The burden of stroke and modifiable risk factors in Ethiopia: A systemic review and meta-analysis.

BACKGROUND: The burden and contribution of modifiable risk factors of stroke in Ethiopia are unclear. Knowledge about this burden and modifying risk factors is pivotal for establishing stroke prevention strategies. In recent decades, the issue of lifestyle and behavioral modification is a key to improve the quality of life. The modifiable risk factors are an importance as intervention strategies aimed at reducing these factors can subsequently reduce the risk of stroke. So far, many primary studies were conducted to estimate the burden of stroke and modifiable risk factors in Ethiopia. However, the lack of a nationwide study that determines the overall pooled estimation of burden and modifiable risk factors of stroke is a research gap.
METHODS: To conduct this systemic review and meta-analysis, we are following the PRISMA checklist. Three authors searched and extracted the data from the CINAHL (EBSCO), MEDLINE (via Ovid), PubMed, EMcare, African Journals Online (AJOL), and Google scholar. The quality of the primary study was assessed using the Newcastle-Ottawa Scale (NOS) by two independent reviewers. The primary studies with low and moderate risk of bias were included in the final analysis. The authors presented the pooled estimated burden of stroke and its modifiable risk factors. The registered protocol number in PROSPERO was CRD42020221906.
RESULTS: In this study, the pooled burden of hemorrhagic and ischemic stroke were 46.42% (95%CI: 41.82-51.53; I2 = 91.6%) and 51.40% (95%CI: 46.97-55.82; I2 = 85.5%) respectively. The overall magnitude of modifiable risk factor of hypertension, alcohol consumption and dyslipidemia among stroke patients were 49% (95%CI: 43.59, 54.41), 24.96% (95CI%:15.01, 34.90), and 20.99% (95%CI: 11.10, 30.88), respectively. The least proportion of stroke recovery was in the Oromia region (67.38 (95%CI: 41.60-93.17; I2 = 98.1%). Farther more, the proportion of stroke recovery was decreased after 2017 (70.50 (56.80-84.20).
CONCLUSIONS: In our study, more than 90% of stroke patients had one or more modifiable risk factors. All identified modifiable stroke risk factors are major public health issues in Ethiopia. Therefore, strategy is designed for stroke prevention to decrease stroke burden through targeted modification of a single risk factor, or a cluster of multiple risk factors, used on a population, community, or individual level.

Background

Stroke remains the second leading cause of death worldwide with an annual mortality rate of 5·5 million. Fewer women (2·6 million) than men (2·9 million) have died from stroke [1, 2]. The incidence, prevalence, and mortality rate of stroke have increased worldwide, with most of the burden being in the low and middle-income countries including Ethiopia [3, 4]. Hemorrhagic stroke is responsible for more deaths and Disability-Adjusted Life-Years (DALYs). Incidence and mortality of stroke differ between countries, geographical regions, and ethnic groups [5].

Ethiopia faces the unenviable threat of a triple burden of disease: infectious diseases, Non-Communicable Diseases (NCDs), and injuries [6]. Although Ethiopia is progressing towards national health coverage, the country faces the triple burden of diseases [7]. The magnitude of stroke-related deaths in Ethiopia is 6.23% out of total deaths, and the age-adjusted death rate of stroke in the country is 89.82 per 100 000 of the population [8]. Besides, previous reports indicated that 90% of the burden of stroke is attributable to modifiable risk factors [9]. Of this, three-quarters of the stroke burden is attributable to behavioral risk factors [10]. Metabolic factors (high blood pressure, obesity, fasting plasma glucose, cardiac disorder, and total cholesterol) accounted for 72% of stroke DALYs, and behavioral factors (smoking, poor diet, and physical inactivity) accounted for 66% [11-15]. In Ethiopia, a comprehensive nationally representative study on stroke burden and its modifiable risk factor are lacking. Thus, this study aimed to determine the overall pooled burden and its modifiable risk factors of stroke in Ethiopia.

Methods and analysis

Protocol design and registration

A systematic review with a meta-analysis of published and unpublished observational studies was incorporated to assess the burden of stroke and its modifiable risk factors in Ethiopia. To develop this systemic review and the meta-analysis, the authors used the Preferred Reporting Items for Systematic Review and Meta-analysis Protocol (PRISMA-P) [16, 17] and Meta-analysis of Observational Studies in Epidemiology (MOOSE) guideline statement [18]. This systemic review and meta-analysis protocol was registered in the International Registration of Systems Reviews (PROSPERO) with CRD 42020221906.

Eligibility criteria

The eligibility of the study was determined using the following criteria: (1) all facility-based observational studies; (2) all studies conducted in Ethiopia; (3) all studies reporting either the magnitude of any subtypes of stroke or rate of improvement at discharge and modifiable risk factors; and both published and unpublished studies. On the other hand, the authors excluded the following: anonymous reports, case reports, qualitative studies, and texts whose full texts could not be accessed after three email contacts of principal investigators of the particular studies.

Information source and search strategies

We used standardized and well-described methods in this systemic review [16]. Briefly, a search strategy was developed using fundamental concepts in the research question: Medical Subject Headings (MESH), keywords, and synonyms. The search strategy for PubMed: the keywords which we used in our search included terms describing stroke, age, and modifiable risk factors shown in the search strategy as follows: (1) (Stroke [Title] OR “Ischemic stroke”[Title] OR “Ischaemic stroke”[Title] OR “Haemorrhagic stroke”[Title] OR “Hemorrhagic stroke” OR “Cerebral Vascular Accident” OR CVA); (2) (Adults OR “18 years or older”) [Text Word] (3) (Ethiopia) [Text Word] (4) (Hypertension OR “High blood pressure” [Text Word] OR Diabetes [Text Word] OR “Diabetes mellitus” OR “Smoking” OR “Obesity” OR Alcohol OR “Heavy drinking” [Text Word] OR Physical exercise OR “Physical activity” [Text Word] OR (High blood cholesterol level OR “Hypercholesterolemia, Hyperlipidemia” OR “Hyperlipoproteinemia” OR “Arterial fibrillation) [Text Word] (5) #1 AND #2 AND #3 AND #4 (S1 Table).

