Epidemiological profiles and causes of sudden deaths of various ages in Ethiopia: an autopsy-based study

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An autopsy is an important source of epidemiological data, as the considerable causes of sudden death remain hermetic until postmortem examination. This study is devoted to evaluating the sociodemographic, behavioral, clinical and pathological characteristics of sudden deaths of various ages in Ethiopia. Methods This is an observational, prospective, descriptive study that included all sudden deaths observed over 1 year at St. Paul’s Hospital and Millennium Medical College, Addis Ababa, Ethiopia. Results Sudden death (n = 568) accounted for 11.5% (95% CI: 10.6-12.4) of all autopsied cases. There were 482 males and 86 females (M:F ratio of 5.6:1) and a mean age of 44.8±17.349. The peak age group was the fourth and fifth decades, accounting for 43.9% of the cases. Chronic substance abuse and a history of prior illness were declared in 40.1% and 38% of cases of sudden death, respectively. Cardiovascular (36.1%), respiratory (32.6%), and gastrointestinal system (19.5%) pathologies were the most common causes. The leading underlying causes of sudden death were ischemic heart disease and pneumonia. Most (86.6%) sudden deaths occurred outside of a hospital setting. Conclusions Most of the causes of sudden death in Ethiopia can be prevented and treated. The majority of sudden deaths are silent without preexisting symptoms. Therefore, it is vital to develop public health measures that will help educate the community about the importance of recognizing the manifestation of various clinical conditions and the need to seek immediate clinical help. Furthermore, efforts should be made to make healthcare facilities accessible and affordable with adequate diagnostic and management capacity. Documentation of autopsy-based data could provide important epidemiological information to guide medical services, prevention efforts, and control measures. 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F1000Research 2025, 12 :1441 ( https://doi.org/10.12688/f1000research.142511.2 ) NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article. Close Copy Citation Details Export Export Citation Sciwheel EndNote Ref. Manager Bibtex ProCite Sente EXPORT Select a format first Track Share ▬ ✚ Research Article Revised Epidemiological profiles and causes of sudden deaths of various ages in Ethiopia: an autopsy-based study [version 2; peer review: 1 approved, 2 approved with reservations] Alemayehu Shiferaw Lema https://orcid.org/0000-0002-2884-5609 1 , Sesen Tsegaye Tekle 1 Alemayehu Shiferaw Lema https://orcid.org/0000-0002-2884-5609 1 , Sesen Tsegaye Tekle 1 PUBLISHED 05 Feb 2025 Author details Author details 1 Department of Forensic Medicine and Toxicology, St. Paul's Hospital Millennium Medical College, Addis Ababa, Ethiopia, 1271, Ethiopia Alemayehu Shiferaw Lema Roles: Conceptualization, Data Curation, Formal Analysis, Investigation, Methodology, Project Administration, Resources, Software, Supervision, Validation, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing Sesen Tsegaye Tekle Roles: Conceptualization, Data Curation, Formal Analysis, Investigation, Methodology, Project Administration, Resources, Software, Supervision, Validation, Visualization, Writing – Review & Editing OPEN PEER REVIEW DETAILS REVIEWER STATUS Abstract Background Sudden death is an important global public health issue. An autopsy is an important source of epidemiological data, as the considerable causes of sudden death remain hermetic until postmortem examination. This study is devoted to evaluating the sociodemographic, behavioral, clinical and pathological characteristics of sudden deaths of various ages in Ethiopia. Methods This is an observational, prospective, descriptive study that included all sudden deaths observed over 1 year at St. Paul’s Hospital and Millennium Medical College, Addis Ababa, Ethiopia. Results Sudden death (n = 568) accounted for 11.5% (95% CI: 10.6-12.4) of all autopsied cases. There were 482 males and 86 females (M:F ratio of 5.6:1) and a mean age of 44.8±17.349. The peak age group was the fourth and fifth decades, accounting for 43.9% of the cases. Chronic substance abuse and a history of prior illness were declared in 40.1% and 38% of cases of sudden death, respectively. Cardiovascular (36.1%), respiratory (32.6%), and gastrointestinal system (19.5%) pathologies were the most common causes. The leading underlying causes of sudden death were ischemic heart disease and pneumonia. Most (86.6%) sudden deaths occurred outside of a hospital setting. Conclusions Most of the causes of sudden death in Ethiopia can be prevented and treated. The majority of sudden deaths are silent without preexisting symptoms. Therefore, it is vital to develop public health measures that will help educate the community about the importance of recognizing the manifestation of various clinical conditions and the need to seek immediate clinical help. Furthermore, efforts should be made to make healthcare facilities accessible and affordable with adequate diagnostic and management capacity. Documentation of autopsy-based data could provide important epidemiological information to guide medical services, prevention efforts, and control measures. READ ALL READ LESS Keywords Sudden death, Sudden and unexpected natural death, Sudden cardiac death, Causes of death, Autopsy, Natural death, Ethiopia Corresponding Author(s) Alemayehu Shiferaw Lema ( [email protected] ) Close Corresponding author: Alemayehu Shiferaw Lema Competing interests: No competing interests were disclosed. Grant information: The author(s) declared that no grants were involved in supporting this work. Copyright: © 2025 Lema AS and Tekle ST. This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. How to cite: Lema AS and Tekle ST. Epidemiological profiles and causes of sudden deaths of various ages in Ethiopia: an autopsy-based study [version 2; peer review: 1 approved, 2 approved with reservations] . F1000Research 2025, 12 :1441 ( https://doi.org/10.12688/f1000research.142511.2 ) First published: 07 Nov 2023, 12 :1441 ( https://doi.org/10.12688/f1000research.142511.1 ) Latest published: 05 Feb 2025, 12 :1441 ( https://doi.org/10.12688/f1000research.142511.2 ) Revised Amendments from Version 1 This revised manuscript represents a significant enhancement of the previously published work, incorporating several key improvements. Notably, the methods section has been substantially expanded to provide a comprehensive and detailed account of the procedures, ensuring the study's replicability by other researchers. We have also diligently updated the references, incorporating recent publications and replacing some earlier citations with their most current versions. The statistical analysis and interpretation of the data have been meticulously clarified and elaborated upon, offering a more robust understanding of the findings. Furthermore, the discussion section has undergone a thorough revision, providing a more nuanced and insightful analysis of the results in the context of current literature. Finally, we have explicitly addressed the major limitations of this study, justifying these limitations and providing appropriate recommendations for future research. To gain a deeper understanding of the revisions, please refer to the peer review reports and our detailed author responses included alongside this article. These changes collectively strengthen the rigor and transparency of the research, contributing to a more accurate and complete picture of the study findings. This revised manuscript represents a significant enhancement of the previously published work, incorporating several key improvements. Notably, the methods section has been substantially expanded to provide a comprehensive and detailed account of the procedures, ensuring the study's replicability by other researchers. We have also diligently updated the references, incorporating recent publications and replacing some earlier citations with their most current versions. The statistical analysis and interpretation of the data have been meticulously clarified and elaborated upon, offering a more robust understanding of the findings. Furthermore, the discussion section has undergone a thorough revision, providing a more nuanced and insightful analysis of the results in the context of current literature. Finally, we have explicitly addressed the major limitations of this study, justifying these limitations and providing appropriate recommendations for future research. To gain a deeper understanding of the revisions, please refer to the peer review reports and our detailed author responses included alongside this article. These changes collectively strengthen the rigor and transparency of the research, contributing to a more accurate and complete picture of the study findings. See the authors' detailed response to the review by Lorraine Du Toit-Prinsloo See the authors' detailed response to the review by Joseph Westaby See the authors' detailed response to the review by Martina Modena READ REVIEWER RESPONSES Introduction Sudden death is an important global public health issue, especially when it occurs in apparently healthy individuals due to the bearing these losses have on individuals, families, communities and wider society. The definition of sudden death varies according to authorities and conventions. 1 According to the World Health Organization (WHO), death is considered a sudden death (SD) when a nonviolent and unexpected death occurs within 24 hours after the commencement of a fatal illness. 2 The frequency and pattern of sudden death in different parts of the world vary greatly due to the diversity of prevalent diseases in various nations and due to diverse genetic and environmental factors. 3 , 4 Sudden unexpected natural death is often the initial clinical appearance of an underlying condition in people who had previously been asymptomatic and seemingly healthy. 3 , 5 Furthermore, since many of these deaths are unwitnessed and unattended by clinicians, the extent of the problem is difficult to determine. In this circumstance, an autopsy is an initial and sole opportunity to determine and document the precise cause of death. 1 , 4 , 6 In Ethiopia, SD is regarded as a type of medicolegal death for which an autopsy is required to determine the cause. Public health authorities, therefore, depend heavily on vital statistics systems with a focus on the cause of death (COD) for formulating their programs, both curative and preventive specialist services. Mortality statistics are an essential component of the nation’s vital statistics system. They are the ingredients to measure population growth and provide a demographic perspective for the planning of development in social services. Cause-specific mortality rates are crucial measures of population health trends. There are several challenges in interpreting epidemiological information in resource-limited settings, including a lack of uniformity and low quality of death certificates as well as the utilization of verbal autopsies. 6 – 8 Thus, vital health information may not reach the national registry, which could prevent the implementation of crucial interventions and prevention measures. Accurate evidence on causes of death is necessary to recognize the general epidemiological profile of diseases in Ethiopia and to support decision-makers in prioritizing the public health agenda. An autopsy is an important source of epidemiological data, as the considerable causes of SD remain hermetic until postmortem examination. 1 Therefore, epidemiological autopsy-based data on sudden death causes are vital to understand the characteristics of the affected population and customize public health programs. To our knowledge, this is the first study paper on SD in Ethiopia and is devoted to documenting the sociodemographic, behavioral, clinical and pathological characteristics of sudden death cases of various ages. Methods This is an observational, prospective, descriptive study that included all sudden unexpected death with a known natural cause of death observed from July 1, 2019, to June 30, 2020 , in the Department of Forensic Medicine and Toxicology of St. Paul’s Hospital and Millennium Medical College (SPHMMC), Addis Ababa, Ethiopia. SPHMMC is a tertiary hospital and medical college governed by a board under the Federal Ministry of Health. SPHMMC in Addis Ababa and Aider Hospital in the Tigray region were the only two centers in the country providing forensic medicine and toxicology services during the study period. The Department of Forensic Medicine and Toxicology, SPHMMC, offers postmortem services to almost all regions of Ethiopia, except cases from the Tigray region served by Aider Hospital. This study included all SD cases (according to the WHO definition) brought for autopsy from July 1, 2019, to June 30, 2020. The WHO defines SD as death that occurs within 24 hours after the disease’s commencement in a person not known to have been diagnosed with a serious disease, accident, or poisoning. 2 In consideration of this definition, two factors were considered: 1) the time of onset of terminal signs or symptoms until death and (2) the expectation of death at the time of occurrence. The definition of the onset of terminal signs or symptoms used in this study was the time when an individual had to change his activity because of the illness. The time of death was defined as the time an individual was pronounced dead. For unwitnessed deaths in which an individual was known to have been alive within 24 hours before the pronounced time of death, they were considered sudden death. The second factor in deciding whether or not the death was sudden was the unexpected nature of the occurrence. The degree of disability reported before death was used as a measure of the expectation of death at the time of the event. Individuals who died but were confined to their homes, health facilities, or other related institutions due to illness for more than 24 hours before death were not considered unexpected deaths and were not included. Principal investigators and five well-trained medical doctors collected the data. Information on the biodata of the cases, clinical data and circumstances of the death was collected from all potential sources, such as police files, medical records, and direct interviews with the eyewitnesses, relatives, and friends of the deceased. The duration of hospital stay before death was extracted from the hospital record, autopsy referral papers, and police requests. Full postmortem examinations were carried out in each instance using the Letulle evisceration procedure, systematically inspecting all cavities, including the cranial, cervical, thoracic, and abdominal cavities. The standard gross examination of the heart was conducted following several key steps. 6 First, the pericardium was checked for any abnormalities and opened to explore the pericardial cavity. Second, the anatomy of the great arteries was checked, with the pulmonary artery opened in situ to identify any emboli, before being transected 3 cm above the respective valves. The pulmonary veins were then transected, and the superior vena cava was transected 2 cm above the junction of the right atrial appendage to preserve the sinus node. The inferior vena cava was transected near the diaphragm. When congenital heart disease or aortic dissection were suspected, the recommended examination procedure was followed. 