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Putri Amelia,1 Najib Advani,2 Aman B Pulungan,2 Mulyadi M Djer,2 Badriul Hegar,2 Yogi Prawira,2 Rubiana Sukardi3 1Department of Child Health, Faculty of Medicine, Universitas Sumatera Utara, Medan, Indonesia; 2Department of Child Health, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia; 3Center of Integrated Cardiac Service, Dr. Cipto Mangunkusumo Hospital, Jakarta, IndonesiaCorrespondence: Putri Amelia, Department of Child Health, H. Adam Malik Hospital/ Faculty of Medicine, Universitas Sumatera Utara, Jalan Dokter Mansyur No. 5, Padang Bulan, Medan, 20155, Indonesia, Email putri.amelia@usu.ac.idBackground: Blalock-Taussig (BT) is a palliative procedure that preserves blood circulation to the lungs and alleviates cyanosis in patients with congenital heart diseases and reduced pulmonary blood flow. BT shunt remains a routinely performed procedure in developing countries before definitive surgery. However, evidence on predictor factors of mortality after this procedure is still scarce in Indonesia. This study evaluated the predictive factors of mortality after the BT shunt procedure.Methods: This retrospective study evaluated the medical record data of all postoperative BT shunt patients at Dr. Cipto Mangunkusumo Hospital, Jakarta, Indonesia, from 2016 to 2020. We performed univariate and multivariate analyses to identify the predictors of in-hospital mortality.Results: The total subjects in this study were 197 children, 107 (54.3%) boys and 90 (45.7%) girls. The median values for age and body weight at the time of surgery were 20 months (11 days – 32 years) and 7.9 (2.7– 42) kg. The most prevalent diagnosis was the Tetralogy of Fallot, found in 80 (40.6%) patients. In-hospital postoperative mortality was 20.8% (41 patients). Based on multivariate analysis, predictors associated with mortality were weight < 4.25 kg (OR 20.9; 95% CI 7.4– 59.0; p < 0.0001) and emergency procedures (OR 3.5; 95% CI 1.3– 9.5; p = 0.016).Conclusion: The mortality rate after BT shunt at PJT Rumah Sakit Cipto Mangunkusumo was 20.8%. Based on multivariate analysis, weight < 4.25 kg and emergency procedures are two predictors of mortality in BT shunt.Keywords: Blalock-Taussig shunt, congenital heart disease, Indonesia, mortality

Introduction: Congenital rubella syndrome (CRS) is associated with severe birth defects, that lead to disability in later life. Hence, early detection and intervention are needed to prevent permanent disability and mortality in children with CRS. We evaluated the time to diagnosis or correction intervention related to survival rate using survival analysis., Methodology: A retrospective cohort study was conducted to evaluate the follow-up of CRS-confirmed cases from 2011-2018 at a national referral hospital in Jakarta, Indonesia. Parents of eligible children who registered in the national CRS registry as laboratory-confirmed CRS cases were contacted through phone calls or home visits and interviewed about the current situation of their child's health. We also obtained clinical data from the medical records., Results: Fifty children, age 4 to 14 years, identified with laboratory-confirmed CRS were included in this study. Half (54%) of these children were female. All were born from mothers with no previous rubella vaccination history. Ophthalmic abnormalities such as congenital cataracts (88%) were the most common birth defect. Multiple congenital abnormalities including congenital heart disease, ocular abnormalities, and auditory defects were identified in 52% of the children. Based on Kaplan-Meier analysis, 50% of children were diagnosed at four months. Ophthalmic corrections such as cataract surgery were performed earlier than heart or auditory correction, with 50% of children undergoing eye correction one month after the diagnosis., Conclusions: There is a vital need to implement CRS surveillance in Indonesia to know the burden of CRS and reinforce the preventive actions, including vaccination against rubella., Competing Interests: No Conflict of Interest is declared, (Copyright (c) 2024 Nina D Putri, Mulya R Karyanti, Adhi Teguh P Iskandar, Najib Advani, Setyo Handryastuti, Irawan Mangunatmadja, Tri J Airlangga, Shindy C Aprianti, Meka M Rahman, Prillye D Octaviantie, Nabila M Salma, Hartono Gunardi, Rita S Sitorus, Hindra I Satari, Ari Prayitno.)

Neutrophil-to-lymphocyte ratio (NLR) as a predictor in determining low cardiac output syndrome (LCOS) has not been widely reported. The aim of this study was to explore the role of pre-surgery, 0-, 4-, and 8-hour post-surgery NLR as predictors of LCOS incidence after open heart surgery in children with congenital heart disease (CHD). This study used a prognostic test with a prospective cohort design and was conducted from December 2020 until June 2021 at the cardiac intensive care unit (CICU) of Dr. Cipto Mangunkusumo Hospital, Jakarta, Indonesia. The subject consisted of children aged one month to 18 years who underwent open heart surgery using a cardiopulmonary bypass (CPB) machine. A receiver operating characteristic curve was applied to identify the predictive performance of NLR for poor outcomes (LCOS incidence). Out of 90 patients included in the study, 25 (27.8%) of them developed LCOS between 3 to 53 hours post-surgery. All NLR values (pre-surgery and 0-, 4-, and 8-hours post-surgery) were associated with the incidence of LCOS. Pre-surgery NLR (cut-off value ≥0.88) had a fair predictive value (area under curve (AUC) 70; 95%CI: 57-83) for predicting LCOS incidence with sensitivity and specificity of 64% and 64.62%, respectively. NLR 0-hour post-surgery (cut-off value ≥4.73) had a good predictive value (AUC 81; 95%CI: 69-94) for predicting LCOS incidence, with 80% sensitivity and 80% specificity. NLR 4- and 8-hours post-surgery had very good predictive values (AUC 97%; 95%CI: 92-100 and 98; 95%CI: 94-100, respectively), with cut-off values ≥6.19 and ≥6.78, had the same 92% sensitivity and the same 96% sensitivity. The presence of LCOS was associated with mortality (odds ratio of 5.11 with 95%CI: 3.09-8.46). This study highlights that pre-surgery, 0-, 4-, and 8-hours post-surgery NLR can be predictors of LCOS after open heart surgery in children with CHD., Competing Interests: All the authors declare that there are no conflicts of interest., (© 2024 The Author(s).)

