Publications by authors named "Chin Seng Gan"

18 Publications

  • Page 1 of 1

Comparative Analysis of Pediatric COVID-19 Infection in Southeast Asia, South Asia, Japan, and China.

Am J Trop Med Hyg 2021 Jun 15. Epub 2021 Jun 15.

Duke-NUS Medical School, Singapore.

There is a scarcity of data regarding coronavirus disease 2019 (COVID-19) infection in children from southeast and south Asia. This study aims to identify risk factors for severe COVID-19 disease among children in the region. This is an observational study of children with COVID-19 infection in hospitals contributing data to the Pediatric Acute and Critical Care COVID-19 Registry of Asia. Laboratory-confirmed COVID-19 cases were included in this registry. The primary outcome was severity of COVID-19 infection as defined by the World Health Organization (WHO) (mild, moderate, severe, or critical). Epidemiology, clinical and laboratory features, and outcomes of children with COVID-19 are described. Univariate and multivariable logistic regression models were used to identify risk factors for severe/critical disease. A total of 260 COVID-19 cases from eight hospitals across seven countries (China, Japan, Singapore, Malaysia, Indonesia, India, and Pakistan) were included. The common clinical manifestations were similar across countries: fever (64%), cough (39%), and coryza (23%). Approximately 40% of children were asymptomatic, and overall mortality was 2.3%, with all deaths reported from India and Pakistan. Using the multivariable model, the infant age group, presence of comorbidities, and cough on presentation were associated with severe/critical COVID-19. This epidemiological study of pediatric COVID-19 infection demonstrated similar clinical presentations of COVID-19 in children across Asia. Risk factors for severe disease in children were age younger than 12 months, presence of comorbidities, and cough at presentation. Further studies are needed to determine whether differences in mortality are the result of genetic factors, cultural practices, or environmental exposures.
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http://dx.doi.org/10.4269/ajtmh.21-0299DOI Listing
June 2021

International Nosocomial Infection Control Consortium (INICC) report, data summary of 45 countries for 2013-2018, Adult and Pediatric Units, Device-associated Module.

Am J Infect Control 2021 Apr 24. Epub 2021 Apr 24.

Surveillance Department, Infection Control Directorate, Ministry Of Health, Kuwait City, Kuwait.

Background: We report the results of INICC surveillance study from 2013 to 2018, in 664 intensive care units (ICUs) in 133 cities, of 45 countries, from Latin-America, Europe, Africa, Eastern-Mediterranean, Southeast-Asia, and Western-Pacific.

Methods: Prospective data from patients hospitalized in ICUs were collected through INICC Surveillance Online System. CDC-NHSN definitions for device-associated healthcare-associated infection (DA-HAI) were applied.

Results: We collected data from 428,847 patients, for an aggregate of 2,815,402 bed-days, 1,468,216 central line (CL)-days, 1,053,330 mechanical ventilator (MV)-days, 1,740,776 urinary catheter (UC)-days. We found 7,785 CL-associated bloodstream infections (CLAB), 12,085 ventilator-associated events (VAE), and 5,509 UC-associated urinary tract infections (CAUTI). Pooled DA-HAI rates were 5.91% and 9.01 DA-HAIs/1,000 bed-days. Pooled CLAB rate was 5.30/1,000 CL-days; VAE rate was 11.47/1,000 MV-days, and CAUTI rate was 3.16/1,000 UC-days. P aeruginosa was non-susceptible (NS) to imipenem in 52.72% of cases; to colistin in 10.38%; to ceftazidime in 50%; to ciprofloxacin in 40.28%; and to amikacin in 34.05%. Klebsiella spp was NS to imipenem in 49.16%; to ceftazidime in 78.01%; to ciprofloxacin in 66.26%; and to amikacin in 42.45%. coagulase-negative Staphylococci and S aureus were NS to oxacillin in 91.44% and 56.03%, respectively. Enterococcus spp was NS to vancomycin in 42.31% of the cases.

Conclusions: DA-HAI rates and bacterial resistance are high and continuous efforts are needed to reduce them.
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http://dx.doi.org/10.1016/j.ajic.2021.04.077DOI Listing
April 2021

Malaysian outcome of acute necrotising encephalopathy of childhood.

Brain Dev 2021 Apr 7;43(4):538-547. Epub 2021 Jan 7.

Division of Paediatric Intensive Care, Department of Paediatrics, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.

