Abstract
Background:
Although clinical stability recognition was considered an early outcome in patients with pneumonia. Therefore, this study aimed to determine the time to clinical stability among pediatric patients with severe pneumonia in Southwest Ethiopia.
Methods:
A prospective follow-up study was conducted with 422 pediatric patients from June to November 2022 at a public hospitals. Data were analyzed using Epi-data and STATA, with the Kaplan-Meier survival estimate and Cox regression to assess time to stability and predictors. The proportional hazard model and Kaplan-Meier survival estimate graph were used to determine the time to clinical stability. Bivariate and multivariable Cox regression analysis were used to determine predictors of time to clinical stability.
Results:
In this study, children were followed for a total of 2718 person-days, with an incidence rate of 13.50% for clinical stability per 100 person-day observations. The median time to reach clinical stability was 5 days, and approximately 86.97% of pediatric patients with severe pneumonia achieved clinical stability. The most frequently observed abnormal parameter was elevated temperature, while lower oxygen saturation levels were associated with a longer time to clinical stability. Despite a thorough analysis, no statistically significant predictors were identified.
Conclusion:
In this study, most pediatric patients with severe pneumonia remained clinically stable throughout the follow-up period. The median time to clinical stability was 5 days, which was longer compared to other studies. Future research should focus on identifying predictors of delayed clinical stability using alternative analytical methods and larger sample sizes. Efforts should be made by stakeholders to reduce the time to clinical stability for pediatric patients.
Introduction
According to the World Health Organization (WHO) definition, severe pneumonia is diagnosed in children with a history of cough or reported breathing difficulty and at least one of the following: Oxygen saturation <90%, severe respiratory distress, general danger signs, increased respiratory rate (RR > 50 b/ minute in children aged 2 months to 12 months, RR > 40 b/ minute in children aged 12 months-59 months, RR >30/minute in children aged 60 months and above.1,2
Pneumonia continues to be the biggest killer worldwide of children under 5 years of age and most childhood pneumonia deaths are due to severe pneumonia.3,4 Although the implementation of safe, effective, and affordable interventions has reduced, pneumonia mortality still accounts for nearly one-fifth of childhood deaths worldwide.3,5,6
Childhood pneumonia is still a significant clinical and public health problem. Ethiopia has a high incidence of pneumonia, a high rate of hospitalization, and a higher risk of mortality, and is categorized among the top 5 nations with the highest number of pneumonia deaths. 7 In Ethiopia, no published evidence was found on time of clinical stability among pediatric patients.
Even though there are simple interventions to prevent it and effective low-cost medications to control and treat the infection, pneumonia remains one of the most common reasons for hospitalization in children adding to the family’s economic burden in resource-poor areas where parents need to pay for treatment at the point of care.8,9
After initiation of appropriate empirical antibiotic therapy, the majority of patients who are hospitalized with severe pneumonia show evidence of clinical improvement, and the process of clinical improvement starts when a patient becomes clinically stable.10,11
Clinical stability, defined as the resolution of infectious parameters, is key in the evaluation of severe pneumonia and is an essential determining factor in the length of hospital admission.11,12 Thus, in hospitalized patients with severe pneumonia time to clinical stability (TCS) could be considered a feasible indicator of the ongoing inflammatory response to infection. 13
Assessment of treatment response and thereby the concept of clinical stability, has become an important component of pneumonia management and Identification of clinical stability has several implications in clinical practice and clinical research. 10 In clinical practice, the ability to predict the time clinical stability (TCS) enables the health care providers to alter antibiotics, facilitate a timely admission, or arrange a suitable discharge, 14 duration of antibiotic therapy, and site of care within hospital settings. 15
Previous study findings in different countries have shown that patients have different times to be stable clinically and treatment outcomes. The study conducted in Spain indicates that the median time to clinical stability was 4 days (IQR, 2-6 days). 12 The study conducted in Switzerland 11 revealed that patients with younger age, less co-morbidity, fewer signs or symptoms, less respiratory compromise, and a lower platelet count are more likely to reach early clinical stability.
