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  1. Ong BB, Wong JJ, Hashim J
    Malays J Pathol, 2004 Jun;26(1):35-41.
    PMID: 16190105
    It is well known that diagnostic accuracy of the clinical cause of death has not improved despite advances in diagnostic techniques. We aimed to investigate the accuracy of the clinical cause of death compared with the autopsy cause of death and to see if the Coroner's autopsy can play a role in clinical audit. Our study population consisted of all autopsies where the deceased was hospitalised or resuscitated at the Accident and Emergency Unit of the University of Malaya Medical Centre before death, performed during the period July 1998 to June 2000. The cases were subdivided according to natural and unnatural causes of deaths. Natural deaths were further subdivided in relation to the main organ systems involved while unnatural deaths were subcategorised into trauma, poisoning and burns. The rate of agreement between clinical and autopsy cause of death was further compared with duration of survival in the hospital. Of 132 autopsies included in this study, 115 were Coroner's autopsies. 78% of cases showed agreement between clinical and autopsy cause of death. The agreement rate in Coroner's cases was 80.0%. For natural and unnatural causes, the agreement rate was 56.7% and 84.3% respectively. There were 6 cases (4.5%) where an initial accurate diagnosis might have altered the prognosis of the deceased. In general, the rate of agreement increased with duration of survival of patients. However, this was no longer observed after a survival of more than 28 days. Our findings agree with other similar studies. The diagnostic accuracy of cause of death has not improved despite the modernisation in medical technology. The autopsy still plays an important role in clinical audit and medical education.
  2. Wong JJ, Tan HL, Lee SW, Chang KTE, Mok YH, Lee JH
    Pediatr Pulmonol, 2020 04;55(4):1000-1006.
    PMID: 32017471 DOI: 10.1002/ppul.24674
    OBJECTIVE: This study delineates the disease trajectory of patients with pediatric acute respiratory distress syndrome (PARDS) defined by the Pediatric Acute Lung Injury Consensus Conference (PALICC) definition, and evaluates the impact of comorbidities on outcomes.

    METHODS: This prospective study over November 2017-October 2019 was conducted in a single-center multidisciplinary pediatric intensive care unit (PICU) and included patients <21years of age with PARDS. Clinical history of those requiring mechanical ventilation for <3 days was interrogated and cases in which the diagnosis of PARDS were unlikely, identified. The impact of chronic comorbidities on clinical outcomes, in particular, pulmonary disease and immunosuppression, were analyzed.

    RESULTS: Eighty-five of 1272 PICU admissions (6.7%) met the criteria for PARDS and were included. Median age and oxygenation indexes were 2.8 (0.6, 8.3) years and 10.6 (7.6, 15.4), respectively. Overall mortality was 12 out of 85 (14.1%). Despite fulfilling criteria in 6/85 (7.1%), hypoxemia contributed by bronchospasm, mucus plugging, fluid overload, and atelectasis was quickly reversible and PARDS was unlikely in these patients. Comorbidities (57/85 [67.1%]) were not associated with worsened outcomes. However, pre-existing pulmonary disease and immunosuppression were associated with severe PARDS (12/20 [60.0%] vs 19/65 [29.2%]; P = .017), extracorporeal membrane oxygenation use (5/20 [25.0%] vs 3/65 [4.6%]; P = .016) and reduced ventilator free days (VFD) (15 [0, 19] vs 21 [6, 23]; P = .039), compared with those without them.

    CONCLUSION: A small percentage of children fulfilling the PALICC definition had quickly reversible hypoxemia with likely alternate pathophysiology to PARDS. Patients with pulmonary comorbidities and immunosuppression had a more severe course of PARDS compared with others.

