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Background: The clinical characteristics of pediatric critically ill patients who need referral to a tertiary hospital is often unknown in resource limited settings where constraints in diagnosis capacity, resources, and infrastructures are common. There is a need to increase insight in the characteristics of these patients for capacity building strengthening and appropriate resource allocation. The aim of this study was to describe the clinical characteristics and outcomes of critically ill children who are referred to a tertiary referral teaching hospital in Yogyakarta., Methods: A prospective observasional study was carried out from July 1st, 2022 -January 31st, 2023 which included all critically ill pediatric patients who were referred through the Integrated Referral System (SISRUTE) to the Pediatric Intensive Care Unit (PICU) of dr. Sardjito hospital. We excluded patients who were referred with a request for admission to the PICU, but were not admitted to the PICU due to their stable condition and lack of the need for intensive care., Result: During the study period, we received 1046 emergency referral requests for pediatric patients via SISRUTE, of those, 562 (53.7%) patients were critically ill. The reasons of PICU referral request were the need of solely intensive care 504 (89.7%), the need of multidisciplinary team care, including intensive care 57 (10.1%) and parents request 1 (0.3%). The pre-referral emergency diagnosis was shock 226 (40.3%), respiratory distress/failure 151 (26.7%), central nervous system (CNS) dysfunction 135 (24.1%), trauma 33 (5.9%) and sepsis 17 (3%). Of the 562 critically ill PICU referral requests, 473 (84.2%) requests were accepted. One hundred and eighty-one (58.7%) patients were finally admitted to the PICU, 125 (40.3%) admitted to our regular ward due to stable condition, 4 (1.3%) patients died in Emergency Departement (ED). The remaining accepted patients on request did not arrive in our facility due to various reasons. The mean (SD) response time was 9.1 (27.6) minutes. The mean (SD) transfer time was 6.45 (4.73) hours. Mean (SD) PICU and hospital length of stay was 6.7 (8.3) days and 10.2 (9.2) days respectively. PICU and hospital mortality was 24.3% and 29.7%, respectively., Conclusion: The mortality rate for critically ill pediatric patients referred to a tertiary PICU still high, with shock being the most common pre-referral emergency diagnosis. There is a discrepancy between the referring hospital's and the referral hospital's indication for PICU admission. The time required to reach the referral hospital is quite lengthy., (© 2024. The Author(s).)

Background: Wastewater-based epidemiology (WBE) surveillance has been proposed as an early warning system (EWS) for community SARS-CoV-2 transmission. However, there is limited data from low-and middle-income countries (LMICs). This study aimed to assess the ability of WBE surveillance to detect SARS-CoV-2 in formal and informal environments in Indonesia using different methods of sample collection, to compare WBE data with patterns of clinical cases of COVID-19 within the relevant communities, and to assess the WBE potential to be used as an EWS for SARS-CoV-2 outbreaks within a community., Materials and Methods: We conducted WBE surveillance in three districts in Yogyakarta province, Indonesia, over eleven months (27 July 2021 to 7 January 2022 [Delta wave]; 18 January to 3 June 2022 [Omicron wave]). Water samples using grab, and/or passive sampling methods and soil samples were collected either weekly or fortnightly. RNA was extracted from membrane filters from processed water samples and directly from soil. Reverse-transcription quantitative real-time polymerase chain reaction (RT-qPCR) was performed to detect the SARS-CoV-2 N and ORF1ab genes., Results: A total of 1,582 samples were collected. Detection rates of SARS-CoV-2 in wastewater reflected the incidence of community cases, with rates of 85% at the peak to 2% at the end of the Delta wave and from 94% to 11% during the Omicron wave. A 2-week lag time was observed between the detection of SARS-CoV-2 in wastewater and increasing cases in the corresponding community., Conclusion: WBE surveillance for SARS-CoV-2 in Indonesia was effective in monitoring patterns of cases of COVID-19 and served as an early warning system, predicting the increasing incidence of COVID-19 cases in the community., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Murni et al. 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 author and source are credited.)