Although studies have been conducted in Ethiopia on the survival status, and length of hospital stay and their predictors, no studies have been conducted on time to clinical stability among pediatric patients. Although an agreement exists on the importance of determining the time to clinical stability as an early outcome in patients with pneumonia, there is not enough scientific literature in Ethiopia. Therefore, this study aimed to determine the time to clinical stability among pediatric patients with severe pneumonia admitted to public hospitals, in Southwest Ethiopia.
Methods and Materials
Study Area and Period
This study was conducted in 4 selected public Hospitals, in the Southwest region of Ethiopia from June 2022 and November 30, 2022. MizanTepi University Teaching Hospital (MTUTH), G/TsadikShawo General Hospital, Tepi General Hospital and Wacha Primary Hospital were selected using a lottery method from 8 public hospitals. The MTUTH is located 584 km from Addis Ababa, and it serves as a referral center. Tepi General Hospital is located 622 km from Addis Ababa. The G/tsaddik Shewa General Hospital is in the Keffa zone of Bonga town, which is 464 km from Addis Ababa, and the Wacha primary Hospital is in Wacha-maji town. These Hospitals provide outpatient care and inpatient services for pediatric patients.
Study Design
This multi-center institution-based prospective follow-up study was conducted among pediatric patients with severe pneumonia.
Source and Study Population
All pediatric patients (1 month to 15 years) with severe pneumonia admitted to public hospitals, in Southwest Ethiopia were the source population. All sampled/selected/pediatric patients with severe pneumonia admitted during the data collection period were the study population.
Eligibility Criteria
All pediatric patients admitted with severe pneumonia (791) that were in age categories of 1 month to 15 years were eligible and pediatric patients with severe pneumonia that had age below 1 month and above 15 years, patients with normal physiologic parameters, patients with incomplete follow-up, and patients readmitted were excluded.
Sample Size Determination, Sampling Technique, and Procedure
The sample size for this study was determined by using a single population proportion formula, 16 considering a 95% confidence level, margin of error (0.05), and proportion (P) of time to clinical stability from severe pneumonia as 50%, since there is no previous study conducted in Ethiopia the sample was calculated as:
n = (1.96)2 × 0.5 × (1−0.5)/(0.05)2 = 384: After adding a non-response rate of 10% (19.2 ≈ 20), the final sample size was 422.
The sample size was proportionally allocated to each hospital using the formula:
Study Variables
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Operational Definitions and Measurements
Data Collection Tools and Procedures
After reviewing the literature10,14,17,18 the tool was adapted and prepared in English translated into local language, and re-translated back to English. Data were collected through face-to-face interviews with mothers and day-to-day patient follow-up using medical charts and vital sign sheets. From admission through discharge, data for 4 physiologic parameters, such as temperature, heart rate, respiratory rate, and level of oxygen saturation were measured every 6 hours daily as part of routine patient care. Blood pressure measurements were not recorded during data collection due to the absence of a child-size blood pressure (BP) apparatus from each hospital.
Data Processing, Analysis, and Presentation
Data were entered into Epi-data Manager version 4.4.2.1 for coding, editing, and cleaning, and exported to Stata version 17 for analysis. Kaplan Meier and log-rank tests were performed to describe the time to clinical stability among children with severe pneumonia. Bivariate and multivariable analyses were performed using the Cox regression model to identify significant predictors of time to clinical stability after declaring the data for survival analysis. Finally, tables, charts, and texts were used to present the study results.
Data Quality Control and Quality Assurance
A pretest was conducted on 5% of the sample size before the actual data collection period then editions and modifications were made to the actual data collection tool. One day of training was provided for data collectors and supervisors on the process, objectives, and ethical issues of data collection. Supervisors regularly checked the completed questionnaires and provided immediate feedback to data collectors daily.
Patient and Public Involvement
The study participants were not involved in the development of the research question, or the design, conduct, reporting, implementation, or dissemination plans or evaluation of the study.
Ethical Approval and Informed Consent
This study was approved by the research ethics committee of Mizan Tepi university, College of Health Science, and an ethical clearance letter was obtained with reference number HSC/00101/2014. Mothers/caregivers of the study participants were informed about the objectives and purposes of the study. Informed consent was taken from parents/caregivers. To ensure confidentiality of the information, the names of the participants were not written in any part of the questionnaire. All methods in the study were performed by the declaration of Helsinki as a statement of ethical principles for medical research involving human subjects.