Objective: Describe the outcome of a Malaysian cohort of children with acute necrotising encephalopathy (ANE).

Method: Retrospective study of children with ANE seen at University of Malaya Medical Centre from 2014 to 2019. All clinical details including ANE-severity score (ANE-SS), immunomodulation treatment and neurodevelopmental long-term outcome were collected.

Results: Thirteen patients had ANE and brainstem death occurred in 5. In 10 patients (77%) viruses were isolated contributing to ANE: 8 influenza virus, 1 acute dengue infection, and 1 acute varicella zoster infection. The ANE-SS ranged 2-7: 9 were high risk and 4 were medium risk. Among the 8 survivors; 1 was lost to follow-up. Follow-up duration was 1-6 years (median 2.2). At follow-up among the 4 high-risk ANE-SS: 2 who were in a vegetative state, 1 remained unchanged and 1 improved to severe disability; the other 2 with severe disability improved to moderate and mild disability respectively. At follow-up all 3 medium-risk ANE-SS improved: 2 with severe disability improved to moderate and mild disability respectively, while 1 in a vegetative state improved to severe disability. Early treatment with immunomodulation did not affect outcome.

Conclusion: Our ANE series reiterates that ANE is a serious cause of encephalopathy with mortality of 38.5%. All survivors were in a vegetative state or had severe disability at discharge. Most of the survivors made a degree of recovery but good recovery was seen in 2. Follow-up of at least 12 months is recommended for accurate prognostication. Dengue virus infection needs to be considered in dengue endemic areas.
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http://dx.doi.org/10.1016/j.braindev.2020.12.003DOI Listing
April 2021

Traumatic Brain Injury Outcomes in 10 Asian Pediatric ICUs: A Pediatric Acute and Critical Care Medicine Asian Network Retrospective Study.

Pediatr Crit Care Med 2021 04;22(4):401-411

Duke-NUS Medical School, Singapore.

Objectives: Traumatic brain injury remains an important cause of death and disability. We aim to report the epidemiology and management of moderate to severe traumatic brain injury in Asian PICUs and identify risk factors for mortality and poor functional outcomes.

Design: A retrospective study of the Pediatric Acute and Critical Care Medicine Asian Network moderate to severe traumatic brain injury dataset collected between 2014 and 2017.

Setting: Patients were from the participating PICUs of Pediatric Acute and Critical Care Medicine Asian Network.

Patients: We included children less than 16 years old with a Glasgow Coma Scale less than or equal to 13.

Interventions: None.

Measurements And Main Results: We obtained data on patient demographics, injury circumstances, and PICU management. We performed a multivariate logistic regression predicting for mortality and poor functional outcomes. We analyzed 380 children with moderate to severe traumatic brain injury. Most injuries were a result of road traffic injuries (174 [45.8%]) and falls (160 [42.1%]). There were important differences in temperature control, use of antiepileptic drugs, and hyperosmolar agents between the sites. Fifty-six children died (14.7%), and 104 of 324 survivors (32.1%) had poor functional outcomes. Poor functional outcomes were associated with non-high-income sites (adjusted odds ratio, 1.90; 95% CI, 1.11-3.29), Glasgow Coma Scale less than 8 (adjusted odds ratio, 4.24; 95% CI, 2.44-7.63), involvement in a road traffic collision (adjusted odds ratio, 1.83; 95% CI, 1.04-3.26), and presence of child abuse (adjusted odds ratio, 2.75; 95% CI, 1.01-7.46).

Conclusions: Poor functional outcomes are prevalent after pediatric traumatic brain injury in Asia. There is an urgent need for further research in these high-risk groups.
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http://dx.doi.org/10.1097/PCC.0000000000002575DOI Listing
April 2021

Health-related quality of life and developmental outcome of children on home mechanical ventilation in a developing country: A cross-sectional study.

Pediatr Pulmonol 2020 12 1;55(12):3477-3486. Epub 2020 Oct 1.

Department of Paediatrics, University of Malaya Medical Center, Kuala Lumpur, Malaysia.

Background: Provision of home mechanical ventilation (HMV) to children with chronic respiratory insufficiency enhances growth and quality of life. The hypothesis was that health-related quality of life (HRQoL) and the development of these children were poorer than in healthy children.

Objectives: To determine the HRQoL and developmental outcome of children on HMV.

