Incidence and predictors of severe acute malnutrition mortality in children aged 6-59 months admitted at Pawe general hospital, Northwest Ethiopia.

BACKGROUND: Severe acute malnutrition (SAM) is defined as a weight-for-height < -3z scores of the median WHO growth standards, or visible severe wasting or the presence of nutritional edema. SAM related mortality rates in under-five children are well documented in Ethiopia but data on their predictors are limited. We aimed to document factors associated with SAM related mortality to inform better inpatient management.
METHODS: A facility-based retrospective cohort study was conducted among children admitted due to SAM at Pawe General Hospital, Northwest Ethiopia, from the 1st of January 2015 to the 31st of December 2019. Data from the records of SAM children were extracted using a standardized checklist. Epi-Data version 3.2 was used for data entry, and Stata version 14 was used for analysis. Bi-variable and multivariable Cox regression analyses were conducted to identify predictors of mortality. Variables with P<0.05 were considered significant predictors of mortality.
RESULTS: Five-hundred sixty-eight SAM cases were identified of mean age was 27.4 (SD± 16.5) months. The crude death rate was 91/568 (16.02%) and the mean time to death was determined as 13 (±8) days. Independent risk factors for death were: (i) vomiting AHR = 5.1 (1.35-21.1, p = 0.026), (ii) diarrhea AHR = 2.79 (1.46-5.4, p = 0.002), (iii) needing nasogastric therapy AHR = 3.22 (1.65-6.26, p = 0.001), (iv) anemia AHR = 1.89 (1.15-3.2, p = 0.012), and (v) being readmitted with SAM AHR = 1.7 (1.12-2.8, p = 0.037).
CONCLUSION: SAM mortality was high in under-five children in our setting. The identified risk factors should inform treatment and prevention strategies. Improved community health education should focus on healthy nutrition and seeking early treatment. Inpatient mortality may be reduced by stricter adherence to treatment guidelines and recognizing early the key risk factors for death.

Introduction

Malnutrition remains one of the most common causes of morbidity and mortality in children throughout the world. It is responsible directly or indirectly for 60% of the 10.9 million deaths annually among under-five children and two-thirds of these deaths occur during the first year of life [1]. Childhood under-nutrition incorporates a combination of nutrition disorders that include underweight, wasting, stunting, and micronutrient deficiency [2,3]. Underweight (low weight-for-age) is a composite measure of wasting and stunting (low height-for-age) while wasting (low weight-for-height) is acute malnutrition due to a recent failure of nutrition (e.g. lack of food) or a recent infection like diarrhea causing weight loss. Severe acute malnutrition is defined as either a weight-for-height < -3z scores of the median WHO growth standard, a mid-upper-arm circumference (MUAC) < 115 mm, visible severe wasting, or the presence of nutritional edema [2,4]. Although SAM occurs globally and may affect all ages, infants and young children are most vulnerable, as they have higher nutritional requirements for growth and development [5], and sub Saharan Africa bears the greatest burden of SAM [6]. The peak age for SAM is 6–18 months, which is the time of fast growth and brain development [7].

Globally, in 2018 one in 12 of the estimated 52 million children under five had SAM [8], and 2.9 million of these children were admitted for inpatient treatment [8,9]. Despite the availability of outpatient treatment, 50% of SC admitted children with SAM die due to inappropriate care [10] and one important reason is poor adherence to SAM therapeutic guidelines [11]. Other factors include the presence of danger signs seen in sicker children like lethargy, hypoglycemia and hypothermia as well as bradycardia, capillary refill > 2 seconds, weak pulse volume and impaired level of consciousness [12].

The World Health Organization (WHO) has developed SAM management guidelines that, ifstrictly followed, should reduce the mortality to less than 10%. Mortality from SAM has, however, persistently remained between 10 and 40% in many hospitals in Sub Saharan Africa, despite the use of these guidelines. Malnutrition in Ethiopia has long been a contributing cause of death in infants and young children with estimates of 270,000 deaths each year [13]. According to the 2014 Health and Health-Related Indicators (HHRI), SAM was the third leading cause of mortality in Ethiopia and accounted for 8.1% of all deaths in under-five children [2,14,15]. This high mortality has been commonly attributed to HIV infection, lack of maternal participation in feeding programs, inadequate care and prescription errors, and over-prescription of intravenous therapies and blood transfusions. SAM in Ethiopia still accounts for 20% of pediatric hospital admissions and 30% of inpatient deaths [16]. Few studies have been conducted in Ethiopia to determine the predictors of inpatient mortality in SAM affected children. Indeed, no such study has been done in North West Ethiopia yet this region has the highest prevalence of SAM in Ethiopia. We, therefore, assessed the incidence and predictors of SAM related mortality rate in children under five undergoing inpatient treatment for SAM.