A pretest of the search strategy by two authors was performed in PubMed. The actual electronic search was done from November 20 to 25, 2020. Two independent authors were implemented the electronic search in the following electronic databases: CINAHL (EBSCO), MEDLINE (via Ovid), PubMed, EMcare, AJOL, and Google scholar search engines. Finally, the search process was presented in a PRISMA flow chart.

Study selection

Two of the reviewers (TWA and BWA) screened the titles and abstracts of each article to find potentially eligible studies. After removing duplicates, the search results were exported to End-Note software (version X7 Thomson Reuters, New York, NY) to create a bibliographical database of the retrieved references. The selection process was conducted in two stages: first screening of titles and abstracts against the predetermined inclusion/exclusion criteria, followed by a second screening of the full text of the research reports identified as probably relevant in the initial screening. Both stages were carried out independently by two authors (TWA and AG), and disagreements were resolved by discussion with another author (BWA).

Data extraction process and quality assessment

The abstract and full-text review data abstraction was done by three independent authors (TWA, BZ, and AG) using a pre-piloted data extraction format prepared in the MicrosoftTM Excel spreadsheet. Disagreement in data abstraction between the first two and third authors was resolved by a fourth independent author (BWA). From each observational study, we had extracted data regarding participant gender, study year, region, sample size, study design, and first author name. In addition to these data, the proportion of ischemic stroke, hemorrhagic stroke, improvement at discharge, and each modifiable risk factor (hypertension, diabetes mellitus, alcohol consumption, smoking, heart disease, lack of physical activities, cholesterol, and obesity) was also extracted from each primary study.

Before analysis, prevalence transformation was carried out. The Newcastle-Ottawa Scale (NOS) was used to assess the quality of the included studies. The NOS had three categorical criteria with a maximum score of ten points. The assessment tool contains representatives of the sample, sample size, non-respondents, and ascertainment of exposure, independent blind assessment, and statistical test. Based on NOS, a score of 6 out of 10 was considered as good quality. To maintain the validity of this review, we only included primary studies with fair to good quality [17-19].

The primary outcome of this study was the pooled overall burden of stroke and its modifiable risk factors among stroke patients in Ethiopia. Stroke was defined as rapidly developing clinical signs of focal, or at times, global disturbance of cerebral function, lasting more than 24 hours or leading to death with no apparent cause other than a vascular origin [20, 21].

Quality assessment

The risk of bias of included studies was assessed using the 10-item rating scale developed by Hoy et al. for prevalence studies [22]. The assessment tool has a representative sample size, data collection method, reliability, and validity of study tools, case definition, and prevalence periods of the studies. Researchers categorized each observational article study as having a low risk of bias (“yes” answers to domain questions) or a high risk of bias (“no” answers to domain questions). Each study was assigned a score of 1 (Yes) or 0 (No) for each domain, and these domain scores added to give an overall study quality score. Scores of 8–10 were considered as having a “low risk of bias,” 6–7 a “moderate risk,” and 0–5 a “high risk.” For the least risk of bias classification, discrepancies between the reviewers resolved via consensus.

Data analysis

Heterogeneity test and publication bias

Heterogeneity between the findings of the primary studies was assessed by using Cochran’s Q test and quantified with the I-square statistics. A P-value of less than 0.1 was considered to suggest statistically significant heterogeneity. A heterogeneity was considered a small number of studies and their heterogeneity in design [23]. Heterogeneity classifications were: I-square values below 25% low, 25–75% moderate, and above 75% high [24]. Thus, the random-effect model was used to pool the burden of stroke and its modifiable risk factors since the studies were found heterogeneous [25].

We used the random-effect model to investigate the source of heterogeneity. The meta-analysis was weighted to account for the residual between-study heterogeneity (i.e., heterogeneity not explained by the covariate in the regression [26]. Publication bias was assessed by visual inspection of funnel plots based on the shape of the graph (subjective assessment). The symmetrical graph was interpreted to suggest an absence of publication bias, whereas an asymmetrical one indicated the presence of publication bias.

We employed Begg’s and Egger’s weighted regression to identify the source of publication bias (objective assessment). P-values less than 0.05 were considered as the presence of significant publication bias [27, 28]. We also applied a leave-out sensitivity analysis to estimate whether the pooled effect size was affected by a single studies. A leave-one-out sensitivity analysis was performed to confirm whether there were study potentially biased the direction of the pooled estimate. Subgroup analyses by region and type of study setup (hospitals) was carried out because of significant heterogeneity between studies (i.e., I2 = 96.5%, p<0.05).

Statistical analysis

Data was analyzed in Stata Version 14. Data was presented in the evidence table and summarized using descriptive statistics. The effect measure for outcome variables was computed using the “Metaprop” command for meta-analysis of the proportion in Stata. In this review, the overall burden of stroke, rate of improvement, and common modifiable risk factors were calculated together with their corresponding 95% CI. A forest plot was generated to display the pooled burden of strokes and its common modifiable risk stroke at 95% CI, the author’s name, study year, and study weights.

Result

Study selection process

From electronic databases, we retrieved 986 observational studies. After screening their titles and abstracts, 644 duplications were removed using Endnote X7. Of the remaining 342 articles, 315 articles were excluded because their titles and abstracts were not in line with our inclusion criteria (full article not found, different population, different setting, and different outcome). Finally, 27 articles were included for this systemic review and meta-analysis (Fig 1).

Fig 1

Flow chart to a selection of studies for a systematic review and meta-analysis of the proportion of adherence to healthy lifestyle modification of people with hypertension in Ethiopia 2020.

Study characteristics

Overall, we selected a total of 27 observational studies in this systematic review and meta-analysis. We included a total of 5,845 participants. Among them, 2,647 participants were male, and 3,228 participants improved at the time of discharge. The number of participants in each study ranged from 73 to 503. The most retrieved studies (n = 8) were from Oromia [29-36] followed by Addis Ababa (n = 7) [37-43], Amhara (n = 7) [44-50], Tigray region (n = 4) [51-54], and Southern Nations Nationalities and People’s (SNNP) (n = 1) [55].