Very preterm infants are at a high risk of developing feeding intolerance; however, there are no widely accepted definitions of feeding intolerance. This study aimed to develop a scoring system for feeding intolerance in very preterm infants by combining clinical symptoms and ultrasonography (US) findings. This prospective cohort study included very preterm and/or very low birth weight infants. We defined feeding intolerance as the inability to achieve full feeding (150 ml/kg/day) by 14 days of life. The clinical findings included vomiting, abdominal distention, and gastric fluid color. US findings included intestinal peristaltic frequency, gastric residual volume, peak systolic velocity, and the resistive index of the superior mesenteric artery. We conducted multivariate analyses to evaluate the potential predictors and developed a scoring system to predict feeding intolerance. A total of 156 infants fulfilled the eligibility criteria; however, 16 dropped out due to death. The proportion of patients with feeding intolerance was 60 (42.8%). Based on the predictive ability, predictors of feeding intolerance were determined using data from the US at 5-7 days of age. According to multivariate analysis, the final model consisted of 5 predictors: abdominal distention (score 1), hemorrhagic gastric fluid (score 2), intestinal peristaltic movement ≤18x/2 min (score 2), gastric fluid residue >25% (score 2), and resistive index >0.785 (score 2). A score equal to or above 5 indicated an increased risk of feeding intolerance with a positive predictive value of 84.4% (95% confidence interval:73.9-95.0) and a negative predictive value of 76.8% (95% confidence interval:68.4-85.3). The scoring system had good discrimination (area under the receiver operating characteristic curve:0.90) and calibration ( p  = 0.530) abilities. This study developed an objective, accurate, easy, and safe scoring system for predicting feeding intolerance based on clinical findings, 2D US, and color Doppler US., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Ifran, Hegar, Rohsiswatmo, Indriatmi, Yuniarti, Advani, Santoso, Masui, Hikmahrachim, Huysentruyt and Vandenplas.)

Objective: The aim of this study is to assess the potential of Spherical Cap Studs (SCS) as a substitute for conventional speed bumps, with a focus on limiting two wheeler speed while minimizing discomfort to riders by comparing the speed reduction capabilities and discomfort levels associated with SCS and speed bumps., Methods: The study uses experimental approach to compare the speed limiting ability and discomfort caused to rider by the proposed SCS and a standard speed bump. Speed profiles were developed for two wheelers passing over both SCS and speed bump. The parameter employed to compare speed profiles is the Mean Absolute Percentage Difference (MAPD), offering valuable insights into how effectively the two traffic calming measures reduce two wheeler speeds. To compare discomfort, the study calculates the 'Vibration Dose Value' (VDV) experienced by riders when traversing both speed bump and SCS. Additionally, 'Static Compressive Stress' (S e ) applied to the spinal cord is also calculated in both scenarios., Results: The analysis of speed profiles reveals an MAPD value of 13.70% indicating that SCS exhibits speed reduction capabilities comparable to traditional speed bump. In terms of discomfort, the VDV for two wheelers passing over a speed bump is measured at 5.92 m/s 1.75 , whereas the VDV for SCS is found to be 5.16 m/s 1.75 . Similarly, the Static Compressive Stress (S e ) experienced at a speed bump is 0.60 MPa, in contrast to the 0.33 MPa recorded for SCS. This data underscores a noteworthy 12.8% reduction in VDV and a substantial 45.57% reduction in S e ., Conclusion: The study's findings support the potential adoption of SCS as an effective alternative to conventional speed bumps for controlling two wheeler speeds. SCS demonstrate a speed reduction capability similar to that of traditional speed bumps while significantly alleviating discomfort for riders. SCS is expected to be a promising solution for traffic calming purposes in various settings, such as markets, residential areas, institutional campuses, and parking lots.