Methods: This cross-sectional study used the TNO-AZL Preschool children's Quality Of Life (TAPQOL; <5 years old) and Health Utilities Index (HUI) 2/3 (≥5 years old) to assess the quality of life and the Schedule of Growing Skills-II to assess development. Instruments were used on children currently or previously on HMV (≥3 months) and compared with age and sex-matched controls.

Results: Sixty-five patients and 130 controls were recruited. Patients' median (interquartile range) age was 3.12 (1.65, 5.81) years. Patients had significantly lower TAPQOL scores in the domains of lung, liveliness, positive mood, social functioning, motor functioning, and communication, and lower HUI 2/3 scores in hearing, sensation, pain, speech, mobility, ambulatory, dexterity, and self-care domains. The developmental outcome of patients was poorer in all domains. However, patients had fewer behavioral problems. Those with respiratory tract disease and without comorbidities had better HRQoL and developmental scores. Having a parent as the primary caregiver was associated with better speech and language skills.

Conclusions: HRQoL and the developmental outcome are lower in children on HMV compared to controls. Children with respiratory tract disease and without comorbidities have a better outcome. Parents play a crucial role in the acquisition of speech.
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http://dx.doi.org/10.1002/ppul.25083DOI Listing
December 2020

Six-year study on peripheral venous catheter-associated BSI rates in 262 ICUs in eight countries of South-East Asia: International Nosocomial Infection Control Consortium findings.

J Vasc Access 2021 Jan 14;22(1):34-41. Epub 2020 May 14.

Kerala Institute of Medical Sciences, Thiruvananthapuram, India.

Background: Short-term peripheral venous catheter-associated bloodstream infection rates have not been systematically studied in Asian countries, and data on peripheral venous catheter-associated bloodstream infections incidence by number of short-term peripheral venous catheter days are not available.

Methods: Prospective, surveillance study on peripheral venous catheter-associated bloodstream infections conducted from 1 September 2013 to 31 May 2019 in 262 intensive care units, members of the International Nosocomial Infection Control Consortium, from 78 hospitals in 32 cities of 8 countries in the South-East Asia Region: China, India, Malaysia, Mongolia, Nepal, Philippines, Thailand, and Vietnam. For this research, we applied definition and criteria of the CDC NHSN, methodology of the INICC, and software named INICC Surveillance Online System.

Results: We followed 83,295 intensive care unit patients for 369,371 bed-days and 376,492 peripheral venous catheter-days. We identified 999 peripheral venous catheter-associated bloodstream infections, amounting to a rate of 2.65/1000 peripheral venous catheter-days. Mortality in patients with peripheral venous catheter but without peripheral venous catheter-associated bloodstream infections was 4.53% and 12.21% in patients with peripheral venous catheter-associated bloodstream infections. The mean length of stay in patients with peripheral venous catheter but without peripheral venous catheter-associated bloodstream infections was 4.40 days and 7.11 days in patients with peripheral venous catheter and peripheral venous catheter-associated bloodstream infections. The microorganism profile showed 67.1% were Gram-negative bacteria: (22.9%), spp (10.7%), (5.3%), spp. (4.5%), and others (23.7%). The predominant Gram-positive bacteria were (11.4%).

Conclusions: Infection prevention programs must be implemented to reduce the incidence of peripheral venous catheter-associated bloodstream infections.
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http://dx.doi.org/10.1177/1129729820917259DOI Listing
January 2021

The impact of high frequency oscillatory ventilation on mortality in paediatric acute respiratory distress syndrome.

Crit Care 2020 01 31;24(1):31. Epub 2020 Jan 31.

Children's Intensive Care Unit, Department of Pediatric Subspecialties, KK Women's and Children's Hospital, 100 Bukit Timah Road, Singapore, 229899, Singapore.

Background: High-frequency oscillatory ventilation (HFOV) use was associated with greater mortality in adult acute respiratory distress syndrome (ARDS). Nevertheless, HFOV is still frequently used as rescue therapy in paediatric acute respiratory distress syndrome (PARDS). In view of the limited evidence for HFOV in PARDS and evidence demonstrating harm in adult patients with ARDS, we hypothesized that HFOV use compared to other modes of mechanical ventilation is associated with increased mortality in PARDS.

