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The authors have addressed the reviewers' concerns in detail.
[# PeerJ Staff Note - this decision was reviewed and approved by John Measey, a PeerJ Section Editor covering this Section #]
I agree with both of the reviewers that some clarifications in the manuscript would be of benefit, and there are some areas where formatting is required. I look forward to seeing the changes.
- The introduction identifies the current knowledge gap clearly – including the use of sedation routinely in practice, and the utility of the ACTH stimulation. The introduction is focused on the necessary background for this particular study and is an appropriate length.
- The study objective and hypothesis are both clearly written.
- Small typo in LN 198 – ‘administration’
- Discussion provides appropriate clinical context for the results of the study, and is suitable length that is relevant to the results/hypothesis of this study. The limitations outlined are reasonable.
- Reference citation is appropriate and supportive of the introductory section, methods chosen, and discussion points made by the authors.
- Tables clearly present the data generated by this study and are a helpful resource to fully understand the results.
- Appropriate design for researching the objective/clinical question posed by the research team. The study reports using a 4-way repeated measures along with a placebo control and randomization to group.
- Methodology description contains sufficient detail without being excessive.
- Inclusion and exclusion criteria are outlined.
- Ln 165: I’m not sure of this journal’s guidelines, but I would advocate for the term ‘sex’ rather than ‘gender’ for the dogs, as the latter takes into consideration social and cultural factors in addition to biological sex.
Two small clarification questions related to your design:
- can you clarify that the Cerenia was administered after all samples were collected? As written it appears so (nausea persisting through end of sample collection), just wanting to make sure my interpretation is correct.
- Was the 7 day washout period based on a particular half life drug clearance?
Findings and conclusions are clearly communicated, and align with the research question/objective. The study outcome is a meaningful addition to the current knowledge base in this area.
Statistical interpretation of the results appears sound, and methodology (including crossover, washout period, and analysis appears appropriate)
There were some unexpected findings (e.g., mild increases in post-ACTH cortisol after saline administration) which were explained well.
One other general comment that could be considered in the discussion further: From the M&M section, the 90 and 120 minute time interval between butorphanol/trazodone, or dexmedetomidine, and collection of basal sample appears to be based on the maximal effect of the drug on cortisol levels. However, the additional hour for the post-ACTH cortisol sample is then at 2.5 to 3 hours following administration of sedation. From the available evidence is the cortisol still expected to be suppressed at these time intervals too? Also there is a comment in the discussion about how 90-minutes might not be the peak effect for trazodone – any reasoning of why you suspect this?
This manuscript presents answers for a commonly posed clinical question. It is well written and clearly presents the findings.
• The structure of the article mostly conforms to PeerJ standards. There are minor edits needed to fully conform to PeerJ standards. These include:
1. references being italicized within the manuscript
2. providing the full or complete name of journals in the reference list
3. adhering to guidelines for capitalization of article titles in the reference list (e.g. references 1, 5, 10, 15 and 17)
• The two provided tables are clearly labelled and well described. In my opinion, Table 1 is not needed as this information could be included in the text (see specific comment for line 174 in the attached document).
No comment.
• Overall, the conclusions are quite well stated; however, I did recommend some revisions (see the attached detailed review report).
• A limitation not mentioned is the low number of dogs used (n = 12). This could be discussed with the other limitations.
• If it is possible based on PeerJ standards, it would be nice to also include cortisol results in standard international units (nmol/L) along with the already provided results in conventional units (µg/dL). This makes it more accessible for a global readership.
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