  3. Looh SC, Soo ZMP, Wong JJ, Yam HC, Chow SK, Hwang JS
    Toxins (Basel), 2022 01 11;14(1).
    PMID: 35051027 DOI: 10.3390/toxins14010050
    Leukotoxin A (LtxA) is the major virulence factor of an oral bacterium known as Aggregatibacter actinomycetemcomitans (Aa). LtxA is associated with elevated levels of anti-citrullinated protein antibodies (ACPA) in rheumatoid arthritis (RA) patients. LtxA targets leukocytes and triggers an influx of extracellular calcium into cytosol. The current proposed model of LtxA-mediated hypercitrullination involves the dysregulated activation of peptidylarginine deiminase (PAD) enzymes to citrullinate proteins, the release of hypercitrullinated proteins through cell death, and the production of autoantigens recognized by ACPA. Although model-based evidence is yet to be established, its interaction with the host's immune system sparked interest in the role of LtxA in RA. The first part of this review summarizes the current knowledge of Aa and LtxA. The next part highlights the findings of previous studies on the association of Aa or LtxA with RA aetiology. Finally, we discuss the unresolved aspects of the proposed link between LtxA of Aa and RA.
  4. Wong JJ, Purbojati RW, Tan RS, Pettersson S, Koh AS
    ESC Heart Fail, 2022 Dec;9(6):4366-4368.
    PMID: 36071622 DOI: 10.1002/ehf2.14139
  5. Chong LA, Khalid F, Khoo TB, Teh SH, Kuan GL, Aina Mariana AM, et al.
    Med J Malaysia, 2017 02;72(1):32-36.
    PMID: 28255137 MyJurnal
    INTRODUCTION: Awareness for paediatric palliative care has resulted in the impetus for paediatrician-led palliative care services across Malaysia. However, there is paucity of local data on patients receiving hospital-based paediatric palliative care. We aim to review the clinical spectrum of patients referred to these services.

    METHODS: An observational study of children aged between 0-18 years receiving palliative care at 13 hospitals between 1st January and 31st December 2014 was carried out.

    RESULTS: There were 315 patients analysed, 90 (28.6%) and 46 (14.6%) were neonates and adolescents respectively. The main ICD-10 diagnostic categories for all patients were identified to be 'Congenital malformations, deformations and chromosomal abnormalities' 117 (37.1%), 'Diseases of nervous system' 76 (24.1%) and 'Neoplasms' 60 (19.0%). At referral 156 (50%) patients had holistic needs assessments. Patients with 'Diseases of nervous system' were assessed to have significantly more physical needs than the other two diagnostic categories. Majority of patients who knew of their diagnosis and prognosis were those with malignancy. Over a fifth of referrals were at their terminal admission. Of 144 who died, 111 (77.1%) had advanced care plans. There was bereavement follow-up in 98 (68.1%) patients.

    CONCLUSION: Patients referred for palliative care have varied diagnoses and needs. To ensure all paediatricians are competent to deliver quality care to all children, further education and training initiatives is imperative.

  6. Wong JJ, Phan HP, Phumeetham S, Ong JSM, Chor YK, Qian S, et al.
    Crit Care Med, 2017 Jul 26.
    PMID: 28749854 DOI: 10.1097/CCM.0000000000002623
    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.

  7. Samransamruajkit R, Wong JJ, Smathakane C, Anantasit N, Sunkonkit K, Ong J, et al.
    Pediatr Crit Care Med, 2021 08 01;22(8):713-721.
    PMID: 33729727 DOI: 10.1097/PCC.0000000000002680
    OBJECTIVES: Pediatric sepsis remains a major health problem and is a leading cause of death and long-term disability worldwide. This study aims to characterize epidemiologic, therapeutic, and outcome features of pediatric severe sepsis and septic shock in three Asian countries.

    DESIGN: A multicenter retrospective study with longitudinal clinical data over 1, 6, 24, 48, and 72 hours of PICU admission. The primary outcome was PICU mortality. Multivariable logistic regression analysis was used to identify factors at PICU admission that were associated with mortality.

    SETTING: Nine multidisciplinary PICUs in three Asian countries.

    PATIENTS: Children with severe sepsis or septic shock admitted to the PICU from January to December 2017.

    INTERVENTION: None.