Methods and materials

Study area, design and setting

The study was conducted in the Pediatric ward of the Pawe general and referral hospital (PGRH) in the North Western province of Benishangul Gumuz, which is 560 km from Addis Ababa, the capital city of Ethiopia [17,18]. According to the 2019 national population projection, this region has an estimated 1.21 million inhabitants [19]. The Pediatric ward has 152 beds and a separate SC center for children with SAM. Ethiopia has adopted the WHO SAM treatment guidelines of under-five children using three phases: phase I, the transition phase, and phase II. In all phases, admitted children are treated empirically for infections, hypoglycemia, and resuscitated to restore electrolyte balance.

Study design

This was a facility-based retrospective cohort study that was conducted among SAM children under five years who were admitted to PGRH, Northwest Ethiopia, from the 1st of January 2015 to the 31st of December 2019.

Sample size determination

We determined the sample size using the single population proportion formula: n = (Za/2)2P (1-P)/d2 and a 95% confidence level (Za/2) = 1.96. Assuming an overall mortality rate from research 46% [3], a margin of error of 5%, and allowing an additional 15% for incomplete data, the sample size was 438 children. In the event, we found 578 records between January 1, 2015 and December 31st 2019 and included them in the study.

Outcome ascertainment

The dependent variable was death while an inpatient. The independent variables assessed included medical characteristics of children at enrolment.

Definitions

Admission criteria: The WHO SAM definition for children aged 6–59 months of age was used; either a weight-for-height < -3z scores of the median WHO growth standards, or MUAC <115 mm, visible severe wasting, or the presence of nutritional edema [20]. Discharged/declared cured: this was defined as a child whose weight-for-height/length is ≥ -2z scores without edema for at least 2 weeks or a MUAC >115 mm and no edema for at least 2 weeks [5].

Defaulted/lost to following up: a child who was not seen for at least two consecutive days after starting treatment [2]. Anemia in children defined as hemoglobin concentration <11 g/dL [21].

Data collection instrument and quality controls

A standard and pre-tested data extraction form was used to extract the required information from the case notes of SAM children [1]. Before the actual data collection, the prepared checklist of variables was pretested on 28 case notes of SAM children from Jawi primary hospital. A 2-day training was given for three diploma nurses and one BSc public health officer on the objectives of the study, variables of interest and maintaining data confidentiality. Strict follow-up and supervision were carried out during data collection by the principal investigators and feedback was given on a daily basis. The collected data were checked for inconsistencies, coding errors, completeness, accuracy, clarity, and missing values.

Data processing and analysis

Data were entered using Epi-Data version 4.2 statistical software and exported to STATA (SE) R-14 version statistical software for further analysis. We used Cox proportional hazards regression models with robust sandwich covariance matrix estimates to account for repeated measurements for each child. Kaplan–Meier survival analysis was used to determine the cumulative probability of death for all children and the mean time to death. Variables with P-value < 0.25 in the bi-variable Cox regression analysis were included in the multivariable Cox regression model. We tested the assumptions of the Cox Proportional Hazards model using Schoenfeld residuals. Variables with an adjusted hazard ratio (AHR) and 95% confidence interval (CI) and a P value <0.05 were considered as significant predictors of inpatient mortality.

Ethical statement and consent

The institutional review board (IRB) of Debre Markos University approved the study protocol Ref. No: HSC/984/16/12. A formal letter was submitted to PGRH requesting permission for the data collection. Data security and participants’ confidentiality were maintained at all levels of data management.

Results

Baseline socio-demographic and clinical characteristics

After excluding 10 (1.74%) files due to incompleteness, we reviewed 568 files of SAM cases registered for treatment from 1st January 2015 to December 31 2020. Of the included children (Table 1), slightly more than half, 324 (57.04%) were females. The majority of children 356 (62.68%) were aged 6–24 months and the mean age was 26.28 (SD = ±16.04) months. Just over three quarters were rural residents, almost two thirds were breastfeeding, and the majority, 457 (80.46%), were newly admitted SAM cases. More than half (318) of the SAM cases were due to wasting and the remaining 153 and 97 had marasmus-kwashiorkor and kwashiorkor, respectively. Wasting was observed mostly in the 6–24 months age group.

Table 1

Baseline socio-demographic characteristics of 568 severe acute malnutrition admitted children in Pawe general hospital from 2015–2019.

