Complications Associated with Peripherally Inserted Central Catheters (PICC) in People Undergoing Autologous Hematopoietic Stem Cell Transplantation (HSCT) in Home Hospitalization

Round 1

Reviewer 1 Report

Thank you for including me as a reviewer for this paper, entitled "Complications associated with peripherally inserted central catheter (PICC) in people undergoing autologous hematopoietic stem cell transplantation (HSCT) in home hospitalization." This study warrants publication however it requires revisions if it is to be considered for publication. Overall, this paper tries to describe PICC complications in home-transplant setting compared to in-hospital, however the overall story telling of this article seems to not focus on this until halfway through the paper, instead seemingly discussing their data as complications of transplant. I recommend extensive revisions to the writing style and overall storytelling in order for the authors to adequately make their argument to readers.

Abstract:

More results should be discussed - instead of declaring vague significance and saying "among others" - directly state the best results you feel would make readers want to read this paper. If word counts are an issue, purpose and methodology can be reduced. Additionally, was this a non-inferiority study? What metrics were you using to declare non-inferiority with the conclusion?

Introduction:

I find some of the language difficult to read in terms of language/syntax. Avoiding passive language will help with readability.

Line 48: Third phase of transplant deserves further explanation if it is to be used.

The introduction should discuss the risks of home PICCs, in terms of possible contaminations in the home environment, etc without constant nursing care. Do home transplants get nursing care? More substance on PICC utilization should be discussed

Does this paper truly have a hypothesis? Before reviewing data did your group expect home transplant care of PICC lines to be safer or more risky? 

Methods:

The first line deserves to be a complete sentence. 

Would other central catheters such as ports of tunneled lines be included or excluded? I'm, assuming all patients had PICCS but this was not directly stated.

Line 74: "An investigator selected cases and controls"... this deserves to be better explained because this would otherwise be extremely vulnerable to selection bias, risking any and all claims in this paper. This was mentioned, but this method will be strengthened if selection metrics were better listed out in the methods. There were 20 home auto-HSCTs in the trial period, were those all of the transplants or were there others outside of the selection period? 

Line 90: Check for unnecessary capitalizations of some words

Results:

Tables 1&2 : Please use proper decimals instead of commas when reporting percentages and p-values

Table 2: What specific catheter complications are included? This could be described in the body of the manuscript.

P values of 0.000 would be more accurate to report p>0.001

Did any patients in either cohort even require ICU stay? Did any have septic shock? Did any home-cohort patients need to be admitted to the hospital or ICU for infection or line complications?

I am confused reading the paragraph starting on line 105, and it may just be grammar/syntax... Are you describing the incidence of prophylactic antibiotic administration in hospital vs home conditioning? Which antibiotics were used? This is listed later in the discussion but it should be described earlier.

Paragraph starting with line 106: I do not understand what "the process" or "process days" are. Please clarify.

Paragraph starting on line 126: Which pathogens were isolated in blood cultures? It would add a lot to this paper to describe which organisms grew - potentially showing more MDRO and iatrogenic infections in-hospital vs native flora infections at home would be really strong data and should be fully described.

Paragraph starting on line 130: More should be described regarding all findings on Figure 1. Overall erythema in hospital is the only obviously frequent side effect, but all others should be described - this is what you named your paper after. Any relevant statistics for all of these metrics should be included. I suspect these are underpowered but this still should be acknowledged.

Figure 1: This graphic should be the major focus of your paper. P-values and/or confidence intervals should be presented here. Also infections (maybe of any kind) should be included here as well. If feasible, this table should be in the same font as the rest of the manuscript. Graphing as percentages instead of number of encounters would also be more appropriate.

Paragraph starting on line 138: This should also be where you mention that neutropenic fever was 8.5x more likely to occur in hospital.

Table 3: Commas again should be replaced by decimals, and confidence intervals should be shown graphically if able.

It is later acknowledged that prophylactic antibiotics were different for multiple patients based upon protocols - this not only needs to be defined but should be statistically accounted for using ANOVA

Discussion:

I like that you highlight that higher Karnofsky scores help select better candidates for home care. Were there any low range Karnofsky patients in the home cohort? If so were they more likely to experience an adverse event with their PICC?

Paragraph starting with line 152: What protocols were used to designate each antibiotic, and what is the antibiotic used in the hospital? The difference in infections and neutropenic fever is a strong point to your article but differences in prophylactic antibiotics could be a key reason why this difference happens. These factors should be better acknowledged to avoid any bias with the data.

Paragraph starting in line 168: I think at some point in this article it needs to be declared for certain what types of lines are being used. Does everyone have an upper-extremity PICC, or are they using other types of central lines? Some line types may be more prone to infection, this should be defined and acknowledged.

For in-hospital line care, what education and training do nurses receive to maintain central line care? This should be described since it was acknowledged that patients receive education for home care.

More limitations should be acknowledged. This study is under-powered - more significant claims can be made if more patients were studied. This study also does not take into account other factors that influence care - type of line (if there are any differences), infection type, prophylactic antibiotic use, and specific types of biases such as recency bias and selection bias are not discussed.