    MEASUREMENT AND MAIN RESULTS: A total of 271 children were included in this study. Median (interquartile range) age was 4.2 years (1.3-10.8 yr). Pneumonia (77/271 [28.4%]) was the most common source of infection. Majority of patients (243/271 [90%]) were resuscitated within the first hour, with fluid bolus (199/271 [73.4%]) or vasopressors (162/271 [59.8%]). Fluid resuscitation commonly took the form of normal saline (147/199 [74.2%]) (20 mL/kg [10-20 mL/kg] over 20 min [15-30 min]). The most common inotrope used was norepinephrine 81 of 162 (50.0%). Overall PICU mortality was 52 of 271 (19.2%). Improved hemodynamic variables (e.g., heart rate, blood pressure, and arterial lactate) were seen in survivors within 6 hours of admission as compared to nonsurvivors. In the multivariable model, admission severity score was associated with PICU mortality.

    CONCLUSIONS: Mortality from pediatric severe sepsis and septic shock remains high in Asia. Consistent with current guidelines, most of the children admitted to these PICUs received fluid therapy and inotropic support as recommended.

  8. Gan CS, Wong JJ, Samransamruajkit R, Chuah SL, Chor YK, Qian S, et al.
    Pediatr Crit Care Med, 2018 10;19(10):e504-e513.
    PMID: 30036234 DOI: 10.1097/PCC.0000000000001667
    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.

  9. Wong JJ, Liu S, Dang H, Anantasit N, Phan PH, Phumeetham S, et al.
    Crit Care, 2020 01 31;24(1):31.
    PMID: 32005285 DOI: 10.1186/s13054-020-2741-x
    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 

  10. Johnson CD, Haldeman S, Nordin M, Chou R, Côté P, Hurwitz EL, et al.
    Eur Spine J, 2018 09;27(Suppl 6):786-795.
    PMID: 30151808 DOI: 10.1007/s00586-018-5723-9
    PURPOSE: The purpose of this report is to describe the Global Spine Care Initiative (GSCI) contributors, disclosures, and methods for reporting transparency on the development of the recommendations.

    METHODS: World Spine Care convened the GSCI to develop an evidence-based, practical, and sustainable healthcare model for spinal care. The initiative aims to improve the management, prevention, and public health for spine-related disorders worldwide; thus, global representation was essential. A series of meetings established the initiative's mission and goals. Electronic surveys collected contributorship and demographic information, and experiences with spinal conditions to better understand perceptions and potential biases that were contributing to the model of care.

    RESULTS: Sixty-eight clinicians and scientists participated in the deliberations and are authors of one or more of the GSCI articles. Of these experts, 57 reported providing spine care in 34 countries, (i.e., low-, middle-, and high-income countries, as well as underserved communities in high-income countries.) The majority reported personally experiencing or having a close family member with one or more spinal concerns including: spine-related trauma or injury, spinal problems that required emergency or surgical intervention, spinal pain referred from non-spine sources, spinal deformity, spinal pathology or disease, neurological problems, and/or mild, moderate, or severe back or neck pain. There were no substantial reported conflicts of interest.

    CONCLUSION: The GSCI participants have broad professional experience and wide international distribution with no discipline dominating the deliberations. The GSCI believes this set of papers has the potential to inform and improve spine care globally. These slides can be retrieved under Electronic Supplementary Material.

  11. Johnson CD, Haldeman S, Chou R, Nordin M, Green BN, Côté P, et al.
    Eur Spine J, 2018 09;27(Suppl 6):925-945.
    PMID: 30151805 DOI: 10.1007/s00586-018-5720-z
    PURPOSE: Spine-related disorders are a leading cause of global disability and are a burden on society and to public health. Currently, there is no comprehensive, evidence-based model of care for spine-related disorders, which includes back and neck pain, deformity, spine injury, neurological conditions, spinal diseases, and pathology, that could be applied in global health care settings. The purposes of this paper are to propose: (1) principles to transform the delivery of spine care; (2) an evidence-based model that could be applied globally; and (3) implementation suggestions.