Methods: Patients with PARDS from 10 paediatric intensive care units across Asia from 2009 to 2015 were identified. Data on epidemiology and clinical outcomes were collected. Patients on HFOV were compared to patients on other modes of ventilation. The primary outcome was 28-day mortality and secondary outcomes were 28-day ventilator- (VFD) and intensive care unit- (IFD) free days. Genetic matching (GM) method was used to analyse the association between HFOV treatment with the primary outcome. Additionally, we performed a sensitivity analysis, including propensity score (PS) matching, inverse probability of treatment weighting (IPTW) and marginal structural modelling (MSM) to estimate the treatment effect.

Results: A total of 328 patients were included. In the first 7 days of PARDS, 122/328 (37.2%) patients were supported with HFOV. There were significant differences in baseline oxygenation index (OI) between the HFOV and non-HFOV groups (18.8 [12.0, 30.2] vs. 7.7 [5.1, 13.1] respectively; p < 0.001). A total of 118 pairs were matched in the GM method which found a significant association between HFOV with 28-day mortality in PARDS [odds ratio 2.3, 95% confidence interval (CI) 1.3, 4.4, p value 0.01]. VFD was indifferent between the HFOV and non-HFOV group [mean difference - 1.3 (95%CI - 3.4, 0.9); p = 0.29] but IFD was significantly lower in the HFOV group [- 2.5 (95%CI - 4.9, - 0.5); p = 0.03]. From the sensitivity analysis, PS matching, IPTW and MSM all showed consistent direction of HFOV treatment effect in PARDS.

Conclusion: The use of HFOV was associated with increased 28-day mortality in PARDS. This study suggests caution but does not eliminate equivocality and a randomized controlled trial is justified to examine the true association.
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http://dx.doi.org/10.1186/s13054-020-2741-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6995130PMC
January 2020

Congenital myasthenic syndrome with novel pathogenic variants in the COLQ gene associated with the presence of antibodies to acetylcholine receptors.

J Clin Neurosci 2020 Feb 10;72:468-471. Epub 2019 Dec 10.

Genetic Medicine Unit, Department of Paediatrics, University of Malaya Medical Centre, Kuala Lumpur, Malaysia. Electronic address:

Congenital myasthenic syndrome (CMS) is a heterogeneous group of inherited disorder which does not associate with anti-acetylcholine receptor (AChR) antibody. The presence of AChR autoantibody is pathogenic and highly sensitive and specific for autoimmune myasthenia gravis (MG). We describe 2 children from unrelated families who presented with hypotonia, ptosis and fatigability in early infancy with anti-AChR antibodies detected via ELISA on 2 separate occasions in the sera. Both were treated as refractory autoimmune MG due to poor clinical response to acetylcholinesterase inhibitor and immunotherapy. In view of the atypical clinical features, genetic studies of CMS were performed and both were confirmed to have novel pathogenic mutations in the COLQ gene. To the best of our knowledge, the presence of anti-AChR antibody in COLQ-related CMS has never been reported in the literature. The clinical presentation of early onset phenotype, and refractoriness to acetylcholinesterase inhibitor and immunotherapy should prompt CMS as a differential diagnosis.
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http://dx.doi.org/10.1016/j.jocn.2019.12.007DOI Listing
February 2020

Non-Invasive Ventilation in Children with Paediatric Acute Respiratory Distress Syndrome.

Ann Acad Med Singap 2019 07;48(7):224-232

Children's Intensive Care Unit, Department of Paediatric Subspecialties, KK Women's and Children's Hospital, Singapore.

Introduction: Evidence supporting non-invasive ventilation (NIV) in paediatric acute respiratory distress syndrome (PARDS) remains sparse. We aimed to describe characteristics of patients with PARDS supported with NIV and risk factors for NIV failure.

Materials And Methods: This is a multicentre retrospective study. Only patients supported on NIV with PARDS were included. Data on epidemiology and clinical outcomes were collected. Primary outcome was NIV failure which was defined as escalation to invasive mechanical ventilation within the first 7 days of PARDS. Patients in the NIV success and failure groups were compared.

Results: There were 303 patients with PARDS; 53/303 (17.5%) patients were supported with NIV. The median age was 50.7 (interquartile range: 15.7-111.9) months. The Paediatric Logistic Organ Dysfunction score and oxygen saturation/fraction of inspired oxygen (SF) ratio were 2.0 (1.0-10.0) and 155.0 (119.4- 187.3), respectively. Indications for NIV use were increased work of breathing (26/53 [49.1%]) and hypoxia (22/53 [41.5%]). Overall NIV failure rate was 77.4% (41/53). All patients with sepsis who developed PARDS experienced NIV failure. NIV failure was associated with an increased median paediatric intensive care unit stay (15.0 [9.5-26.5] vs 4.5 [3.0-6.8] days; <0.001) and hospital length of stay (26.0 [17.0-39.0] days vs 10.5 [5.5-22.3] days; = 0.004). Overall mortality rate was 32.1% (17/53).