The smallest sample size was 73 obtained from a study conducted at Shashemene Referral Hospital, Ethiopia [29]. The largest sample size was 503 reported from a study done at Ayder Comprehensive Specialized Hospital, Northern Ethiopia [52]. Most studies dealt with hypertension as a modifiable risk factor of stroke (n = 24) [29–34, 36, 37, 38, 39–41, 43–46, 48, 50–55] followed by Atrial Fibrillation (AF) (n = 17) [30–32, 37, 38, 40, 41, 44–50–55], Diabetes mellitus (DM) (n = 15) [30, 31, 33, 37, 39–41, 44–46, 48, 49, 55–57], heart disease other than AF (n = 14) [29, 30, 32, 37, 38, 41, 43, 45–47, 49, 50, 54, 55], and high cholesterol levels (n = 7) [32, 33, 35, 37, 44, 48, 49, 51, 55] (Table 1).

Table 1

Study characteristics of included articles for the final systematic review and meta-analysis on the burden of modifiable risk factors and rate of improvement at discharge after stroke in Ethiopia 2020.

Authors name	Study year	Region	Sample size	Study design	Burden of Stroke reported outcome percentage (95% CI)
					Ischemic stroke	Hemorrhagic stroke	Female	Male	Improvement at discharge	NOS score
Asgedome SW.et al	2019	Tigray	216	R	55.6	44.4	58.3	41.7	77.8	8
Asres AK. et al	2018	AA	170	CC	51.2	37.6	42.9	57.1	72.4	7
Baye M. et al	2018	Amhara	448	R	31.5	68.5	58.0	42.0	59.8	8
Bedassa T. et al	2018	Oromia	242	R	64.3	35.7	-*	-*	-*	5
Beyene DT. et al	2017	Oromia	367	R	35.7	64.31	36.2	63.8	26.4	8
Dandena A. et al	2019	Oromia	283	P	43.1	44.5	35.0	65.0	-*	6
Deresse B. et al	2014	SNNP	163	P	50.3	49.7	33.7	66.3	85.3	8
Erkabu SG. et al	2016	Amhara	303	R	59.4	40.6	37	63.0	89.0	7
Fekadu G.et al	2017	Oromia	116	P	51.7	48.3	37.1	62.9	-*	6
Fekadu G.et al	2017	Oromia	116	CC	48.3	41.6	37.1	62.9	78.4	8
Fekadu G.et al	2017	Oromia	364	CC	42.3	57.7	42.9	57.7	94.0	7
Gebremariam SA. et al	2014	Tigray	142	CC	55.6	38.0	45.8	54.2	47.9	8
Gebreyohannes EA.et al	2017	Amhara	208	R	57.7	Not	57.7	42.3	87.5	7
Gedefa B. et al	2016	AA	163	R	35.6	64.4	43.6	56.4	69.9	8
Gelan Y. et al	2016	AA	227	CC	49.8	48.9	30.0	70.0	70.0	7
Greffie. ES et al	2013	Amhara	98	R	69.4	30.6	53.1	46.9	87.0	7
Gufue ZH. et al	2019	Tigray	503	R	56.6	43.4	50.1	49.9	85.1	7
Kassaw A.et al	2018	AA	170	R	51.2	48.8	42.9	57.1	80.0	8
Kefale B. et al	2019	Oromia	111	R	80.1	18.0	50.5	49.5	83.8	7
Mekonen HH.et al	2018	Tigray	89	R	32.6	36.6	63.2	51.7	-*	5
Mulat B. et al	2015	Amhara	427	R	56.7	43.3	63.2	36.8	-*	6
Mulugeta H. et al	2019	Amhara	162	R	50.0	30.0	53.7	46.3	27.2	7
Sultan M. et al	2014	AA	301	p	53.8	17.9	42.5	57.5	80.7	8
Tamirat KS. et al	2017	Amhara	151	R	60.3	39.7	50.3	49.7	90.7	7
Temesgen TG.et al	2017	Oromia	73	R	65.8	34.2	42.5	57.5	54.8	6
Zenebe G. et al	2001	AA	128	CC	43	57.0	39.8	61.7	-*	6
Zewdie A. et al	2016	AA	104	CC	44.2	55.8	44.0	56.0	-*	5

R: Retrospective, P: Prospective, CC: Cross-Sectional, AA: Addis Ababa, NOS: Newcastle-Ottawa Scale

-*: The variable was not reported in the primary study.

Quality appraisal

The quality score of the included study ranged from 5 to 8 to a mean score of 7.04 (SD = 0.94). Out of 27 studies, 21 (77.78%) studies received a low risk of bias. 5 studies [29–31, 36, 39, 44, 49, 51, 55] had a high risk of case definition, five studies [29, 30, 35, 45, 55] had random selection bias, and 14 studies [29, 33–35, 39, 41, 46, 47, 51, 53, 56] had a high risk of representation bias (S2 Table).

The magnitude of strokes in Ethiopia

From the total rank of twenty-seven primary studies, twenty-five studies provided information on the proportion of hemorrhagic stroke. Twenty-six studies also provide information on stroke proportion in females and males. Twenty primary studies reported the rate of improvement at discharge after stroke. As presented in the forest plot (Figs 2 and 3), the pooled estimate proportion of hemorrhagic and ischemic stroke were 46.42% (95%CI: 41.82–51.53; I2 = 91.6%) and 51.40% (95%CI: 46.97–55.82; I2 = 85.5%) respectively. The pooled estimate of stroke among females was 45.07% (95%CI: 41.80–48.35; I2 = 80.3%) and males was 54.70% (95%CI: 51.32–58.08; I2 = 79.5%) (S1 File).

Fig 2

Forest plot of in the proportion of hemorrhagic stroke in Ethiopia, 2020.

Fig 3

Forest plot of in the proportion of ischemic stroke in Ethiopia, 2020.

The magnitude of modifiable risk factors of stroke in Ethiopia

We investigated the magnitude of modifiable risk factors of stroke among the included studies. The proportion of DM among stroke patients ranged from 5.2% [54] to 21.6% [39]. To estimate the magnitude of DM among stroke patient, we used a total of 3356 stroke patients. Accordingly, our pooled analysis showed that 14.722% (95%CI: 9.51, 19.94; I2 = 95.8) of stroke patients had DM. In this review, stroke patients who had hypertension ranged from 24.1% [33] to 75.2% [32].

We studied a total of 5064 stroke patients to determine the pooled magnitude of hypertension in stroke patients. Consequently, we found that the overall pooled estimation of hypertension among stroke patients was 49% (95CI%:43.59, 54.41; I2 = 91.6%). Furthermore, the proportion of alcohol consumption (more than two drinks in a day for men and more than one drink in a day for women) among stroke patients included in this study ranged from 10.4% (55) to 41.4% (48). Our meta-analysis revealed that 24.96% (95%CI: 15.01, 34.90; I2 = 92.7) of stroke patients had a history of harmful alcohol intake (Table 2).