Variables	Characters	Frequency %
Sex	Male	244(42.96)
	Female	324 (57.2)
Residence	Urban	126(22.18)
	Rural	442(77.82)
Age	Between 6–24 month	355(62.68)
	Between 24–48 month	160(28.17)
	Above ≥48 month	53(9.15)
SAM types	Wasting (marasmus)	318(55.99)
	Marasmus Kwashiorkor	153(26.94)
	Kwashiorkor (edematous)	97(17.08)
TB	Present	70 (12.32%)
	Absent	498 (87.68%)
HIV	Positive	40 (7.04%)
	Negative	528 (92.96%)
Skin dermatitis	Absent	353(61.8%)
	Present	217(38.2%)
Pneumonia	Present	296 (52.11%)
	Absent	272 (47.89%)
Anemia	Absent	399(70.75%)
	Present	169(29.75%)
Malaria	Present	42(7.39%)
Vomiting	Absent	281(47.89)
	Present	296(52.13)
Fever ≥37.5°C)	Absent	265(46.65)
	Present	303(53.35)
Diarrhea	Absent	257(45.2)
	Present	311(54.75)
Breastfeeding status	No breastfeed	207(36.4)
	Yes breastfeed	361(63.56)
Admission type	New admission	457(80.46)
	Re-admission	111(19.54)
Nasogastric tube inserted	Yes	243(41.02)
	No	325(58.98)
Vitamin A supplementation	Given	470 (82.7)
	Not given	98 (17.25)
Folic acid	Given	406 (71.48)
	Not given	162 (28.52)
Deworming	Given	242 (42.61)
	Not given	326 (57.39)
Blood transfusion during admission	Given	123 (21.65)
	Not given	445 (78.35)

Co-morbidities

More than half the children were febrile on admission and 217 had dermatitis; 307 cases had comorbidities like SAM with diarrhea, pneumonia or anemia. 296 (52.11%) children had pneumonia at baseline, while 42 (7.39%) had a positive blood film for malaria. 528 (92.96%) children were HIV negative. Supplementary treatments included vitamin A, folic acid, deworming, and blood transfusions.

Inpatient treatment outcomes

Of the 568 children, 91 (16.02%) died while in hospital with 32 and 24 deaths occurring in phase I and the transition phase, respectively (Table 2). The mean time to death was 13 (±8) days. Of the total 568 SAM, 326 children were cured and the remaining 106 and 45 were lost to follow-up and transferred to other care facilities, respectively. Our outcome data compared to the national Sphere reference standards are shown in Table 3.

Table 2

Outcomes according to the World Health Organization phases.

Indicators		Phase 1	Transition phase	Phase 2	Total
1	Deaths	32 (35.16%)	24 (26.37%)	35 (38.4%)	91(16.02%)
2	Cure	97(29.7%)	105(32.2%)	124(38.03%)	326 (57.39%)
3	Lost to follow up	11(10.3%)	34(32.07%)	61(57.5%)	106 (18.66%)
4	Transferred out	6(13.3%)	30(66.6%)	9(2%)	45 (7.92%)
	Total	146(25.7%)	193(33.9%)	229(40.3%)	568 (100%)

Table 3

Performance indicators achieved at Pawe general and referral hospital from 2015–2019 compared to the national Sphere reference standards (N = 568).

Parameter		Performance of Pawe General hospital (N = ~ 5 years)	SPHERE project reference values
	Indicator of Performance	Achievement	Overall	Acceptable	Alarming
1	Cure rate	326 (57.39%)	77.9%	>75%	<50%
2	Incidence of death	91 (16.02%)	12.3%	<15%	>25%
3	Lost to follow-up	106 (18.66%)	5.2%	<10%	>15%
4	Transfer out	45 (7.92%)	4.4%	____	____
	Total	568 (100%)	100	-----	-------

Incidence rate of mortality

At the end of follow-up, there were 5,146 days of observation days for an incidence rate of 1.77 deaths per 100 days and the overall probability of death was 19.28% (95% CI: 14.6–40.5).

Predictors of SAM mortality

In the bi-variable analysis living in rural areas, hemoglobin level < 11 g/dl, admission types, nasogastric therapy at admission, vomiting during admission, malnutrition types, diarrhea, MUAC, deworming, WFA, HFA, IV fluid, and breastfeeding status were found to be significant predictors of mortality. In the multivariable Cox-regression analysis, only five variables were found to be predictors of mortality (Table 4). These were: (i) vomiting AHR = 5.1 (1.35–21.1, p = 0.026), (ii) diarrhea AHR = 2.79 (1.46–5.4, p = 0.002), (iii) needing nasogastric therapy AHR = 3.22 (1.65–6.26, p = 0.001) (iv) anemia AHR = 1.89 (1.15–3.2, p = 0.012), and (v) being re-admitted with SAM AHR = 1.7 (1.12–2.8, p = 0.037).

Table 4

Bi-variable and multivariable Cox regression for predictors of mortality.