Conclusion: The use of NIV in children with PARDS was associated with high failure rate. As such, future studies should examine the optimal selection criteria for NIV use in these children.
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July 2019

Differences Between Pulmonary and Extrapulmonary Pediatric Acute Respiratory Distress Syndrome: A Multicenter Analysis.

Pediatr Crit Care Med 2018 10;19(10):e504-e513

Children's Intensive Care Unit, Department of Pediatric Subspecialties, KK Women's and Children's Hospital, Singapore.

Objectives: Extrapulmonary pediatric acute respiratory distress syndrome and pulmonary pediatric acute respiratory distress syndrome are poorly described in the literature. We aimed to describe and compare the epidemiology, risk factors for mortality, and outcomes in extrapulmonary pediatric acute respiratory distress syndrome and pulmonary pediatric acute respiratory distress syndrome.

Design: This is a secondary analysis of a multicenter, retrospective, cohort study. Data on epidemiology, ventilation, therapies, and outcomes were collected and analyzed. Patients were classified into two mutually exclusive groups (extrapulmonary pediatric acute respiratory distress syndrome and pulmonary pediatric acute respiratory distress syndrome) based on etiologies. Primary outcome was PICU mortality. Cox proportional hazard regression was used to identify risk factors for mortality.

Setting: Ten multidisciplinary PICUs in Asia.

Patients: Mechanically ventilated children meeting the Pediatric Acute Lung Injury Consensus Conference criteria for pediatric acute respiratory distress syndrome between 2009 and 2015.

Interventions: None.

Measurements And Main Results: Forty-one of 307 patients (13.4%) and 266 of 307 patients (86.6%) were classified into extrapulmonary pediatric acute respiratory distress syndrome and pulmonary pediatric acute respiratory distress syndrome groups, respectively. The most common causes for extrapulmonary pediatric acute respiratory distress syndrome and pulmonary pediatric acute respiratory distress syndrome were sepsis (82.9%) and pneumonia (91.7%), respectively. Children with extrapulmonary pediatric acute respiratory distress syndrome were older, had higher admission severity scores, and had a greater proportion of organ dysfunction compared with pulmonary pediatric acute respiratory distress syndrome group. Patients in the extrapulmonary pediatric acute respiratory distress syndrome group had higher mortality (48.8% vs 24.8%; p = 0.002) and reduced ventilator-free days (median 2.0 d [interquartile range 0.0-18.0 d] vs 19.0 d [0.5-24.0 d]; p = 0.001) compared with the pulmonary pediatric acute respiratory distress syndrome group. After adjusting for site, severity of illness, comorbidities, multiple organ dysfunction, and severity of acute respiratory distress syndrome, extrapulmonary pediatric acute respiratory distress syndrome etiology was not associated with mortality (adjusted hazard ratio, 1.56 [95% CI, 0.90-2.71]).

Conclusions: Patients with extrapulmonary pediatric acute respiratory distress syndrome were sicker and had poorer clinical outcomes. However, after adjusting for confounders, it was not an independent risk factor for mortality.
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http://dx.doi.org/10.1097/PCC.0000000000001667DOI Listing
October 2018

Bickerstaff's brainstem encephalitis with overlapping Guillain-Barré syndrome: Usefulness of sequential nerve conduction studies.

Brain Dev 2018 Jun 17;40(6):507-511. Epub 2018 Feb 17.

Division of Neurology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.