Results
In this study, from 791 pediatric patients with severe pneumonia, only 422 patients were sampled and completed the follow-up during the study period.
Socio-Demographic Characteristics
In this study, more than half of the children with pneumonia were males (56.40%), of which approximately 86.13% were clinically stable during the time of follow-up. Approximately, 58.29% of the children were from urban residents, and 85.37% of them were clinically stable. Most of the study participants (62%) were under the age category of 1 to 5 years, and only 15.27% of them were clinically unstable during their hospital stay (Table 1).
Socio-Demographic Characteristics of Pediatric Patients Admitted With Severe Pneumonia, Southwest Ethiopia, 2022/23(N = 422).
Nutritional and Feeding Status of Pediatric Patients
In this study, only 9.48% of the children with pneumonia had a history of underweight during birth. Approximately 78.67% of the children had a history of exclusive breastfeeding during their childhood and more than eighty percent (81.04%) had been breast-feeding at the time of their hospitalization (Table 2).
Nutritional Status and Mode of Feeding to Pediatric Patients Admitted With Severe Pneumonia, Southwest Ethiopia, 2022/23(N = 422).
Danger Signs and Therapeutics Regimen of Pediatric Patients
In this study, more than half (65.88%) of the children with severe pneumonia had a history of taking antibiotics medication before admission to the hospital even though most of them were clinically stable after hospitalization. Ceftriaxone was the most prescribed antibiotic in the hospital for treating severe pneumonia and the majority (85.72%) of the children with severe pneumonia had taken it during their hospitalization.
Approximately 82.94% of the children hospitalized with severe pneumonia had altered consciousness during their admission. Around 11.85% of children were unable to breastfeed, drink, and eat during admission, and 9.72% had abnormal body movement. More than half (55.45%) of the children had a previous history of acute respiratory infection (Table 3).
Danger Sign and Therapeutics Regimen of Pediatric Patients Admitted With Severe Pneumonia, Southwest Ethiopia, 2022/23(N = 422).
Co-morbidity in this study includes HIV infection, malaria, asthma, TB, etc.
The Age-Specific Proportion of Abnormal Physiological Parameters During Admission
In this study, Temperature 68.96% (95% CI: 65-73) was the most common abnormal parameter with median time to clinical stability was 1.25 days, followed by an abnormal level of oxygen saturation of 55.92% (95% CI: 51.13-60.61) with median time to clinical stability of 2.25 days: and an abnormal respiratory rate of 54.74% (95% CI: 49.94-59.45) with median time to clinical stability of 2 days. The least physiological parameter was heart rate abnormality which accounts for 28.67% (95% CI: 24.54-33.19) with its median time to clinical stability was 1 day (Table 4).
The Age-Specific Proportion of Abnormal Physiologic Parameters Among Pediatric Patients Admitted With Severe Pneumonia, Southwest Ethiopia, 2022/23 (N = 422).
Incidence Rate and Median Time to Clinical Stability Among Pediatric Patients With Severe Pneumonia
In this study, Children were followed for 2718 person-day observations, with an incidence rate of 13.50% (95% CI: 12.19-14.96) clinical stability per 100 person-day-observations.
In this study, the overall median time to reach clinical stability among pediatric patients with severe pneumonia was approximately 5 days (95% CI: 4-8), which indicates that 50% of the patients among those having clinical stability during hospitalization were clinically stable around 5 days after admission. Kaplan-Meier survival graph also affirms that the median time to clinical stability of children was 5 days (Figure 1 and Supplemental Figure 2).

Overall Kaplan-Meier estimate of clinical stability among pediatric patients admitted with severe pneumonia, 2022/23(N = 422).
Comparison of Time to Clinical Stability Functions for Different Groups of Variables
Comparisons of time to clinical stability differences between different groups of categorical variables were done using the Kaplan-Meier survival graph and statistical log-rank test to check for the existence of the time to clinical stability difference was significant or insignificant among various levels of the categorical predictors.
