Predicting Beta-Lactam Target Non-Attainment in ICU Patients at Treatment Initiation: Development and External Validation of Three Novel (Machine Learning) Models
, Tim M. J. Ewoldt 1,2,4,†, Ravish N. Gangapersad 1,2, Matthias Gijsen 5,6, Nestor Parolya 7, Chantal J. A. R. Kats 8, Isabel Spriet 5,6, Henrik Endeman 4, Jasper J. Haringman 9, Reinier M. van Hest 10, Birgit C. P. Koch 1,2 and Alan Abdulla 1,2
on behalf of the DOLPHIN Investigators
Round 1
Reviewer 1 Report
Comments and Suggestions for AuthorsThe article is well written and understandable from a scientific point of view. For this reason, I only have a few suggestions and comments that would improve the article.
1) Why did the authors not include procalcitonin (PCT) in the analysis? Please explain.
2) It would be useful to also consider subgroups of the diseases (e.g. are there differences to oncological patients or patients with polytrauma).
3) How many patients had sepsis or pneumonia? How many patients were ventilated? How many patients were given ß-lactams without severe signs of infection?
4) Was it possible to establish a correlation with microbiological results (e.g. E. coli or St. aureus)?
5) Would it also be useful to consider the known resistances in intensive care units?
Author Response
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Author Response File: 
Author Response.pdf
Reviewer 2 Report
Comments and Suggestions for Authors1. Manuscript is well written and study is well conceptualised
2.why hieght was taken as one of factor in model . How it affects Beta lactatms physiology in body ?
3. Liver function test and Kidney function ,Blood pressure and Cardiac functions may also have been used in analysis -Any such derangement in them may affect attainment of appropriate level of Beta lactams in body
4. Cases with Other comorbidity (in ICU patients) like Tuberculosis , Diabetes may also be considered as factors
5. Ethical clearance (document number must be included in script)
6. What was criteria for choosing specific 5-6 Beta lactam antibiotic only and leaving others (please justify)
7 . does pk/Pd is a part of your models for evaluation?
Author Response
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Author Response File: Author Response.pdf
Reviewer 3 Report
Comments and Suggestions for AuthorsDear authors
Thnaks to let me review this manuscript.
The most important I do not have access to supp data.
From my part only a little details to conclude the manuscript
4.1.2. Pharmacodynamic target attainment --> could the author extend more about the LC-MS (model,paramaeter used, so on)
4.1.4. Model development --> it could great a short summary about each models (differences, limitations and advantages)
2.3. Online beta-lactam target non-attainment predictor --> if the author want to offer a kind webpage, my advice is to include a link for instructions. Sorry because I am mot sure what I shoud write .......
Linking to above mentioned, I miss a visual example during the discussion.
Thanks
Author Response
Please see the attachment.
Author Response File: Author Response.pdf