6 The coronary arteries were serially sectioned every 3-4 mm from their origin to their distal portion to check for any thrombosis or atherosclerosis. The heart chambers were opened and inspected in the direction of blood flow. Finally, the hearts were weighed after dissection and had their chambers washed to remove any blood clots. All organs were dissected, examined and checked for signs of gross pathological changes and violence. Autopsied specimens (whole organs or organ pieces) were fixed in 10% formalin for histopathological examination. Multiple sections with thicknesses of 4-5 mm were taken. The tissues were processed, subjected to paraffin sectioning at a thickness of 4 micrometers and then stained using hematoxylin and eosin staining. In addition, toxicological screening, biochemical tests, and microbiology were performed in selected cases. However, genetic testing was not part of the investigations due to the absence of appropriate facilities in our setting. A structured data collection form was used to obtain all relevant clinical, epidemiological and pathological data. The predesigned data collection form was pretested in 50 cases to maintain data quality, and the necessary amendment was made to the form before the actual data collection. Data entry was performed using Microsoft Excel 2016 and exported to the Statistical Package for Social Science (SPSS window version 26) for analysis. Descriptive summary measures were used to characterize sociodemographic, behavioral, clinical characteristics and circumstances of death. A chi-square test was used to compare categorical variables, and the level of significance was set at a p-value <0.05. Ethics approval was obtained from the SPHMMC Institutional Review Board (Ethical clearance reference no: PM 23/188). The study was conducted as per the Declaration of Helsinki. All information was treated anonymously and confidentially using unique identification codes rather than individual names and identifications. Results Epidemiological characteristics A total of 4,942 medicolegal autopsies were performed during the study period, of which 568 cases were due to SD, accounting for 11.5% (95% CI: 10.6-12.4) of the total autopsied cases. The youngest case was a 1-day-old male newborn, and the oldest was a 98-year-old man, with a mean age of 44.8±17.349 years. Males (n = 482/586) were predominant over females (n = 86/586) at a ratio of 5.6:1. 36 The maximum number of sudden deaths (24.3%) was in the age group of 31-40 years, followed by 41-50 years, which represents 19.6% of all SD cases. SD was less prevalent in extreme age groups, less than 10 years (1.8%) and over 70 years (6.7%). Males outnumbered females in all age groups. The fourth decade was the most predominant age group seen in males and females, accounting for 23.9% and 26.7% of total sex-specific cases, respectively. The number of cases by age and sex is summarized in Figure 1 . Figure 1. Age and sex distribution of sudden death cases (n=568). More than two-thirds of the cases of SD (70%) belonged to urban areas, whereas 30% of cases were from rural areas. There was a statistically significant difference between the residence of the SD cases and sex (p<0.001). Among the cases of sudden death, 54.7% of females lived in rural areas and 45.3% lived in urban areas. 25.7% of males lived in rural areas and 74.3% lived in urban areas. Most of the cases were from Addis Ababa city, the capital city of Ethiopia, accounting for 59.2% (n=336) of cases, followed by the Oromia region (23.6%), and the remaining 17.2% were from six other regions of the country. Table 1 summarizes the sociodemographic characteristics of the cases of sudden death. Table 1. Summary of sociodemographic characteristics of sudden death cases. Sociodemographic characteristics Category Frequency Percentage Sex Male 482 84.9 Female 86 15.1 Residence Urban 397 70.0 Rural 171 30.0 Region/Administrative city Addis Ababa 336 59.2 Oromia 134 23.6 SNNPRS * 54 9.5 Amhara 28 4.9 Diredawa 7 1.2 Harar 4 0.7 Afar 3 0.5 Gambela 2 0.4 Occupation Not applicable (<18 years/student) 37 6.5 Employed 325 57.2 Unemployed 49 8.6 Retired 5 0.9 Unknown 152 26.8 Education Preschool 10 1.8 Illiterate 68 12.0 Primary school 22 3.9 Middle school 69 12.1 High school 165 29.0 Graduate/more 68 12.0 Unknown 166 29.2 Marital Status Unmarried 103 18.1 Married 237 41.7 Divorced 15 2.6 Widowed/r 57 10.1 Unknown 156 27.5 Religion Orthodox 181 31.9 Protestant 141 24.8 Muslim 85 15.0 Catholic 11 1.9 Unknown 150 26.4 * SNNRS-Southern Nations Nationalities and Peoples’ Regional States. Clinical characteristics and habits of substance abuse data Substance use was reported in approximately 40.1% (n=228) of all SD cases. Chronic alcohol use was reported in 24.3% of cases, followed by khat (Catha edulis) and cigarettes in 9.3% and 6.5%, respectively. Moreover, 10% of the cases use two or more of these substances. There was a statistically significant relationship between substance abuse and sex (p<0.001) and residence (p=0.004). Specifically, substance abuse was reported in 32% of males, in contrast to just 4.7% of females. Among individuals with documented substance use, 77.8% resided in urban areas. A different distribution was observed for chronic alcohol use and sex (p<0.001). Chronic alcohol use was documented in 27.8% of males compared to only 4.7% of females. More than one-third of cases (38%) had a history of prior chronic medical illness, and diabetes mellitus (n=97 cases, 17.1%) was the most common disease. In 5.8% of cases, there is a history of SD in first-degree relatives. There was a statistically significant relationship between the presence of a prior chronic illness and sex (p=0.022). No prior chronic illness was reported in 39.5% of female cases and in 26% of male cases. Table 2 summarizes the clinical characteristics and habits of substance use and SD in first-degree relatives of SD cases. Table 2. Clinical characteristics and habits of substance abuse data in sudden death cases. Clinical and habit data Frequency Percentage History of prior illness lifetime 216 38 Diabetes Mellitus 97 17.1 Hypertension 78 13.7 Ischemic heart disease 4 0.7 Valvular heart disease 4 0.7 Unspecified cardiac disease 1 0.2 Asthma 7 1.2 Chronic obstructive pulmonary disease 4 0.7 Liver disease 12 2.1 Peptic ulcer disease 3 0.5 HIV 4 0.7 Chronic kidney disease 2 0.4 History of sudden death first-degree relative 33 5.8 Unspecified cardiac disease 13 2.3 Ischemic heart disease 3 0.5 Asthma 10 1.8 Chronic obstructive pulmonary disease 3 0.5 Cerebrovascular accident 4 0.7 Substance abuse 228 40.1 Alcohol 138 24.3 Cigarette 37 6.5 Khat 53 9.3 More than one abovementioned substances 57 10 Last medical visit 568 100 Days 107 18.8 Weeks 86 15.2 Months 118 20.8 Years 16 2.8 Unknown 241 42.4 Circumstances of sudden death More than three-quarters of the cases were found dead (68%, n=387/568 cases), followed by cases who died at the time of arrival or after a short period of arrival in health facilities (23.1%, n=131/568 cases). Approximately 6.3% (n=36 /568 cases) died instantaneously. Prodromal signs and symptoms were reported in 178 cases of SD. Of these 178 cases, 70.8% (n=126) sought medical help. The most common terminal signs and symptoms of SD were chest pain (n=45 cases), followed by dyspnea (n=43 cases) and syncope (n=42 cases). Of the 178 cases, 42.1% died within 1 hour of the onset of symptoms, while 36% and 21.9% of the cases died between 1-6 hours and 6-24 hours of the onset of symptoms, respectively. The majority of sudden death incidents occurred at home in 34.9% (n=198) of the cases, followed by public places and health facilities in 30.3% and 23.4%, respectively. Causes of sudden unexpected deaths Cardiovascular system diseases (CVS) were the leading causes of SD, accounting for 36.1% of all SD cases. This was followed by respiratory and gastrointestinal system pathologies, accounting for 32.6% and 19.5%, respectively. Central nervous system (CNS) and genitourinary system (GUS) pathologies were the least prevalent causes of death, accounting for 10.6% and 1.2%, respectively. Male cases were affected more than female cases in each system, except in the GUS, in which female cases were prevalent. There was a statistically significant difference between the causes of death by organ system and sex, p<0.004. Comparisons of COD by organ system and sex are summarized in Table 3 . Table 3. Comparisons of COD by organ system and sex. System Frequency/Percentage p-value Male Female Total Cardiovascular system 176 (85.9) 29 (14.1) 205 (36) 0.017 * Respiratory system 160 (86.5) 25 (13.5) 185 (32.6) 0.003 * Gastrointestinal system 97 (87.4) 14 (12.6) 111 (19.5) 0.474 Central nervous system 47 (78.3) 13 (21.7) 60 (10.6) 0.414 Genitourinary system 2 (28.6) 5 (71.4) 7 (1.2) 0.008 * Total 482 (84.9) 86 (15.1) 568 (100) <0.001 * * Significant. Ischemic heart disease (IHD) and pneumonia are the most common underlying causes of SD. The underlying COD in each organ system is detailed in Table 4 . Pneumonia was the most common cause of sudden death in the first, third, and fourth decades of life and the second leading COD after the fifth decade following IHD. Ischemic heart disease was the most common COD in general and in both sexes, was the leading cause after the fifth decade and was the second most common COD in the age group of 21-40 years. Table 5 summarizes the common causes of SD by age group. Table 4. Underlying COD distributed by system and sex. System Number of deaths Percentage of all deaths Male Female Total Cardiovascular system 176 29 205 36.1 Ischemic heart diseases 124 19 143 25.2 Cardiomyopathies 29 1 30 5.3 Rheumatic valvular heart diseases 11 7 18 3.2 Ruptured aorta aneurysm 6 1 7 1.2 Infectious diseases (pericarditis and myocarditis) 6 1 7 1.2 Respiratory system 160 25 185 32.6 Pneumonia 95 11 106 18.7 Tuberculosis 33 3 36 6.3 Asthma 8 7 15 2.6 Chronic obstructive pulmonary disease 11 1 12 2.1 Pulmonary embolism 5 1 6 1.1 Lung abscess 3 2 5 0.9 Respiratory tract carcinoma 5 0 5 0.9 Gastrointestinal system 97 14 111 19.5 Liver diseases 54 5 59 10.3 Liver abscess 2 0 2 0.4 Pancreatitis 34 8 42 7.4 Pancreatic abscess 2 1 3 0.5 Perforation of gastric/duodenal ulcer 3 0 3 0.5 Intestinal perforation 1 0 1 0.2 Intestinal tuberculosis 1 0 1 0.2 Central nervous system 47 13 60 10.6 Subarachnoid hemorrhage 23 6 29 5.1 Spontaneous intraparenchymal hemorrhage 14 5 19 3.3 Infectious diseases (meningitis and brain abscess) 8 1 9 1.6 Infarction 1 0 1 0.2 Hydrocephalus with meningomyelocele 1 0 1 0.2 Space Occupying lesion 0 1 1 0.2 Genitourinary system 2 5 7 1.2 Pregnancy-related causes 0 5 5 0.9 Kidney diseases (perinephric abscess) 2 0 2 0.4 Total 482 86 568 100.0 Table 5. The most common causes of sudden death by age group. Age group in years (frequency of sudden death cases) The most common cause of sudden death Frequency of cases (percentage) 0-10 (n = 10) Pneumonia 7(70) Meningitis 2(20) 11-20 (n = 26) Pancreatitis 7(26.9) Rheumatic valvular heart diseases 4(15.4) 21-30 (n =92) Pneumonia 16(17.4) Ischemic heart diseases 14(15.2) Pancreatitis 12(13) Cardiomyopathies 10(10.9) 31-40 (n =138) Pneumonia 27(19.6) Ischemic heart diseases 26(18.8) Liver diseases 15(10.9) 41-50 (n =111) Ischemic heart diseases 31(27.9) Pneumonia 20(18) Liver diseases 16(14.4) 51-60 (n = 92) Ischemic heart diseases 33(35.9) Pneumonia 14(15.2) Liver diseases 12(13) 61-70 (n = 60) Ischemic heart diseases 18(30) Pneumonia 11(18.3) Chronic liver diseases 10(16.7) Cardiomyopathies 7(11.7) 71-98 (n = 39) Ischemic heart diseases 18(46.2) Pneumonia 8(20.5) The most common COD among CVS was ischemic heart disease, accounting for 69.8% of CVS deaths and 25.2% of all sudden deaths, that is, the leading cause of SD overall and in both sexes. Cardiomyopathy was the second most common COD in the CVS category and caused 5.3% of all sudden deaths ( Table 4 ). Only 4.4% of cases among these categories of sudden deaths had previously been diagnosed with cardiovascular disease. In the cardiovascular category of sudden death, the modifiable cardiovascular risk factors (CVRFs) identified were diabetes mellitus in 31.7% (65/205) and hypertension in 17.6% (36/205) of the cases. Furthermore, a history of alcohol, khat, and smoking was declared in 45 cases. Chronic alcohol use was the most common substance used and was reported in 38 (18.5%) of 205 cases. This was followed by the use of khat and cigarettes, each of which was reported in 14 cases (6.8%). The most common terminal symptoms reported among CVS category of sudden death were syncope (n=39 cases) and chest pain (n=25 cases). In 61 of 205 cases (29.8%), there were no previous symptoms, and SD was the first manifestation of sudden cardiac death. There was a statistically significant difference between the CVS causes and sex (p=0.019). Among SD cases attributed to CVS causes, 86.7% of SD from ischemic heart diseases, 96.7% of SD from cardiomyopathies, and 71.9% of SD from other CVS causes occurred in males ( Table 4 ). The most common respiratory pathology was pneumonia in 57.2% of respiratory cases and 18.7% of all sudden deaths, that is, the second most common underlying cause of SD in general and in both sexes. This was followed by tuberculosis in 19.5% of respiratory cases and 6.3% of all sudden deaths ( Table 4 ). A history of substance abuse was reported in 24.8% (n=46) of 185 cases of sudden death from respiratory pathology. Chronic alcohol use was the most common substance used and was reported in 37 (20%) of 185 cases. This was followed by smokers and chronic khat use, each reported in 13 cases. The most common terminal signs and symptoms reported among respiratory causes of sudden death were dyspnea (n=34 cases, 18.4%) and chest pain (n=20 cases, 10.8%). Gastrointestinal system (GIS) pathologies were the third leading cause of SD, occurring in 97 (19.5%) cases. Liver and pancreatic diseases were the two most common causes of sudden death among GIS pathologies, accounting for 53.2% (n=59 cases) and 37.8% (n=42 cases), respectively ( Table 4 ). A history of substance use was reported in 46.8% (n= 52) of 111 cases of sudden death from GIS pathology. Chronic alcohol use was the most common substance used and was reported in 45% (n=50/111) of victims, followed by khat and cigarettes in 19.8% and 4.5% of cases, respectively. The most common terminal signs and symptoms reported among the GIS causes of sudden death were abdominal pain (n=24 cases, 21.6%) and vomiting (n=7 cases, 6.3%). CNS pathologies were the fourth most common cause of SD, occurring in 10.6% (n=60 cases) of all sudden deaths. Subarachnoid hemorrhage and spontaneous intraparenchymal hemorrhage were the two common CNS pathologies, which occurred in 48.3% (29/60) and 31.7% (5/22) of cases, respectively ( Table 4 ). The least common cause of sudden death was related to GUS, which accounted for 1.2% of all sudden deaths. There was a statistically significant difference between the pathologies of GUS and sex, where p=0.48. There was a female preponderance of 71.4% and a mean age of 32.14±18.614 years. Pregnancy-related sudden deaths were the main cause of death in this group, occurring in five cases. Three of them died from obstetric bleeding (two cases of postpartum hemorrhage and one case of antepartum hemorrhage). A postpartum hemorrhage occurred after delivery at home in a rural area. Two cases of SD were due to rupture of ectopic pregnancy in 15- and 22-year-old single women, in which the family did not know the pregnancy status of the deceased. Discussion This is the first study article on sudden deaths in Ethiopia and is devoted to evaluating the sociodemographic, behavioral, clinical and pathological characteristics of 568 sudden deaths of various ages in Ethiopia. The frequency and pattern of sudden death in different parts of the world vary greatly due to the diversity of prevalent diseases in various nations and due to various genetic and environmental factors. 3 , 4 The present study reveals that sudden unexpected death with a known natural cause of death constitutes approximately 11.5% (95% CI: 10.6-12.4) of all autopsy cases. This finding matches those of other developing countries. 3 This finding is inconsistent with that reported in developed countries. 5 , 9 It is challenging to compare the magnitude of SD in different parts of the globe because it varies mainly as a function of the diversity of prevalent diseases in various nations and due to diverse genetic and environmental factors. 3 , 4 Furthermore, various definitions of SD, inclusion criteria and age groups that were evaluated in the study all contribute to the variation in SD incidence described in different studies. The findings revealed a mean age of 44.8±17.349 years. This is consistent with the studies conducted in Nigeria and Libya. 3 , 4 , 10 The maximum number of sudden death cases (24.3%) was in the age group of 31-40 years, followed by 41-50 years, representing 19.6% of all SD cases. This finding matches various studies. 11 – 13 All of these studies noted that middle age groups of 30 to 50 years are at high risk for SD. This finding appears to reflect behavioral and environmental factors that impact the health of society resulting from urbanization, the shift to a Western lifestyle, and the rapid nutritional transition and sedentary lifestyle with increased substance abuse habits. Of 568 sudden death cases, men (n = 482/586) were predominant over women (n = 86/586), with a ratio of 5.6:1. The observed male predominance aligns with other studies. 