    METHODS: The Global Spine Care Initiative (GSCI) meetings and literature reviews were synthesized into a seed document and distributed to spine care experts. After three rounds of a modified Delphi process, all participants reached consensus on the final model of care and implementation steps.

    RESULTS: Sixty-six experts representing 24 countries participated. The GSCI model of care has eight core principles: person-centered, people-centered, biopsychosocial, proactive, evidence-based, integrative, collaborative, and self-sustaining. The model of care includes a classification system and care pathway, levels of care, and a focus on the patient's journey. The six steps for implementation are initiation and preparation; assessment of the current situation; planning and designing solutions; implementation; assessment and evaluation of program; and sustain program and scale up.

    CONCLUSION: The GSCI proposes an evidence-based, practical, sustainable, and scalable model of care representing eight core principles with a six-step implementation plan. The aim of this model is to help transform spine care globally, especially in low- and middle-income countries and underserved communities. These slides can be retrieved under Electronic Supplementary Material.

  12. Haldeman S, Nordin M, Chou R, Côté P, Hurwitz EL, Johnson CD, et al.
    Eur Spine J, 2018 09;27(Suppl 6):776-785.
    PMID: 30151809 DOI: 10.1007/s00586-018-5722-x
    PURPOSE: Spinal disorders, including back and neck pain, are major causes of disability, economic hardship, and morbidity, especially in underserved communities and low- and middle-income countries. Currently, there is no model of care to address this issue. This paper provides an overview of the papers from the Global Spine Care Initiative (GSCI), which was convened to develop an evidence-based, practical, and sustainable, spinal healthcare model for communities around the world with various levels of resources.

    METHODS: Leading spine clinicians and scientists around the world were invited to participate. The interprofessional, international team consisted of 68 members from 24 countries, representing most disciplines that study or care for patients with spinal symptoms, including family physicians, spine surgeons, rheumatologists, chiropractors, physical therapists, epidemiologists, research methodologists, and other stakeholders.

    RESULTS: Literature reviews on the burden of spinal disorders and six categories of evidence-based interventions for spinal disorders (assessment, public health, psychosocial, noninvasive, invasive, and the management of osteoporosis) were completed. In addition, participants developed a stratification system for surgical intervention, a classification system for spinal disorders, an evidence-based care pathway, and lists of resources and recommendations to implement the GSCI model of care.

    CONCLUSION: The GSCI proposes an evidence-based model that is consistent with recent calls for action to reduce the global burden of spinal disorders. The model requires testing to determine feasibility. If it proves to be implementable, this model holds great promise to reduce the tremendous global burden of spinal disorders. These slides can be retrieved under Electronic Supplementary Material.

  13. Tobias DK, Merino J, Ahmad A, Aiken C, Benham JL, Bodhini D, et al.
    Nat Med, 2023 Oct;29(10):2438-2457.
    PMID: 37794253 DOI: 10.1038/s41591-023-02502-5
    Precision medicine is part of the logical evolution of contemporary evidence-based medicine that seeks to reduce errors and optimize outcomes when making medical decisions and health recommendations. Diabetes affects hundreds of millions of people worldwide, many of whom will develop life-threatening complications and die prematurely. Precision medicine can potentially address this enormous problem by accounting for heterogeneity in the etiology, clinical presentation and pathogenesis of common forms of diabetes and risks of complications. This second international consensus report on precision diabetes medicine summarizes the findings from a systematic evidence review across the key pillars of precision medicine (prevention, diagnosis, treatment, prognosis) in four recognized forms of diabetes (monogenic, gestational, type 1, type 2). These reviews address key questions about the translation of precision medicine research into practice. Although not complete, owing to the vast literature on this topic, they revealed opportunities for the immediate or near-term clinical implementation of precision diabetes medicine; furthermore, we expose important gaps in knowledge, focusing on the need to obtain new clinically relevant evidence. Gaps include the need for common standards for clinical readiness, including consideration of cost-effectiveness, health equity, predictive accuracy, liability and accessibility. Key milestones are outlined for the broad clinical implementation of precision diabetes medicine.
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