Bickerstaff's brainstem encephalitis (BBE) is a rare immune-mediated disorder characterized by ophthalmoplegia, ataxia and disturbance of consciousness, which may overlap with Guillain-Barré syndrome (GBS) if there is additional limb weakness. We report a 7-month-old boy presented with ophthalmoplegia followed by a rapidly ascending paralysis of all four limbs and disturbance of consciousness. The initial impression was BBE with overlapping GBS. This was supported by sequential nerve conduction study (NCS) findings compatible with an acute inflammatory demyelinating polyneuropathy (AIDP). He received intravenous pulse methylprednisolone, intravenous immunoglobulin and plasmapharesis with complete clinical recovery after 6 weeks of illness and improved NCS findings from week 16. This is the first case of paediatric BBE with overlapping GBS with an AIDP subtype of GBS. It expands the clinical spectrum of this condition in children. Our case highlights the importance of sequential NCS in paediatric BBE with overlapping GBS for accurate electrophysiological diagnosis and prognosis particularly if the first NCS findings are not informative.
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http://dx.doi.org/10.1016/j.braindev.2018.02.001DOI Listing
June 2018

Diphtheric encephalitis and brain neuroimaging features.

J Clin Neurosci 2017 Nov 1;45:155-157. Epub 2017 Sep 1.

Division of Paediatric Neurology, Department of Paediatrics, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia. Electronic address:

We report a rare case of paediatric diphtheria complicated with encephalitis. A 6-year-old boy who did not receive his scheduled diptheria-tetanus-pertusis vaccination presented with one episode of generalised convulsive seizure. His illness was preceded by a 3day history of fever associated with enlarged exudative tonsils with a pseudomembrane. He was commenced on intravenous penicillin and oral erythromycin. However, he developed progressive encephalopathy with focal neurological deficit which required intubation on day 5 of illness. Throat swab polymerase chain reaction for diphtheria toxin A and B were positive and diphtheria antitoxin was given. Magnetic resonance imaging (MRI) of brain showed T2-weighted hyperintensities over the anterior cingulate gyri, insular cortex and cerebellum. This is the first reported MRI finding of diphtheric encephalitis. Our report highlights the importance of neuroimaging in diagnosing diphtheric encephalitis particularly in cases with unremarkable cerebrospinal findings.
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http://dx.doi.org/10.1016/j.jocn.2017.08.024DOI Listing
November 2017

Risk Stratification in Pediatric Acute Respiratory Distress Syndrome: A Multicenter Observational Study.

Crit Care Med 2017 Nov;45(11):1820-1828

1Children's Intensive Care Unit, Department of Pediatric Subspecialities, KK Women's and Children's Hospital, Singapore. 2Duke-NUS Medical School, Singapore. 3Pediatric Intensive Care Unit, National Children's Hospital, Hanoi, Vietnam. 4Department of Pediatrics, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand. 5Pediatric Intensive Care Unit, Department of Pediatrics, Khoo Teck Puat-National University Children's Medical Institute, National University Hospital, Singapore. 6Department of Pediatrics, Sarawak General Hospital, Kuching, Malaysia. 7Pediatric Intensive Care Unit, Beijing Children's Hospital, Capital Medical University, Beijing, China. 8Division of Pediatric Critical Care, Department of Pediatrics, King Chulalongkorn Memorial Hospital, Bangkok, Thailand. 9Pediatric Department, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand. 10Department of Pediatrics, University Malaya Medical Centre, University of Malaya, Kuala Lumpur, Malaysia. 11Children's Hospital of Chongqing Medical University, Chongqing, China. 12Center for Quantitative Medicine, Duke-NUS Medical School, Singapore.

Objectives: The Pediatric Acute Lung Injury Consensus Conference developed a pediatric specific definition for acute respiratory distress syndrome (PARDS). In this definition, severity of lung disease is stratified into mild, moderate, and severe groups. We aim to describe the epidemiology of patients with PARDS across Asia and evaluate whether the Pediatric Acute Lung Injury Consensus Conference risk stratification accurately predicts outcome in PARDS.

Design: A multicenter, retrospective, descriptive cohort study.

Setting: Ten multidisciplinary PICUs in Asia.

Patients: All mechanically ventilated children meeting the Pediatric Acute Lung Injury Consensus Conference criteria for PARDS between 2009 and 2015.

Interventions: None.