4 , 11 , 14 , 15 Several factors may contribute to this gender difference. The known cardioprotective effects of estrogen in premenopausal women, which can lower cardiovascular risk, likely play a role. 4 Beyond biological factors, the higher prevalence of substance use among men, which was also evident in our study, is another potentially contributing psychosocial factor. 14 Furthermore, the relatively high male-to-female ratio observed here can be partially attributed to the higher male-to-female ratio (3.7:1) of autopsy cases within the study period. In our study, the majority (70%) of SD cases were from urban areas, which is consistent with other similar studies. 4 , 11 This is due to the sedentary lifestyle and westernization with the increased smoking and alcohol consumption habits adopted by people in urban areas. In addition, the stress levels of urban and rural life are well known to differ. According to the current study, more than three-quarters of sudden deaths were unwitnessed. This could be because the shorter the survival period, the more likely it would go unnoticed, meaning that the likelihood of death being unwitnessed or unattended is directly correlated with the duration of survival. Our study found that chest pain, dyspnea, and syncope were the most common terminal symptoms reported in 68.6% of SD cases. These are the principal symptoms of cardiovascular and respiratory diseases, which were the two leading causes of SD. The finding of chest pain as the most common prodromal symptom coincided with a study in South Africa. 15 In light of this, we advise emergency medical professionals to pay more attention to people who exhibit these prodromal symptoms. The fact that 86.6% of all sudden deaths occurred outside of a hospital setting shows that the majority of these cases may not have known about their underlying medical problems or may not have been able to pay for the necessary medical care. This shows that most cases of SD are silent without preexisting symptoms. Therefore, it is vital to develop public health measures that will help educate the community about the importance of recognizing the manifestation of various clinical conditions and the need to seek immediate clinical help. Furthermore, efforts should be made to make healthcare facilities accessible and affordable with adequate diagnostic and management capacity. Two additional findings from this study further support this view. The first is that 34% of the SD cases had visits to medical facilities in the weeks before death, followed by deaths at home, which could be an indication that the diagnosis was incorrect, that therapy had failed, or that the deceased or caretakers lacked sufficient financial power to complete further investigation or management. The other reason is the high frequency of SD cases from chronic illnesses diagnosed for the first time at autopsy. The occurrence of SD in males outnumbers females in all systems except GUS. Our findings coincided with other similar studies. 4 , 15 In the current study, men were predominantly affected by cardiovascular causes of sudden natural death, and a significant association was observed between CVS disease and sex. Our findings coincided with other similar studies. 3 , 10 , 16 The fact that men are more frequently exposed to CVS pathologies can be attributed to the fact that estrogen hormone in women acts as a protective factor against most cardiovascular events, explaining the male preponderance that coexists with the high prevalence of CVS causes of sudden death. 3 , 10 Furthermore, it could also be the result of men’s higher rates of substance misuse compared to women, as well as higher levels of financial stress. Cardiovascular and respiratory diseases are the most common causes of SD. These results are consistent with those of various studies conducted in different parts of the world. 1 , 3 , 4 , 15 , 17 , 18 The fact that CVS pathologies are becoming the leading cause of SD could probably be the shift to the Western type of lifestyle that our societies are acquiring. The most common underlying cause of SD is ischemic heart disease. This finding is consistent with those of various studies conducted in different parts of the world. 1 , 4 , 5 , 15 , 17 , 18 Cardiomyopathy was the second most common COD in the cardiovascular system, accounting for 5.3% of all sudden deaths. This agrees with the result achieved in Libya. 4 Cardiomyopathies can be inherited and therefore it is important to screen surviving blood relatives for these conditions. 19 In many series, sudden cardiac death (SCD) is the initial manifestation of the condition in 20%–40% of cases. 16 , 20 In the current study, 29.8% of cases of cardiovascular death had no antecedent symptoms, and SD was the first manifestation of sudden cardiac death in 29.8% of cases, which is consistent with many similar studies. 16 , 20 Approximately 6.3% of all cases (n=36) experienced instantaneous death. Among these, a substantial majority, 88.9% (n=32), were attributed to cardiovascular (CVS) causes, specifically ischemic heart disease and cardiomyopathies. The remaining cases were due to spontaneous intracranial hemorrhage. Because SD is frequently the first sign of the disease, it is impossible to detect high-risk individuals, making the prevention of SCD considerably more challenging. Primary prevention is highly challenging because early identification of subjects in the community who are at a high risk of SCD is impossible owing to the significant percentage of SCD occurring in individuals with no previously known disease. However, sudden cardiac deaths have a relatively high prevalence of CVRFs. The risk of SCD in asymptomatic subjects with CVRFs is higher than that in the general population but lower than that of symptomatic patients with a diagnosed condition. 16 As a result, early identification and management of modifiable CVRFs is one potential strategy to reduce the burden of sudden cardiac deaths in the community. In this study, significantly higher CVRF frequencies were observed in SCD cases, including diabetes mellitus (31.7%), hypertension (17.6%), and substance addiction (22%). Therefore, community education on preventive strategies, early detection, and control of CVRFs together with preventive strategies for substance abuse would be effective for the prevention of SD. Respiratory causes of SD accounted for 32.6% of cases in the current study. Pneumonia was the leading cause of death in the respiratory system, representing 18.7% of sudden death cases, making it the second most common cause of SD. This is closely followed by tuberculosis, comprising 6.3% of all sudden death cases. This is consistent with the results achieved in Libya and South Africa. 4 , 17 Gastrointestinal pathologies were the third leading cause of SD, occurring in 111 (19.5%) cases. Liver and pancreatic pathologies were the two most common causes of sudden death among GIS pathology, accounting for 53.2% (n=59 cases) and 37.8% (n=42 cases), respectively. Hepatic and pancreatic pathologies together contribute to 90.1% of GIS causes of sudden death and are generally the third and fourth underlying causes of death, respectively. This finding is inconsistent with various similar studies showing that CNS pathologies are the third most common cause of SD. 3 , 4 , 15 , 17 , 18 A possible explanation could be the high frequency of substance abuse reported among cases of SD from GIS pathology. A history of substance abuse was reported in 46.8% (n= 52) of 111 cases of sudden death from GIS pathology. Chronic alcohol use was the most common substance used and was reported in 50 (45%) of 111 cases, followed by khat and cigarettes in 19.8% and 4.5% of cases, respectively. Alcohol has a causative association with both liver and pancreatic diseases. 14 , 21 – 24 Additionally, there is a growing body of evidence linking khat to the emergence of both acute and chronic liver disease. 25 – 28 Khat (Catha edulis), a plant that is chewed for its psychedelic effects, is widely used in the eastern and southern parts of Ethiopia, but less frequently in the northern region. 25 Central nervous system pathologies accounted for 10.6% of SD cases in this study. Cerebrovascular accidents were the most common causes (81.7% of all CNS causes), followed by infectious causes (15% of all CNS causes). This is in agreement with a study from Türkiye. 15 The number of male versus female cases in all organ systems was higher except for GUS. Our findings coincided with various studies. 4 , 15 , 17 The reason is that in our study, a high frequency of maternal deaths was recorded. While this study provides valuable insights into the epidemiological data necessary for planning medical services, prevention and control activities, education, and further research, it is important to acknowledge its limitations. Notably, 6.2% of the total autopsy cases remained undetermined during the study period, indicating a need for additional examinations. Although samples were collected for histolopathology (mainly H&E), toxicological screening, biochemical tests and microbiology in selected cases, molecular autopsy facilities were not available in our context. As a result, cases in which the cause of death could not be established due to advanced putrefaction or incomplete ancillary examinations, such as molecular autopsy, were excluded from the study. This exclusion of undetermined cases may potentially affect or underestimate the prevalence estimates. Traditional autopsy techniques, though essential, may not always reveal the cause of death, particularly in cases of sudden unexplained death (SUDs). To overcome this limitation, molecular autopsy should be utilized. Molecular autopsy involves genetic analysis to investigate sudden death, and is particularly useful in cases where traditional autopsy findings are negative or only show non-diagnostic results. It is also instrumental in the diagnosis of inherited conditions, such as cardiomyopathies. 19 SUDs are frequently due to underlying inherited arrhythmogenic cardiac diseases, and molecular autopsy helps identify these causes. Identifying the cause of death using molecular autopsy is vital for medico-legal inquiries and it also guides cascade genetic screening of the victim’s relatives. It is important to note that molecular autopsy aims at identifying the cause of death, which may be particularly relevant for risk prediction in family members, and the management of those at risk. 29 – 31 Studies conducted in resource-limited facilities often share similar limitations, particularly concerning genetic testing. 32 – 35 Considering the future and to mitigate similar limitations, and with the likely expanding role of molecular autopsy, the preservation of DNA samples from all cases is critical to enable future investigations. Additionally, the weight of the deceased was not measured during the postmortem examination due to a malfunctioning body weight scale during the study period, leading to the omission of a key variable: body mass index. Therefore, it is crucial to consider these factors in future research. Despite these limitations, our study stands out as the first nationwide prospective autopsy-based study that comprehensively includes epidemiological, clinical, and pathological characteristics of all sudden unexpected natural deaths over a one-year period. In every case, we gathered information from all available sources and conducted complete postmortem autopsies. Conclusions Sudden death is an important global public health issue. Cardiovascular, respiratory and gastrointestinal system pathologies were the most common causes. The two main underlying causes of sudden death were ischemic heart disease and pneumonia. Although the causes of SD observed in the current study were comparable to those previously reported elsewhere, the rate of occurrence of certain conditions was different, particularly the higher frequency of liver and pancreatic pathologies. The association of these diseases with chronic alcohol and khat (Catha Edulis) abuse was also documented. Most of the causes of SD in Ethiopia can be prevented and treated. The majorities of sudden deaths are silent without preexisting symptoms and occur outside a hospital setting. Therefore, it is vital to develop public health measures that will help educate the community about the importance of recognizing the manifestation of various clinical conditions and the need to seek immediate clinical help. Furthermore, efforts should be made to make healthcare facilities accessible and affordable with adequate diagnostic and management capacity. Documentation of autopsy-based data could provide important epidemiological information to guide medical services, prevention efforts, and control measures. Data availability Figshare: Epidemiological profiles and causes of sudden deaths of various ages in Ethiopia: an autopsy-based study, https://doi.org/10.6084/m9.figshare.24152004 . 36 Data are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0). 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[Dataset]. figshare. 2023. Publisher Full Text Comments on this article Comments (0) Version 2 VERSION 2 PUBLISHED 07 Nov 2023 ADD YOUR COMMENT Comment Author details Author details 1 Department of Forensic Medicine and Toxicology, St. Paul's Hospital Millennium Medical College, Addis Ababa, Ethiopia, 1271, Ethiopia Alemayehu Shiferaw Lema Roles: Conceptualization, Data Curation, Formal Analysis, Investigation, Methodology, Project Administration, Resources, Software, Supervision, Validation, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing Sesen Tsegaye Tekle Roles: Conceptualization, Data Curation, Formal Analysis, Investigation, Methodology, Project Administration, Resources, Software, Supervision, Validation, Visualization, Writing – Review & Editing Competing interests No competing interests were disclosed. Grant information The author(s) declared that no grants were involved in supporting this work. Article Versions (2) version 2 Revised Published: 05 Feb 2025, 12:1441 https://doi.org/10.12688/f1000research.142511.2 version 1 Published: 07 Nov 2023, 12:1441 https://doi.org/10.12688/f1000research.142511.1 Copyright © 2025 Lema AS and Tekle ST. This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Download Export To Sciwheel Bibtex EndNote ProCite Ref. Manager (RIS) Sente metrics Views Downloads F1000Research - - PubMed Central info_outline Data from PMC are received and updated monthly. - - Citations open_in_new 0 open_in_new 0 open_in_new SEE MORE DETAILS CITE how to cite this article Lema AS and Tekle ST. Epidemiological profiles and causes of sudden deaths of various ages in Ethiopia: an autopsy-based study [version 2; peer review: 1 approved, 2 approved with reservations] . F1000Research 2025, 12 :1441 ( https://doi.org/10.12688/f1000research.142511.2 ) NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS track receive updates on this article Track an article to receive email alerts on any updates to this article. TRACK THIS ARTICLE Share Open Peer Review Current Reviewer Status: ? Key to Reviewer Statuses VIEW HIDE Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Version 2 VERSION 2 PUBLISHED 05 Feb 2025 Revised Views 0 Cite How to cite this report: Du Toit-Prinsloo L. Reviewer Report For: Epidemiological profiles and causes of sudden deaths of various ages in Ethiopia: an autopsy-based study [version 2; peer review: 1 approved, 2 approved with reservations] . F1000Research 2025, 12 :1441 ( https://doi.org/10.5256/f1000research.177058.r364673 ) The direct URL for this report is: https://f1000research.com/articles/12-1441/v2#referee-response-364673 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 14 Feb 2025 Lorraine Du Toit-Prinsloo , School of Medicine and Public Health, The University of Newcastle, Callaghan, New South Wales, Australia Approved VIEWS 0 https://doi.org/10.5256/f1000research.177058.r364673 I am comfortable with ... Continue reading READ ALL I am comfortable with changing my opinion to Approved Competing Interests: No competing interests were disclosed. I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Du Toit-Prinsloo L. Reviewer Report For: Epidemiological profiles and causes of sudden deaths of various ages in Ethiopia: an autopsy-based study [version 2; peer review: 1 approved, 2 approved with reservations] . F1000Research 2025, 12 :1441 ( https://doi.org/10.5256/f1000research.177058.r364673 ) The direct URL for this report is: https://f1000research.com/articles/12-1441/v2#referee-response-364673 