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  1. Lake NJ, Phua J, Liu W, Moors T, Axon S, Lek M
    J Neuromuscul Dis, 2023 Mar 31.
    PMID: 37005889 DOI: 10.3233/JND-221552
    BACKGROUND: Recessive pathogenic variants in LAMA2 resulting in complete or partial loss of laminin α2 protein cause congenital muscular dystrophy (LAMA2 CMD). The prevalence of LAMA2 CMD has been estimated by epidemiological studies to lie between 1.36-20 cases per million. However, prevalence estimates from epidemiological studies are vulnerable to inaccuracies owing to challenges with studying rare diseases. Population genetic databases offer an alternative method for estimating prevalence.

    OBJECTIVE: We aim to use population allele frequency data for reported and predicted pathogenic variants to estimate the birth prevalence of LAMA2 CMD.

    METHODS: A list of reported pathogenic LAMA2 variants was compiled from public databases, and supplemented with predicted loss of function (LoF) variants in the Genome Aggregation Database (gnomAD). gnomAD allele frequencies for 273 reported pathogenic and predicted LoF LAMA2 variants were used to calculate disease prevalence using a Bayesian methodology.

    RESULTS: The world-wide birth prevalence of LAMA2 CMD was estimated to be 8.3 per million (95% confidence interval (CI) 6.27 -10.5 per million). The prevalence estimates for each population in gnomAD varied, ranging from 1.79 per million in East Asians (95% CI 0.63 -3.36) to 10.1 per million in Europeans (95% CI 6.74 -13.9). These estimates were generally consistent with those from epidemiological studies, where available.

    CONCLUSIONS: We provide robust world-wide and population-specific birth prevalence estimates for LAMA2 CMD, including for non-European populations in which LAMA2 CMD prevalence hadn't been studied. This work will inform the design and prioritization of clinical trials for promising LAMA2 CMD treatments.

  2. Phua J, Joynt GM, Nishimura M, Deng Y, Myatra SN, Chan YH, et al.
    JAMA Intern Med, 2015 Mar;175(3):363-71.
    PMID: 25581712 DOI: 10.1001/jamainternmed.2014.7386
    Little data exist on end-of-life care practices in intensive care units (ICUs) in Asia.
  3. Phua J, Joynt GM, Nishimura M, Deng Y, Myatra SN, Chan YH, et al.
    Intensive Care Med, 2016 Jul;42(7):1118-27.
    PMID: 27071388 DOI: 10.1007/s00134-016-4347-y
    PURPOSE: To compare the attitudes of physicians towards withholding and withdrawing life-sustaining treatments in intensive care units (ICUs) in low-middle-income Asian countries and regions with those in high-income ones, and to explore differences in the role of families and surrogates, legal risks, and financial considerations between these countries and regions.

    METHODS: Questionnaire study conducted in May-December 2012 on 847 physicians from 255 ICUs in 10 low-middle-income countries and regions according to the World Bank's classification, and 618 physicians from 211 ICUs in six high-income countries and regions.

    RESULTS: After we accounted for personal, ICU, and hospital characteristics on multivariable analyses using generalised linear mixed models, physicians from low-middle-income countries and regions were less likely to limit cardiopulmonary resuscitation, mechanical ventilation, vasopressors and inotropes, tracheostomy and haemodialysis than those from high-income countries and regions. They were more likely to involve families in end-of-life care discussions and to perceive legal risks with limitation of life-sustaining treatments and do-not-resuscitate orders. Nonetheless, they were also more likely to accede to families' requests to withdraw life-sustaining treatments in a patient with an otherwise reasonable chance of survival on financial grounds in a case scenario (adjusted odds ratio 5.05, 95 % confidence interval 2.69-9.51, P 

  4. Phua J, Faruq MO, Kulkarni AP, Redjeki IS, Detleuxay K, Mendsaikhan N, et al.
    Crit Care Med, 2020 05;48(5):654-662.
    PMID: 31923030 DOI: 10.1097/CCM.0000000000004222
    OBJECTIVE: To assess the number of adult critical care beds in Asian countries and regions in relation to population size.

    DESIGN: Cross-sectional observational study.

    SETTING: Twenty-three Asian countries and regions, covering 92.1% of the continent's population.

    PARTICIPANTS: Ten low-income and lower-middle-income economies, five upper-middle-income economies, and eight high-income economies according to the World Bank classification.

    INTERVENTIONS: Data closest to 2017 on critical care beds, including ICU and intermediate care unit beds, were obtained through multiple means, including government sources, national critical care societies, colleges, or registries, personal contacts, and extrapolation of data.

    MEASUREMENTS AND MAIN RESULTS: Cumulatively, there were 3.6 critical care beds per 100,000 population. The median number of critical care beds per 100,000 population per country and region was significantly lower in low- and lower-middle-income economies (2.3; interquartile range, 1.4-2.7) than in upper-middle-income economies (4.6; interquartile range, 3.5-15.9) and high-income economies (12.3; interquartile range, 8.1-20.8) (p = 0.001), with a large variation even across countries and regions of the same World Bank income classification. This number was independently predicted by the World Bank income classification on multivariable analysis, and significantly correlated with the number of acute hospital beds per 100,000 population (r = 0.19; p = 0.047), the universal health coverage service coverage index (r = 0.35; p = 0.003), and the Human Development Index (r = 0.40; p = 0.001) on univariable analysis.