Covariate	Categories	Survival status		CHR (95%CI)	AHR (95%CI)	P-value
		Death	Censored
Age of children	6–24 Month	68(11.9%)	186(32.74%)	1
	24–48 month	22(3.8%)	145(25.5%	0.9 (0.57–1.4)	1.2 (0.73–2.01)	0.443
	≥48 month	1(0.18%)	46(8.1%)	0.61 (0.59–4.4)	2.1 (0.82–3.9)	0.27
Sex	Male	30(5.3%)	214(37.6%)	1.13 (0.89–1.43)	0.96 (0.61–1.53)	0.859
	Female	61(10.7%)	263(46.3%)	1	1
Admission types	New	67(11.79%)	183(32.2%)	1	1
	Re-admission	24(4.2%)	294(51.6%)	1.7 (2.4–6.1)	1.7 (1.03–2.8)	0.037*
NGT	Yes	79(13.9%)	164(28.7%)	2.3 (2.3–6.99)	3.22(1.65–6.26)	0.001*
	No	12(2.2%)	313(55.09%)	1	1
Vomiting	Yes	88(15.5%)	208(36.5%)	2.34 (1.28–4.3)	5.1(1.35–21.2)	0.026*
	No	3(5.4%)	269(47.4%)	1	1
Anemia	Present	64(11.3%)	105(18.3%)	4.2 (2.6–3.67)	1.89(1.2–3.12)	0.012*
	Absent	27(4.8%)	372(65.3%)	1	1
Diarrhea	Yes	79(13.9%)	232 (40.7%)	5.6 (2.99–10.6)	2.79 (1.46–5.4)	0.002*
	No	12(2.1%)	245(43.01%)	1	1

Discussion

In this retrospective study, we have shown that the overall crude incidence of mortality was 16% with more than half of deaths occurring early in the first and the transition phases. This overall mortality rate is higher compared to other studies in Ethiopia like Mekele hospital, 3.8% [4], Tigray general hospital, 6.65% [4], Dilla referral hospital, 7.57% [11], Bahir-Dare referral hospital, 7.7% [22], and the Hawassa University Comprehensive Specialized Hospital (HU-CSH) in Southern Ethiopia, 10.8% [23]. One difference might be that these are university/tertiary referral hospitals which provide excellent care. A high proportion (a little under 20%) of our patients was lost to follow up which was likely due to their absconding/self-discharging because they could not afford to pay for their care. It is probable that many such children also died so our death rate may be underestimated. We also report that the mean time to death after admission was 13 (±8) days. This is similar to that reported from Gondar specialized referral hospital, 12 days [2], but quicker than the HU-CSH, 17 days [23], Mekele Ayder referral hospital, 41.2 days [4], and Shebedino hospital, 36 days [24].

We identified five independent risk factors for death. Vomiting had the highest risk for death, 5-fold compared to no vomiting on admission, and is consistent with findings at North Gondar [25]. Vomiting may cause or exacerbate dehydration leading to renal impairment and the need for NGT or IV fluids. Moreover, we observed an almost 3-fold death increased with diarrhea in line with the studies in Lusaka, [26], Gondar [25], and in Southern Ethiopia [24]. Diarrhea will also cause hypovolemic and exacerbate the deleterious effects of vomiting. The use of an NGT was also associated with mortality, just over 3-fold, and this association has also been reported in studies from Gondar [2] and Dilla [10] referral hospitals. Our study revealed that anemia was another significant factor for death and was associated with an almost 2-fold increased likelihood of death compared to those with no anemia. This may be explained by the deleterious effects of anemia, a poor response to transfusion, and/or a delayed transfusion due to the large number of patients to attend to. The association of anemia and death has also been reported by others in Gondar [2], Nekemte referral hospital [27], and in South Africa had (2.5-fold risk) [28]. A child may experience more than one episode of SAM, depending on the improvement of the underlying factors during inpatient treatment [29], but if re-admitted with a relapse, then the risk of death is doubled. Other factors that may be important in our setting include serving a poor pastoralist community, delayed presentation, lack of maternal participation in feeding programs, over prescription of intravenous therapies, early discontinuation of treatment due to insufficient financial means [2], and poor adherence of WHO SAM treatment guidelines [11,30]. One study from Uganda also identified WHO defined danger signs on admission, namely, lethargy, hypoglycemia, hypothermia, bradycardia, capillary refill > 2 seconds, weak pulse volume and impaired level of consciousness [12]. We did not record these clinical details nor did we collect data on biochemical indices and the socioeconomic status of caregivers. Therefore, the interpretation and application of our findings for clinical decisions and policy should take into account these limitations.

Conclusion

The SAM mortality rate was high in our children from one stabilizing center in northern Ethiopia. We identified five important factors for death, vomiting, diarrhea, NGT, anemia, and being readmitted with SAM whilst others have identified important clinical signs associated with death. Health education on seeking early medical care, adherence to guidelines and reducing the early abandonment of treatment because of lack of money may improve child survival in our setting.

Final data set of SAM.

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8 Jun 2021

PONE-D-21-11027

INCIDENCE AND PREDICTORS OF SEVERE ACUTE MALNUTRITION MORTALITY RATE AMONG CHILDRENS FROM 6-59 MONTHS IN STABILIZING CENTER AT PAWE GENERAL HOSPITALS, NORTHWEST, ETHIOPIA 2020.