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Respond or Comment COMMENT ON THIS REPORT Version 1 VERSION 1 PUBLISHED 07 Nov 2023 Views 0 Cite How to cite this report: Westaby J. Reviewer Report For: Epidemiological profiles and causes of sudden deaths of various ages in Ethiopia: an autopsy-based study [version 2; peer review: 1 approved, 2 approved with reservations] . F1000Research 2025, 12 :1441 ( https://doi.org/10.5256/f1000research.156070.r287008 ) The direct URL for this report is: https://f1000research.com/articles/12-1441/v1#referee-response-287008 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 14 Jun 2024 Joseph Westaby , Cardiovascular and genomics research institute, St George's University of London, London, UK Approved with Reservations VIEWS 0 https://doi.org/10.5256/f1000research.156070.r287008 The article by Lema et al, is an observational study characterising all sudden deaths observed at a single forensic centre in Ethiopia. They report sudden death was 11.5% of all cases autopsied with 5.6 times as many males than females ... Continue reading READ ALL The article by Lema et al, is an observational study characterising all sudden deaths observed at a single forensic centre in Ethiopia. They report sudden death was 11.5% of all cases autopsied with 5.6 times as many males than females and a mean age of 45. Cardiovascular causes were most common with ischaemic heart disease as the leading cause. They highlight the importance of epidemiological data derived from autopsy studies to inform provision of medical services. This is a study that adds to the literature on sudden death showing its causes from Ethiopia. There are a number of improvements that I recommend that the authors make and I would be happy to re-review the paper following their emendations. Methods Individuals who died but were not confined to their homes, health facilities, or other related institutions due to illness for more than 24 hours before death were not considered unexpected deaths and were not included. Do the authors mean not? Results Figure 1: It would be best not to display the last three bars labelled as total as it does not allow you to appreciate the differences between the decades of age There was a statistically significant difference between the residence of the victims and sex (p<0.001). It is not made clear which sex lived more commonly where. Did males more frequently live in the city or the country? There was a statistically significant relationship between substance abuse and sex (p<0.001) and residence (p=0.004). A different distribution was observed for chronic alcohol use and sex (p<0.001). It is not made clear what these relationships are? Was it more common in males and in the city? Was alcohol more common in males or females? There was a statistically significant relationship between the presence of a prior chronic illness and sex (p=0.022). Were males or females more likely to have prior chronic illness? Table 3: It would be useful to put percentages for each sex for each cause so the differences between males and females are readily appreciable. There was a statistically significant difference between the CVS causes and sex (p=0.019). Was it more common males? Discussion The findings revealed a mean age of 44.8117.349 years. Giving the mean age as a whole number would be more appropriate Of 224 sudden death cases, men (n = 482/586) were predominant over women (n = 86/586), with a ratio of 5.6:1. This finding is consistent with many similar studies. 1 , 3 , 4 , 11 , 14 , 15 Only two of these studies have a ratio of 5:1, most of these have ratios of 2:1 male:female which is more usual in the literature. Could the authors please speculate as to why they have such a high male to female ratio. Are females autopsied less than males? What percentage of the 4,942 medicolegal autopsies were female? The occurrence of SD in males outnumbers females in all systems except GUS. Our findings coincided with those of the studies conducted in Tukey. 4 , 15 Turkey is spelt wrong. They may wish to use its new name “Türkiye”. Reference four is from Libya not Turkey. Our findings coincided with the results of the United Kingdom. 3 , 10 , 16 Refences are for two studies from Nigeria and one from Spain. None are from the UK. They should include references from the UK. Cardiomyopathy was the second most common COD in the cardiovascular system, accounting for 5.3% of all sudden deaths. This agrees with the result achieved in Libya. 4 It would be important to say that the cardiomyopathies may be inherited and therefore it is important to screen surviving blood relatives for these conditions. (Reference-1) Is the work clearly and accurately presented and does it cite the current literature? Partly Is the study design appropriate and is the work technically sound? Yes Are sufficient details of methods and analysis provided to allow replication by others? Yes If applicable, is the statistical analysis and its interpretation appropriate? No Are all the source data underlying the results available to ensure full reproducibility? Yes Are the conclusions drawn adequately supported by the results? Yes References 1. Sheppard MN, Westaby J, Zullo E, Fernandez BVE, et al.: Sudden arrhythmic death and cardiomyopathy are important causes of sudden cardiac death in the UK: results from a national coronial autopsy database. Histopathology . 2023; 82 (7): 1056-1066 PubMed Abstract | Publisher Full Text Competing Interests: No competing interests were disclosed. Reviewer Expertise: Cardiovascular pathology, sudden death, various cardiac conditions, anatomy of the heart I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Westaby J. Reviewer Report For: Epidemiological profiles and causes of sudden deaths of various ages in Ethiopia: an autopsy-based study [version 2; peer review: 1 approved, 2 approved with reservations] . F1000Research 2025, 12 :1441 ( https://doi.org/10.5256/f1000research.156070.r287008 ) The direct URL for this report is: https://f1000research.com/articles/12-1441/v1#referee-response-287008 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Author Response 05 Feb 2025 Alemayehu S. Lema , Department of Forensic Medicine and Toxicology, St. Paul's Hospital Millennium Medical College, Addis Ababa, 1271, Ethiopia 05 Feb 2025 Author Response Dear Reviewer, We sincerely appreciate the time and effort you dedicated to providing such a comprehensive and constructive review. Your feedback has been extremely valuable in shaping the quality of ... Continue reading Dear Reviewer, We sincerely appreciate the time and effort you dedicated to providing such a comprehensive and constructive review. Your feedback has been extremely valuable in shaping the quality of this work. We have thoroughly reviewed and incorporated your suggestions throughout the revised manuscript. Please find our detailed responses to each comment below. Method section Response: The statement, "Individuals who died but were not confined to their homes, health facilities, or other related institutions due to illness for more than 24 hours before death were not considered unexpected deaths and were not included," inadvertently used the phrase "not confined." This was an error; the intended criteria were that individuals that were confined. We appreciate the reviewer for identifying this inaccuracy. The statement has now been amended to read: "Individuals who died but were confined to their homes, health facilities, or other related institutions due to illness for more than 24 hours before death were not considered unexpected deaths and were not included." Result section 2.1. Figure 1 and table 3 Following your recommendations, we have made specific modifications to the presentation of results. In Figure 1, we've removed the "total" bars to improve the visual clarity of age-related trends, enabling a better appreciation of differences across decades. In Table 3, we have included sex-specific percentages for each cause, facilitating a direct comparison of male and female distributions. Statistical data presentation Response: Thank you so much, and comments are accommodated. All the statistical analysis and interpretation of the data have been meticulously clarified and elaborated upon, offering a more robust understanding of the findings. Mean age The mean age (±SD) is corrected to 44.8 ± 17.349 years. The previous version incorrectly presented the standard deviation within the mean, writing it as 44.8117.349 years. This has now been rectified. Discussion section 3.1. Male: female ratio Response: Thank you for this critical and insightful comment. We acknowledge the discrepancy in male-to-female ratios compared to some studies in the literature. The references for this section have been appropriately amended to reflect this. We have now included a detailed discussion of potential reasons for the observed gender disparity in our study. Issues regarding inherited cardiomyopathies Response: Thank you for this critical and pertinent suggestion. We agree that it is essential to highlight the potential for inherited cardiomyopathies. We have now included a statement in the discussion emphasizing the importance of screening surviving blood relatives for these conditions, and we have added the suggested reference. Issues regarding inherited cardiomyopathies Response: Thank you for this critical and pertinent suggestion. We have addressed all concerns regarding the citations and references. This includes updating the reference list to ensure accurate representation of study locations and replacing older references with more current literature, where possible. Additionally, we have incorporated many recent and all suggested references. Dear Reviewer, We sincerely appreciate the time and effort you dedicated to providing such a comprehensive and constructive review. Your feedback has been extremely valuable in shaping the quality of this work. We have thoroughly reviewed and incorporated your suggestions throughout the revised manuscript. Please find our detailed responses to each comment below. Method section Response: The statement, "Individuals who died but were not confined to their homes, health facilities, or other related institutions due to illness for more than 24 hours before death were not considered unexpected deaths and were not included," inadvertently used the phrase "not confined." This was an error; the intended criteria were that individuals that were confined. We appreciate the reviewer for identifying this inaccuracy. The statement has now been amended to read: "Individuals who died but were confined to their homes, health facilities, or other related institutions due to illness for more than 24 hours before death were not considered unexpected deaths and were not included." Result section 2.1. Figure 1 and table 3 Following your recommendations, we have made specific modifications to the presentation of results. In Figure 1, we've removed the "total" bars to improve the visual clarity of age-related trends, enabling a better appreciation of differences across decades. In Table 3, we have included sex-specific percentages for each cause, facilitating a direct comparison of male and female distributions. Statistical data presentation Response: Thank you so much, and comments are accommodated. All the statistical analysis and interpretation of the data have been meticulously clarified and elaborated upon, offering a more robust understanding of the findings. Mean age The mean age (±SD) is corrected to 44.8 ± 17.349 years. The previous version incorrectly presented the standard deviation within the mean, writing it as 44.8117.349 years. This has now been rectified. Discussion section 3.1. Male: female ratio Response: Thank you for this critical and insightful comment. We acknowledge the discrepancy in male-to-female ratios compared to some studies in the literature. The references for this section have been appropriately amended to reflect this. We have now included a detailed discussion of potential reasons for the observed gender disparity in our study. Issues regarding inherited cardiomyopathies Response: Thank you for this critical and pertinent suggestion. We agree that it is essential to highlight the potential for inherited cardiomyopathies. We have now included a statement in the discussion emphasizing the importance of screening surviving blood relatives for these conditions, and we have added the suggested reference. Issues regarding inherited cardiomyopathies Response: Thank you for this critical and pertinent suggestion. We have addressed all concerns regarding the citations and references. This includes updating the reference list to ensure accurate representation of study locations and replacing older references with more current literature, where possible. Additionally, we have incorporated many recent and all suggested references. Competing Interests: None Close Report a concern Respond or Comment COMMENTS ON THIS REPORT Author Response 05 Feb 2025 Alemayehu S. Lema , Department of Forensic Medicine and Toxicology, St. Paul's Hospital Millennium Medical College, Addis Ababa, 1271, Ethiopia 05 Feb 2025 Author Response Dear Reviewer, We sincerely appreciate the time and effort you dedicated to providing such a comprehensive and constructive review. Your feedback has been extremely valuable in shaping the quality of ... Continue reading Dear Reviewer, We sincerely appreciate the time and effort you dedicated to providing such a comprehensive and constructive review. Your feedback has been extremely valuable in shaping the quality of this work. We have thoroughly reviewed and incorporated your suggestions throughout the revised manuscript. Please find our detailed responses to each comment below. Method section Response: The statement, "Individuals who died but were not confined to their homes, health facilities, or other related institutions due to illness for more than 24 hours before death were not considered unexpected deaths and were not included," inadvertently used the phrase "not confined." This was an error; the intended criteria were that individuals that were confined. We appreciate the reviewer for identifying this inaccuracy. The statement has now been amended to read: "Individuals who died but were confined to their homes, health facilities, or other related institutions due to illness for more than 24 hours before death were not considered unexpected deaths and were not included." Result section 2.1. Figure 1 and table 3 Following your recommendations, we have made specific modifications to the presentation of results. In Figure 1, we've removed the "total" bars to improve the visual clarity of age-related trends, enabling a better appreciation of differences across decades. In Table 3, we have included sex-specific percentages for each cause, facilitating a direct comparison of male and female distributions. Statistical data presentation Response: Thank you so much, and comments are accommodated. All the statistical analysis and interpretation of the data have been meticulously clarified and elaborated upon, offering a more robust understanding of the findings. Mean age The mean age (±SD) is corrected to 44.8 ± 17.349 years. The previous version incorrectly presented the standard deviation within the mean, writing it as 44.8117.349 years. This has now been rectified. Discussion section 3.1. Male: female ratio Response: Thank you for this critical and insightful comment. We acknowledge the discrepancy in male-to-female ratios compared to some studies in the literature. The references for this section have been appropriately amended to reflect this. We have now included a detailed discussion of potential reasons for the observed gender disparity in our study. Issues regarding inherited cardiomyopathies Response: Thank you for this critical and pertinent suggestion. We agree that it is essential to highlight the potential for inherited cardiomyopathies. We have now included a statement in the discussion emphasizing the importance of screening surviving blood relatives for these conditions, and we have added the suggested reference. Issues regarding inherited cardiomyopathies Response: Thank you for this critical and pertinent suggestion. We have addressed all concerns regarding the citations and references. This includes updating the reference list to ensure accurate representation of study locations and replacing older references with more current literature, where possible. Additionally, we have incorporated many recent and all suggested references. Dear