PONE-D-19-32738

Risk factors associated with nosocomial infections among end stage renal disease patients undergoing hemodialysis: A systematic review

PLOS ONE

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: No

Reviewer #2: Yes

Reviewer #3: Yes

Reviewer #4: Yes

Reviewer #5: Yes

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2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: I Don't Know

Reviewer #2: N/A

Reviewer #3: No

Reviewer #4: Yes

Reviewer #5: Yes

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3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

Reviewer #4: Yes

Reviewer #5: Yes

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4. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

Reviewer #4: Yes

Reviewer #5: Yes

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5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: Saad Hanif Habbasi has considered 9 studies in order to evaluate the risk factor associated with nosocomial infections among the ESRD ( End-Stage Renal Disease) hemodialyzed patients.

The argument is crucial and has a big impact in the national health services and in the daily life of patients.

However there are some considerations.

Firstly the author should specify the type and the site of vascular access for hemodialysis.

The 2006 KDOQI vascular access guidelines considers AV fistula the first option followed by prothesic grafts if AV fistula is not possible. So the long term vascular catheter should be placed as last choice . Sometimes it could be necessary to occur to a vascular catheter temporarily if fistula is not matured and it should be indicated for how long.

It is well known that vascular catheter for dialysis has a higher risk of bloodstream infections in comparison to AV fistula. In addition patients who are cvc dependent for dialysis are more sick than patients with AV fistula

Secondly the nine studies are conducted in different period of time and this makes results difficult to be interpreted. Recent data show a reduction of CLABSIs (central line–associated bloodstream infection) since 2001 as a result of prevention programs in many hospitals around the world. In additon in the 2016 the CDC ( Centers for Disease Control and Prevention) estimates that CLABSIs decreased by 50% between 2008-2014 .

Finally the risk of bacteremia and infections depends on the intrinsic defence mechanism and therapies of patients. Most of the studies included elderly people who are more exposed to risk of hospitalisation and nosocomial infections because of the accumulation of comorbid disease with age and poor adherence to medical treatment.

Reviewer #2: In this manuscript, dr. Aftab and colleagues performed a systematic literature review aimed at identifying risk factors for noscomial infections in patients with end-stage renal failure undergoing hemodyalisis.

The topic is relevant, given the expected increase in the number of patients who will require intermittent hemodyalisis in the next future, and costs associated with noscomial infections. The manuscript is overall well conducted from a methodological point of view, with multiple databases searched, description of search strategy, independent screening, and risk of bias assessment.

The major flaw of this study is lack of a statistical analysis of the results, although I acknowlegde that the type of study make it difficult to perform a quantitative analysis.

I have a few comments for the Authors which I hope will help them to improve their manuscript:

1. The introduction is too long. I suggest to shorten it, and to focus on why the Authors decided to undertake this study

2. Given that no quantitative analysis was performed, the paragraph can be deleted. A sentence a the end of the Methods section is sufficient

3. Please provide a list of the 41 major exclusions, together with references, in a Supplementary Appendix

4. Please rewrite the Discussion, underlying the relationship of present study to previous literature, the significance of study findings, what present study add to current knowledge, and future directions. The detailed discussion of each risk factor is not necessary

Minor comment

1. in the paragraph "Characteristics of the Selected Studies" on lines 11-13 the Authors write "in some studies, there were participants aged 12 years and above". As per exclusion criteria, all studies with participants aged < 12 should have been excluded.

Reviewer #3: I am grateful for the opportunity to review the manuscript entitled "Risk factors associated with nosocomial infections among end stage renal disease patients undergoing hemodialysis: A systematic review ".

I have some comments for the author. I hope that my comments may contribute improving your papers.

Manuscript is well written, really clear and sections length is adequate. Moreover,reference are uptodate.

Nonetheless, there are two main issues.

1)There are few studies included. Nine studies are a limited number for a systematic review. Moreover, studies included are different in study design, population, inclusion/exclusion criteria and ESRD definition.

2)Lack of meta-analysis is probably the major issue of this paper. Without a proper analysis I believe most of your results and discussion remain unproven. I would suggest author to try to synthetize results whenever possible for key outcomes.

Introduction:You begin your manuscrit with the second reference, please number the reference accordingly to first appearance.

Minor issues:

Data extraction: I think it would be useful to include the data extraction form as supplementary material

Risk of Bias/Quality: Explain your strategy to overcome disagreements between assessors

Data synthesis: "A systematic review was performed to make sure that all data synthesis done was sourced from the maximum possible, and complete collection of relevant literature" I believe this sentence may expanded in order to clarify your efforts. (Examples: reference check, contacting the authors, contacting fields experts)

Results: "In some studies, there were participants aged above 12 years" The sentence is not clear. Inclusion criteria is >12 years, so all participants have to be aged > 12 years old. Please explain.