Table 2

The pooled effect of common modifiable risk factors among the primary studies of stroke in Ethiopia.

Modifiable risk factors	Estimated pooled proportion (95%CI)	I-squared (%)
Hypertension	49 (43.59, 54.41)	91.6
Diabetes mellitus	14.72 (9.51, 19.94)	95.8
Atrial fibrillation	19.21 (13.96, 24.46)	94.4
Other heart disease	20.11 (14.27, 25.95)	94.2
Dyslipidemia	20.99 (11.10, 30.88)	96.4
Smoking	10.38 (6.27, 14.94)	86.0
Obesity	11.64 (2.48, 20.79)	95.3
Alcohol	24.96 (15.01, 34.90)	92.7

Other heart Disease: Congestive heart failure, Structural heart disease, Myocardia friction.

Recovery from stroke in Ethiopia

The proportion of improvement during discharge after stroke among the included primary studies was ranged from 26.4% [30] to 94% [36]. We included 2321 stroke patients to estimate the pooled proportion of improvement at the time of discharge. The pooled improvement status of stroke during discharge in Ethiopia was 72.28% (95%CI: 62.48, 82.08; I2 = 96.5%) (Fig 4).

Fig 4

Forest plot of the proportion of recover during discharge after stroke in Ethiopia, 2020.

Publication bias

Both funnel plots of precision asymmetry and Egger’s intercept test showed no publication bias in the primary studies. Visual examination of the funnel plot showed symmetric distribution. Additionally, Egger’s intercept test was -0.147 (95% CI: -0.26, 1.18) p > 0.05 (0.102), and as judged by Egger’s test, there was no evidence of publication bias present at a 5% significance level (Fig 5).

Fig 5

Meta funnels presentations of the proportion of recover after stroke in Ethiopia, 2020, whereby SE PIV (standard error of proportion) plotted on the Y-axis and log PIV (logarithm of proportion).

Subgroup analysis

Due to the heterogeneity of included studies, we performed a subgroup analysis using the following study characteristics: region, sample size, and study year. We applied the random-effect model for reporting the pooled proportion of clinical outcomes during discharge in the subgroup analysis. Accordingly, the highest recovery rate (74.51) was observed from the Addis Ababa region (69.84–79.17; I2 = 34.5%). The least pooled proportion of recovery (67.38) was in the Oromia region (95%CI: 41.60–93.17; I2 = 98.1%). The subgroup analysis by study year showed that the pooled proportion of recovery rate after stroke during discharge was 75.59% (95%CI 64.28–86.9; I2 = 92.1%) for studies conducted before 2017 (Table 3).

Table 3

Subgroup analysis of recovery after stroke by region, sample size, and study year in Ethiopia 2020.

Variables	Characteristics	Estimated stroke recover during discharge (95% CI; I2 = %)
Region	Oromia	67.38 (41.60–93.17; I2 = 98.1)
	Addis Ababa	74.51 (69.84–79.17; I2 = 34.5)
	Amhara	73.44 (50.29–96. 59; I2 = 97.9)
	Tigray	70.19 (47.10–93.28; I2 = 95.7)
	SNNPR	Single study
Sample size	<223 (median)	72.41 (60.00–83.82; I2 = 96.0)
	> = 223 (median)	72.05 (527.44–91.66; I2 = 97.5)
Study year	Before 2017	75.59 (64.28–86.9; I2 = 92.1)
	After 2017	70.50 (56.80–84.20; I2 = 92.1)

SNNPR: South Nations, Nationalities and People Region.

Meta-regression and sensitivity analysis

The subgroup analysis showed that heterogeneity across the studies was widespread. To identify the source of heterogeneity, we conducted a meta-regression and sensitivity analysis. During the meta-regression analysis, we applied the following study covariance: study years and region. However, the results showed that none of these variables were a statistically significant source of heterogeneity. We also performed a sensitivity analysis to find the influence of each study on the overall effect size. No single study affected the overall pooled proportion of clinical outcomes of stroke among stroke patients in Ethiopia (Table 4, Fig 6).

Table 4

Meta-regression output to explore the heterogeneity of the pooled proportion of clinical outcome of stroke in Ethiopia, 2020.

Variables	Coefficients	P-value	95% CI
Study Year	-4.83	0.538	-21.03, 11.35
Region
Addis Ababa	-10.68	0.660	-61.37, 40.01
Amhara	-11.67	0.626	-61.63, 38.29
Oromia	-17.72	0.468	-68.44, 33.01
Tigray	-14.83	0.563	-68.26, 38.61

Fig 6

One-leave-out sensitivity analysis for studies conducted on the pooled estimated proportion of stroke clinical outcome in Ethiopia, 2020.

Discussion

This study aimed to determine the overall proportion of stroke burden and modifiable risk factors in Ethiopia. Of all stroke cases in our review, more than half (51.40%) of stroke patients in Ethiopia had ischemic subtype of stroke. While this finding was similar to study in Kenya (56.1%) [56]. It was much lower when compared to studies conducted in China (81.9–91.7%) [57, 58], Burkina Faso (61.63%) [59], Iran (76.5–81.9%) [60, 61], and a 22 countries case-control study (78%) [13]. The difference in culture and economic status, lifestyle difference, poor management of modifiable risk factors, and difference in the preventive strategies in the general public could be the reasons for the difference.

In this study, a higher prevalence of stroke was observed in males (54.70%) as compared to females (45.07%). A systematic review of epidemiological studies on Western European surveys has shown similar results with stroke being more common in males than females [62]. This gender difference is a hormonal makeup. The male sex is a known risk factor for stroke in humans, and female progesterone has a neuroprotective role in stroke [63]. There are clear differences in body size and vascular anatomy that are associated with an increased risk of stroke in males [64]. But females suffer from stroke at older ages making them more prone to die from stroke than males [65].

Our meta-analysis showed that almost half (49%) of all stroke patients had hypertension. Previous evidence has also shown that 75.8% of stroke patients had hypertension [59], hypertensive individuals are two to four times more likely to have a stroke [13, 57, 66]. Hypertension has remained the leading modifiable risk factor of stroke morbidity and mortality since 1990 [67]. People who can maintain normal blood pressure can decrease the risk of stroke by 30 to 40% [68].