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Reviewer #1: This is an interesting paper addressing a very important topic in Pediatrics health. However, the manuscript is full of English grammar errors, the methods are not clear while results are unstructured. Find my full comments attached.

Reviewer #2: Thank you very much for the opportunity to review this manuscript on incidence and predictors of mortality in children with SAM.

The introduction focuses on malnutrition broadly as well as SAM specifically, but sometimes it is unclear which of these definitions the authors are referring to. It might be beneficial if the authors mainly focus on SAM and the rationale for examining predictors of mortality in children with SAM. There is also a description of past research looking at predictors of mortality described in the introduction, and there have been other studies done in this area in addition to the one cited, so it would be useful for the authors to explain how their study adds to the literature.

This analysis used data from 2008 and the end of 2012. (However, later on, the inclusion criteria are stated as children admitted between 2015-2019 so it is unclear what years were used.) If the admissions were between 2008 and 2012, what are the potential limitations of using data from several years ago, and why were more recent data not considered? The authors should also discuss changes in treatment protocols over time, as updates to the WHO guidelines were released in 2013 for example. It would also be important to explain the admission criteria for this treatment centre.

Minor comments

In the abstract and the introduction, the authors use the idiom “lion’s share” which may not be familiar to all readers, so perhaps this could be changed to more common terminology and to specify whether this is about the absolute number of deaths or mortality rates in sub-Saharan Africa versus other regions.

It appears there may be a typo in the abstract in which authors say that the mortality rate was observed within 4578 days.

In the abstract, is also unclear what the authors mean by “not take in” F-75/F-100 formula. Do the authors mean feeding difficulties or loss of appetite, or that children were not provided these formulas?

The sample size calculation is unclear, and appears that it may be appropriate for a prospective study rather than a retrospective analysis.

The terms kwashiorkor and marasmus should be replaced by oedematous malnutrition and severe wasting, respectively.

In the results section, the authors describe the mean weights of children with SAM, yet it would be more useful to provide z-scores if possible since it is difficult to interpret weights alone.

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Reviewer #2: No

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Submitted filename: INCIDENCE AND PREDICTORS OF SEVERE ACUTE MALNUTRITION MORTALITY RATE AMONG CHILDRENS FROM 6.docx

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27 Jun 2021

Dear Reviewers thanks what you forward comments and question in our manuscript for publication

Indeed we all editors , reviewers and authors worked for reduction of infant and children mortality

especially we authors conduct this original research on the silent killer crisis issue of sever acute malnutrition among children admitted in stabilizing center .

All efforts made for benefit of the study subject based on scientific intervention . The benefit of publication of this research is multi lateral for Ethiopia, also in study area .There for Please consider in the positive way for publication process .

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7 Jul 2021

PONE-D-21-11027R1

INCIDENCE AND PREDICTORS OF SEVERE ACUTE MALNUTRITION MORTALITY RATE CHILDREN AGE 6-59 MONTHS ADMITTED IN STABILIZING CENTER PAWE GENERAL HOSPITAL, NORTHWEST ETHIOPIA 2020

PLOS ONE

Dear Dr. Kebede,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

Please submit your revised manuscript by 31st of August. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

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We look forward to receiving your revised manuscript.

Kind regards,

Walter R. Taylor

Academic Editor

PLOS ONE

Dear Fassikaw Bedebe,

I have been though the paper in some detail and seen that you have made a lot of effort to improve it.

The quality of the English remains quite low and must be improved before I can accept the paper. Please, if you can, find a native speaker.

A few general comments. The paper is quite long and in repetitive in places. Please use line numbers for the next revision so I can more easily point out any changes.

Here are some additional points.

Abstract

Replace lion’s share with most

paw – is Pawe hospital, please correct

Anaemia is defined as Hb < 11 g/dL in the text but it is < 10 g/dL in the Abstract. Please correct.

Study design & area

Not clear about the percentages of beds – 29% and 25% are stated.

Independent variables

The terms kwashiorkor and marasmus should be replaced by oedematous malnutrition and severe wasting, respectively.

Define all abbreviations like ARTI WFA etc

MUAC definitions vary from < 115cm to <=115 cm. Please correct this.

The inclusion and exclusion criteria are the same

Dependent variable. It is not clear when death has to take place – is it as an inpatient in the stabilising centre or some time after discharge?

CO morbidity

One in 5 = 20% not 11.98%. Please just report the %s and numerators and denominators

Remove and etc

Antimalarial treatment i.e. short course or was it really antimalarial prophylaxis ? Please state which drugs were used and for how long.

Please tell us what is in F75and F100 and what the indications are to give one or the other

Mortality incidcne

I do not understand where the median follow up period of 13.5 days comes from. Please tell us how long children were admitted in the SC and how long the follow up period was after discharge.