Background: The coronavirus disease 2019 (COVID-19) has resulted in an unprecedented research response, demonstrating exceptional examples of rapid research and collaboration. There is however a need for greater coordination, with limited resources and the shifting global nature of the pandemic resulting in a proliferation of research projects underpowered and unable to achieve their aims. Methods: The UK Collaborative on Development Research (UKCDR) and Global Research Collaboration for Infectious Disease Preparedness (GloPID-R), two funder coordination groups have collaborated to develop a live database of funded research projects across the world relating to COVID-19. Drawing data continually from their members and further global funding bodies, as of 15 th July 2021 the database contains 12,419 projects, funded by 255 funders, taking place across 149 countries representing an investment of at least $4.9 billion. To our knowledge it is one of the most comprehensive databases. The database is aligned to the World Health Organisation and GloPID-R Global Research Roadmap: 2019 Novel Coronavirus. It is being used by the WHO, governments and multi-lateral policy makers, research funders and researchers. This living mapping review aims to supplement the database by providing an open accessible and frequently updated resource summarising the characteristics of the COVID-19 funded research portfolio. Both descriptive and thematic analysis will be presented and updated frequently to aid interpretation of the global COVID-19 funded research portfolio. Results: In this version five analysis we provide an updated detailed descriptive analysis of the database (three months after version four) and focus our thematic analysis on research gaps, research areas in need of coordination, study populations and research locations (with a focus on resource-limited countries). Conclusions: As the global funding response to COVID-19 plateaus, this living mapping review helps both funders and researchers to prioritise resources to areas where there is continued unmet research need., Competing Interests: Competing interests: GB-L and AML are both employed by the Canadian Institutes of Health Research funder and undertook this work as a contribution to GloPID-R’s work. The other authors declare no competing interests., (Copyright: © 2022 Norton A et al.)

Background: The alternative device to close perimembranous ventricular septal defect (pmVSD) has been searched for better result, less complications and applicable for infants. However, the ideal device is still unavailable. We aimed to evaluate the effectiveness and outcome of transcatheter pmVSD closure using the KONAR-multi functional occluder (MFO)., Methods: Clinical, procedural, follow-up data of pmVSD patients with symptom of heart failure or evidence of significant left to right shunt, growth failure, recurrent respiratory tract infection, and history of endocarditis who underwent transcatheter closure using the MFO were prospectively evaluated., Results: Between January 2016 and December 2017, there were complete records of 132 pmVSD children closed using MFO from eleven centers in Indonesia. The median of age was 4.5 (0.3-17.4) years; weight 14.8 (3.5-57) kg, defect size at the smallest part 3.4 (1.0-8.1) mm, flow ratio 1.6 (1.3-4.9), mean pulmonary artery pressure 18 (7-79) mmHg, fluoroscopy time 18 (3.8-91) and procedural time 75 (26-290) minutes. A retrograde approach was done in 41 (31%) patients. Procedures succeeded in first attempt in 126 (95.4%), failed in three and migration in three patients. Six of eight infants with congestive heart failure were closed successfully. Of 126 patients with successful VSD closure, 12 months follow-up were completed in all patients. The rate of complete occlusion at 1 month, 3 months, 6 months and 12 months after intervention were 95.2%, 97.6%, 99.2%, and 99.2%, respectively. New-onset aortic regurgitation and moderate tricuspid regurgitation developed only in five and three patients. Neither complete atrioventricular block, nor other complications occurred., Conclusion: Transcatheter closure of pmVSD using the MFO is safe, effective, and feasible in infants and children., Competing Interests: The authors have no competing interests to declare., (Copyright: © 2022 The Author(s).)

Introduction: Transmission of Group A Streptococcus from asymptomatic children to their surrounding carries a risk of acute rheumatic fever in susceptible people., Aim and Objectives: We aimed to investigate the prevalence and predictors of GAS carrier state and evaluate the antibiotic sensitivity pattern of GAS in Jakarta, Indonesia., Material and Methods: We enrolled 201 asymptomatic schoolchildren (6-12 years) using stratified random sampling from a primary school in Jakarta. None of the children had a history of rheumatic fever or rheumatic heart disease. All participants underwent physical examination, and laboratory tests include complete blood count, erythrocyte sedimentation rate, C-reactive protein, antistreptolysin O titer, and throat swab culture., Results: The prevalence of GAS carrier was 13.9% (95% confidence interval: 9.2%-18.6%) in our study. On multivariate analysis, tonsillar enlargement was found to be the only predicting factor of GAS carrier ( P = 0.03). GAS was sensitive to penicillin G, erythromycin, vancomycin, clindamycin, chloramphenicol, azithromycin, and tetracycline in 100%, 89%, 86%, 75%, 68%, 68%, and 32% of patients, respectively., Conclusion: The GAS carrier state is common among school-age children affecting approximately 13.9% children. Tonsillar enlargement is a significant finding predictive of GAS carrier state. All isolates are still sensitive to penicillin and mostly sensitive to erythromycin but are increasingly resistant to tetracycline., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Annals of Pediatric Cardiology.)

