Research Priorities for Diabetic Ketoacidosis: An Evidence and Gap Mapping Review

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

The paper is well structured in sections, the ideas are clearly presented. The diabetic ketoacidosis (DKA) is common complication of diabetes as the literature research provides many results. 1131 results were shown by the search on PubMed database. After screen, 18 studies were removed as non-human, 345 were duplicates so eventually 768 remained as qualified for the analysis. Out of the 768 studies 118 were interventional meaning 15,4%, 52 studies were pediatric and 66 adult studies. From the 118 interventional studies 26 were qualified as high-quality studies (systematic reviews and meta-analysis) 88 were medium-quality while 4 were low-quality.
The literature analysis shown that the two most populated interventional areas of evidence include fluid administration and insulin infusions. Various other analysis were performed among the studies such as as biochemical parameters and complications in fluid administration, fluid choice and volume/rate of fluid administration, volume of fluid use, balanced crystalloids versus normal saline. The current paper is focused on fluid and insulin administration. The conclusions say that the current literature can still be improved in terms of the DKA management optimization and patient centered outcomes (focused on some items such as mortality and days alive and so on) are still under-investigated.

Author Response

The paper is well structured in sections, the ideas are clearly presented. The diabetic ketoacidosis (DKA) is common complication of diabetes as the literature research provides many results. 1131 results were shown by the search on PubMed database. After screen, 18 studies were removed as non-human, 345 were duplicates so eventually 768 remained as qualified for the analysis. Out of the 768 studies 118 were interventional meaning 15,4%, 52 studies were pediatric and 66 adult studies. From the 118 interventional studies 26 were qualified as high-quality studies (systematic reviews and meta-analysis) 88 were medium-quality while 4 were low-quality.
The literature analysis shown that the two most populated interventional areas of evidence include fluid administration and insulin infusions. Various other analysis were performed among the studies such as as biochemical parameters and complications in fluid administration, fluid choice and volume/rate of fluid administration, volume of fluid use, balanced crystalloids versus normal saline. The current paper is focused on fluid and insulin administration. The conclusions say that the current literature can still be improved in terms of the DKA management optimization and patient centered outcomes (focused on some items such as mortality and days alive and so on) are still under-investigated.

 

RESPONSE:

 

Thank you for your detailed review and kind words.

We agree that the highlighted gaps require dedicated research programs to improve outcomes for patients with DKA.

Reviewer 2 Report

Comments and Suggestions for Authors

This is review article aimed to present an overview of the current body of literature and identifies evidence gaps in relation to therapeutic interventions for DKA. They analysed substantial number of clinical studies. The intervention domains were fluid therapy, insulin therapy, electrolyte replacement, adjunct therapies and admission type. Gaps were identified with scant evidence to guide prophylactic electrolyte administration, enteral intake and adjunctive therapy (thiamine, bicarbonate). Well-investigated interventions such as fluids and insulin administration, substantial gaps were found, especially for patient-centred and healthcare service outcomes. This area of investigation is very interesting and important having in mind that DKA is still life –threatening situation.

1. Please add strength and limitations of your study at the end of Discussion section
2. I can not open Supplementary figure 1 and the one in the manuscript is too small, and this is the main Figure in the manuscript, it must be available and clear

Author Response

This is review article aimed to present an overview of the current body of literature and identifies evidence gaps in relation to therapeutic interventions for DKA. They analysed substantial number of clinical studies. The intervention domains were fluid therapy, insulin therapy, electrolyte replacement, adjunct therapies and admission type. Gaps were identified with scant evidence to guide prophylactic electrolyte administration, enteral intake and adjunctive therapy (thiamine, bicarbonate). Well-investigated interventions such as fluids and insulin administration, substantial gaps were found, especially for patient-centred and healthcare service outcomes. This area of investigation is very interesting and important having in mind that DKA is still life –threatening situation.

1. Please add strength and limitations of your study at the end of Discussion section

RESPONSE:

Thank you for pointing this out. A paragraph at the end of the discussion section has been added to detail the strengths and weaknesses of this study.

1. I can not open Supplementary figure 1 and the one in the manuscript is too small, and this is the main Figure in the manuscript, it must be available and clear

RESPONSE:

We are sorry that the reviewer was unable to open the supplement. It is a html file with an interactive evidence gap map. We suggest trying a range of different browsers. Theoretically any browser should be able to open the html file.

Round 2

Reviewer 2 Report

Comments and Suggestions for Authors

I opened Supplementary Fig 1 now, and it is correct. I have no further questions.