Measurements And Main Results: Data on epidemiology, ventilation, adjunct therapies, and clinical outcomes were collected. Patients were followed for 100 days post diagnosis of PARDS. A total of 373 patients were included. There were 89 (23.9%), 149 (39.9%), and 135 (36.2%) patients with mild, moderate, and severe PARDS, respectively. The most common risk factor for PARDS was pneumonia/lower respiratory tract infection (309 [82.8%]). Higher category of severity of PARDS was associated with lower ventilator-free days (22 [17-25], 16 [0-23], 6 [0-19]; p < 0.001 for mild, moderate, and severe, respectively) and PICU free days (19 [11-24], 15 [0-22], 5 [0-20]; p < 0.001 for mild, moderate, and severe, respectively). Overall PICU mortality for PARDS was 113 of 373 (30.3%), and 100-day mortality was 126 of 317 (39.7%). After adjusting for site, presence of comorbidities and severity of illness in the multivariate Cox proportional hazard regression model, patients with moderate (hazard ratio, 1.88 [95% CI, 1.03-3.45]; p = 0.039) and severe PARDS (hazard ratio, 3.18 [95% CI, 1.68, 6.02]; p < 0.001) had higher risk of mortality compared with those with mild PARDS.

Conclusions: Mortality from PARDS is high in Asia. The Pediatric Acute Lung Injury Consensus Conference definition of PARDS is a useful tool for risk stratification.
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http://dx.doi.org/10.1097/CCM.0000000000002623DOI Listing
November 2017

3-Methylglutaconic aciduria, a frequent but underrecognized finding in carbamoyl phosphate synthetase I deficiency.

Clin Chim Acta 2017 Aug 17;471:95-100. Epub 2017 May 17.

Department of Human Genetics, Technical University Munich, Munich, Germany; Institute of Human Genetics, Helmholtz Zentrum, Neuherberg, Germany; Department of Pediatrics, Salzburger Landeskliniken (SALK) and Paracelsus Medical University (PMU), Salzburg, Austria. Electronic address:

The urea cycle disorder carbamoyl phosphate synthetase I deficiency is an important differential diagnosis in the encephalopathic neonate. This intoxication type inborn error of metabolism often leads to neonatal death or severe and irreversible damage of the central nervous system, even despite appropriate treatment. Timely diagnosis is crucial, but can be difficult on routine metabolite level. Here, we report ten neonates from eight families (finally) diagnosed with CPS1 deficiency at three tertiary metabolic centres. In seven of them the laboratory findings were dominated by significantly elevated urinary 3-methylglutaconic acid levels which complicated the diagnostic process. Our findings are both important for the differential diagnosis of patients with urea cycle disorders and also broaden the differential diagnosis of hyperammonemia associated with 3-methylglutaconic aciduria, which was earlier only reported in TMEM70 and SERAC1 defect.
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http://dx.doi.org/10.1016/j.cca.2017.05.023DOI Listing
August 2017

Thirteen years of invasive and noninvasive home ventilation for children in a developing country: A retrospective study.

Pediatr Pulmonol 2017 04 6;52(4):500-507. Epub 2016 Oct 6.

Department of Pediatrics, University of Malaya, Kuala Lumpur, Malaysia.

Introduction: Home ventilation (HV) for children is growing rapidly worldwide. The aim was to describe (1) the sociodemographic characteristics of children on HV and (2) the indications for, means and outcome of initiating HV in children from a developing country.

Methodology: This retrospective study included patients sent home on noninvasive or invasive ventilation, over 13 years, by the pediatric respiratory unit in a single center. Children who declined treatment were excluded.

Results: Seventy children were initiated on HV: 85.7% on noninvasive ventilation, 14.3% on invasive ventilation. There was about a threefold increase from 2001-2008 (n = 18) to 2009-2014 (n = 52). Median (range) age of initiating HV was 11 (1-169) months and 73% of children were <2 years old. Common indications for HV were respiratory (57.2%), chest/spine anomalies (11.4%), and neuromuscular (10.0%). Fifty-two percent came off their devices with a median (interquartile range) usage duration of 12 (4.8, 21.6) months. Ten children (14.3%) died with one avoidable death. Children with neuromuscular disease were less likely to come off their ventilator (0.0%) compared to children with respiratory disease (62.1%). Forty-one percent of parents bought their equipment, whereas 58.6% borrowed their equipment from the medical social work department and other sources.

Conclusion: HV in a resource-limited country is possible. Children with respiratory disease made up a significant proportion of those requiring HV and were more likely to be weaned off. The mortality rate was low. The social work department played an important role in facilitating early discharge. Pediatr Pulmonol. 2017;52:500-507. © 2016 Wiley Periodicals, Inc.
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http://dx.doi.org/10.1002/ppul.23569DOI Listing
April 2017

Sulthiame-induced drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome.

Eur J Paediatr Neurol 2016 Nov 1;20(6):957-961. Epub 2016 Aug 1.