Background: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a common enzyme deficiency, prevalent in many malaria-endemic countries. G6PD-deficient individuals are susceptible to hemolysis during oxidative stress, which can occur from exposure to certain medications, including 8-aminoquinolines used to treat Plasmodium vivax malaria. Accordingly, access to point-of-care (POC) G6PD testing in Brazil is critical for safe treatment of P. vivax malaria., Methodology/principal Findings: This study evaluated the performance of the semi-quantitative, POC STANDARD G6PD Test (SD Biosensor, Republic of Korea). Participants were recruited at clinics and through an enriched sample in Manaus and Porto Velho, Brazil. G6PD and hemoglobin measurements were obtained from capillary samples at the POC using the STANDARD and HemoCue 201+ (HemoCue AB, Sweden) tests. A thick blood slide was prepared for malaria microscopy. At the laboratories, the STANDARD and HemoCue tests were repeated on venous samples and a quantitative spectrophotometric G6PD reference assay was performed (Pointe Scientific, Canton, MI). G6PD was also assessed by fluorescent spot test. In Manaus, a complete blood count was performed. Samples were analyzed from 1,736 participants. In comparison to spectrophotometry, the STANDARD G6PD Test performed equivalently in determining G6PD status in venous and capillary specimens under varied operating temperatures. Using the manufacturer-recommended reference value thresholds, the test's sensitivity at the <30% threshold on both specimen types was 100% (95% confidence interval [CI] venous 93.6%-100.0%; capillary 93.8%-100.0%). Specificity was 98.6% on venous specimens (95% CI 97.9%-99.1%) and 97.8% on capillary (95% CI 97.0%-98.5%). At the 70% threshold, the test's sensitivity was 96.9% on venous specimens (95% CI 83.8%-99.9%) and 94.3% on capillary (95% CI 80.8%-99.3%). Specificity was 96.5% (95% CI 95.0%-97.6%) and 92.3% (95% CI 90.3%-94.0%) on venous and capillary specimens, respectively., Conclusion/significance: The STANDARD G6PD Test is a promising tool to aid in POC detection of G6PD deficiency in Brazil., Trial Registration: This study was registered with ClinicalTrials.gov (identifier: NCT04033640)., Competing Interests: The authors have declared that no competing interests exist.

Background: The coronavirus disease 2019 (COVID-19) has resulted in an unprecedented research response, demonstrating exceptional examples of rapid research and collaboration. There is however a need for greater coordination, with limited resources and the shifting global nature of the pandemic resulting in a proliferation of research projects underpowered and unable to achieve their aims., Methods: The UK Collaborative on Development Research (UKCDR) and Global Research Collaboration for Infectious Disease Preparedness (GloPID-R), two funder coordination groups have collaborated to develop a live database of funded research projects across the world relating to COVID-19. Drawing data continually from their members and further global funding bodies, as of 15th April 2021 the database contains 10,608 projects, funded by 201 funders, taking place across 142 countries representing an investment of at least $4.7 billion. To our knowledge it is one of the most comprehensive databases. The database is aligned to the World Health Organisation  and GloPID-R Global Research Roadmap: 2019 Novel Coronavirus. It is being used by the WHO, governments and multi-lateral policy makers, research funders and researchers. This living mapping review aims to supplement the database by providing an open accessible and frequently updated resource summarising the characteristics of the COVID-19 funded research portfolio. Both descriptive and thematic analysis will be presented and updated frequently to aid interpretation of the global COVID-19 funded research portfolio., Results: In this version four analysis we provide an updated detailed descriptive analysis of the database (three months after version three) and focus our thematic analysis on research gaps, research areas in need of coordination, study populations and research locations (with a focus on resource-limited countries)., Conclusions: As the global funding response to COVID-19 plateaus, this living mapping review helps both funders and researchers to prioritise resources to areas where there is continued unmet research need., Competing Interests: Competing interests: GB-L and AML are both employed by the Canadian Institutes of Health Research funder and undertook this work as a contribution to GloPID-R’s work. The other authors declare no competing interests., (Copyright: © 2021 Norton A et al.)

Background: The coronavirus disease 2019 (COVID-19) has resulted in an unprecedented research response, demonstrating exceptional examples of rapid research and collaboration. There is however a need for greater coordination, with limited resources and the shifting global nature of the pandemic resulting in a proliferation of research projects underpowered and unable to achieve their aims. Methods: The UK Collaborative on Development Research (UKCDR) and Global Research Collaboration for Infectious Disease Preparedness (GloPID-R), two funder coordination groups have collaborated to develop a live database of funded research projects across the world relating to COVID-19. Drawing data continually from their members and further global funding bodies, as of 15 th January 2021 the database contains 7,778 projects, funded by 101 funders, taking place across 136 countries representing an investment of at least $3.8 billion. To our knowledge it is one of the most comprehensive databases. The database is aligned to the World Health Organisation (WHO) Global Research Roadmap: 2019 Novel Coronavirus. It is being used by the WHO, governments and multi-lateral policy makers, research funders and researchers. This living mapping review aims to supplement the database by providing an open accessible and frequently updated resource summarising the characteristics of the COVID-19 funded research portfolio. Both descriptive and thematic analysis will be presented and updated frequently to aid interpretation of the global COVID-19 funded research portfolio. Results: In this version three analysis we provide an updated detailed descriptive analysis of the database (three months after version two) and focus our thematic analysis on research gaps, research areas in need of coordination, study populations and research locations (with a focus on resource-limited countries). Conclusions: As the global funding response to COVID-19 plateaus, this living mapping review helps both funders and researchers to prioritise resources to areas where there is continued unmet research need., Competing Interests: Competing interests: GB-L and AML are both employed by the Canadian Institutes of Health Research funder and undertook this work as a contribution to GloPID-R’s work. The other authors declare no competing interests., (Copyright: © 2021 Norton A et al.)