Though hypertension is the main reported modifiable risk factor of stroke among the included primary studies, the pooled proportion of hypertension among stroke patients found in the current study is lower than the previous studies conducted in Burkina Faso [59], Iran [61], China [58], Bosnia-Herzegovina [69], Nigeria [70], and Bangladesh [71]. The possible explanation for this variation might be due to the lack of diagnostic modalities and proficiency, level of income, hypertension awareness, treatment, and control [72].

Above limit, alcohol consumption is a well-established risk factor of stroke. In our review, alcohol consumption is the second most common modifiable risk factor of stroke. Almost one-fourth (24.96%) of stroke patients had a history of alcohol consumption. Because harmful amounts of alcohol intake can trigger AF–a type of irregular heartbeat. Atrial fibrillation increases the risk of stroke by five times because it can cause blood clots to form in the heart. If these clots move up into the brain, it can lead to stroke [73].

In a review of 84 studies of alcohol consumption and cardiovascular disease, alcohol consumption >60 g/day increased the risk of incident stroke by 62% as compared to abstinence from alcohol [74]. The pooled proportion of alcohol consumption among stroke patients in Ethiopia was higher than a study conducted in Nigeria [72]. The possible explanation for this variation might be the lack of diagnostic modalities and proficiency; measured dyslipidemia in the medical record before the occurrence of stroke. Another reason for this variation is the lack of an effective community action to control alcohol consumption in Ethiopia [75, 76].

In our study, dyslipidemia is the third most common modifiable risk factor of stroke. More than two-tenths (20.99%) of stroke patients had dyslipidemia. Dyslipidemia promotes cervical or coronary atherosclerosis, which predisposes to athero-thrombotic and cardio-embolic stroke [77]. Our review is comparable with a previous study conducted in Nigeria [70]. However, this estimated proportion of dyslipidemia among stroke patients is lower than a study conducted in Bosnia-Herzegovina [69], and China [58].

The reasons for the above results could be attributed to the following: first, the dramatic increases in the prevalence of many known risk factors for chronic diseases such as unhealthy lifestyles (decreased physical activity, smoking, alcohol consumption, and westernized diet) [78, 79]. Second, the impact of rapid urbanization (increased risk of obesity) [80]. In Nigeria, dyslipidemia in stroke patients is closely linked to western diet and physically inactive lifestyle behaviors [81].

Diabetes is a well-established risk factor for stroke, and our analysis showed that diabetes mellitus is the fourth most common comorbidity of stroke. More than one-tenth (14.72%) of stroke patients had diabetes mellitus. Diabetes causes various micro-vascular and macro-vascular changes ending in major clinical complications [82]. The findings are comparable to the previous studies conducted in Nigeria [70]; higher than the studies done in Burkina Faso [59], sub-Saharan African [83], and a systematic review and meta-analysis done in Ethiopia respectively [84]. However, this proportion of diabetes mellitus among stroke patients is lower than studies done in Bosnia-Herzegovina [69] and Iran [61].

The result found in this study showed that the overall pooled estimated proportion of recovery after stroke in Ethiopia was 72.28% (95%CI: 62.48, 82.08). This finding is in line with the ideal proportional recovery rule of stroke [85-87] but lower than the goal set for 2015 (85%) in the Helsingborg Declaration 2006 [88]. This result is still lower than the previous studies conducted in Bosnia-Herzegovina [69], Iran [61], sub-Saharan Africa [83], and Kenya [89]. The possible reason might be a sup-optimal management protocol for stroke patients and lack of skilled personnel, appropriate treatment, and diagnostic agents in Ethiopia [90]. However, this result is relatively higher than previous studies conducted in Ghana [91].

The subgroup analyses by year of studies showed that the overall pooled proportion of recovery rate after stroke was higher among studies conducted before 2017. The lowest pooled proportion of recovery rate of stroke in this study population after 2017 may reflect the increased exposure to risk factors for stroke due to ongoing epidemiological and demographic transitions.

Limitations

There is considerable heterogeneity across the included studies. The observed heterogeneity may be attributed to differences in the study design, the quality of the studies, and sensitivity. Since our study focused on in-patient, it cannot externally validate to the general population.

Implication

This study has many implications for clinical practice and future research. First, develop effective strategies to practice healthy life habit to prevent stroke burden. Second, there has been an increasing emphasis on the need for stroke services managed in the health care service, the community and rehabilitations service. Third, identifying the challenges to amend modifiable stroke risk factors is the first step in developing evidence-based interventions to promote short and long-term health outcomes and quality of life. Future research should focus on developing and testing a conceptual model that can use accessibility to screening, treatment, sociocultural aspects of stroke risk factor modification in a national context. Finally, to give a long-term reduction in burden of stroke and modifiable risk factor-related co-morbidity, researchers should assess ways to extend and sustain lifestyle modifiable risk factors and recovery rate after in this population.

Conclusion

There is a high burden of stroke with a high rate of modifiable risk factors in Ethiopia. More than 90% of patients had one or more modifiable risk factors. Therefore, efforts should be focused on the primary prevention of stroke. Efforts should be taken to lower blood pressure, limit alcohol intake, early screen and treatment of atrial fibrillation and diabetes timely, quit smoking and improve physical activity.

PRISMA check list.

(DOCX)

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Figs 1 and 2.

Forest plot of in the proportion of stroke among female and male in Ethiopia, 2020.

(DOCX)

Click here for additional data file.

Search strategy applied to PubMed database in the current review.

(DOCX)

Click here for additional data file.

Risk of bias assessment tool of eligible articles by using the Hoy 2012 tool.

(DOCX)

Click here for additional data file.

Scoring of the quality of articles by authors using the Newcastle-Ottawa quality assessment tool.

(XLSX)

Click here for additional data file.

Data extraction speared sheet.

(XLSX)

Click here for additional data file.

21 Apr 2021

PONE-D-21-01404

Patient recovery from stroke and modifiable risk factors in Ethiopia: a systemic review and meta-analysis.

PLOS ONE

Dear Dr. Abate,

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 Jun 05 2021 11:59PM. 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:

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'.

