-->PONE-D-26-08886-->-->In-hospital survival and factors associated with mortality among adults with impaired consciousness in intensive care in Benin, a low-resource setting: a retrospective cohort study-->-->PLOS One

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Reviewers' comments:

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

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Reviewer #1: Partly

Reviewer #2: Yes

Reviewer #3: Yes

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

Reviewer #1: No

Reviewer #2: Yes

Reviewer #3: Yes

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Reviewer #1: Yes

Reviewer #2: No

Reviewer #3: Yes

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Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

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-->5. Review Comments to the Author

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Reviewer #1:  This manuscript presents a retrospective cohort study of ICU patients with impaired consciousness in Benin, evaluating survival and predictors of in-hospital mortality using Kaplan–Meier and Cox proportional hazards models.

The study addresses an important and underreported area: critical care outcomes in low-resource African settings, which aligns with global health priorities such as those promoted by the World Health Organization and World Federation of Intensive and Critical Care Medicine.

A. Strengths

1. Important data from an understudied region

2. Reasonable sample size (n=416)

3. Appropriate use of survival analysis

4. Time-varying effects modeling

5. Bootstrap validation

6. Generally clear manuscript structure

7. STROBE reporting acknowledged

B. Major weaknesses

However, several methodological and interpretative issues limit the study’s impact:

1. Causal interpretation of management variables (oxygen therapy, intubation)

2. Confounding by indication

3. Poor clarity regarding ICU resources

4. Weak characterization of coma etiology

5. Incomplete reporting of survival modeling

6. Potential selection bias

7. Interpretation occasionally overreaches

C. Abstract

Strengths

The abstract is structured and concise.

Issues

1. Missing design details

Should mention:

single-center

retrospective cohort

2. Inconsistent terminology

Use coma consistently.

3. Overinterpretation

The sentence:

suggesting substantial gaps in essential critical care delivery

This is speculative because ICU capacity was not measured.

Better wording:

suggesting possible limitations in essential critical care resources

D. Introduction

Strengths

Good global context

Logical flow

Clear research question

Issues

1. Literature review insufficient

Several key African ICU outcome studies are missing.

Examples that should be referenced:

African ICU mortality reviews

Critical illness outcomes in LMICs

For example studies by:

Adhikari et al.

Riviello et al.

Baker et al.

Without this context, the literature review feels incomplete.

2. Conceptual framing

The study mixes two themes:

coma epidemiology

ICU capacity in LMICs

But does not clearly define which is primary.

Better framing:

Focus should be

outcomes of coma in a resource-limited ICU

E. Methods

This is the strongest section, but still has several issues.

1. Study design

Well described.

However:

Issue

The database creation timeline is confusing.

Data collected:

2015–2017 (patients)

database built 2019

extracted 2025

Add clarification:

Who entered the data?

Was quality checked?

Was double entry performed?

2. Inclusion criteria

GCS 3–14.

This is unusual.

Standard coma definitions are:

GCS ≤ 8.

You should justify why GCS 9–14 were included.

Otherwise the cohort mixes:

coma

altered consciousness

mild neurologic impairment

This increases heterogeneity.

3. Variables

Selection is reasonable.

However major predictors of ICU mortality are missing:

Missing variables:

mechanical ventilation duration

vasopressor use

Infection/sepsis

stroke vs metabolic coma

APACHE or SOFA score

This limits interpretability.

4. Statistical model

Overall well done.

Strengths:

Kaplan–Meier survival

Cox regression

VIF for multicollinearity

bootstrap validation

sensitivity analysis

This is statistically sound.

Major statistical concern

Confounding by indication.

Variables like:

intubation

ventilation

oxygen therapy

reflect severity of illness, not treatment effects.

Example:

Patients receiving oxygen likely had better physiological reserve, not that oxygen reduced mortality.

Therefore:

Interpretation as protective intervention is incorrect.

The manuscript repeatedly implies causality.

This must be corrected.

F. Results

Strengths

Clear presentation.

Major issue: Oxygen therapy finding

Result:

HR = 0.58

Interpreted as protective.

But likely represents:

triage bias

survivorship bias

resource allocation

Example scenario:

patients dying rapidly may never receive oxygen

Therefore the conclusion

oxygen therapy reduces mortality is not supported.

Better interpretation:

receipt of oxygen therapy was associated with lower mortality, possibly reflecting differences in patient severity or resource allocation.