Background: The coronavirus disease 2019 (COVID-19) has resulted in an unprecedented research response, demonstrating exceptional examples of rapid research and collaboration. There is however a need for greater coordination, with limited resources and the shifting global nature of the pandemic resulting in a proliferation of research projects underpowered and unable to achieve their aims. Methods: The UK Collaborative on Development Research (UKCDR) and Global Research Collaboration for Infectious Disease Preparedness (GloPID-R), two funder coordination groups have collaborated to develop a live database of funded research projects across the world relating to COVID-19. Drawing data continually from their members and further global funding bodies, as of 15 th October 2020 the database contains 5,084 projects, funded by 71 funders, taking place across 134 countries representing an investment of at least $1.7 billion. To our knowledge it is one of the most comprehensive databases, covering a wide breadth of research disciplines. The database is aligned to the World Health Organisation (WHO) Global Research Roadmap: 2019 Novel Coronavirus. It is being used by the WHO, governments and multi-lateral policy makers, research funders and researchers. This living mapping review aims to supplement the database by providing an open accessible and frequently updated resource summarising the characteristics of the COVID-19 funded research portfolio. Both descriptive and thematic analysis will be presented and updated frequently to aid interpretation of the global COVID-19 funded research portfolio. Results: In this three-month update analysis we provide an updated detailed descriptive analysis of the database and focus our thematic analysis on research gaps, research areas in need of coordination, study populations and research locations (with a focus on resource-limited countries). Conclusions: This living mapping review will help both funders and researchers to prioritise resources to underfunded areas where there is greatest research need and facilitate further strategic collaboration., Competing Interests: Competing interests: GB-L and AML are both employed by the Canadian Institutes of Health Research funder and undertook this work as a contribution to GloPID-R’s work. The other authors declare no competing interests., (Copyright: © 2020 Norton A et al.)

Background: The coronavirus disease 2019 (COVID-19) has resulted in an unprecedented research response, demonstrating exceptional examples of rapid research and collaboration. There is however a need for greater coordination, with limited resources and the shifting global nature of the pandemic resulting in a proliferation of research projects underpowered and unable to achieve their aims. Methods: The UK Collaborative on Development Research (UKCDR) and Global Research Collaboration for Infectious Disease Preparedness (GloPID-R), two funder coordination groups have collaborated to develop a live database of funded research projects across the world relating to COVID-19. Drawing data continually from their members and further global funding bodies, as of 15 th July 2020 the database contains 1,858 projects, funded by 25 funders, taking place across 102 countries. To our knowledge it is one of the most comprehensive databases, covering a wide breadth of research disciplines. The database is aligned to the World Health Organisation (WHO) Global Research Roadmap: 2019 Novel Coronavirus. It is being used by the WHO, governments and multi-lateral policy makers, research funders and researchers. This living systematic review aims to supplement the database by providing an open accessible and frequently updated resource summarising the characteristics of the COVID-19 funded research portfolio. Both descriptive and thematic analysis will be presented and updated frequently to aid interpretation of the global COVID-19 funded research portfolio. Results: In this baseline analysis we provide the first detailed descriptive analysis of the database and focus our thematic analysis on research gaps, study populations and research locations (with a focus on resource-limited countries). Conclusions: This living systematic review will help both funders and researchers to prioritise resources to underfunded areas where there is greatest research need and facilitate further strategic collaboration., Competing Interests: Competing interests: GB-L and AML are both employed by the Canadian Institutes of Health Research funder and undertook this work as a contribution to GloPID-R’s work. The other authors declare no competing interests., (Copyright: © 2020 Norton A et al.)

Safe access to the most effective treatment options for  Plasmodium vivax  malaria are limited by the absence of accurate point-of-care testing to detect glucose-6-phosphate dehydrogenase (G6PD) deficiency, the most common human genetic disorder. G6PD-deficient patients are at risk of life-threatening hemolysis when exposed to 8-aminoquinolines, the only class of drugs efficacious against  P. vivax  hypnozoites. Until recently, only qualitative tests were available in most settings. These can identify patients with severe G6PD deficiency (mostly male) but not patients with intermediate G6PD deficiency (always female). This has led to and reinforced a gap in awareness in clinical practice of the risks and implications of G6PD deficiency in females-who, unlike males, can have a heterozygous genotype for G6PD. Increasing recognition of the need for radical cure of   P. vivax , first for patients' health and then for malaria elimination, is driving the development of new point-of-care tests for G6PD deficiency and their accessibility to populations in low-resource settings. The availability of user-friendly, affordable, and accurate quantitative point-of-care diagnostics for the precise classification of the three G6PD phenotypes can reduce sex-linked disparities by ensuring safe and effective malaria treatment, providing opportunities to develop supportive counseling to enhance understanding of genetic test results, and improving the detection of all G6PD deficiency phenotypes in newborns and their family members., Competing Interests: Competing interests: PATH supports a portfolio of G6PD diagnostic test development efforts. PATH has no financial interests in the commercialisation of any resulting products., (Copyright: © 2020 Chu CS et al.)