In this study from the log rank, children without exclusive breastfeeding history(p = 0.0075), having antibiotic history before admission,(p = 0.0021), with alerted consciousness( P = .0357), nutritional status of wasted (P = .0363) having co-morbidity(p = 0.000), and history of previous acute respiratory infection (P = .000) had a significant difference to their probability of clinical stability with their counterparts( they have a lower probability of clinical stability), While no probability of clinical stability differences in the remaining group of variables (Supplemental Table 1). the Kaplan-Meier survival graph shows the clinical stability function for different categorical variables to support the log-rank result (Supplemental Figure 1).
Discussion
This multi-center institution-based prospective follow-up study was conducted to determine the time to clinical stability among pediatric patients with severe pneumonia. In this study, the overall median time to reach clinical stability among pediatric patients with severe pneumonia was approximately 5 days, which is in line with studies conducted in Spain, 12 and Boston, 19 where the median time to clinical stability was 4 days (IQR, 2-6 days) and 3 to 7 days respectively.
However, the time spent on clinical stability among pediatric patients with severe pneumonia in this study was higher than that in the other previous studies conducted at the Children’s Hospital of Philadelphia, 18 where the median time to clinical stability (TCS) among children was less than 24 hours. The reason for this difference might be variations in the severity of pneumonia among patients. This study was conducted among pediatric patients with severe pneumonia but the study in Philadelphia, 18 was conducted among patients with community-acquired pneumonia. However, this is open to future research to understand the real impact of severity index scores on time to clinical stability.
Another reason also might be varying methods of clinical practice and contextual factors among developing countries (Ethiopia) and Philadelphia lead to variation in the level of quality of care and socioeconomic variation that may lead to different times for clinical stability among pediatric patients. In Ethiopia, patients have a longer time to reach clinical stability whereas in Philadelphia have a shorter time to reach clinical stability.
In this study, the median time to clinical stability for each abnormal physiological parameter was 1 day (95% CI: 1-3), 2 days (95% CI: 1-4), 2.25 days (95% CI: 1-3.57), and 1.25 (95% CI: 1-3) days for abnormal heart rate, respiratory rate, low level of oxygen saturation and temperature respectively. This was supported by a previous study conducted in Boston, 19 which indicates that the median time to stability for heart rate was 2 days, and 3 days for respiratory rate, and temperature.
In this study, oxygen saturation has a longer time to clinical stability which is supported by the previous findings of the study conducted in the USA, 17 indicating that the use of supplemental oxygen had the longest TCS. This might be because there is an increased severity of pneumonia in pediatric patients who have abnormal oxygen saturation and the need for supplemental oxygen, which in turn may take a longer time to achieve clinical stability. However, this is open to further rigorous study to determine the actual variation of time to clinical stability among patients with abnormal oxygen saturation levels and other abnormal physiological parameters using a comparative approach.
Temperature 68.96% (95% CI: 65-73) was the most common abnormal parameter, followed by an abnormal level of oxygen saturation 55.92% (95% CI: 51.13-60.61). This result was in contrast with a study conducted in the USA, 17 which revealed that the most common abnormal parameter was respiratory rate (81.4%), followed by abnormal temperature (71.4%). This variation might be because of the different socio-demographic characteristics between countries (Ethiopia and America).
This study could have significant clinical and research implications; It may assist healthcare professionals in determining the optimal time for clinical improvement, enabling them to make informed decisions about adjusting treatment plans or considering discharge. This, in turn, could help reduce unnecessary prolonged hospital stays and excessive antibiotic use, ultimately enhancing patient outcomes. 18
By identifying the expected time for clinical stability, healthcare providers can more easily recognize when a child is not improving as anticipated. The ability to predict time to clinical stability (TCS) enables the health care provider to alter antibiotics appropriately, facilitate a timely intensive care unit(ICU) admission, or ensure a timely discharge, allowing for prompt intervention and more effective management of potential complications, thereby enhancing clinical outcomes in the treatment of severe pediatric pneumonia. 14
Future researchers should conduct using alternative analytical techniques or larger sample sizes may help in identifying significant predictors of time to clinical stability. The role of unmeasured factors such as environmental and seasonal influences on the incidence of pneumonia among children should also be examined in the future.
