific criteria for each item, as this is vital for the interpretation of the whole study. For example, why were patients after cardiac surgery excluded and not put into subgroup analysis, etc.
Our study was carried out in the general ICU of the Anesthesiology and Reanimation clinic. Patients undergoing cardiac surgery in our hospital are admitted to the “Cardiovascular ICU” in the postoperative period. Therefore, patients undergoing cardiac surgery are not included in the “General ICU” patient population. The error that caused the confusion in the article has been corrected. Patients undergoing cardiac surgery are not included in our exclusion and inclusion criteria (Page 2, Line 66-71).
-) Methods: Please cite the guideline you refer to (page 2, line 83). Are these recommendations in line with international guidelines? Transfusion treshholds / triggers have been a widely discussed topic in the recent years.
We cited the guideline referred (Page 2, Line 85 / Ref 15).
These recommendations have been prepared in accordance with international guidelines. This local guide has been prepared in accordance with the guidelines of the world health organization (WHO), the American Association of Anesthesiologists (ASA), and current literature.
As you mentioned, transfusion thresholds/triggers are a hotly debated topic in recent years. Current information on this subject is also mentioned in our article (Page 10, Line 330-338).
-) Methods: How were patients screened for the development of AF, and how exactly was AF diagnosed (ECG, how long,...)?
Patients diagnosed with new-onset AF, including paroxysmal AF, defined as rhythm classification by continuous ECG monitoring or 12-lead ECG, were included in our study. Patients were screened according to the diagnosis code from the computer-based data system in accordance with the retrospective design of the study and were included in the study if they met other inclusion criteria (Page 2, Line 66-67).
-) Results/methods: Do you think further stratifying the Hb levels into more subgroups than just anemic yes/no would provide us with more detailed information?
Dear Referee, we totally agree with your comments. Therefore, a substudy was planned by dividing the Hb levels in the current study into subgroups. We think that the results to be obtained with detailed statistics will provide more comprehensive information to the literature.
-) Results/methods: How many of your patients have been ventilated (invasively/non-invasively)? Details on this would be very interesting.
In total, 1756 patients were ventilated. The patients who received MV support in the anemia group were found to be statistically significantly higher (p<0.001). 75% of patients diagnosed with NOAF and 72% of patients not diagnosed with NOAF received mechanical ventilator support. There was no statistical difference between the two groups (p=0.227). The obtained data are added to Table 1 and Table 3 (Page 5 and 7).
-) Discussion: Please structure this better, e.g. through subheadings, in order to provide a better reading experience.
In line with your suggestion, sub-headings have been added to the discussion section to provide a better reading experience.
-) Discussion: Have you thought about the impact of volume substitution and / or postoperative ventilation settings on AF rates (both have already been published) - they could have impacted on your results and acted as non-identified confounders.
Our study included all critically ill patients treated in the ICU, and postoperative patients comprised 25.5% of all patients. In the ICU, patients were managed according to standard transfusion guidelines as outlined in the method section. Therefore, there is no difference between patients in terms of volume substitution and management of ventilation settings in the ICU. However, naturally, a significant difference was found between patients with and without anemia in terms of RBC transfusion volume (Table 1). RBC volumes were found to be similar between patients with and without NOAF (Table 3). However, as you said, the blood volumes and mechanical ventilation settings applied to the patients in our study could not be studied as a sub-analysis. The current situation has been added to the limitations section of the study (Page 11, Line 393-395).
*The grammatical errors in the article have been corrected with professional help.
ALL CHANGES WERE MARKED IN YELLOW IN THE TEXT!!
Author Response File: 
Author Response.docx
Reviewer 2 Report
This is a clinical study, which examined whether there was a correlation between NOAF and anemia in older patients hospitalized in the ICU. In this paper, the authors found a strong correlation between anemia and NOAF in patients in the ICU, but the results were rough. Although this is clinically important, this reviewer has some comments as described below.
Major comments:
1. Line 60. The number of enrolled patients should go to the Results section. Above all, in lines 118-119, the authors described that all enrolled patients were 8634. Regarding the enrolled, included, and excluded patients, the authors should clearly show the flow chart in a figure.
2. Further, they should show the exclusion criteria in the Methods section.
3. In the definition of anemic and non-anemic conditions, which data were used? On admission? How about the decrease of Hb during the hospitalization?