IV is a parenteral method so please delete.

References

The text has a reference 29 but the reference list stops at 20.

Repetitive text:

Descriptive analyses such as tables, graphs, Kaplan–Meier survival curves, and the log-rank test were performed.

Discussion

The mean waiting time is reported but this is not defined in the Methods section. Please clarify.

I do not see the relevance of mentioning stunting and overweight.

Table 3.

Please explain I the text about different treatment phases.

Please send back the paper when it is ready.

yours sincerely,

Walter Taylor

15 Aug 2021

Thank for devoting your invaluable time with my manuscript reviewing

In fact Sever acute malnutrition is silent killing crisis in Ethiopia especially on under-five children

so please consider

Submitted filename: Response to Reviewers .edited.docx

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31 Aug 2021

PONE-D-21-11027R2

INCIDENCE AND PREDICTORS OF SEVERE ACUTE MALNUTRITION MORTALITY RATE FOR CHILDREN AGE 6-59 MONTHS ADMITTED IN STABILIZING CENTER, NORTHWEST ETHIOPIA 2020

PLOS ONE

Dear Mr. Kedebe ,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

Please submit your revised manuscript by 30th of September. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

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If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see:  http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols . Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at  https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols .

We look forward to receiving your revised manuscript.

Kind regards,

Walter RJ Taylor

Academic Editor

PLOS ONE

Additional Editor Comments:

Dear Mr. Kedebe,

I have read the paper and it is an improvement on the previous revision. However, the English is not yet at a standard that can be accepted. Please find a good or native speaker to revise it.

There are also a number of areas in the paper that are unclear and inconsistent.

These are detailed below.

Yours sincerely,

Bob Taylor.

The death rate percentages vary within the manuscript. Please sort this out.

The Abstract talks of a a “means follow….” But later refers to this as “waiting time.” Both are unclear to me, Please clarify.

The Abstract reports a survival of 88.23% when the overall mortality is 16.7%. The total exceeds 100%. Please clarify.

Page 3

However, 50% of children with SAM die during treatment…… reference 13 reports a cumulative survival rate of ~85% so where does the 50% mortality come from?

and in fact, the majority (1.5%–40%) – In English, the majority usually means > 50%. Delete this.

Page 10

Nearly one in five (11.98%), and one fourth (29.2%) study participants

1 in 5 = 20%, a lot higher than 11.98%. Please amend. Please always show the numerators when you show a %.

Page 11. Please delete etc.

Page 11. 91 (16.23%) then IDR = 16.29%. Please note the death rate in the Abstract 16.7% in the Abstract. Please make sure the crude death rate is the same throughout the paper.

I don’t see the point in reporting the death rate after 1, 2 and 3 weeks etc. We should be able to see this for the KM curve.

Page 12

Among 568, study participants, 91(16.29%) SAM admitted cases developed the event of inters. INTEREST

Page 13

Death rate 16.73% and the 16.7 on the next line.

The average (mean) waiting time of 13.5 days in this study is in agreement with the finding in Gondar 12days[5].

Is this correct? What is the waiting time? It has not been defined in the M&M section.

I do not understand what this sentence means:

“The elucidation for this finding might be an instant similarity management team with a medical supply set.”

Page 14

“Furthermore, as indicated by the results of this study, the cumulative survival probabilities on 7th, 14th, 21st, and 28th day was 97.8%,84.48%,60.5%,56.5%and 48.9%, respectively.”

Consider removing this. What does it tell us? Moreover, we have 4 time intervals but five death rates.

Page 15

Pease complete this sentence: This is comparable with a study conducted by work et al. [37],

Table 1.

What drug is this – Premaquinin?

Table 2. Mean waiting time - what is this?

Table 3 Death rate 16.02%. please correct.

Figure 3. This shows that the cumulative survival rate over 30 days is 0%. Please correct.

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

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4 Sep 2021

Thanks dear reviewers for devoting your time and enthusiastic way of revising my manuscript for fruit full ways of my efforts

Submitted filename: Response to Reviewers .edited.docx

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16 Sep 2021

A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.

A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.

An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols.

We look forward to receiving your revised manuscript.

Kind regards,

Walter RJ Taylor

Academic Editor

PLOS ONE

Journal Requirements:

Additional Editor Comments (if provided):

Dear Mr. Kebede,

Thankyou for sending an updated revision.

The quality of the English is better but still needs to be improved before the paper can be published. Most of the errors are easily fixed by a native speaker.

I have a few specific points.

Abstract

“During SAM inpatient treatment recovery, transfer out, lost follow-up, and death was found 326 (57.39%), 106(18.66%), 46 (8.10%), and 91(16.02%), respectively. The overall incidence of the mortality rate was 16.03 per 100 (95%CI: 13.86; 20.04) person-days observations.”