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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,

Miguel A. Barboza, MD, MSc

Academic Editor

PLOS ONE

Journal Requirements:

When submitting your revision, we need you to address these additional requirements.

Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at

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At this time, please address the following queries:

2a)           Please clarify the sources of funding (financial or material support) for your study. List the grants or organizations that supported your study, including funding received from your institution.

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Please include your amended statements within your cover letter; we will change the online submission form on your behalf.

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4. Thank you for submitting the above manuscript to PLOS ONE. During our internal evaluation of the manuscript, we found significant text overlap between your submission and the following previously published works, some of which you are an author.

https://bmcneurol.biomedcentral.com/articles/10.1186/s12883-020-01870-6

https://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0229698

https://bmcpublichealth.biomedcentral.com/articles/10.1186/s12889-019-7505-7

We would like to make you aware that copying extracts from previous publications, especially outside the methods section, word-for-word is unacceptable. In addition, the reproduction of text from published reports has implications for the copyright that may apply to the publications.

Please revise the manuscript to rephrase the duplicated text, cite your sources, and provide details as to how the current manuscript advances on previous work. Please note that further consideration is dependent on the submission of a manuscript that addresses these concerns about the overlap in text with published work.

We will carefully review your manuscript upon resubmission, so please ensure that your revision is thorough.

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

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: Yes

Reviewer #2: Yes

Reviewer #3: Yes

**********

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

Reviewer #1: Yes

Reviewer #2: No

Reviewer #3: I Don't Know

**********

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

**********

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: No

Reviewer #2: No

Reviewer #3: No

**********

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: This is a good effort by the authors highlighting the burden of modifiable risk factors in stroke. The methodology and analysis approach is commendable.

However there are few points the need consideration:

1. There are multiple language errors, grammatical mistakes, typing errors which alter the meaning of what the authors may be trying to convey.

2. There is use of different fonts in different sections of the manuscript, which the authors need to address.

3. The discussion section needs to highlight the reasons for the difference in results of each significant risk factor when compared to other studies quoted.

4. The conclusion should emphasize how this study adds to literature; authors should point out feasible strategies suggested by them that can help address the modifiable risk factors in Ethiopia.

Reviewer #2: The authors tried to review stroke outcomes and modified risk factors in Ethiopia. I would like to thank the authors for trying to address the topic in caption.

I have the following comments for the authors, hoping these will make the article more plausible to readers:

1. Revise the research type as "review" not "research article"

2. Explain the operational definition you have used regarding "alcohol consumption", its broad term, is it any alcohol consumption?

3. You have not used "AJOL: database. However, most of articles from Ethiopia were published on local and regional journals; which are indexed by AJOL. So, I believe by not including AJOL in your searching process, you may miss many articles from Ethiopia.

4. You have also included un-published articles. But how did you access this un-published articles? because I know there are many published and un-published articles from our departments you haven't included.

5. The search key words are very few, to capture all modifiable stroke risk factor. Please explain this issue.

6. In the Analysis process, since the authors mentioned meta-analysis, they should present their results in "Forest plot", which they didn't included.

7. Please revise your discussion section by comparing your findings with other regions mainly focusing on points unique to this region.

8. Include your data extraction detail tables as a supplementary file for detail evaluation of your work.

Reviewer #3: Dear Editor,

Thanks for choosing me to review articles in your prestigious journal. I read the Research entitled: Patient recovery from stroke and modifiable risk factors in Ethiopia: a systemic review and meta-analysis. Here are some of my comments to the manuscript which needs from my point of view good English editing.

The Title: was unclear and ambiguous as one doesn’t understand whether the authors would investigate the impact of modifiable risk factors on recovery after stroke or would study both items in one research. It’s clear also that the patient in their results studied more items like magnitude of stroke in Ethiopia, stroke sub-types in Ethiopia, so this title should be changed to (for example): Burden of stroke in Ethiopia.

In the Abstract:

Background:

• Line 2,3 : The contribution of modifiable risk factors to the increasing global and regional burden of stroke is unclear. This sentence is not correct as the contribution of modifiable risk factors to the global burden of stroke is well studied in the international literature, so they should remove the word global from the sentence and specify the sentence to be regional (in Ethiopia).

• Line 3: crucial for informing stroke prevention strategies. This sentence is wrong, they should write for establishing stroke prevention strategies and I suggest that, the language of the paper should be revised by native speaker to be more clear and informative.

• Line 5: one of the keys to improving the quality of life. To improve not to improving, and as I said before the language of paper should be revised and rewritten by native speaker .

Conclusion: needs to be rewritten , it should be more concise and informative

Background:

• The introduction part was concise and clear, however as I said before need English editing.

• Page 3, Lines 17-20: should be removed as they are inconsistent with the research idea

• Page 4: Line 3 is a repetition to line 1, should be removed.

Methods and Analysis:

• Well written

The Results

Well written, however it needs like other manuscript parts English editing to be easier and more concise

• Magnitude of strokes in Ethiopia

The manuscript title was about the recovery from stroke and the modifiable risk factors, and in the results section there is big paragraph about the magnitude of stroke in Ethiopia without any hint in the abstract section or the title, this is should be considered by the authors, I recommend to change the title to for example: Burden of stroke in Ethiopia would be more informative

The discussion:

• The discussion part is poorly written. The authors should focus on comparing their findings with the similar publications from the same region, they should focus on African publications and when they compare with other international publications, there are many publications focusing on African American for example, but comparing their results with Chinese population is misleading as Asian population have distinct characters, distribution of risk factors and distinct pattern of atherosclerosis (intracranial mainly) which is different from African population.

**********

6. 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.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: Yes: Ivy Anne Sebastian

Reviewer #2: Yes: Biniyam A. Ayele, MD

Reviewer #3: No

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

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: PO Review_IS.pdf

Click here for additional data file.

8 May 2021

Response to Reviewers

Response to editor and reviewers’

Response to the editor:

We thank you and the reviewers for a thorough reading and constructive criticism of our manuscript and for the opportunity to revise and resubmit. We are pleased to submit the improved research article, including a proposed comment, “The burden of stroke and modifiable risk factors in Ethiopia: a systemic review and meta-analysis with a manuscript ID of PONE-D-21-01404”

1. General Comments:

#1. COMMENT: Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming.

RESPONSE: We have checked and attest that all formatting and style requirements have

been met PLOS ONE's style requirements.