Conclusions and Recommendations
Assessing clinical stability is also important because it has implications for resource use, including the use of hospital beds and the ability to safely discharge patients, and thereby has an impact on the economic burden associated with Pneumonia. Temperature was the most common abnormal parameter and low level of oxygen saturation had a longer time to achieve clinical stability.
The time to clinical stability was slightly prolonged with an overall median time to clinical stability of 5 days, and patients need a longer hospital stay to reach clinical stability. Therefore, attention should be given to pediatric patients with severe pneumonia to reduce time to clinical stability and treatment costs, even though additional study is also needed to further validate these findings. Healthcare providers and other stakeholders should provide timely initiation of appropriate therapeutic interventions for patients with severe pneumonia.
Strength and Limitations
Strength
The study was conducted using prospective follow-up and primary data, which increased data accuracy and reliability, and symptoms of pneumonia could be easily obtained in a prospective study. This study was conducted in a multi-center which increases the reliability of data for the larger context of different study areas.
Limitation
This study has been conducted on a small sample size may result in less precise estimates that are not broadly representative of the large population of children. In addition, the study was conducted only at public hospitals, which might not be representative of private hospitals in Ethiopia. Therefore, a prospective population-based study of pneumonia hospitalizations is required in Ethiopia. This study also analyzed data from June 2022 to November 2022, which can significantly influence the incidence, types of pneumonia, and body temperature measurement in children, and the selected timeframe may be subject to some seasonal bias.
Supplemental Material
sj-docx-1-gph-10.1177_30502225251346878 – Supplemental material for Time to Clinical Stability Among Pediatric Patients With Severe Pneumonia: Southwest Ethiopia: Prospective Follow-Up Study
Supplemental material, sj-docx-1-gph-10.1177_30502225251346878 for Time to Clinical Stability Among Pediatric Patients With Severe Pneumonia: Southwest Ethiopia: Prospective Follow-Up Study by Belete Fenta Kebede, Yalemtsehay Dagnaw Genie, Tsegaw Biyazin Tesfa, Aynalem Yetwale Hiwot, Emebet Adugnaw, Esmelalem Mihretu and Nigatu Desalegn in Sage Open Pediatrics
Supplemental Material
sj-jpeg-2-gph-10.1177_30502225251346878 – Supplemental material for Time to Clinical Stability Among Pediatric Patients With Severe Pneumonia: Southwest Ethiopia: Prospective Follow-Up Study
Supplemental material, sj-jpeg-2-gph-10.1177_30502225251346878 for Time to Clinical Stability Among Pediatric Patients With Severe Pneumonia: Southwest Ethiopia: Prospective Follow-Up Study by Belete Fenta Kebede, Yalemtsehay Dagnaw Genie, Tsegaw Biyazin Tesfa, Aynalem Yetwale Hiwot, Emebet Adugnaw, Esmelalem Mihretu and Nigatu Desalegn in Sage Open Pediatrics
Footnotes
Acknowledgements
It is our pleasure to thank the pediatric ward staff of each hospital for giving us the necessary information that we require. Our special appreciation extended to the study participants, data collectors, and supervisors. Study area, and period, design, population, and eligibility criteria, sampling procedure, ethics approval and consent to participate of in the method and material section of this manuscript were previously published by Elsevier Inc. Journal of global pediatrics, found at
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Abbreviations
CI: Confidence Interval, DM: Diabetes Mellitus, HIV: immune deficiency Virus, MTUTH: Mizan Tepi University Teaching Hospital, TCS: Time to clinical stability, WFA: weight for age, WFH: weight for height, WHO: World Health Organization
ORCID iDs
Author Contributions
All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis, and interpretation, or all these areas; took part in drafting, revising, or critically reviewing the article; gave final approval of the version to be published; and agreed to be accountable for all aspects of the work.
Funding
The author(s) received no financial support for the research, authorship, and/or publication of this article.
Declaration of Conflicting Interests
The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Data Availability Statement
The raw data file could be provided for research purposes only, upon request, via e-mail from the corresponding author.
Supplemental Material
Supplemental material for this article is available online.
References
Supplementary Material
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