4. The authors mentioned RBC transfusion, but they did not show the data in tables. They should put the data.
5. What were the anemia causes?
6. In atrial fibrillation, left atrial diameter is very important. Cardiac ultrasound data is required.
7. Hypovolemia is also associated with atrial fibrillation. The authors should add this issue, including bleeding.
Author Response
REVIEWER 2
Dear Referee,
With reference to your letter, please find enclosed my revised manuscript covering you’re your valuable comments and corrections.
The manuscript has become much better, owing to your comments.
Yours sincerely,
---------
This is a clinical study, which examined whether there was a correlation between NOAF and anemia in older patients hospitalized in the ICU. In this paper, the authors found a strong correlation between anemia and NOAF in patients in the ICU, but the results were rough. Although this is clinically important, this reviewer has some comments as described below.
Major comments:
- Line 60. The number of enrolled patients should go to the Results section. Above all, in lines 118-119, the authors described that all enrolled patients were 8634. Regarding the enrolled, included, and excluded patients, the authors should clearly show the flow chart in a figure.
The flow chart of the work has been arranged on your valuable suggestion and added to the result section as Figure 1 (Page 4).
- Further, they should show the exclusion criteria in the Methods section.
Exclusion criteria have been mentioned in the methods section (Page 2, Line 67-71).
- In the definition of anemic and non-anemic conditions, which data were used? On admission? How about the decrease of Hb during the hospitalization?
The definition of anemic and non-anemic conditions was based on the hemoglobin data at the time of admission to the intensive care unit.
- The authors mentioned RBC transfusion, but they did not show the data in tables. They should put the data.
In line with your suggestion, the data on Erythrocyte transfusion have been added to Table 1 and Table 3 (Page 5 and 7).
- What were the anemia causes?
The causes of anemia were mostly anemia of chronic disease and age-related malnutrition problems. Comorbid diseases such as coronary artery disease, diabetes mellitus, cerebrovascular disease, renal failure, and cancer were statistically significantly higher in anemic patients (Page 9, Line 268-271).
- In atrial fibrillation, left atrial diameter is very important. Cardiac ultrasound data is required.
In line with your suggestion, cardiac ultrasound data has been added to Table 3 (Page 7).
- Hypovolemia is also associated with atrial fibrillation. The authors should add this issue, including bleeding.
Based on your valuable suggestion, a short paragraph on hypovolemia and bleeding associated with atrial fibrillation has been added to the discussion section (Page 10, Line 314-320).
*The grammatical errors in the article have been corrected with professional help.
ALL CHANGES WERE MARKED IN YELLOW IN THE TEXT!!
Author Response File: Author Response.docx
Round 2
Reviewer 1 Report
Dear authors,
Thank you for addressing all my comments so thoroughly. The manuscript has been strongly improved.
Author Response
Dear Referee,
We are grateful for your valuable comments.
The manuscript became much better, owing to your comments.
Yours sincerely,
Reviewer 2 Report
This clinical study was revised, and this reviewer has still a major comment as described below.
Major comment:
1. Lines 60-61. Here in the Methods section, the authors should describe who and how they enrolled the patients, not the enrolled number. After exclusion from 8634 patients, the number was 2426, which was one of the results. Thus, it would be “All patients were enrolled, who received intensive care treatment in a single center between January 1st, 2012, and November 30th, 2021. They were obtained using structured query language queries from the EMRall-QlinICUImdSoftMetavision clinical decision support system and evaluated retrospectively.”
Author Response
Dear Referee,
We are grateful for your valuable comments.
The manuscript became much better, owing to your comments.
Yours sincerely,
---------------
This clinical study was revised, and this reviewer has still a major comment as described below.
Major comment:
- Lines 60-61. Here in the Methods section, the authors should describe who and how they enrolled the patients, not the enrolled number. After exclusion from 8634 patients, the number was 2426, which was one of the results. Thus, it would be “All patients were enrolled, who received intensive care treatment in a single center between January 1st, 2012, and November 30th, 2021. They were obtained using structured query language queries from the EMRall-QlinICUImdSoftMetavision clinical decision support system and evaluated retrospectively.”
In line with your valuable suggestion, the necessary correction has been made in the methods section (Page 2, Line 60-63).
ALL CHANGES WERE MARKED IN YELLOW IN THE TEXT!!
Author Response File: Author Response.docx