#2. COMMENT: The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. At this time, please address the following queries…

RESPONSE: The authors received no specific funding for this work.

#3. COMMENT: Please include captions for your Supporting Information files at the end of your manuscript, and update any in-text citations to match accordingly.

RESPONSE: We include all capitation

#4. COMMENT: Thank you for submitting the above manuscript to PLOS ONE. During our internal evaluation of the manuscript, we found significant text overlap between your submission and the following previously published works, some of which you are an author.

RESPONSE: We revise the manuscript to rephrase the duplicated text.

2. Review Comments to the Author

REVIEWER #1 COMMENTS

1. COMMENT: There are multiple language errors, grammatical mistakes, typing errors which alter the meaning of what the authors may be trying to convey.

RESPONSE: the language expert copyedited the manuscript for language, spelling, grammar and sentence structure.

2. COMMENT: There is use of different fonts in different sections of the manuscript, which the authors need to address.

RESPONSE: Thank you this comment. We make uniform of fonts throughout the manuscript.

3. COMMENT: The discussion section needs to highlight the reasons for the difference in results of each significant risk factor when compared to other studies quoted.

RESPONSE: We try to highlight the reason from the different results of each significant risk factor when compared to other studies quoted.

4. COMMENT: The conclusion should emphasize how this study adds to literature; authors should point out feasible strategies suggested by them that can help address the modifiable risk factors in Ethiopia.

RESPONSE: We accept the comment and we emphasize feasible strategies in the nation- Ethiopia.

REVIEWER #2 COMMENTS

1. COMMENT: Revise the research type as "review" not "research article"

RESPONSE: we accept the comment and replace research article" by “review”

2. COMMENT: Explain the operational definition you have used regarding "alcohol consumption", its broad term, is it any alcohol consumption?

RESPONSE: when to say alcohol consumption, more than two drinks in a day for men and more than 1 drink in a day for women

3. COMMENT: You have not used "AJOL: database. However, most of articles from Ethiopia were published on local and regional journals; which are indexed by AJOL. So, I believe by not including AJOL in your searching process, you may miss many articles from Ethiopia.

RESPONSE: we included AJOL for a data bases

4. COMMENT: You have also included un-published articles. But how did you access this un-published articles? Because I know there are many published and un-published articles from our departments you haven't included.

RESPONSE: we access the institutional repository (like Jimma University, Addis Ababa University). If you have an included article, please share a link and we are ready to included

5. COMMENT: The search key words are very few, to capture all modifiable stroke risk factor. Please explain this issue.

RESPONSE: we select the most public health important modifiable factors

6. COMMENT: In the Analysis process, since the authors mentioned meta-analysis, they should present their results in "Forest plot", which they didn't included.

RESPONSE: we try to present the result in ‘Forest plot’ in figure 2 to figure 4.

7. COMMENT: Please revise your discussion section by comparing your findings with other regions mainly focusing on points unique to this region.

RESPONSE: we try to discuss by comparing our findings with other regions mainly focusing on points unique to this region.

8. COMMENT: Include your data extraction detail tables as a supplementary file for detail evaluation of your work.

RESPONSE: we include data extraction detail tables as a supplementary file.

REVIEWER #3 COMMENTS

1. COMMENT: The Title: was unclear and ambiguous as one doesn’t understand. So this title should be changed to (for example): Burden of stroke in Ethiopia.

RESPONSE: we changed the tittle as recommended “Burden of stroke and modifiable risk factors in Ethiopia: a systemic review and meta-analysis.”

On abstract part

2. COMMENT: abstract on back ground, line 2, 3. This sentence is not correct as the contribution of modifiable risk factors to the global burden of stroke is well studied in the international literature, so they should remove the word global from the sentence and specify the sentence to be regional (in Ethiopia).

RESPONSE: the sentence is specified in regional context-Ethiopia.

3. COMMENT: Back ground line 3: crucial for informing stroke prevention strategies. This sentence is wrong, they should write for establishing stroke prevention strategies and I suggest that, the language of the paper should be revised by native speaker to be more clear and informative.

RESPONSE: we accept the comment and write as the reviewer suggestion.

4. COMMENT: back ground line 5: one of the keys to improving the quality of life. To improve not to improving, and as I said before the language of paper should be revised and rewritten by native speaker

RESPONSE: we accept the comment and write as the reviewer suggestion.

5. COMMENT: Conclusion: needs to be rewritten, it should be more concise and informative.

RESPONSE: we try to revised the conclusion section.

Submitted filename: Response to Reviewers.docx

Click here for additional data file.

9 Jun 2021

PONE-D-21-01404R1

The burden of stroke and modifiable risk factors in Ethiopia: a systemic review and meta-analysis.

PLOS ONE

Dear Dr. Abate,

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 Jul 24 2021 11:59PM. 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:

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: 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,

Miguel A. Barboza, MD, MSc

Academic Editor

PLOS ONE

Journal Requirements:

Additional Editor Comments (if provided):

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

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 #1: (No Response)

Reviewer #3: All comments have been addressed

**********

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 #1: Yes

Reviewer #3: Yes

**********

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

Reviewer #1: Yes

Reviewer #3: 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 #1: Yes

Reviewer #3: 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 #1: No

Reviewer #3: 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 #1: 1. After reviewing the corrected manuscript, I would like to bring forward my concerns to the authors. Although the content of the paper is good, however the language errors and grammatical mistakes in the document are still far too many to consider this as a meaningful submission. The typing errors, missing verbs and punctuations completely take away from what the authors are trying to convey. I strongly recommend that they take the help of an English language expert to thoroughly revise the whole manuscript before submission.

2. In my previous review I had submitted an attachment with many comments and edits (apart from comments), however those have not been addressed at all. I urge the authors to go through the attachments submitted along with the comments as well before submitting their revisions.

3. The references are not in the correct format and there is no uniformity. Authors names as well as journal names are missing. Authors need to re-write this whole section and present the bibliography correctly.

4. I would like to re-iterate that the authenticity and content of a paper are just as important as the presentation, for acceptance to any journal. I request the authors to thoroughly go through the document again and make relevant edits before submission.

Reviewer #3: (No Response)

**********

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.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: No

Reviewer #3: Yes: Ahmed Nasreldein

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

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: plosone review_IS.pdf

Click here for additional data file.