I do not understand why there are two different rates for mortality.

I would suggest you replace “Operational words” with Definitions.

“or mid-upper-arm circumference ≤115 mm, or presence of bilateral edema, and failed appetite test should be admitted for inpatient care[23].”

The current MUAC definition is <115 mm. Please change. The cited reference is fine.

Discussion

The Sphere cut off is <10% but <11% in the Abstract. Please correct.

Conclusion

A majority usually means > 50% so please amend this sentence. Why not say that mortality in your series was high and half the deaths occurred within 2 weeks.

Then list the key factors and suggest clinical care be focused preferentially on these risk factors.

Tables.

Table 1.

I cannot find the drug “Permaquinin” on Google or in the Ethiopian Guidelines for treating SAM. Please tell us the name of this drug.

Table 2.

Please explain what “Waiting time” means.

Table 4.

This is unclear. Is it showing an overall survival rate for all the children? If so, 21.09% survival is much less than the reported survival in the paper:

“At the end of this study period, 326 (57.39%) admitted under-five children had been cured”

Figures.

Labelling of the Y axes of the 3 figures has been cut away. Please make sure we can see the labels.

Figure 3.

This makes no sense to me. It shows a very low survival rate. I suggest you either remove this Figure or put in the correct KM curve.

Figure 7.

Analysis is not spelt correctly on the X-axis.

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

17 Sep 2021

Thanks to be with my manuscript and devoting your time of reviewing

Submitted filename: Response to Reviewers Version 4.docx

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5 Oct 2021

A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.

A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.

An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols.

We look forward to receiving your revised manuscript.

Kind regards,

Walter RJ Taylor

Academic Editor

PLOS ONE

Additional Editor Comments:

Dear Mr. Kebede,

Thankyou for sending an updated revision.

The quality of the English is a little better but it is clear that you have not been able to find a native speaker to help you with the language.

Below are several of the more serious errors in language that I request you amend.

Introduction

Childhood under-nutrition incorporates a combination of nutrition disorders that included underweight

“that include…”

recent failure to received

“to receive”

Globally in 2018, 52 Million under-five-years -children in one in twelve of this age group -are

suff ering from SAM

“Globally in 2018, 1 in 12 of the estimated 52 million children under five had SAM.”

The one underline reason is health care provider's poor adherence to world health organization SAM therapeutic guidelines [1], besides to late coming of the patient for treatment[11]

“One important reason is poor adherence to… and another is late presentation.”

Malnutrition in Ethiopia is a long-term silent killing crisis, especially for infants, and children yet contribute to an estimated 270,000 deaths of under-five children each year [12].

“…, especially for infants, and contributes to an……”

Despite Ethiopia launching the Seqota declaration to end up severe acute malnutrition death by

“to end…”

Although, the magnitude of mortality among SAM admitted under-five children were a good document in Ethiopia, survival

“Although the….. children is well documented in….”

Methods

The Pediatric ward is among the five inpatient departments found in Pawe general hospital with 252 beds for inpatient treatment [20, 21]. Thought, the stabilizing center is separately built with single-based beds for children in SAM patient's treatments.

“The Pediatric ward is among the five inpatient departments found in Pawe general hospital with 252 beds for inpatient treatment [20, 21] and a separate stabilizing center for children with SAM.”

In all phases admitted children were, treated and prevented for infections, resuscitated, restored electrolyte balance, hypoglycemia, and hypothermia.

“In all phases admitted children are treated empirically for infections, hypoglycemia and hypothermia and resuscitated to restore electrolyte balance.”

Results

In this study, the outcome of interest is the SAM inpatient death, and death was defined as

following after inpatient admission to report of death during treatment observation.

“In this study, the outcome of interest was inpatient death due to SAM.”

Operational words

Hgb levels mainly classified into two ways: No anemia >11 g/dL, and Anemia≤10.9 g/dl [25].

Please check this. To me it should be <11 and >=11 g/dL.

Result

and the mean age was participants was 26.28 (SD = ±16.04) months.

“and the mean age was 26.28 (SD = ±16.04) months.”

The majority, 356 (62.68 %) of children have aged between 6-24 months years Vs. bottom number 47 (8.27%)of ≥48-month children.

This sentence is very unclear. Suggest you change it to: “ The majority of children, 356 (62.68 %), were aged between 6-24 months.”

majority of 38(41.11%) deaths were reported at Phase I within 24-144 hours after admission. Inversely, 124(38.6%) SAM admitted children declared as cured at phase II (Table3).

“majority of deaths, 38 (41.11%), were reported during Phase I within 24-144 hours after admission whilst 124 (38.6%) of SAM children were cured in phase II (Table3). “

Which was higher than the national SPHERE reference (<11%) [9]. This difference might be due to delayed presentation to the health institution (SC) and discontinuation of treatment by the financial limit to buy accessory drugs and foods after admissions [5] beside to worthless contribution of health care providers poor adherence to world health organization's SAM treatment guidelines [1, 27].