Background: Hemodialysis (HD) is the modality of renal replacement therapy (RRT) with the highest mortality rate. The identification of prognostic factors will help achieve better outcomes among HD patients. In this study, we sought to conduct a survival analysis and determine the predictors of mortality among adult Indonesian HD patients using data obtained from Indonesian Renal Registry (IRR)., Methods: This is a retrospective cohort study which reviewed all adult hemodialysis patients in Indonesia based on the records of IRR during 2007-2022. Variables analyzed in this study include age, sex, etiology of CKD, cause of death, HD frequency, and initial vascular access. A 5-year follow-up was performed until the outcome of death or drop out was found., Results: Among 99,552 eligible patients, the mean survival length was 1536.21 ± 2.50 days. The 5-year survival rate was 77%. Cox proportional hazard regression model revealed demographic and clinical characteristics that are significantly associated with mortality: male sex (HR: 1.038, 95% CI 1.002-1.075), age of 60 years or older (HR: 1.329, 95% CI 1.281-1.379), diabetic nephropathy (HR: 1.347, 95% CI 1.249-1.452), twice-weekly hemodialysis frequency (HR: 1.080, 95% CI 1.011-1.155), initial vascular accesses with femoral vein puncture (HR: 2.710, 95% CI 2.568-2.860), and CVC (HR: 2.992, 95% CI 2.848-3.144)., Conclusions: The 5-year survival rate of Indonesian HD patients is 77. Male sex, age of HD onset at 60 years or older, diabetic nephropathy, twice-weekly HD frequency, and the initial vascular accesses with femoral vein puncture and CVC are associated with increased risk of mortality., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Rotavirus infection is a common cause of severe diarrheal disease and a major cause of deaths and hospitalizations among young children. Incidence of rotavirus has declined globally with increasing vaccine coverage. However, it remains a significant cause of morbidity and mortality in low-income countries where vaccine access is limited and efficacy is lower. The oral human neonatal vaccine RV3-BB can be safely administered earlier than other vaccines, and recent trials in Indonesia have demonstrated high efficacy. In this study, we use a stochastic individual-based model of rotavirus transmission and disease to estimate the anticipated population-level impact of RV3-BB following delivery according to either an infant (2, 4, 6 months) and neonatal (0, 2, 4 months) schedule. Using our model, which incorporated an age- and household-structured population and estimates of vaccine efficacy derived from trial data, we found both delivery schedules to be effective at reducing infection and disease. We estimated 95-96% reductions in infection and disease in children under 12 months of age when vaccine coverage is 85%. We also estimate high levels of indirect protection from vaccination, including 78% reductions in infection in adults over 17 years of age. Even for lower vaccine coverage of 55%, we estimate reductions of 84% in infection and disease in children under 12 months of age. While open questions remain about the drivers of observed lower efficacy in low-income settings, our model suggests RV3-BB could be effective at reducing infection and preventing disease in young infants at the population level.

Competing Interests: We declare no competing interests.