Division of Paediatric Neurology, Department of Paediatrics, University of Malaya, Kuala Lumpur, Malaysia.

Background: Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a rare and potentially life-threatening acute drug-induced hypersensitivity reaction. Antiepileptic drugs (AEDs) predominantly aromatic AEDs are commonly reported in DRESS. To date there are no reports of sulthiame AED causing DRESS syndrome.

Method: We report a 10-year-old girl of Indian descent with AED resistant epilepsy on maintenance sodium valproate and clonazepam. Sulthiame AED was initiated to try to improve her seizure control. Five weeks after commencing sulthiame, she developed fever with a diffuse erythematous morbilliform maculopapular rash, elevated transaminases and atypical lymphocytes. At day 3 of illness, she deteriorated with worsening elevation of liver transaminases, thrombocytopenia, progression of rash, hepatosplenomegaly, pneumonitis and markedly elevated inflammatory markers. Immunomodulatory treatment of pulse methylprednisolone was given from day 7 which was associated with improvement inflammatory markers and complete resolution of rash from day 30 of illness.

Results: The diagnosis of sulthiame-induced DRESS syndrome was made based on clinical, laboratory and skin histology findings. She was HLA-B heterozygous for HLA-B15:123 and 15:240 and HLA-A homozygous for HLA-A11:01:09. Both these HLA-A and HLA-B typing has not been reported before in cutaneous drug reactions.

Conclusion: This is the first reported case of sulthiame-induced DRESS syndrome. Our case expands the list of possible susceptible HLA alleles associated with cutaneous drug reactions. It also raises the awareness of possible DRESS syndrome among patients commenced on sulthiame who will require immediate discontinuation of sulthiame and consideration of prompt treatment of corticosteroids.
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http://dx.doi.org/10.1016/j.ejpn.2016.07.023DOI Listing
November 2016

Impact of infection control training for interns on PICU-acquired bloodstream infections in a middle-income country.

Singapore Med J 2015 Sep;56(9):506-12

Department of Paediatrics, Faculty of Medicine, University Malaya, Malaysia ; Paediatric Intensive Care Unit, University Malaya Medical Center, Malaysia.

Introduction: The present study aimed to determine the impact of an extended infection control training programme, which was conducted for all interns posted to the Department of Paediatrics, on the incidence of paediatric intensive care unit (PICU)-acquired bloodstream infections (BSIs) in University Malaya Medical Centre, Malaysia.

Methods: The development of nosocomial BSIs during the baseline period (1 January-31 October 2008) and intervention period (1 November-31 December 2009) was monitored. During the intervention period, all paediatric interns underwent training in hand hygiene and aseptic techniques for accessing vascular catheters.

Results: A total of 25 patients had PICU-acquired BSIs during the baseline period, while 18 patients had PICU-acquired BSIs during the intervention period (i.e. infection rate of 88 per 1,000 and 41 per 1,000 admissions, respectively). The infections were related to central venous catheters (CVCs) in 22 of the 25 patients who had PICU-acquired BSIs during the baseline period and 11 of the 18 patients who had PICU-acquired BSIs during the intervention period. Thus, the incidence rates of catheter-related BSIs were 25.2 per 1,000 CVC-days and 9.3 per 1,000 CVC-days, respectively (p < 0.05). The Paediatric Risk of Standardised Mortality III score was an independent risk factor for PICU-acquired BSIs and the intervention significantly reduced this risk.

Conclusion: The education of medical interns on infection control, a relatively low-cost intervention, resulted in a substantial reduction in the incidence of PICU-acquired BSIs.
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http://dx.doi.org/10.11622/smedj.2015135DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4582130PMC
September 2015

Regular paracetamol in severe dengue: a lethal combination?

Singapore Med J 2013 Feb;54(2):e35-7

Department of Paediatrics, University Malaya Medical Centre, Kuala Lumpur 59100, Malaysia.

An eight-month-old female infant with severe dengue disease, who was repeatedly given therapeutic paracetamol for severe dengue, developed fulminant liver failure with encephalopathy, gastrointestinal haemorrhage and severe coagulopathy. She responded to supportive measures and N-acetylcysteine infusion. This case highlights the potential danger of administering repeated therapeutic doses of paracetamol in childhood severe dengue disease with hepatitis.
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http://dx.doi.org/10.11622/smedj.2013037DOI Listing
February 2013
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