Author Response

We want to thank the time reviewers spent carrying out a thorough review of our manuscript. We have studied the proposed revisions. They are reasonable, and we do believe that they will increase the quality of the manuscript if we address them correctly,

In the following lines, we respond point by point to the considerations from the reviewers.

Sincerely

The authors

Author Response File: Author Response.docx

Reviewer 2 Report

1. The home-care group was only 20 patients. Please calculate its power and show it in the method section.

2. What are the indications of home care or hospital care? Is the disease in the hospital group more severe than in the home group? 

3. Can you tell us more about the PICC care at home? How is education carried out?

4. Catheter complications are related to indwelling time, antibiotic prophylaxis, patient nutrition, immunology, and nursing skill. This study showed that the incidence of bacteremia was higher in the hospital group. what is the reason? PICC complications may not differ if antibiotic prophylaxis regimens are similar in both groups

Author Response

We want to thank the time reviewers spent carrying out a thorough review of our manuscript. We have studied the proposed revisions. They are reasonable, and we do believe that they will increase the quality of the manuscript if we address them correctly,

In the following lines, we respond point by point to the considerations from the reviewers.

Sincerely

The authors

Author Response File: Author Response.docx

Round 2

Reviewer 1 Report

Thank you for allowing me to provide further review for this paper. The recent revisions have vastly strengthened the article, and some additional changes may help it become a finished product ready for publication.

The readability and English language use has improved vastly, however there are still some places worth revising, especially for passive language use and overall. Example of such in the abstract: "The need generated by the SARS-CoV-2 pandemic..." would read stronger as "The SARS-CoV-2 pandemic generated the need to...". Another example in the end of the introduction: "The starting hypothesis of this work is that..." would read stronger as "We hypothesized that there is no difference...". Etc.

 

The discussion and conclusions just need a little extra work too. I am glad to see the acknowledgement of limitations to the study. I think a great summary would highlight how this study at least describes the safety and minimal PICC complications for home care patients, and that a high Karnoffsky score helps justify candidates for such homecare, as this too is in and of itself a selection bias. However, with this selection, patients in this sample size can safely stay at home, with less PICC complications. Sicker patients may be more prone to complications inherent to their health status, in addition to in-hospital factors such as nosocomial bacterial exposure and prophylactic management differences.

Author Response

We want to thank the time reviewers spent carrying out a thorough review of our manuscript. We have studied the proposed revisions. They are reasonable, and we do believe that they will increase the quality of the manuscript if we address them correctly, In the following lines, we respond point by point to the considerations from the reviewers. Sincerely The authors
COMMENTARIES TO EDITOR
Reviewer: 1
The readability and English language use has improved vastly, however there are still some places worth revising, especially for passive language use and overall. Example of such in the abstract: "The need generated by the SARS-CoV-2 pandemic..." would read stronger as "The SARS-CoV-2 pandemic generated the need to...". Another example in the end of the introduction: "The starting hypothesis of this work is that..." would read stronger as "We hypothesized that there is no difference...". Etc.	We appreciate the reviewer's comment. The text has been revised again according to your suggestions.
The discussion and conclusions just need a little extra work too. I am glad to see the acknowledgement of limitations to the study. I think a great summary would highlight how this study at least describes the safety and minimal PICC complications for home care patients, and that a high Karnoffsky score helps justify candidates for such homecare, as this too is in and of itself a selection bias. However, with this selection, patients in this sample size can safely stay at home, with less PICC complications. Sicker patients may be more prone to complications inherent to their health status, in addition to in-hospital factors such as nosocomial bacterial exposure and prophylactic management differences.	We appreciate the reviewer's comment. This sentence has been included at the end of the discussion section following these recommendations: “An adequate selection of patients for home transplant (comprehensive assessment, Karnofsky, etc.) allows for minimum safety and complications in managing PICCs, reducing hospital risk factors such as nosocomial bacterial exposure and possible differences in prophylactic management”.

Author Response File: Author Response.docx

Reviewer 2 Report

1. some mistakes in tables. The title of the variable should be presented as "variables" and "n" showed be in italics. Why "PR" in table 1 was bold?

2. I was confused that you want to delete figure 1 or not?

   

Author Response

We want to thank the time reviewers spent carrying out a thorough review of our manuscript. We have studied the proposed revisions. They are reasonable, and we do believe that they will increase the quality of the manuscript if we address them correctly, In the following lines, we respond point by point to the considerations from the reviewers. Sincerely The authors.
COMMENTARIES TO EDITOR
Reviewer: 2
1. some mistakes in tables. The title of the variable should be presented as "variables" and "n" showed be in italics. Why "PR" in table 1 was bold?	The comment is appreciated. The indicated errata have been modified.
2. I was confused that you want to delete figure 1 or not?	The comment is appreciated. Following the instructions of another reviewer, the information has been included in Table 3 and Figure 1 has been eliminated so as not to duplicate the information.

Author Response File: Author Response.docx