Objective: To describe the prevalence and determinants of vitamin D deficiency (VDD) among healthy children aged between 0 and 18 years living in South-East Asia (SEA)., Design: We systematically searched Ovid MEDLINE and Ovid EMBASE for observational studies assessing VDD among healthy children in the SEA region as the primary or secondary outcome from database inception to 6 April 2021. PubMed was used for e-pubs and publications not indexed in Medline. Publications that included abstracts in English were included. We performed a systematic review to describe the prevalence of VDD in SEA children., Results: Our initial search identified 550 publications with an additional 2 publications from manual screening. Of those, 21 studies from 5 different countries (Thailand, Indonesia, Vietnam, Malaysia and Cambodia) were summarised and included in forest plots. The prevalence of VDD (<50 nmol/L) ranged from 0.9% to 96.4%, with >50% of newborns having VDD, and severe VDD (<30 nmol/L) ranged from 0% to 55.8%. Female sex and urban living were the most common determinants of VDD., Conclusions: VDD among healthy children living in the SEA region is common. Efforts to detect VDD and the implementation of preventive measures, including education on safe sun exposure and oral vitamin D supplementation or food fortification, should be considered for key target groups, including adolescent females and pregnant and lactating women to improve the vitamin D status of newborns., Protocol Registration Number: This study is registered with PROSPERO (CRD42020181600)., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Wastewater-based epidemiology (WBE) surveillance as an early warning system (EWS) for monitoring community transmission of SARS-CoV-2 in low- and middle-income country (LMIC) settings, where diagnostic testing capacity is limited, needs further exploration. We explored the feasibility to conduct a WBE surveillance in Indonesia, one of the global epicenters of the COVID-19 pandemic in the middle of 2021, with the fourth largest population in the world where sewer and non-sewered sewage systems are implemented. The feasibility and resource capacity to collect samples on a weekly or fortnightly basis with grab and/or passive sampling methods, as well as to conduct qualitative and quantitative identification of SARS-CoV-2 ribonucleic acid (RNA) using real-time RT-PCR (RT-qPCR) testing of environmental samples were explored., Materials and Methods: We initiated a routine surveillance of wastewater and environmental sampling at three predetermined districts in Special Region of Yogyakarta Province. Water samples were collected from central and community wastewater treatment plants (WWTPs), including manholes flowing to the central WWTP, and additional soil samples were collected for the near source tracking (NST) locations (i.e., public spaces where people congregate)., Results: We began collecting samples in the Delta wave of the COVID-19 pandemic in Indonesia in July 2021. From a 10-week period, 54% (296/544) of wastewater and environmental samples were positive for SARS-CoV-2 RNA. The sample positivity rate decreased in proportion with the reported incidence of COVID-19 clinical cases in the community. The highest positivity rate of 77% in week 1, was obtained for samples collected in July 2021 and decreased to 25% in week 10 by the end of September 2021., Conclusion: A WBE surveillance system for SARS-CoV-2 in Indonesia is feasible to monitor the community burden of infections. Future studies testing the potential of WBE and EWS for signaling early outbreaks of SARS-CoV-2 transmissions in this setting are required., Competing Interests: The authors have declared that no competing interests exist.

Background: Screening of critical congenital heart disease (CCHD) using pulse oximetry is a routine procedure in many countries, but not in Indonesia. This study aimed to evaluate the feasibility of implementing CCHD screening with pulse oximetry for newborns in Yogyakarta, Indonesia., Methods: A cross-sectional study was conducted at four hospitals in Yogyakarta, Indonesia. Newborns aged 24-48 hours who met the inclusion criteria were screened on the right hand and left or right foot using a pulse oximeter. Positive results were indicated by: either (1) SpO 2 level < 90% in one extremity, (2) SpO 2 level of 90-94% in both right hand and either foot on three measurements conducted 1 hour apart, or (3) a saturation difference > 3% between the upper and lower extremity on three measurements conducted 1 hour apart. Positive findings were confirmed by echocardiography., Results: Of 1452 newborns eligible for screening, 10 had positive results and were referred for echocardiographic evaluation. Of those, 8 (6 per 1000 live birth, 8/1452) had CCHD. Barriers found during screening processes were associated with hospital procedures, equipment, healthcare personnel, and condition of the newborn., Conclusion: Pulse oximetry screening might be feasible to be implemented within the routine newborn care setting for CCHD in Indonesia. In order to successfully implement pulse oximetry screening to identify CCHD in Indonesia, the barriers will need to be addressed., (© 2022. The Author(s).)