“This was higher than the national SPHERE reference (<11%) [9] and might be due to delayed presentation to the health institution (SC), early discontinuation of treatment due to insufficient financial means admissions [5], and poor adherence to WHO SAM guidelines [1, 27].”

A child may experience more than one episode of SAM relapsing, depending on the improvement of the underlying factors during inpatient [31]. Likewise, in this report death hazard was two times increased for re-admitted (relapsed) SAM cases as compared with new SAM inpatient SAM cases.

“A child may experience more than one episode of SAM, depending on the improvement of the underlying factors during inpatient treatment [31]. SAM relapses have a two-fold hazard of death.”

A new analysis of the multiple burdens of malnutrition within nations provides novel insights into the degree of childhood stunting, anemia, and overweight. This exposes 29% of the experience of re-admissions[32].

This sentence does not make any sense. I suggest you delete it.

The finding in Lusaka, Zambia [33], Gonder referral hospitals [34], Southern Ethiopia. [2], and Irena [33] revealed that SAM children admitted with baseline diarrhea were increased the risk of mortality rate as compared with counter groups, which is similar with twice hazards of death increased in our study finding. This is might be due to children having more than three episodes of stool loss per day is highly associated with the cleaning of micronutrients from their body and shunting of intracellular fluids causes hypovolemic shock.

“In Lusaka, Zambia [33], Gonder referral hospitals [34], Southern Ethiopia. [2], and Irena [33], SAM children admitted with baseline diarrhea had an increased risk of death, consistent with our two-fold increase in death, which may be due to combination of fluid and electrolyte loss and possible hypovolemic shock.”

Delete this sentence: This could be due to the shrinking of the intracellular potassium pumping balance of the body homeostatic.

Limitations

it failed to consider a broad range of factors like some biochemical and individual bases economic status of caregivers’ might introduce a high array of missing confounders. As such, the interpretation and application of the finding for decision and policy direction should account for these inherent limitations of the study.

“it failed to consider a broad range of factors like some biochemical indices and the socioeconomic status of care givers. Therefore, interpretation the interpretation and application of the finding for decision and policy direction should account for these inherent limitations of the study.”

Figure 1.

Please change the title to something like “Number of SAM children admitted to Pawe hospital.”

Figure 2. Kaplan-Meier estimated survival……

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

7 Oct 2021

Dear editor we would like to thanks to be with this manuscript

Submitted filename: Response to Reviewers Version 4.docx

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25 Oct 2021

A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.

A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.

An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols.

We look forward to receiving your revised manuscript.

Kind regards,

Walter RJ Taylor

Academic Editor

PLOS ONE

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

Submitted filename: PONE-D-21-11027_R5_editor.pdf

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26 Oct 2021

Thanks for devoting your time to review this manuscript

Submitted filename: Response to Reviewers Version 4-5.docx

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10 Nov 2021

14 Nov 2021

I had address the issue raised the language part by senior researcher and for final step it is resolved please make it accept and make swift for finale publications steps thanks for your comment

Submitted filename: Response to Reviewers Version 4-5.docx

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7 Jan 2022

11 Jan 2022

Thanks for your comment

For the purpose of good information containing on back ground information of the study area, we were changed reference No.19 of the old version articles entitled as “UNICEF. Situation Analysis of Children and Women:Beni shangul-Gumuz Region. REPORT 2019” by

“Time to Develop and Predictors for Incidence of Tuberculosis among Children Receiving Antiretroviral Therapy; Tuberculosis Research and Treatment 2021, 2021:6686019.” Kebede F, Kebede T, Kebede B, Abate A, Jara D, Negese B, Shawano T.

However by the request of acadmic editore ways of new papers cited or retracted have been forbiden as a rules of PLOS ONE Journal Requirements

We have been corrected to be the first article on citation at reference No.19”

In short we have maintiend previouse citated article on the paper emetoled as “UNICEF. Situation Analysis of Children and Women:Beni shangul-Gumuz Region. REPORT 2019”

Please look at reference No-19

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17 Jan 2022

INCIDENCE AND PREDICTORS OF SEVERE ACUTE MALNUTRITION MORTALITY IN CHILDREN AGED 6-59 MONTHS ADMITTED AT PAWE GENERAL HOSPITAL, NORTHWEST ETHIOPIA

PONE-D-21-11027R8

Dear Dr. Kebede,

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.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

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Kind regards,

Walter RJ Taylor

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

17 Feb 2022

PONE-D-21-11027R8

Incidence and predictors of severe acute malnutrition mortality in children aged 6-59 months admitted at Pawe general hospital, Northwest Ethiopia

Dear Dr. Kebede:

I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department.

If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact onepress@plos.org.

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on behalf of

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PLOS ONE