In low- and middle-income countries, many women experience anemia during pregnancy due to insufficient dietary intake of key micronutrients, parasitic infections, hemoglobinopathies, and chronic infections. Maternal anemia increases perinatal risks for both mothers and infants, and slow progress to reduce the prevalence may be due in part to the lack of affordable tools to quantify hemoglobin levels in antenatal care (ANC) clinics. A simple, inexpensive, accurate, and robust diagnostic is needed to measure hemoglobin in ANC. This study evaluated the performance and usability of the TrueHb Hemometer. A cross-sectional diagnostic accuracy study was conducted to compare the accuracy of the TrueHb and the HemoCue® 201+ using capillary samples. Next, analytical performance (precision, coefficient of variation, R2) of the TrueHb was evaluated in varying environmental conditions using linearity panels with serial dilutions of venous blood samples. Lastly, the usability of the TrueHb Hemometer was assessed across three domains (effectiveness, efficiency, and satisfaction) by 20 ANC providers in Ghana. Capillary blood test results were not well correlated (R2 = 0.35) between the TrueHB and HemoCue201+, but 80% of TrueHb measurements were within +/-1.0 g/dl of the HemoCue® 201+ hemoglobin values. Precision tests indicated similar mean values across the three environmental conditions (CV<6%). At 21°C, the TrueHb follows a linear relationship (R2≥0.96) but does not generate accurate readings below 4.0 g/dl. At 30°C and 37°C, the TrueHb follows a linear relationship (R2 > 0.90) but begins to underestimate the hemoglobin concentration below 7.0 g/dl. The usability study identified potential failure modes due to inadequate instructions and device feedback. With some modifications, both to the product and to the instructions for use, the TrueHb may be suitable for use in ANC settings to help fill the diagnostic gap for anemia screening during pregnancy. Further testing is required with anemic populations in LMIC settings., Competing Interests: Author DS is employed by Akendi, a user experience, service design, strategy and research corporation. All authors received support for this research from The Bill & Melinda Gates Foundation. This does not alter the authors’ adherence to PLOS ONE policies on sharing data and materials.

Safe access to the most effective treatment options for  Plasmodium vivax  malaria are limited by the absence of accurate point-of-care testing to detect glucose-6-phosphate dehydrogenase (G6PD) deficiency, the most common human genetic disorder. G6PD-deficient patients are at risk of life-threatening hemolysis when exposed to 8-aminoquinolines, the only class of drugs efficacious against  P. vivax  hypnozoites. Until recently, only qualitative tests were available in most settings. These accurately identify patients with severe G6PD deficiency (mostly male) but not patients with intermediate G6PD deficiency (always female). This has led to and reinforced a gap in awareness in clinical practice of the risks and implications of G6PD deficiency in females-who, unlike males, can have a heterozygous genotype for G6PD. Increasing recognition of the need for radical cure of  P. vivax , first for patients' health and then for malaria elimination, is driving the development of new point-of-care tests for G6PD deficiency and their accessibility to populations in low-resource settings. The availability of simple, affordable, and accurate point-of-care diagnostics for the precise classification of the three G6PD phenotypes can reduce sex-linked disparities by ensuring safe and effective malaria treatment, providing opportunities to develop supportive counseling to enhance understanding of genetic test results, and improving the detection of all G6PD deficiency phenotypes in newborns and their family members., Competing Interests: Competing interests: PATH supports a portfolio of G6PD diagnostic test development efforts. PATH has no financial interests in the commercialisation of any resulting products., (Copyright: © 2020 Chu CS et al.)

Background and Objectives: Iron-induced cardiomyopathy remains the leading cause of mortality in β-thalassemia major patients. The T2* magnetic resonance imaging (MRI) technique is the gold standard for iron load detection, yet it is expensive and not widely available especially in the developing countries. Some previous studies showed that QTc interval could be used as an early detection of cardiac iron overload. This study aimed to evaluate the diagnostic value of QTc interval as a marker of early detection of cardiac iron overload in adolescent beta thalassemia major patients., Methods: We prospectively evaluated electrocardiography (ECG) parameter of QTc interval in 50 β-thalassemia major patients aged 10-18 years. All participants had a 12-lead ECG evaluation, echocardiogram and cardiac MRI T2* examination within three months (average 15 days). They were categorized as cardiac iron overload (MRI T2* < 20 millisecond) and non-cardiac iron overload (MRI T2* > 20 millisecond)., Results: Of the 50 patients, the male to female ratio was 1.08:1 and the mean age was 13.7 ± 2.43 years. All participants showed normal systolic and diastolic function using conventional echocardiography. The mean QTc interval was significantly different between cardiac iron overload group (464.44 ± 20.35 ms) and noncardiac iron overload group (431.09 ± 32.29) (p= 0.001). Diagnostic study of QTc interval resulted in AUC 0.8 (p= 0.002). Calculated sensitivity and specificity of QTc interval were 0.88 and 0.73 respectively, with cut-off point of 449 ms., Conclusion: Cardiac iron overload is associated with QTc prolongation in adolescents. QTc interval of 449 ms could be considered as a cut-off point of cardiac iron overload.

Background: Evaluating outcome and identifying predictors of major complications among children undergoing cardiac surgery are essential to improve care. We evaluated short-term outcomes of postcardiac surgery and predictors of major complications in a national referral hospital in Indonesia., Methods: A prospective cohort study was conducted from April 2014 to March 2015 on all children undergoing cardiac surgery. Participants were followed up from the time of surgery until hospital discharge and 30-day mortality. We performed univariate and multivariate logistic regression using STATA 12-1 to identify predictors of postsurgical major complications., Results: A total of 257 patients (median age: 36 months) were recruited; 217 (84.1%) had complications, including low cardiac output syndrome (19.8%), arrhythmia (18.6%), sepsis (17.4%), and pleural effusion (14.8%). Forty-nine (19%) patients had major complications, including cardiac arrest (5%), need for emergency chest opening (3.9%), and multiple organ failure (7.4%). 12.8% died during hospital stay, and 30-day mortality was 13.6%. Predictors of major complications were cyanotic congenital heart disease (odds ratio [OR]: 4.6, 95% confidence interval [CI]: 1.5-14.2), longer duration of cardiopulmonary bypass (CPB, OR: 4.4, 95% CI: 1.5-13.4), high inotropes (OR: 13.1, 95% CI: 3.2-54.2), and increase in lactate >0.75 mmol/L/h or more in the first 24 h (OR: 37.1, 95% CI: 10.1-136.3)., Conclusion: One-fifth of children undergoing cardiac surgery experienced major complications with around 13% mortality. Cyanotic congenital heart disease, longer duration of CPB, high inotropes on leaving operating theater, and increase in blood lactate are associated with major complications in children after cardiac surgery., Competing Interests: There are no conflicts of interest.