G. Survival analysis

Median survival = 5 days

This is extremely short.

Interpretation should consider:

Possible explanations:

late ICU admission

limited life-support resources

high prevalence of irreversible brain injury

absence of neurocritical care

These are not discussed sufficiently.

H. Discussion

Generally well written.

However there are several issues.

1. Comparison with literature

Comparisons are limited.

Important to contextualize with African ICU mortality rates, which are typically:

30–50%

67% is very high.

Possible reasons should be discussed:

delayed ICU admission

lack of ventilators

lack of imaging

infectious etiologies

2. Interpretation of TBI result

Finding:

TBI protective (HR 0.66)

Explanation given:

selection bias

This is reasonable.

But other explanations:

TBI patients younger

reversible pathology

ICU admission bias

Better discussion needed.

3. Overinterpretation

The paper repeatedly suggests:

strengthening oxygen therapy will improve survival.

This is not proven by observational data.

The language should be softened.

I. Limitations

This section is good but incomplete.

Missing limitations:

1. Confounding by indication

Major issue for treatment variables.

2. Selection bias

Only ICU patients included.

3. Lack of cause-of-coma classification

Major weakness.

4. Lack of severity scores

No APACHE / SOFA.

J. Conclusion

The conclusion is mostly appropriate.

But this line overreaches:

oxygen therapy could substantially reduce preventable deaths

Better:

ensuring reliable oxygen availability may represent a priority area for strengthening essential critical care.

K. Tables

Tables are clear.

Minor issues:

Table 2

Continuous variables reported with HR per unit.

Interpretability could improve if scaled:

Example:

SBP per 10 mmHg.

L. Key revisions needed:

1. Clarify cohort definition

Explain inclusion of GCS 9–14.

2. Improve literature review

Add African ICU studies.

3. Address confounding by indication

Interpret treatment variables cautiously.

4. Expand limitations

5. Clarify database creation

6. Improve discussion of extremely high mortality

Reviewer #2:   PONE-D-26-08886

In-hospital survival and factors associated with mortality among adults with impaired consciousness in intensive care in Benin, a low-resource setting: a retrospective cohort study

In this retrospective cohort study, the authors examined in-hospital survival and factors associated with mortality among adults with impaired consciousness admitted to an ICU in Benin. Among 416 patients, mortality was high (67.1%) with a median survival of five days. Mortality was associated with age, GCS score, systolic blood pressure, body temperature, and oxygen therapy.

Comments

The introduction should be more reflective of the title of the Manuscript, the Authors start with a broad discussion on critical care systems, based on the title the focus should be more about coma/impaired consciousness as a clinical entity and its epidemiology.

The Authors should better clarify why the study relies on data from 2015–2017. It is unclear if there is still relevance regarding these findings, as ICU capacity or practices in Benin might have changed since.

The definition of impaired consciousness requires clarifications: The inclusion of patients with GCS 3–14 introduces substantial clinical heterogeneity, particularly between mild impairment and deep coma, this should be discussed by the Authors, and a sensitivity analysis could be considered.

The short median survival time suggests high early mortality. The authors should emphasize this finding and better link it to potential gaps in early critical care delivery.

The first section of the discussion should be revised to include the aim of the study and a conceptual summary of the results

Several terms appear to be used interchangeably throughout the manuscript (“impaired consciousness,” “coma,” and “comatose” are used to describe the study population, despite inclusion criteria spanning GCS 3–14;“in-hospital mortality” and “ICU mortality,” as well as “survival time,” “time to death,” and “ICU length of stay,” are used without clear distinction). The Authors should standardize terminology and ensure consistent use of key terms across all sections of the manuscript

Reviewer #3:  The authors have addressed the previous comments well, and the manuscript has improved significantly.

The study is clear, well organized, and the methods are appropriate. The statistical analysis is adequate, and the results support the conclusions. The discussion is balanced and reflects the limitations of the study.

This work provides useful data from a low-resource setting, which is important and adds value to the literature.

I have no major concerns.

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Reviewer #1: No

Reviewer #2: No

Reviewer #3: Yes:  Abdullah Abbas Saleh Al-Murad

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Survival and factors associated with intensive care unit mortality among adults with impaired consciousness in Benin, a low-resource setting: A retrospective cohort study

PONE-D-26-08886R1

Dear Dr. Sossou,

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

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Kind regards,

Nik Hisamuddin Nik Ab. Rahman

Academic Editor

PLOS One

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