Background: Vaccines have proven to be one of the most effective strategies to control infectious diseases and contributed to childhood survival. While high vaccine coverages provide individual's and herd immunity, age-appropriate vaccination or vaccine timeliness is important for maximum vaccine's protection, but often not evaluated. We aimed to describe the timeliness of childhood vaccination for Indonesian infants and identify risk factors associated with delayed vaccination., Methods: This study was a sub-study of the Indonesian Pneumonia and Vitamin D status (IPAD) study, a community-based cohort study to investigate pneumonia incidence in two districts in Yogyakarta province, Indonesia. Socio-demographic data were obtained from structured interviews and vaccine status was obtained from maternal and child health records. Timely vaccination was defined if the vaccine was received between four days or less before and within 28 days after the recommended age of vaccination., Results: 359 (85%) out of 422 IPAD participants and their immunisation records were included. Between December 2015 and December 2017, vaccination coverage was high and ranged from 96.1% (Measles) to 100% (DTP-HepB-Hib 1). However, two thirds (67%, 242/359) of all participants had received either early or late vaccines, with dose 2 IPV (40%, 143/356), dose 3 IPV (56%, 196/349) and dose 3 DTP-HepB-Hib (29%, 103/354) most delayed, and only 1% received early doses. The main risk factors for untimely vaccination were if the infant was born in a private practice versus in a public health facility (AOR 1.90; 95% CI: 1.18-3.07) and rural residence (AOR 1.84; 95% CI: 1.15-2.94)., Conclusions: Despite high vaccine coverage for Indonesian infants (>95%), two thirds (67%) of infants had untimely vaccinations, with dose 3 IPV (56%) the most delayed. Future strategies should focus on coordination between government, health care providers, and carers to ensure timely access and vaccination of infants to ensure adherence to vaccination schedules., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Objective: To determine the prevalence of vitamin D deficiency in Indonesian children hospitalized with pneumonia and evaluate the association between vitamin D status and severity of pneumonia., Methods: A hospital-based cross-sectional study was conducted from February 2016 to July 2017 in two district hospitals in Yogyakarta province, Indonesia. Infants and young children aged 2-59 months hospitalized with pneumonia were recruited. Serum blood samples were collected on admission and analyzed for total serum 25-hydroxyvitamin D3 and 25-hydroxyvitamin D2 concentrations using liquid chromatography-tandem mass spectrometry. Vitamin D deficiency was defined as a level of serum vitamin D <50 nmol/L. The association between vitamin D deficiency and severity of hospitalized pneumonia according to WHO criteria, including the presence of danger signs, hypoxemia (SpO2 in air below 90%), duration of hospitalization, and admission to Intensive Care Unit (ICU), was analyzed using logistic regression., Results: 133 children with WHO-defined pneumonia were enrolled in the study and 127 (96%) had their vitamin D status determined. The mean vitamin D concentration was 67 (± 24 SD) nmol/L and 19% of participants were vitamin D deficient. Age younger than 6 months was associated with prolonged hospitalization (> 5 days) and low birth weight and poor nutritional status on admission were risk factors for hypoxemia. However, vitamin D status was not associated with the presence of danger signs, duration of hospitalization, or hypoxemia., Conclusions: One in every five children hospitalized with pneumonia was vitamin D deficient. Vitamin D status was not associated with the severity of pneumonia., Competing Interests: The authors have declared that no competing interests exist.

Background: Vitamin D deficiency has been associated with acute respiratory infection (ARI) in early life, but this has not been evaluated in Indonesia. We aimed to determine the incidence of ARI in Indonesian infants, and to evaluate the association with vitamin D deficiency., Methods: From 23 December 2015 to 31 December 2017, we conducted a community-based prospective cohort study in Yogyakarta province. We enrolled 422 pregnant women and followed their infants from birth until 12 months of age for ARI episodes. Vitamin D status was measured at birth and at age six months. We performed Cox proportional hazard regression analysis to evaluate the association between vitamin D deficiency and pneumonia incidence., Results: At study completion, 95% (400/422) of infants retained with a total of 412 child years of observation (CYO). The incidence of all ARI and of WHO-defined pneumonia was 3.89 (95% CI 3.70-4.08) and 0.25 (95% CI 0.21-0.30) episodes per CYO respectively. Vitamin D deficiency at birth was common (90%, 308/344) and associated with more frequent episodes of ARI non-pneumonia (adjusted odds ratio 4.48, 95% CI:1.04-19.34). Vitamin D status at birth or six months was not associated with subsequent pneumonia incidence, but greater maternal sun exposure during pregnancy was associated with a trend to less frequent ARI and pneumonia in infants., Conclusion: ARI, pneumonia, and vitamin D deficiency at birth were common in Indonesian infants. Minimising vitamin D deficiency at birth such as by supplementation of mothers or safe sun exposure during pregnancy has the potential to reduce ARI incidence in infants in this setting., Competing Interests: The authors have declared that no competing interests exist.