Glucose-6-phosphate dehyrdgoenase (G6PD) deficiency is a common X-linked genetic trait, with an associated enzyme phenotype, whereby males are either G6PD deficient or normal, but females exhibit a broader range of G6PD deficiencies, ranging from severe deficiency to normal. Heterozygous females typically have intermediate G6PD activity. G6PD deficiency has implications for the safe treatment for Plasmodium vivax malaria. Individuals with this deficiency are at greater risk of serious adverse events following treatment with the only curative class of anti-malarials, 8-aminoquinolines, such as primaquine. Quantitative diagnostic tests for G6PD deficiency are complex and require sophisticated laboratories. The commonly used qualitative tests, do not discriminate intermediate G6PD activities. This has resulted in poor understanding of the epidemiology of G6PD activity in females and its corresponding treatment ramifications. New simple-to-use quantitative tests, and a momentum to eliminate malaria, create an opportunity to address this knowledge gap. While this will require additional resources for clinical studies, adequate operational research, and appropriate pharmacovigilance, the health benefits from this investment go beyond the immediate intervention for which the G6PD status is first diagnosed.

Background: Iron-induced cardiomyopathy remains the leading cause of mortality in patients with β-thalassemia major. Iron overload cardiomyopathy, which may be reversible through iron chelation, is characterized by early diastolic dysfunction. Amino-terminal pro-brain natriuretic peptide (NT-proBNP) is a sensitive biomarker of diastolic dysfunction., Aim: The aim of the study is to evaluate the diagnostic value of NT-proBNP as a surrogate marker of iron overload examined with magnetic resonance imaging T2-star (MRI T2*)., Methods: Sixty-eight β-thalassemia major patients (10-18 years) with no signs of heart failure underwent NT-proBNP measurement before routine transfusion. All participants prospectively underwent cardiac MRI T2* examination within 3 months (median 19 days). Patients were divided as cardiac hemosiderosis (cardiac MRI T2* <20 ms) and nonhemosiderosis (cardiac MRI T2* >20 ms)., Results: Of 68 patients, the male-to-female ratio was 1:1.1 and the median age was 14.1 years (range: 10-17.8 years). NT-proBNP levels were not different between hemosiderosis and nonhemosiderosis patients ( P = 0.233). Further receiver operating characteristic analysis resulted in no significant correlation of NT-proBNP and MRI T2* (area under the curve 0.393, P = 0.233)., Conclusion: Measurement of NT-proBNP levels cannot be used for early detection of cardiac iron overload in adolescent with β-thalassemia major., Competing Interests: There are no conflicts of interest.

Background: there is clearly growing population of young adults with potentially important coronary artery disease after Kawasaki disease (KD) during childhood, and cardiologist must be prepared to take care for them. As Kawasaki disease in adolescent and adult is rare and under-recognized, it is important to study data on patient presentations which may permit development of diagnostic criteria and treatment guidelines for this age group.This study aimed to compare the clinical profile of KD between adolescents (>10 years of age) and children ≤10 years., Methods: This is a cross sectional study. A total of 1150 KD cases (age 1-192 months) during the period of January 2003-December 2016 were analyzed. The clinical profile of subjects aged >10 years (adolescents) and  ≤10 years (children) at acute phase of KD were compared., Results: we found 17 cases of KD in adolescents among 1150 total cases (1.5%). Incomplete KD was more often seen in adolescents compared to children ≤ 10 years of age (59% vs. 29%). Some clinical features were more frequently seen in children than in adolescents, e.g. conjunctivitis (85% in ≤ 10 years of age vs. 65% in > 10 years), mucosal changes (94% vs. 77%), rash (86% vs. 59%), and hand/foot changes (68% vs. 41%). While other clinical features were more often seen in adolescents, e.g., cervical lymphadenopathy (82% vs. 39%) and coronary dilatation (47% vs. 29%). Laboratory results (hemoglobin, leukocytes, erythrocyte sedimentation rate and C-reactive protein) did not differ much between the two groups., Conclusion: Kawasaki disease in adolescents has some different clinical profile from that of younger age. Majority of adolescent patients have incomplete presentation. Some clinical features such as conjunctivitis, mucosal changes, rash, and hand/foot changes are more often seen in children ≤ 10 years compared to in adolescents, while cervical lymphadenopathy and coronary dilatation are more frequently seen in adolescents. The ratio of male to female is much higher in adolescents.