Reviewer, We sincerely appreciate the time and effort you dedicated to providing such a comprehensive and constructive review. Your feedback has been extremely valuable in shaping the quality of this work. We have thoroughly reviewed and incorporated your suggestions throughout the revised manuscript. Please find our detailed responses to each comment below. Method section Response: The statement, "Individuals who died but were not confined to their homes, health facilities, or other related institutions due to illness for more than 24 hours before death were not considered unexpected deaths and were not included," inadvertently used the phrase "not confined." This was an error; the intended criteria were that individuals that were confined. We appreciate the reviewer for identifying this inaccuracy. The statement has now been amended to read: "Individuals who died but were confined to their homes, health facilities, or other related institutions due to illness for more than 24 hours before death were not considered unexpected deaths and were not included." Result section 2.1. Figure 1 and table 3 Following your recommendations, we have made specific modifications to the presentation of results. In Figure 1, we've removed the "total" bars to improve the visual clarity of age-related trends, enabling a better appreciation of differences across decades. In Table 3, we have included sex-specific percentages for each cause, facilitating a direct comparison of male and female distributions. Statistical data presentation Response: Thank you so much, and comments are accommodated. All the statistical analysis and interpretation of the data have been meticulously clarified and elaborated upon, offering a more robust understanding of the findings. Mean age The mean age (±SD) is corrected to 44.8 ± 17.349 years. The previous version incorrectly presented the standard deviation within the mean, writing it as 44.8117.349 years. This has now been rectified. Discussion section 3.1. Male: female ratio Response: Thank you for this critical and insightful comment. We acknowledge the discrepancy in male-to-female ratios compared to some studies in the literature. The references for this section have been appropriately amended to reflect this. We have now included a detailed discussion of potential reasons for the observed gender disparity in our study. Issues regarding inherited cardiomyopathies Response: Thank you for this critical and pertinent suggestion. We agree that it is essential to highlight the potential for inherited cardiomyopathies. We have now included a statement in the discussion emphasizing the importance of screening surviving blood relatives for these conditions, and we have added the suggested reference. Issues regarding inherited cardiomyopathies Response: Thank you for this critical and pertinent suggestion. We have addressed all concerns regarding the citations and references. This includes updating the reference list to ensure accurate representation of study locations and replacing older references with more current literature, where possible. Additionally, we have incorporated many recent and all suggested references. Competing Interests: None Close Report a concern COMMENT ON THIS REPORT Views 0 Cite How to cite this report: Modena M. Reviewer Report For: Epidemiological profiles and causes of sudden deaths of various ages in Ethiopia: an autopsy-based study [version 2; peer review: 1 approved, 2 approved with reservations] . F1000Research 2025, 12 :1441 ( https://doi.org/10.5256/f1000research.156070.r270830 ) The direct URL for this report is: https://f1000research.com/articles/12-1441/v1#referee-response-270830 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 10 Jun 2024 Martina Modena , Interdisciplinary Center for Health Sciences, Scuola Superiore Sant'Anna, Pisa, Italy Approved with Reservations VIEWS 0 https://doi.org/10.5256/f1000research.156070.r270830 This article addresses a major health problem such as sudden death, which has a dramatic impact on families and society. The authors provide an interesting descriptive study on sudden death in Ethiopia. The authors should address the following comments: ... Continue reading READ ALL This article addresses a major health problem such as sudden death, which has a dramatic impact on families and society. The authors provide an interesting descriptive study on sudden death in Ethiopia. The authors should address the following comments: Methods: - “Full postmortem examinations were carried out in each instance using the Letulle evisceration procedure […] Organs were dissected, examined and checked for signs of gross pathological changes and violence. Autopsied specimens (whole organs or organ pieces) were fixed in 10% formalin for histopathological examination. Multiple sections with thicknesses of 4-5 mm were taken. The tissues were processed, subjected to paraffin sectioning at a thickness of 4 micrometers and then stained using hematoxylin and eosin staining.” The authors can provide more details on full postmortem examinations carried out? e.g. body weight and height have been collected? Concerning the histological analysis: was only the hematoxylin-eosin staining performed? the toxicology analysis was performed? The authors could include a small paragraph on heart analysis: e.g. pericardium, heart cavities, valves and coronary arteries have been checked? - Considering the growing importance of molecular autopsy, have any EDTA blood or frozen tissue samples been kept for possible future analysis? Results: Causes of sudden unexpected deaths - “Cardiovascular system diseases (CVS) were the leading causes of SD, accounting for 36.1% of all SD cases. This was followed by respiratory and gastrointestinal system pathologies, accounting for 32.6% and 19.5%, respectively. Central nervous system (CNS) and genitourinary system (GUS) pathologies were the least prevalent causes of death, accounting for 10.6% and 1.2%, respectively.” All described cases of sudden death are explained after autopsy by reaching a certain cause of death. This is surprising considering that in literature the cause of death remains in doubt even after an exhaustive autopsy in several sudden deaths. So, there is usually a proportion of cases remaining "unexplained". I suggest to authors to review the literature and guidelines (some references are more than 10 years old) and to review the results to be sure that all cases have been explained by autopsy. Do all cases have a definite diagnosis at autopsy? Particularly among cases of cardiac death, no probable arrhythmic death was found? Did all cases of sudden cardiovascular death have structural cardiac changes? Is the work clearly and accurately presented and does it cite the current literature? Partly Is the study design appropriate and is the work technically sound? Partly Are sufficient details of methods and analysis provided to allow replication by others? Partly If applicable, is the statistical analysis and its interpretation appropriate? Yes Are all the source data underlying the results available to ensure full reproducibility? Yes Are the conclusions drawn adequately supported by the results? Yes Competing Interests: No competing interests were disclosed. I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Modena M. Reviewer Report For: Epidemiological profiles and causes of sudden deaths of various ages in Ethiopia: an autopsy-based study [version 2; peer review: 1 approved, 2 approved with reservations] . F1000Research 2025, 12 :1441 ( https://doi.org/10.5256/f1000research.156070.r270830 ) The direct URL for this report is: https://f1000research.com/articles/12-1441/v1#referee-response-270830 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Author Response 05 Feb 2025 Alemayehu S. Lema , Department of Forensic Medicine and Toxicology, St. Paul's Hospital Millennium Medical College, Addis Ababa, 1271, Ethiopia 05 Feb 2025 Author Response Dear Reviewer, We sincerely appreciate the time and effort you dedicated to providing such a comprehensive and constructive review. Your feedback has been extremely valuable in shaping the quality of ... Continue reading Dear Reviewer, We sincerely appreciate the time and effort you dedicated to providing such a comprehensive and constructive review. Your feedback has been extremely valuable in shaping the quality of this work. We have thoroughly reviewed and incorporated your suggestions throughout the manuscript. Please find our detailed responses to each comment below. Method section: Details of postmortem examinations procedure Response: Thank you for this valuable suggestion. We have revised the manuscript to include detailed descriptions of the postmortem examinations performed, the ancillary investigations conducted, and the limitations encountered within our setting. As suggested, we have also provided a more thorough description of the gross heart examination. Your feedback has prompted us to include recommendations for improving autopsy facilities and future research, which we believe will be valuable for informing decisions and policies in similar contexts, particularly for forensic pathologists working in resource-limited facilities. Result section: Sudden unexplained deaths Response: Thank you for this valuable suggestion. We have revised the manuscript to provide more detailed descriptions of the included cases. This study focused on all sudden unexpected deaths with a known natural cause. While our findings offer crucial epidemiological data for planning medical services, prevention, control, education, and further research, we acknowledge several limitations that could influence the interpretation of our results. Specifically, 6.2% of total autopsy cases remained undetermined due to the limitations of available resources and facilities, and these cases were therefore excluded from the study. Histopathological examination, largely using Hematoxylin and Eosin (H&E) staining, was performed in all sudden death cases. Toxicological, biochemical, and microbiological investigations are performed on a selective basis, as determined by the forensic pathologist. However, it is important to note that molecular autopsy facilities were not accessible, and tissue specimens were not preserved. This lack of molecular autopsy significantly limited our ability to determine the cause of death in cases of advanced putrefaction or incomplete ancillary examinations and this exclusion of cases with undetermined cause of death may affect the prevalence estimate. This limitation is explicitly discussed in the manuscript. Furthermore, we recognize that sudden unexplained deaths (SUDs) are frequently associated with underlying inherited arrhythmogenic cardiac diseases, which molecular autopsy can help identify. Identifying the cause of death via molecular autopsy is vital not only for medico-legal inquiries but also for guiding cascade genetic screening of the deceased's relatives. This screening is essential for risk prediction in family members and the appropriate management of those identified to be at risk. Your insightful feedback has prompted us to provide relevant recommendations regarding the need for a molecular autopsy facility. We believe that these recommendations will inform decisions and policies in our context and similar settings. As a short-term measure, considering the increasing importance of molecular autopsy, we recommend preserving DNA samples from all SUD cases to facilitate future investigations. These recommendations, we believe, will be particularly valuable for forensic pathologists and stakeholders working in resource-limited facilities. Despite these limitations, our study represents the first nationwide, autopsy-based investigation to comprehensively analyze the epidemiological, clinical, and pathological characteristics of all sudden unexpected natural deaths over a one-year period. We rigorously gathered information from all available sources, performed postmortem autopsies, and collected samples for available ancillary investigations. We believe that this study provides valuable epidemiological insights crucial for planning medical services, prevention, control, education, and further research. References Response: Thank you for this critical and pertinent suggestion. We have diligently updated the references, incorporating recent publications and replacing some earlier citations with their most current versions. Dear Reviewer, We sincerely appreciate the time and effort you dedicated to providing such a comprehensive and constructive review. Your feedback has been extremely valuable in shaping the quality of this work. We have thoroughly reviewed and incorporated your suggestions throughout the manuscript. Please find our detailed responses to each comment below. Method section: Details of postmortem examinations procedure Response: Thank you for this valuable suggestion. We have revised the manuscript to include detailed descriptions of the postmortem examinations performed, the ancillary investigations conducted, and the limitations encountered within our setting. As suggested, we have also provided a more thorough description of the gross heart examination. Your feedback has prompted us to include recommendations for improving autopsy facilities and future research, which we believe will be valuable for informing decisions and policies in similar contexts, particularly for forensic pathologists working in resource-limited facilities. Result section: Sudden unexplained deaths Response: Thank you for this valuable suggestion. We have revised the manuscript to provide more detailed descriptions of the included cases. This study focused on all sudden unexpected deaths with a known natural cause. While our findings offer crucial epidemiological data for planning medical services, prevention, control, education, and further research, we acknowledge several limitations that could influence the interpretation of our results. Specifically, 6.2% of total autopsy cases remained undetermined due to the limitations of available resources and facilities, and these cases were therefore excluded from the study. Histopathological examination, largely using Hematoxylin and Eosin (H&E) staining, was performed in all sudden death cases. Toxicological, biochemical, and microbiological investigations are performed on a selective basis, as determined by the forensic pathologist. However, it is important to note that molecular autopsy facilities were not accessible, and tissue specimens were not preserved. This lack of molecular autopsy significantly limited our ability to determine the cause of death in cases of advanced putrefaction or incomplete ancillary examinations and this exclusion of cases with undetermined cause of death may affect the prevalence estimate. This limitation is explicitly discussed in the manuscript. Furthermore, we recognize that sudden unexplained deaths (SUDs) are frequently associated with underlying inherited arrhythmogenic cardiac diseases, which molecular autopsy can help identify. Identifying the cause of death via molecular autopsy is vital not only for medico-legal inquiries but also for guiding cascade genetic screening of the deceased's relatives. This screening is essential for risk prediction in family members and the appropriate management of those identified to be at risk. Your insightful feedback has prompted us to provide relevant recommendations regarding the need for a molecular autopsy facility. We believe that these recommendations will inform decisions and policies in our context and similar settings. As a short-term measure, considering the increasing importance of molecular autopsy, we recommend preserving DNA samples from all SUD cases to facilitate future investigations. These recommendations, we believe, will be particularly valuable for forensic pathologists and stakeholders working in resource-limited facilities. Despite these limitations, our study represents the first nationwide, autopsy-based investigation to comprehensively analyze the epidemiological, clinical, and pathological characteristics of all sudden unexpected natural deaths over a one-year period. We rigorously gathered information from all available sources, performed postmortem autopsies, and collected samples for available ancillary investigations. We believe that this study provides valuable epidemiological insights crucial for planning medical services, prevention, control, education, and further research. References Response: Thank you for this critical and pertinent suggestion. We