Background: Vitamin D deficiency in infants has been associated with an increased risk of a number of diseases but there are limited data on the prevalence and determinants of vitamin D deficiency from tropical settings with high infant morbidity and mortality., Objective: To determine the prevalence and determinants of vitamin D deficiency in infants at birth and at six months of age in Yogyakarta province, Indonesia., Design: Serum vitamin D of eligible infants was measured in cord blood at birth and at six months of age. Factors associated with vitamin D deficiency (serum 25-hydroxyvitamin D <50 nmol/L) were collected prospectively monthly from birth and concentrations measured by liquid chromatography-tandem mass spectrometry. Independent risk factors were identified by multiple logistic regression., Results: Between December 2015 to December 2017, 350 maternal-newborn participants were recruited and followed up. Vitamin D deficiency was detected in 90% (308/344) of cord blood samples and 13% (33/255) of venous blood samples at six months. Longer time outdoors (≥2 hours per day) and maternal multivitamin intake containing vitamin D during pregnancy were protective against vitamin D deficiency at birth (AOR: 0.10, 95% CI: 0.01-0.90 and AOR: 0.21, 95% CI: 0.06-0.68, respectively). Risk factors for vitamin D deficiency at six months included lower cumulative skin-sun exposure score (AOR: 1.12, 95% CI: 1.04-1.20), severe vitamin D deficiency at birth (AOR: 7.73, 95% CI: 1.20-49.60) and exclusive breastfeeding (AOR: 2.64, 95% CI: 1.07-6.49) until six months. Among exclusively breast fed (EBF) infants, a higher skin-sun exposure score was associated with reduced vitamin D deficiency risk., Conclusion: In equatorial regions, the role of 'safe' morning sun exposure in infants and mothers in populations with medium to dark brown skin pigmentation and effective interventions to prevent vitamin D deficiency in newborns and EBF infants, need further consideration and evaluation., Competing Interests: The authors have declared that no competing interests exist.

Background: Placental or breast milk maternal antibodies can potentially reduce oral rotavirus vaccine efficacy in developing countries. We aimed to examine the relationship between the level of rotavirus specific immunoglobulin A (IgA) and neutralising antibodies (NA) in colostrum and breast milk and cord IgG, with cumulative vaccine take following one and three doses of oral RV3-BB rotavirus vaccine within a Phase IIb trial in Indonesia., Methods: 196 infants received three doses of RV3-BB in a randomized, double-blinded trial, using a neonatal schedule (first dose at 0-5 days of age, n = 61), an infant schedule (first dose at ~ 8 weeks of age, n = 67) or placebo (n = 68). Rotavirus specific IgA and NA in colostrum and breast milk, rotavirus specific cord IgG, Serum IgA and stool excretion were measured., Results: There was little evidence of an association between IgA in colostrum or breast milk and cumulative vaccine take after three doses in the neonatal or infant groups. In the neonatal group, there was a negative association between IgG titre in cord blood and cumulative vaccine take (odds ratio [OR] 0.96; 95% confidence interval [CI] 0.92-1.00; p = 0.03) and serum IgA response (OR 0.94; 95%CI 0.89-0.99; p = 0.02) after one dose of vaccine, which were not evident after three doses in the neonatal or infant groups., Conclusions: Amongst Indonesian infants we did not find an association between IgA in colostrum or breast milk and vaccine take after 3 doses of RV3-BB vaccine. Maternal rotavirus antibodies in breast milk appear to have minimal impact on RV3-BB vaccine take when administered with a short delay in breast-feeding in settings with a high rotavirus disease burden., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background and Objectives: Vitamin D deficiency significantly affects cardiovascular disease risk. Cardiovascular disease is epidemic in nature. Because the prevalence of cardiovascular disease has been increasing in children, it has been changing from an adulthood disease to a childhood disease. Therefore, formulating an effective prevention strategy against cardiovascular disease development in children is crucial., Methods and Study Design: From PubMed, we identified and reviewed studies evaluating the association of vitamin D deficiency with cardiovascular disease risk in children., Results: The mechanism through which vitamin D protects against cardiovascular disease has yet to be fully elucidated. Vitamin D deficiency may be associated with various risk factors for cardiovascular disease that are already manifested in childhood, including obesity, hypertension, dyslipidaemia, insulin resistance, and metabolic syndrome. Vitamin D deficiency has been associated with cardiovascular disease because it promotes vascular stiffness and calcification, leading to atherosclerosis. However, studies investigating the effectiveness of vitamin D in preventing cardiovascular disease risk by using an ideal study design are scant., Conclusions: Vitamin D deficiency in children may increase cardiovascular disease risk, which tends to manifest in childhood. Because data on the association of vitamin D deficiency with cardiovascular disease risk among children are limited and inconclusive, additional studies are required to investigate this association in children in general and in a setting with naturally abundant sun exposure.