23 Jun 2021

Response to Reviewers

Response to editor and reviewer

we thank you and the reviewers for a thorough reading and constructive criticism of our manuscript and for the opportunity to revise and resubmit. We are pleased to submit the improved research article, including a proposed comment, “The burden of stroke and modifiable risk factors in Ethiopia: a systemic review and meta-analysis.”

RESPONSE TO REVIEWER 1

REVIEWER #1 COMMENT:

1. Although the content of the paper is good, however the language errors and grammatical mistakes in the document are still far too many to consider this as a meaningful submission. The typing errors, missing verbs and punctuations completely take away from what the authors are trying to convey. I strongly recommend that they take the help of an English language expert to thoroughly revise the whole manuscript before submission.

RESPONSE: we try to address the comment and one fried who is a language expert help me in editorial technique.

2. In my previous review I had submitted an attachment with many comments and edits (apart from comments), however those have not been addressed at all. I urge the authors to go through the attachments submitted along with the comments as well before submitting their revisions.

RESPONSE: we addressed all the important comment in the revised manuscript.

3. The references are not in the correct format and there is no uniformity. Authors’ names as well as journal names are missing. Authors need to re-write this whole section and present the bibliography correctly.

RESPONSE: we intensive edit the whole reference by using endnote reference manager software.

4. . I would like to re-iterate that the authenticity and content of a paper are just as important as the presentation, for acceptance to any journal. I request the authors to thoroughly go through the document again and make relevant edits before submission.

RESPONSE: we try to thoroughly edit and incorporate all the comment of the reviewer

Submitted filename: Response to Reviewers.docx

Click here for additional data file.

2 Aug 2021

PONE-D-21-01404R2

The burden of stroke and modifiable risk factors in Ethiopia: a systemic review and meta-analysis.

PLOS ONE

Dear Dr. Abate,

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 Sep 16 2021 11:59PM. 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:

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: 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,

Miguel A. Barboza, MD, MSc

Academic Editor

PLOS ONE

Journal Requirements:

Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.

Additional Editor Comments (if provided):

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

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 #1: (No Response)

**********

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 #1: Yes

**********

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

Reviewer #1: 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 #1: 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 #1: 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 #1: The edited document is well-written and conveys this important topic well.

1. The references are however not according to format. Journal abbreviations need to be formatted.

2. Few other minor errors are present, which I have addressed in the attachment.

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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.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: Yes: Ivy Sebastian

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

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: PLOSONE 3.pdf

Click here for additional data file.

12 Aug 2021

Response to editor and reviewer

We thank you and the reviewers for a thorough reading and constructive criticism of our manuscript and for the opportunity to revise and resubmit. We are pleased to submit the improved research article, including a proposed comment, “The burden of stroke and modifiable risk factors in Ethiopia: a systemic review and meta-analysis.”

Response to editorial comment

Comment: Journal Requirements: Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.

RESPONSE: We revised the reference list a cording to journal requirements. Reference ’75: Alcohol and stroke, Factsheet13 (2014). ‘ with ‘Zhang C, Qin Y-Y, Chen Q, Jiang H, Chen X-Z, Xu C-L, et al. Alcohol intake and risk of stroke: a dose–response meta-analysis of prospective studies. International journal of cardiology. 2014;174’ the reason of replacement, the update one more appropriate one.(669-677)’ b

RESPONSE TO REVIEWER 1

REVIEWER #1 COMMENT:

1. The references are however not according to format. Journal abbreviations need to be formatted.

RESPONSE: we used reference manager software (EndNote) and mange according to this software manger.

2. Few other minor errors are present, which I have addressed in the attachment.

RESPONSE: we addressed all comment, which we have found in the attachment comments.

Submitted filename: Response to Reviewers.docx

Click here for additional data file.

23 Sep 2021

PONE-D-21-01404R3The burden of stroke and modifiable risk factors in Ethiopia: a systemic review and meta-analysis.PLOS ONE

Dear Dr. Abate,

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 see minor suggestions from one of the reviewers.

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We look forward to receiving your revised manuscript.

Kind regards,

Miguel A. Barboza, MD, MSc

Academic Editor

PLOS ONE

Journal Requirements:

Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.

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

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 #1: (No Response)

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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 #1: Yes

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

Reviewer #1: Yes

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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 #1: Yes

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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 #1: Yes

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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 #1: Please edit your references. The journal names should be in NLM abbreviated format.

For eg:

"Gorelick PB. The global burden of stroke: persistent and disabling. The Lancet Neurology.

22 2019;18(5):417-8." the correct NLM abbreviation would be Lancet Neurol.

All the references need to be edited in this format. If the authors are unaware, suggest to take help regarding the same before submitting.

**********

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.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: Yes: Ivy Sebastian

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

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.

13 Oct 2021

Response to editor and reviewer

We thank you and the reviewers for a thorough reading and constructive criticism of our manuscript and for the opportunity to revise and resubmit. We are pleased to submit the improved research article, including a proposed comment, “The burden of stroke and modifiable risk factors in Ethiopia: a systemic review and meta-analysis.”

RESPONSE TO EDITORIAL COMMENT AND RESPONSE TO REVIEWER 1

EDITORIAL/REVIEWER #1 COMMENT:

1. Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.

RESPONSE: we used reference manager software (EndNote) and mange according to this software manger. And also rewrite with ‘NLM abbreviation forma’

2. Please edit your references. The journal names should be in NLM abbreviated format.

RESPONSE: we try to edit all reference in NLM abbreviation format.

Submitted filename: Response to Reviewers.docx

Click here for additional data file.

18 Oct 2021

The burden of stroke and modifiable risk factors in Ethiopia: a systemic review and meta-analysis.

PONE-D-21-01404R4

Dear Dr. Abate,

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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If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. 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.

Kind regards,

Miguel A. Barboza, MD, MSc

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

20 Oct 2021

PONE-D-21-01404R4

The burden of stroke and modifiable risk factors in Ethiopia: a systemic review and meta-analysis.

Dear Dr. Abate:

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.

If we can help with anything else, please email us at plosone@plos.org.

Thank you for submitting your work to PLOS ONE and supporting open access.

Kind regards,

PLOS ONE Editorial Office Staff

on behalf of

Dr. Miguel A. Barboza

Academic Editor

PLOS ONE