Reviewer #4: There’s no doubt we should consider this systematical review as an original research: ESRD people are increasing especially in front of life expectancy extension. Health care world may consider main infection risk factors in order to decrease morbidity, mortality and cost effectiveness. Despite we can trace principle elements implicated in ESRD nosocomial infection we don’t know exactly what we have to be afraid of and if we are able to prevent them.

As the author show, a lot of literature meet key words research, but as a matter of facts only few articles really describe patient’s characteristics and nosocomial infections risk factors. If they do usually concentrate themselves on a particular risk factor or subtype of population.

We can declare that results have not been published elsewhere and they have been obtained by proper/ analyses. We found in Cochrane library only a single review focused on “Interventions for preventing infectious complications in hemodialysis patients with central venous catheters” but it doesn’t consider patients characteristics and risk factors.

In this work Authors described in detail the protocol of their systematical review. They declared to follow PRISMA guidelines for the design study and they subscribe the protocol to PROSPERO specifying the registration number.

As a matter of fact the study is conformed to PRISMA statement. Every part is described in sufficient detail and flow chart is clear.

Some data about sources choose has been delete. On the other hand quality of the main studies has been evaluated and described following Otawa criteria. Data extraction form has been good described, considering items author’s name, year and duration of the study, study design, respondents, demographics of the patients (sample size, gender, and age), type of nosocomial infections studied, type of pathogens involved, and risk factors associated with nosocomial infections.

The article adheres to appropriate reporting guidelines and community standards for data availability.

We suggest minor revisions:

1) Please, report the systematic review registration number on PROSPERO in the abstract

2) Risk of bias assessment has been correctly evaluated with Newcastle Ottawa scale (NOS) for observational studies considering three categories: “Selection,” “Comparability,” and “Outcome. Studies have been classified as good, fair and poor quality. It would be useful to describe single limitations of the studies analyzed. In particular 2 have retrospective design and declare this aspect on their discussion.

3) An accurate and comprehensive systematic review has been performed and complete collection of relevant literature. Only qualitative analysis has been undertaken and not statistical analysis has been performed. Authors declare the limitations of their work for heterogeneity nature of the studies considered (retrospective cohort and case control, cross-sectional and longitudinal, prospective). However, it would be interesting to approach a univariate/multivariate analysis of similar studies to evaluate risk ratio or ODDs ratio for hemoglobin level/previous blood transfusion or HD duration in HBV/HCV infection (cross sectional studies). Moreove, HDAP rate, microorganism type, and infection risk in Chronic HD it would be obtained.

4) Methods are exhaustive described, but it would be useful to specify if references authors had been called looking for other works.

5) The manuscript meets the criteria of linguistic clarity and correctness required except for a wrong transcription: table 2, reference 17 (“D’Agata EMC et al, instead of: Erika et al”)

Reviewer #5: Please see attached word document for specific review comments on this manuscript. Thank you for the opportunity to review. I recommend a 'Minor Revision'.

Many Thanks,

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Reviewer #1: No

Reviewer #2: Yes: Alessandro Belletti

Reviewer #3: No

Reviewer #4: No

Reviewer #5: Yes: Pasquale Nardelli

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Risk factors associated with nosocomial infections among end stage renal disease patients undergoing hemodialysis: A systematic review

PONE-D-19-32738R1

Dear Dr. Raja Ahsan Aftab,

We are pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it complies with all outstanding technical requirements.

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Additional Editor Comments (optional):

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #2: All comments have been addressed

Reviewer #4: All comments have been addressed

Reviewer #5: All comments have been addressed

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2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #2: Yes

Reviewer #4: Yes

Reviewer #5: Yes

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #2: Yes

Reviewer #4: N/A

Reviewer #5: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #2: Yes

Reviewer #4: Yes

Reviewer #5: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #2: Yes

Reviewer #4: Yes

Reviewer #5: Yes

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #2: In this manuscript, dr. Aftab and colleagues present a revised version of their manuscript

I believe that all of my comments have been adequately addressed

Reviewer #4: (No Response)

Reviewer #5: I thank the authors for their efforts. I believe the manuscript quality was improved in the review process.

No further comments.

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7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

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Reviewer #2: Yes: Alessandro Belletti

Reviewer #4: No

Reviewer #5: Yes: Pasquale Nardelli, MD