have diligently updated the references, incorporating recent publications and replacing some earlier citations with their most current versions. Competing Interests: None Close Report a concern Respond or Comment COMMENTS ON THIS REPORT Author Response 05 Feb 2025 Alemayehu S. Lema , Department of Forensic Medicine and Toxicology, St. Paul's Hospital Millennium Medical College, Addis Ababa, 1271, Ethiopia 05 Feb 2025 Author Response Dear Reviewer, We sincerely appreciate the time and effort you dedicated to providing such a comprehensive and constructive review. Your feedback has been extremely valuable in shaping the quality of ... Continue reading Dear Reviewer, We sincerely appreciate the time and effort you dedicated to providing such a comprehensive and constructive review. Your feedback has been extremely valuable in shaping the quality of this work. We have thoroughly reviewed and incorporated your suggestions throughout the manuscript. Please find our detailed responses to each comment below. Method section: Details of postmortem examinations procedure Response: Thank you for this valuable suggestion. We have revised the manuscript to include detailed descriptions of the postmortem examinations performed, the ancillary investigations conducted, and the limitations encountered within our setting. As suggested, we have also provided a more thorough description of the gross heart examination. Your feedback has prompted us to include recommendations for improving autopsy facilities and future research, which we believe will be valuable for informing decisions and policies in similar contexts, particularly for forensic pathologists working in resource-limited facilities. Result section: Sudden unexplained deaths Response: Thank you for this valuable suggestion. We have revised the manuscript to provide more detailed descriptions of the included cases. This study focused on all sudden unexpected deaths with a known natural cause. While our findings offer crucial epidemiological data for planning medical services, prevention, control, education, and further research, we acknowledge several limitations that could influence the interpretation of our results. Specifically, 6.2% of total autopsy cases remained undetermined due to the limitations of available resources and facilities, and these cases were therefore excluded from the study. Histopathological examination, largely using Hematoxylin and Eosin (H&E) staining, was performed in all sudden death cases. Toxicological, biochemical, and microbiological investigations are performed on a selective basis, as determined by the forensic pathologist. However, it is important to note that molecular autopsy facilities were not accessible, and tissue specimens were not preserved. This lack of molecular autopsy significantly limited our ability to determine the cause of death in cases of advanced putrefaction or incomplete ancillary examinations and this exclusion of cases with undetermined cause of death may affect the prevalence estimate. This limitation is explicitly discussed in the manuscript. Furthermore, we recognize that sudden unexplained deaths (SUDs) are frequently associated with underlying inherited arrhythmogenic cardiac diseases, which molecular autopsy can help identify. Identifying the cause of death via molecular autopsy is vital not only for medico-legal inquiries but also for guiding cascade genetic screening of the deceased's relatives. This screening is essential for risk prediction in family members and the appropriate management of those identified to be at risk. Your insightful feedback has prompted us to provide relevant recommendations regarding the need for a molecular autopsy facility. We believe that these recommendations will inform decisions and policies in our context and similar settings. As a short-term measure, considering the increasing importance of molecular autopsy, we recommend preserving DNA samples from all SUD cases to facilitate future investigations. These recommendations, we believe, will be particularly valuable for forensic pathologists and stakeholders working in resource-limited facilities. Despite these limitations, our study represents the first nationwide, autopsy-based investigation to comprehensively analyze the epidemiological, clinical, and pathological characteristics of all sudden unexpected natural deaths over a one-year period. We rigorously gathered information from all available sources, performed postmortem autopsies, and collected samples for available ancillary investigations. We believe that this study provides valuable epidemiological insights crucial for planning medical services, prevention, control, education, and further research. References Response: Thank you for this critical and pertinent suggestion. We have diligently updated the references, incorporating recent publications and replacing some earlier citations with their most current versions. Dear Reviewer, We sincerely appreciate the time and effort you dedicated to providing such a comprehensive and constructive review. Your feedback has been extremely valuable in shaping the quality of this work. We have thoroughly reviewed and incorporated your suggestions throughout the manuscript. Please find our detailed responses to each comment below. Method section: Details of postmortem examinations procedure Response: Thank you for this valuable suggestion. We have revised the manuscript to include detailed descriptions of the postmortem examinations performed, the ancillary investigations conducted, and the limitations encountered within our setting. As suggested, we have also provided a more thorough description of the gross heart examination. Your feedback has prompted us to include recommendations for improving autopsy facilities and future research, which we believe will be valuable for informing decisions and policies in similar contexts, particularly for forensic pathologists working in resource-limited facilities. Result section: Sudden unexplained deaths Response: Thank you for this valuable suggestion. We have revised the manuscript to provide more detailed descriptions of the included cases. This study focused on all sudden unexpected deaths with a known natural cause. While our findings offer crucial epidemiological data for planning medical services, prevention, control, education, and further research, we acknowledge several limitations that could influence the interpretation of our results. Specifically, 6.2% of total autopsy cases remained undetermined due to the limitations of available resources and facilities, and these cases were therefore excluded from the study. Histopathological examination, largely using Hematoxylin and Eosin (H&E) staining, was performed in all sudden death cases. Toxicological, biochemical, and microbiological investigations are performed on a selective basis, as determined by the forensic pathologist. However, it is important to note that molecular autopsy facilities were not accessible, and tissue specimens were not preserved. This lack of molecular autopsy significantly limited our ability to determine the cause of death in cases of advanced putrefaction or incomplete ancillary examinations and this exclusion of cases with undetermined cause of death may affect the prevalence estimate. This limitation is explicitly discussed in the manuscript. Furthermore, we recognize that sudden unexplained deaths (SUDs) are frequently associated with underlying inherited arrhythmogenic cardiac diseases, which molecular autopsy can help identify. Identifying the cause of death via molecular autopsy is vital not only for medico-legal inquiries but also for guiding cascade genetic screening of the deceased's relatives. This screening is essential for risk prediction in family members and the appropriate management of those identified to be at risk. Your insightful feedback has prompted us to provide relevant recommendations regarding the need for a molecular autopsy facility. We believe that these recommendations will inform decisions and policies in our context and similar settings. As a short-term measure, considering the increasing importance of molecular autopsy, we recommend preserving DNA samples from all SUD cases to facilitate future investigations. These recommendations, we believe, will be particularly valuable for forensic pathologists and stakeholders working in resource-limited facilities. Despite these limitations, our study represents the first nationwide, autopsy-based investigation to comprehensively analyze the epidemiological, clinical, and pathological characteristics of all sudden unexpected natural deaths over a one-year period. We rigorously gathered information from all available sources, performed postmortem autopsies, and collected samples for available ancillary investigations. We believe that this study provides valuable epidemiological insights crucial for planning medical services, prevention, control, education, and further research. References Response: Thank you for this critical and pertinent suggestion. We have diligently updated the references, incorporating recent publications and replacing some earlier citations with their most current versions. Competing Interests: None Close Report a concern COMMENT ON THIS REPORT Views 0 Cite How to cite this report: Du Toit-Prinsloo L. Reviewer Report For: Epidemiological profiles and causes of sudden deaths of various ages in Ethiopia: an autopsy-based study [version 2; peer review: 1 approved, 2 approved with reservations] . F1000Research 2025, 12 :1441 ( https://doi.org/10.5256/f1000research.156070.r244085 ) The direct URL for this report is: https://f1000research.com/articles/12-1441/v1#referee-response-244085 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 22 Feb 2024 Lorraine Du Toit-Prinsloo , School of Medicine and Public Health, The University of Newcastle, Callaghan, New South Wales, Australia Approved with Reservations VIEWS 0 https://doi.org/10.5256/f1000research.156070.r244085 I am of the opinion that this article provides a good overview of the sudden deaths admitted to a Forensic Medicine Department. The following comments are to be addressed by the authors: Replace the word victims ... Continue reading READ ALL I am of the opinion that this article provides a good overview of the sudden deaths admitted to a Forensic Medicine Department. The following comments are to be addressed by the authors: Replace the word victims with deceased / decedents throughout the manuscript Methods: - " Autopsied specimens (whole organs or organ pieces) were fixed in 10% formalin for histopathological examination. Multiple sections with thicknesses of 4-5 mm were taken. The tissues were processed, subjected to paraffin sectioning at a thickness of 4 micrometers and then stained using hematoxylin and eosin staining." - replace this with ancillary investigations included whole organ retention, histological examination of tissue slides (were there any additional investigations such as microbiology or toxicology done?) Circumstances of death - The statement referring to 36 victims died instantaneously should be further explained in the context - there are only a few causes of death in the forensic setting in my opinion where we can indicate that the death occurred instantaneously. Some of the references pertaining to similar studies reporting on sudden death are more than 10 years old and it would be important to obtain more recent articles if available. It would also be interesting to expand on the nature of these investigations - a full post-mortem examination was conducted, but expanding on the types of ancillary investigations will add value. Is the work clearly and accurately presented and does it cite the current literature? Partly Is the study design appropriate and is the work technically sound? Yes Are sufficient details of methods and analysis provided to allow replication by others? Partly If applicable, is the statistical analysis and its interpretation appropriate? Yes Are all the source data underlying the results available to ensure full reproducibility? Yes Are the conclusions drawn adequately supported by the results? Yes Competing Interests: No competing interests were disclosed. Reviewer Expertise: Forensic Pathology - Sudden Death, Paediatric Pathology I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Du Toit-Prinsloo L. Reviewer Report For: Epidemiological profiles and causes of sudden deaths of various ages in Ethiopia: an autopsy-based study [version 2; peer review: 1 approved, 2 approved with reservations] . F1000Research 2025, 12 :1441 ( https://doi.org/10.5256/f1000research.156070.r244085 ) The direct URL for this report is: https://f1000research.com/articles/12-1441/v1#referee-response-244085 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Author Response 05 Feb 2025 Alemayehu S. Lema , Department of Forensic Medicine and Toxicology, St. Paul's Hospital Millennium Medical College, Addis Ababa, 1271, Ethiopia 05 Feb 2025 Author Response Dear Reviewer, We sincerely appreciate the time and effort you dedicated to providing such a comprehensive and constructive review. Your feedback has been extremely valuable in shaping the quality ... Continue reading Dear Reviewer, We sincerely appreciate the time and effort you dedicated to providing such a comprehensive and constructive review. Your feedback has been extremely valuable in shaping the quality of this work. We have thoroughly reviewed and incorporated your suggestions throughout the manuscript. Please find our detailed responses to each comment below. Method section: Regarding ancillary investigations Response: Thank you for this valuable suggestion. We have revised the manuscript to include detailed descriptions of the ancillary investigations performed, as well as a discussion of the available limitations within our setting. Moreover, your insightful feedback has prompted us to provide detailed recommendations for improving autopsy facilities and future research efforts, which we believe will inform decisions and policies in our and similar contexts. Histopathological examination, largely using Hematoxylin and Eosin (H&E) staining, was performed in all sudden death cases. Toxicological, biochemical, and microbiological investigations are performed on a selective basis, as determined by the forensic pathologist. However, molecular autopsy facilities were not available in our context. Despite these limitations, our study represents the first nationwide, autopsy-based investigation to comprehensively analyze the epidemiological, clinical, and pathological characteristics of all sudden unexpected natural deaths over a one-year period. We rigorously gathered information from all available sources, performed postmortem autopsies, and collected samples for available ancillary investigations. We believe that this study provides valuable epidemiological insights crucial for planning medical services, prevention, control, education, and further research. Circumstances of death Response: Thank you for this critical and pertinent comment. We have clarified the circumstances surrounding the 6.3% (n=36/568) of all SD cases reported as "instantaneous deaths." We have further detailed that, of these 36 cases, 88.9% (n=32) were attributed to cardiovascular (CVS) causes, particularly ischemic heart disease and cardiomyopathies, while the remaining cases involved spontaneous intracranial hemorrhage. Terminology Changes Response: Thank you for this important recommendation. We have replaced the term "victims" with "deceased" or "decedents" or Sudden death cases’’ or ‘’cases’’ throughout the manuscript as suggested. References Response: Thank you for this critical and pertinent suggestion. We have diligently updated the references, incorporating recent publications and replacing some earlier citations with their most current versions. Dear Reviewer, We sincerely appreciate the time and effort you dedicated to providing such a comprehensive and constructive review. Your feedback has been extremely valuable in shaping the quality of this work. We have thoroughly reviewed and incorporated your suggestions throughout the manuscript. Please find our detailed responses to each comment below. Method section: Regarding ancillary investigations Response: Thank you for this valuable suggestion. We have revised the manuscript to include detailed descriptions of the ancillary investigations performed, as well as a discussion of the available limitations within our setting. Moreover, your insightful feedback has prompted