Background: Kawasaki disease (KD) is an acute systemic vasculitis syndrome with a high incidence of coronary aneurysms in untreated children. The majority of aneurysms resulting from KD are known to regress with time., Aims: This study aimed to determine the course and outcome of coronary artery dilatation in patients with KD and ascertain whether there are any differences in the outcomes in the different branches., Setting and Design: This is a retrospective cohort study of patients diagnosed with KD with midterm follow-up data., Methods: Serial echocardiography was performed in all KD patients with coronary dilatation for 1-10½ years. The Kaplan-Meier curve was used for statistical analysis., Results: There were 154 patients with coronary dilatation studied. The frequency of coronary dilatation in acute phase was 33.3% and decreased to 7.9% 6-8 weeks later. Each patient could have dilatations at more than one branch, so the total number of dilatations was 245. The median time needed for regression was 2.6 months (mean: 10.5 months) while the median of follow-up duration was 41 months (mean: 23 months). Small- and medium-sized dilatations had more favorable outcomes compared to the giant ones. Location of dilatation did not influence the outcome., Conclusions: The majority (77.4%) of small- and medium-sized dilatations regress within 2 years, but giant aneurysms tend to persist. The outcome of coronary dilatation is determined by the diameter and not by the location. Regression rate is faster in smaller dilatations. Left main coronary artery is the most frequent location for dilatation., Competing Interests: There are no conflicts of interest.

Objective: To evaluate the incidence of small bowel bacterial overgrowth (SBBO) in children treated with omeprazole, and to test whether probiotics influence the incidence., Methods: A double-blinded, placebo-controlled trial was performed in 70 children treated orally during four weeks with 20mg omeprazole per day. Lactobacillus rhamnosus R0011 (1.9×10(9) cfu) and Lactobacillus acidophilus R0052 (0.1×10(9) cfu) were simultaneously given daily to 36 subjects (probiotic group), while 34 subjects received placebo (placebo group). The diagnosis of SBBO was based on the development of suggestive symptoms, in combination with a positive glucose breath test., Results: After one month of proton pump inhibitor (PPI) treatment, 30% (21/70) had a positive breath test suggesting SBBO; of these 62% were symptomatic. Five children developed SBBO-like symptoms, but had a negative breath test; and 44 (63%) were symptom free and had a negative breath test. There was no difference in the incidence of positive breath tests in the probiotic versus the placebo group (33% vs 26.5%; p=0.13)., Conclusions: Since symptoms suggesting SBBO developed in 26% of PPI-treated children, and since the glucose breath test was abnormal in 72% of these, this side-effect should be more frequently considered. The probiotic tested did not decrease the risk to develop SBBO., (Copyright © 2013 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.)

Aim: Although domperidone is used frequently to treat infant regurgitation, efficacy data are scarce. Cisapride was previously used in the same indication., Methods: Domperidone and cisapride were compared in an investigator-blinded, prospective comparative trial by evaluating (a) the frequency of regurgitation, (b) acid reflux and (c) cardiac side effects in infants regurgitating >4 times/day since >2 weeks and with reflux-associated symptoms of discomfort, after conservative treatment failure., Results: Within the first treatment week, the frequency of regurgitation decreased in both groups, more rapidly in the cisapride group: the median regurgitation decreased from 6.22 to 3.50 in the cisapride group versus from 4.80 to 3.70 in the domperidone group. The decrease in regurgitation was still significant after 1 month: cisapride from 6.22 to 1.55 versus domperidone from 4.80 to 1.25. However, the natural decrease in the incidence of regurgitation induced by age should also be considered. The median reflux index decreased after 1 month in the cisapride group from 3.60 to 1.75 versus from 2.70 to 2.45 in the domperidone group. One child treated with cisapride developed a significant QT prolongation., Conclusion: The decrease in regurgitation was comparable in both groups, although acid reflux decreased more in the cisapride group. Cisapride induced QT prolongation in one infant.

Innocent murmurs in childhood are common, and often they do not reflect cardiac disease. We have performed a prospective review, by means of a questionnaire, to clarify the parental perception of the innocent murmur identified in their child. Whenever possible, depending on age, we also sought the input of the child. Of a cohort of 63 infants and children with innocent murmurs, a response was obtained from 40 parents and 8 children to an initial questionnaire, with 26 parents replying to a second questionnaire a year later. No parent reported any symptoms in their children, or had imposed any restrictions. Of the parents, however three sets considered regular review was necessary. We conclude that the diagnosis of an innocent murmur by a paediatric cardiologist, aided by investigations including cross-sectional echocardiography, and an opportunity for explanation and reassurance, led to the child being treated normally.

Innocent murmurs are common in childhood. They require accurate diagnosis to avoid unnecessary anxiety and/or restrictions. With this in mind, we studied prospectively children diagnosed by a paediatric cardiologist as having innocent murmurs to review the necessity of investigations in excluding organic abnormalities. We included 63 children in the study. The majority had the so-called Still's, or musical/vibratory murmur. None had abnormal investigations, suggesting that such investigations are largely superfluous for the purpose of diagnosis in those patients with innocent murmurs seen by a paediatric cardiologist. They are often done, nonetheless, as part of the assessment and/or expectations of the parent or the referring physician.

A case of Rett syndrome in a-3 1/2 year-old girl is presented. The patient had normal pre and perinatal period and normal psychomotor development till the age of 14 months, followed by behavioural, social and psychomotor regression. Physical examination revealed a below normal head circumference, loss of eye and psychic contact, stereotypic hand movements and gait disturbance. No laboratory test can confirm the diagnosis of Rett syndrome, therefore the diagnosis was established by virtue of history of illness and clinical manifestations. This is the first case of Rett syndrome found and reported in Indonesia.