us to provide detailed recommendations for improving autopsy facilities and future research efforts, which we believe will inform decisions and policies in our and similar contexts. Histopathological examination, largely using Hematoxylin and Eosin (H&E) staining, was performed in all sudden death cases. Toxicological, biochemical, and microbiological investigations are performed on a selective basis, as determined by the forensic pathologist. However, molecular autopsy facilities were not available in our context. Despite these limitations, our study represents the first nationwide, autopsy-based investigation to comprehensively analyze the epidemiological, clinical, and pathological characteristics of all sudden unexpected natural deaths over a one-year period. We rigorously gathered information from all available sources, performed postmortem autopsies, and collected samples for available ancillary investigations. We believe that this study provides valuable epidemiological insights crucial for planning medical services, prevention, control, education, and further research. Circumstances of death Response: Thank you for this critical and pertinent comment. We have clarified the circumstances surrounding the 6.3% (n=36/568) of all SD cases reported as "instantaneous deaths." We have further detailed that, of these 36 cases, 88.9% (n=32) were attributed to cardiovascular (CVS) causes, particularly ischemic heart disease and cardiomyopathies, while the remaining cases involved spontaneous intracranial hemorrhage. Terminology Changes Response: Thank you for this important recommendation. We have replaced the term "victims" with "deceased" or "decedents" or Sudden death cases’’ or ‘’cases’’ throughout the manuscript as suggested. References Response: Thank you for this critical and pertinent suggestion. We have diligently updated the references, incorporating recent publications and replacing some earlier citations with their most current versions. Competing Interests: None Close Report a concern Respond or Comment COMMENTS ON THIS REPORT Author Response 05 Feb 2025 Alemayehu S. Lema , Department of Forensic Medicine and Toxicology, St. Paul's Hospital Millennium Medical College, Addis Ababa, 1271, Ethiopia 05 Feb 2025 Author Response Dear Reviewer, We sincerely appreciate the time and effort you dedicated to providing such a comprehensive and constructive review. Your feedback has been extremely valuable in shaping the quality ... Continue reading Dear Reviewer, We sincerely appreciate the time and effort you dedicated to providing such a comprehensive and constructive review. Your feedback has been extremely valuable in shaping the quality of this work. We have thoroughly reviewed and incorporated your suggestions throughout the manuscript. Please find our detailed responses to each comment below. Method section: Regarding ancillary investigations Response: Thank you for this valuable suggestion. We have revised the manuscript to include detailed descriptions of the ancillary investigations performed, as well as a discussion of the available limitations within our setting. Moreover, your insightful feedback has prompted us to provide detailed recommendations for improving autopsy facilities and future research efforts, which we believe will inform decisions and policies in our and similar contexts. Histopathological examination, largely using Hematoxylin and Eosin (H&E) staining, was performed in all sudden death cases. Toxicological, biochemical, and microbiological investigations are performed on a selective basis, as determined by the forensic pathologist. However, molecular autopsy facilities were not available in our context. Despite these limitations, our study represents the first nationwide, autopsy-based investigation to comprehensively analyze the epidemiological, clinical, and pathological characteristics of all sudden unexpected natural deaths over a one-year period. We rigorously gathered information from all available sources, performed postmortem autopsies, and collected samples for available ancillary investigations. We believe that this study provides valuable epidemiological insights crucial for planning medical services, prevention, control, education, and further research. Circumstances of death Response: Thank you for this critical and pertinent comment. We have clarified the circumstances surrounding the 6.3% (n=36/568) of all SD cases reported as "instantaneous deaths." We have further detailed that, of these 36 cases, 88.9% (n=32) were attributed to cardiovascular (CVS) causes, particularly ischemic heart disease and cardiomyopathies, while the remaining cases involved spontaneous intracranial hemorrhage. Terminology Changes Response: Thank you for this important recommendation. We have replaced the term "victims" with "deceased" or "decedents" or Sudden death cases’’ or ‘’cases’’ throughout the manuscript as suggested. References Response: Thank you for this critical and pertinent suggestion. We have diligently updated the references, incorporating recent publications and replacing some earlier citations with their most current versions. Dear Reviewer, We sincerely appreciate the time and effort you dedicated to providing such a comprehensive and constructive review. Your feedback has been extremely valuable in shaping the quality of this work. We have thoroughly reviewed and incorporated your suggestions throughout the manuscript. Please find our detailed responses to each comment below. Method section: Regarding ancillary investigations Response: Thank you for this valuable suggestion. We have revised the manuscript to include detailed descriptions of the ancillary investigations performed, as well as a discussion of the available limitations within our setting. Moreover, your insightful feedback has prompted us to provide detailed recommendations for improving autopsy facilities and future research efforts, which we believe will inform decisions and policies in our and similar contexts. Histopathological examination, largely using Hematoxylin and Eosin (H&E) staining, was performed in all sudden death cases. Toxicological, biochemical, and microbiological investigations are performed on a selective basis, as determined by the forensic pathologist. However, molecular autopsy facilities were not available in our context. Despite these limitations, our study represents the first nationwide, autopsy-based investigation to comprehensively analyze the epidemiological, clinical, and pathological characteristics of all sudden unexpected natural deaths over a one-year period. We rigorously gathered information from all available sources, performed postmortem autopsies, and collected samples for available ancillary investigations. We believe that this study provides valuable epidemiological insights crucial for planning medical services, prevention, control, education, and further research. Circumstances of death Response: Thank you for this critical and pertinent comment. We have clarified the circumstances surrounding the 6.3% (n=36/568) of all SD cases reported as "instantaneous deaths." We have further detailed that, of these 36 cases, 88.9% (n=32) were attributed to cardiovascular (CVS) causes, particularly ischemic heart disease and cardiomyopathies, while the remaining cases involved spontaneous intracranial hemorrhage. Terminology Changes Response: Thank you for this important recommendation. We have replaced the term "victims" with "deceased" or "decedents" or Sudden death cases’’ or ‘’cases’’ throughout the manuscript as suggested. References Response: Thank you for this critical and pertinent suggestion. We have diligently updated the references, incorporating recent publications and replacing some earlier citations with their most current versions. Competing Interests: None Close Report a concern COMMENT ON THIS REPORT Comments on this article Comments (0) Version 2 VERSION 2 PUBLISHED 07 Nov 2023 ADD YOUR COMMENT Comment keyboard_arrow_left keyboard_arrow_right Open Peer Review Reviewer Status info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Reviewer Reports Invited Reviewers 1 2 3 Version 2 (revision) 05 Feb 25 read Version 1 07 Nov 23 read read read Lorraine Du Toit-Prinsloo , The University of Newcastle, Callaghan, Australia Martina Modena , Scuola Superiore Sant'Anna, Pisa, Italy Joseph Westaby , St George's University of London, London, UK Comments on this article All Comments (0) Add a comment Sign up for content alerts Sign Up You are now signed up to receive this alert Browse by related subjects keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2025 Du Toit-Prinsloo L. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 14 Feb 2025 | for Version 2 Lorraine Du Toit-Prinsloo , School of Medicine and Public Health, The University of Newcastle, Callaghan, New South Wales, Australia 0 Views copyright © 2025 Du Toit-Prinsloo L. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (0) Approved info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions I am comfortable with changing my opinion to Approved Competing Interests No competing interests were disclosed. I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard. reply Respond to this report Responses (0) Du Toit-Prinsloo L. Peer Review Report For: Epidemiological profiles and causes of sudden deaths of various ages in Ethiopia: an autopsy-based study [version 2; peer review: 1 approved, 2 approved with reservations] . F1000Research 2025, 12 :1441 ( https://doi.org/10.5256/f1000research.177058.r364673) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/12-1441/v2#referee-response-364673 keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2024 Westaby J. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 14 Jun 2024 | for Version 1 Joseph Westaby , Cardiovascular and genomics research institute, St George's University of London, London, UK 0 Views copyright © 2024 Westaby J. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (1) Approved With Reservations info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions The article by Lema et al, is an observational study characterising all sudden deaths observed at a single forensic centre in Ethiopia. They report sudden death was 11.5% of all cases autopsied with 5.6 times as many males than females and a mean age of 45. Cardiovascular causes were most common with ischaemic heart disease as the leading cause. They highlight the importance of epidemiological data derived from autopsy studies to inform provision of medical services. This is a study that adds to the literature on sudden death showing its causes from Ethiopia. There are a number of improvements that I recommend that the authors make and I would be happy to re-review the paper following their emendations. Methods Individuals who died but were not confined to their homes, health facilities, or other related institutions due to illness for more than 24 hours before death were not considered unexpected deaths and were not included. Do the authors mean not? Results Figure 1: It would be best not to display the last three bars labelled as total as it does not allow you to appreciate the differences between the decades of age There was a statistically significant difference between the residence of the victims and sex (p<0.001). It is not made clear which sex lived more commonly where. Did males more frequently live in the city or the country? There was a statistically significant relationship between substance abuse and sex (p<0.001) and residence (p=0.004). A different distribution was observed for chronic alcohol use and sex (p<0.001). It is not made clear what these relationships are? Was it more common in males and in the city? Was alcohol more common in males or females? There was a statistically significant relationship between the presence of a prior chronic illness and sex (p=0.022). Were males or females more likely to have prior chronic illness? Table 3: It would be useful to put percentages for each sex for each cause so the differences between males and females are readily appreciable. There was a statistically significant difference between the CVS causes and sex (p=0.019). Was it more common males? Discussion The findings revealed a mean age of 44.8117.349 years. Giving the mean age as a whole number would be more appropriate Of 224 sudden death cases, men (n = 482/586) were predominant over women (n = 86/586), with a ratio of 5.6:1. This finding is consistent with many similar studies. 1 , 3 , 4 , 11 , 14 , 15 Only two of these studies have a ratio of 5:1, most of these have ratios of 2:1 male:female which is more usual in the literature. Could the authors please speculate as to why they have such a high male to female ratio. Are females autopsied less than males? What percentage of the 4,942 medicolegal autopsies were female? The occurrence of SD in males outnumbers females in all systems except GUS. Our findings coincided with those of the studies conducted in Tukey. 4 , 15 Turkey is spelt wrong. They may wish to use its new name “Türkiye”. Reference four is from Libya not Turkey. Our findings coincided with the results of the United Kingdom. 3 , 10 , 16 Refences are for two studies from Nigeria and one from Spain. None are from the UK. They should include references from the UK. Cardiomyopathy was the second most common COD in the cardiovascular system, accounting for 5.3% of all sudden deaths. This agrees with the result achieved in Libya. 4 It would be important to say that the cardiomyopathies may be inherited and therefore it is important to screen surviving blood relatives for these conditions. (Reference-1) Is the work clearly and accurately presented and does it cite the current literature? Partly Is the study design appropriate and is the work technically sound? Yes Are sufficient details of methods and analysis provided to allow replication by others? Yes If applicable, is the statistical analysis and its interpretation appropriate? No Are all the source data underlying the results available to ensure full reproducibility? Yes Are the conclusions drawn adequately supported by the results? Yes References 1. Sheppard MN, Westaby J, Zullo E, Fernandez BVE, et al.: Sudden arrhythmic death and cardiomyopathy are important causes of sudden cardiac death in the UK: results from a national coronial autopsy database. Histopathology . 2023; 82 (7): 1056-1066 PubMed Abstract | Publisher Full Text Competing Interests No competing interests were disclosed. Reviewer Expertise Cardiovascular pathology, sudden death, various cardiac conditions, anatomy of the heart I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. reply Respond to this report Responses (1) Author Response 05 Feb 2025 Alemayehu S. Lema, Department of Forensic Medicine and Toxicology, St. Paul's Hospital Millennium Medical College, Addis Ababa, 1271, Ethiopia Dear Reviewer, We sincerely appreciate the time and effort you dedicated to providing such a comprehensive and constructive review. Your feedback has been extremely valuable in shaping the quality of this work. We have thoroughly reviewed and incorporated your suggestions throughout the revised manuscript. Please find our detailed responses to each comment below. Method section Response: The statement, "Individuals who died but were not confined to their homes, health facilities, or other related institutions due to illness for more than 24 hours before death were not considered unexpected deaths and were not included," inadvertently used the phrase "not confined." This was an error; the intended criteria were that individuals that were confined. We appreciate the reviewer for identifying this inaccuracy. The statement has now been amended to read: "Individuals who died but were confined to their homes, health facilities, or other related institutions due to illness for more than 24 hours before death were not considered unexpected deaths and were not included." Result section 2.1. Figure 1 and table 3 Following your recommendations, we have made specific modifications to the presentation of results. In Figure 1, we've removed the "total" bars to improve the visual clarity of age-related trends, enabling a better appreciation of differences across decades. In Table 3, we have included sex-specific percentages for each cause, facilitating a direct comparison of male and female distributions. Statistical data presentation Response: Thank you so much, and comments are accommodated. All the statistical analysis and interpretation of the data have been meticulously clarified and elaborated upon, offering a more robust understanding of the findings. Mean age The mean age (±SD) is corrected to 44.8 ± 17.349 years. The previous version incorrectly presented the standard deviation within the mean, writing it as 44.8117.349 years. This has now been rectified. Discussion section 3.1. Male: female ratio Response: Thank you for this critical and insightful comment. We acknowledge the discrepancy in male-to-female ratios compared to some studies in the literature. The references for this section have been appropriately amended to reflect this. We have now included a detailed discussion of potential reasons for the observed gender disparity in our study. Issues regarding inherited cardiomyopathies Response: Thank you for this critical and pertinent suggestion. We agree that it is essential to highlight the potential for inherited cardiomyopathies. We have now included a statement in the discussion emphasizing the importance of screening surviving blood relatives for these conditions, and we have added the suggested reference. Issues regarding inherited cardiomyopathies Response: Thank you for this critical and pertinent suggestion. We have addressed all concerns regarding the citations and references. This includes updating the reference list to ensure accurate representation of study locations and replacing older references with more current literature, where possible. Additionally, we have incorporated many recent and all suggested references. View more View less Competing Interests None reply Respond Report a concern Westaby J. Peer Review Report For: Epidemiological profiles and causes of sudden deaths of various ages in Ethiopia: an autopsy-based study [version 2; peer review: 1 approved, 2 approved with reservations] . F1000Research 2025, 12 :1441 ( https://doi.org/10.5256/f1000research.156070.r287008) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/12-1441/v1#referee-response-287008 keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2024 Modena M. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 10 Jun 2024 | for Version 1 Martina Modena , Interdisciplinary Center for Health Sciences, Scuola Superiore Sant'Anna, Pisa, Italy 0 Views copyright © 2024 Modena M. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (1) Approved With Reservations info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions This article addresses a major health problem such as sudden death, which has a dramatic impact on families and society. The authors provide an interesting descriptive study on sudden death in Ethiopia. The authors should address the following comments: Methods: - “Full postmortem examinations were carried out in each instance using the Letulle evisceration procedure […] Organs were dissected, examined and checked for signs of gross pathological changes and violence. Autopsied specimens (whole organs or organ pieces) were fixed in 10% formalin for histopathological examination. Multiple sections with thicknesses of 4-5 mm were taken. The tissues were processed, subjected to paraffin sectioning at a thickness of 4 micrometers and then stained using hematoxylin and eosin staining.” The authors can provide more details on full postmortem examinations carried out? e.g. body weight and height have been collected? Concerning the histological analysis: was only the hematoxylin-eosin staining performed? the toxicology analysis was performed? The authors could include a small paragraph on heart analysis: e.g. pericardium, heart cavities, valves and coronary arteries have been checked? - Considering the growing importance of molecular autopsy, have any EDTA blood or frozen tissue samples been kept for possible future analysis? Results: Causes of sudden unexpected deaths - “Cardiovascular system diseases (CVS) were the leading causes of SD, accounting for 36.1% of all SD cases. This was followed by respiratory and gastrointestinal system pathologies, accounting for 32.6% and 19.5%, respectively. Central nervous system (CNS) and genitourinary system (GUS) pathologies were the least prevalent causes of death, accounting for 10.6% and 1.2%, respectively.” All described cases of sudden death are explained after autopsy by reaching a certain cause of death. This is surprising considering that in literature the cause of death remains in doubt even after an exhaustive autopsy in several sudden deaths. So, there is usually a proportion of cases remaining "unexplained". I suggest to authors to review the literature and guidelines (some references are more than 10 years old) and to review the results to be sure that all cases have been explained by autopsy. Do all cases have a definite diagnosis at autopsy? Particularly among cases of cardiac death, no probable arrhythmic death was found? Did all cases of sudden cardiovascular death have structural cardiac changes? Is the work clearly and accurately presented and does it cite the current literature? Partly Is the study design appropriate and is the work technically sound? Partly Are sufficient details of methods and analysis provided to allow replication by others? Partly If applicable, is the statistical analysis and its interpretation appropriate? Yes Are all the source data underlying the results available to ensure full reproducibility? Yes Are the conclusions drawn adequately supported by the results? Yes Competing Interests No competing interests were disclosed. I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. reply Respond to this report Responses (1) Author Response 05 Feb 2025 Alemayehu S. Lema, Department of Forensic Medicine and Toxicology, St. Paul's Hospital Millennium Medical College, Addis Ababa, 1271, Ethiopia Dear Reviewer, We sincerely appreciate the time and effort you dedicated to providing such a comprehensive and constructive review. Your feedback has been extremely valuable in shaping the quality of this work. We have thoroughly reviewed and incorporated your suggestions throughout the manuscript. Please find our detailed responses to each comment below. Method section: Details of postmortem examinations procedure Response: Thank you for this valuable suggestion. We have revised the manuscript to include detailed descriptions of the postmortem examinations performed, the ancillary investigations conducted, and the limitations encountered within our setting. As suggested, we have also provided a more thorough description of the gross heart examination. Your feedback has prompted us to include recommendations for improving autopsy facilities and future research, which we believe will be valuable for informing decisions and policies in similar contexts, particularly for forensic pathologists working in resource-limited facilities. Result section: Sudden unexplained deaths Response: Thank you for this valuable suggestion. We have revised the manuscript to provide more detailed descriptions of the included cases. This study focused on all sudden unexpected deaths with a known natural cause. While our findings offer crucial epidemiological data for planning medical services, prevention, control, education, and further research, we acknowledge several limitations that could influence the interpretation of our results. Specifically, 6.2% of total autopsy cases remained undetermined due to the limitations of available resources and facilities, and these cases were therefore excluded from the study. Histopathological examination, largely using Hematoxylin and Eosin (H&E) staining, was performed in all sudden death cases. Toxicological, biochemical, and microbiological investigations are performed on a selective basis, as determined by the forensic pathologist. However, it is important to note that molecular autopsy facilities were not accessible, and tissue specimens were not preserved. This lack of molecular autopsy significantly limited our ability to determine the cause of death in cases of advanced putrefaction or incomplete ancillary examinations and this exclusion of cases with undetermined cause of death may affect the prevalence estimate. This limitation is explicitly discussed in the manuscript. Furthermore, we recognize that sudden unexplained deaths (SUDs) are frequently associated with underlying inherited arrhythmogenic cardiac diseases, which molecular autopsy can help identify. Identifying the cause of death via molecular autopsy is vital not only for medico-legal inquiries but also for guiding cascade genetic screening of the deceased's relatives. This screening is essential for risk prediction in family members and the appropriate management of those identified to be at risk. Your insightful feedback has prompted us to provide relevant recommendations regarding the need for a molecular autopsy facility. We believe that these recommendations will inform decisions and policies in our context and similar settings. As a short-term measure, considering the increasing importance of molecular autopsy, we recommend preserving DNA samples from all SUD cases to facilitate future investigations. These recommendations, we believe, will be particularly valuable for forensic pathologists and stakeholders working in resource-limited facilities. Despite these limitations, our study represents the first nationwide, autopsy-based investigation to comprehensively analyze the epidemiological, clinical, and pathological characteristics of all sudden unexpected natural deaths over a one-year period. We rigorously gathered information from all available sources, performed postmortem autopsies, and collected samples for available ancillary investigations. We believe that this study provides valuable epidemiological insights crucial for planning medical services, prevention, control, education, and further research. References Response: Thank you for this critical and pertinent suggestion. We have diligently updated the references, incorporating recent publications and replacing some earlier citations with their most current versions. View more View less Competing Interests None reply Respond Report a concern Modena M. Peer Review Report For: Epidemiological profiles and causes of sudden deaths of various ages in Ethiopia: an autopsy-based study [version 2; peer review: 1 approved, 2 approved with reservations] . F1000Research 2025, 12 :1441 ( https://doi.org/10.5256/f1000research.156070.r270830) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/12-1441/v1#referee-response-270830 keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2024 Du Toit-Prinsloo L. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 22 Feb 2024 | for Version 1 Lorraine Du Toit-Prinsloo , School of Medicine and Public Health, The University of Newcastle, Callaghan, New South Wales, Australia 0 Views copyright © 2024 Du Toit-Prinsloo L. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (1) Approved With Reservations info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions I am of the opinion that this article provides a good overview of the sudden deaths admitted to a Forensic Medicine Department. The following comments are to be addressed by the authors: Replace the word victims with deceased / decedents throughout the manuscript Methods: - " Autopsied specimens (whole organs or organ pieces) were fixed in 10% formalin for histopathological examination. Multiple sections with thicknesses of 4-5 mm were taken. The tissues were processed, subjected to paraffin sectioning at a thickness of 4 micrometers and then stained using hematoxylin and eosin staining." - replace this with ancillary investigations included whole organ retention, histological examination of tissue slides (were there any additional investigations such as microbiology or toxicology done?) Circumstances of death - The statement referring to 36 victims died instantaneously should be further explained in the context - there are only a few causes of death in the forensic setting in my opinion where we can indicate that the death occurred instantaneously. Some of the references pertaining to similar studies reporting on sudden death are more than 10 years old and it would be important to obtain more recent articles if available. It would also be interesting to expand on the nature of these investigations - a full post-mortem examination was conducted, but expanding on the types of ancillary investigations will add value. Is the work clearly and accurately presented and does it cite the current literature? Partly Is the study design appropriate and is the work technically sound? Yes Are sufficient details of methods and analysis provided to allow replication by others? Partly If applicable, is the statistical analysis and its interpretation appropriate? Yes Are all the source data underlying the results available to ensure full reproducibility? Yes Are the conclusions drawn adequately supported by the results? Yes Competing Interests No competing interests were disclosed. Reviewer Expertise Forensic Pathology - Sudden Death, Paediatric Pathology I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. reply Respond to this report Responses (1) Author Response 05 Feb 2025 Alemayehu S. Lema, Department of Forensic Medicine and Toxicology, St. Paul's Hospital Millennium Medical College, Addis Ababa, 1271, Ethiopia Dear Reviewer, We sincerely appreciate the time and effort you dedicated to providing such a comprehensive and constructive review. Your feedback has been extremely valuable in shaping the quality of this work. We have thoroughly reviewed and incorporated your suggestions throughout the manuscript. Please find our detailed responses to each comment below. Method section: Regarding ancillary investigations Response: Thank you for this valuable suggestion. We have revised the manuscript to include detailed descriptions of the ancillary investigations performed, as well as a discussion of the available limitations within our setting. Moreover, your insightful feedback has prompted us to provide detailed recommendations for improving autopsy facilities and future research efforts, which we believe will inform decisions and policies in our and similar contexts. Histopathological examination, largely using Hematoxylin and Eosin (H&E) staining, was performed in all sudden death cases. Toxicological, biochemical, and microbiological investigations are performed on a selective basis, as determined by the forensic pathologist. However, molecular autopsy facilities were not available in our context. Despite these limitations, our study represents the first nationwide, autopsy-based investigation to comprehensively analyze the epidemiological, clinical, and pathological characteristics of all sudden unexpected natural deaths over a one-year period. We rigorously gathered information from all available sources, performed postmortem autopsies, and collected samples for available ancillary investigations. We believe that this study provides valuable epidemiological insights crucial for planning medical services, prevention, control, education, and further research. Circumstances of death Response: Thank you for this critical and pertinent comment. We have clarified the circumstances surrounding the 6.3% (n=36/568) of all SD cases reported as "instantaneous deaths." We have further detailed that, of these 36 cases, 88.9% (n=32) were attributed to cardiovascular (CVS) causes, particularly ischemic heart disease and cardiomyopathies, while the remaining cases involved spontaneous intracranial hemorrhage. Terminology Changes Response: Thank you for this important recommendation. We have replaced the term "victims" with "deceased" or "decedents" or Sudden death cases’’ or ‘’cases’’ throughout the manuscript as suggested. References Response: Thank you for this critical and pertinent suggestion. We have diligently updated the references, incorporating recent publications and replacing some earlier citations with their most current versions. View more View less Competing Interests None reply Respond Report a concern Du Toit-Prinsloo L. Peer Review Report For: Epidemiological profiles and causes of sudden deaths of various ages in Ethiopia: an autopsy-based study [version 2; peer review: 1 approved, 2 approved with reservations] . F1000Research 2025, 12 :1441 ( https://doi.org/10.5256/f1000research.156070.r244085) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/12-1441/v1#referee-response-244085 Alongside their report, reviewers assign a status to the article: Approved - the paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations - A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. 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