    CONCLUSIONS: Critical care bed capacity varies widely across Asia and is significantly lower in low- and lower-middle-income than in upper-middle-income and high-income countries and regions.

  5. Leung CHC, Lee A, Arabi YM, Phua J, Divatia JV, Koh Y, et al.
    Ann Am Thorac Soc, 2021 08;18(8):1352-1359.
    PMID: 33284738 DOI: 10.1513/AnnalsATS.202008-968OC
    Rationale: There are limited data on mechanical discontinuation practices in Asia. Objectives: To document self-reported mechanical discontinuation practices and determine whether there is clinical equipoise regarding protocolized weaning among Asian Intensive Care specialists. Methods: A survey using a validated questionnaire, distributed using a snowball method to Asian Intensive Care specialists. Results: Of the 2,967 invited specialists from 20 territories, 2,074 (69.9%) took part. The majority of respondents (60.5%) were from China. Of the respondents, 42% worked in intensive care units (ICUs) where respiratory therapists were present; 78.9% used a spontaneous breathing trial as the initial weaning step; 44.3% frequently/always used pressure support (PS) alone, 53.4% intermittent spontaneous breathing trials with PS in between, and 19.8% synchronized intermittent mandatory ventilation with PS as a weaning mode. Of the respondents, 56.3% routinely stopped feeds before extubation, 71.5% generally followed a sedation protocol or guideline, and 61.8% worked in an ICU with a weaning protocol. Of these, 78.2% frequently always followed the protocol. A multivariate analysis involving a modified Poisson regression analysis showed that working in an ICU with a weaning protocol and frequently/always following it was positively associated with an upper-middle-income territory, a university-affiliated hospital, or in an ICU that employed respiratory therapists; and negatively with a low-income or lower-middle-income territory or a public hospital. There was no significant association with "in-house" intensivist at night, multidisciplinary ICU, closed ICU, or nurse-patient ratio. There was heterogeneity in agreement/disagreement with the statement, "evidence clearly supports protocolized weaning over nonprotocolized weaning." Conclusions: A substantial minority of Asian Intensive Care specialists do not wean patients in accordance with the best available evidence or current guidelines. There is clinical equipoise regarding the benefit of protocolized weaning.
  6. Phua J, Lim CM, Faruq MO, Nafees KMK, Du B, Gomersall CD, et al.
    J Intensive Care, 2021 Oct 07;9(1):60.
    PMID: 34620252 DOI: 10.1186/s40560-021-00574-4
    BACKGROUND: Asia has more critically ill people than any other part of our planet. The aim of this article is to review the development of critical care as a specialty, critical care societies and education and research, the epidemiology of critical illness as well as epidemics and pandemics, accessibility and cost and quality of critical care, culture and end-of-life care, and future directions for critical care in Asia.

    MAIN BODY: Although the first Asian intensive care units (ICUs) surfaced in the 1960s and the 1970s and specialisation started in the 1990s, multiple challenges still exist, including the lack of intensivists, critical care nurses, and respiratory therapists in many countries. This is aggravated by the brain drain of skilled ICU staff to high-income countries. Critical care societies have been integral to the development of the discipline and have increasingly contributed to critical care education, although critical care research is only just starting to take off through collaboration across groups. Sepsis, increasingly aggravated by multidrug resistance, contributes to a significant burden of critical illness, while epidemics and pandemics continue to haunt the continent intermittently. In particular, the coronavirus disease 2019 (COVID-19) has highlighted the central role of critical care in pandemic response. Accessibility to critical care is affected by lack of ICU beds and high costs, and quality of critical care is affected by limited capability for investigations and treatment in low- and middle-income countries. Meanwhile, there are clear cultural differences across countries, with considerable variations in end-of-life care. Demand for critical care will rise across the continent due to ageing populations and rising comorbidity burdens. Even as countries respond by increasing critical care capacity, the critical care community must continue to focus on training for ICU healthcare workers, processes anchored on evidence-based medicine, technology guided by feasibility and impact, research applicable to Asian and local settings, and rallying of governments for support for the specialty.

    CONCLUSIONS: Critical care in Asia has progressed through the years, but multiple challenges remain. These challenges should be addressed through a collaborative approach across disciplines, ICUs, hospitals, societies, governments, and countries.

  7. Phua J, Kulkarni AP, Mizota T, Hashemian SMR, Lee WY, Permpikul C, et al.
    Lancet Reg Health West Pac, 2024 Mar;44:100982.
    PMID: 38143717 DOI: 10.1016/j.lanwpc.2023.100982
    BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic highlighted the importance of critical care. The aim of the current study was to compare the number of adult critical care beds in relation to population size in Asian countries and regions before (2017) and during (2022) the pandemic.

    METHODS: This observational study collected data closest to 2022 on critical care beds (intensive care units and intermediate care units) in 12 middle-income and 7 high-income economies (using the 2022-2023 World Bank classification), through a mix of methods including government sources, national critical care societies, personal contacts, and data extrapolation. Data were compared with a prior study from 2017 of the same countries and regions.

    FINDINGS: The cumulative number of critical care beds per 100,000 population increased from 3.0 in 2017 to 9.4 in 2022 (p = 0.003). The median figure for middle-income economies increased from 2.6 (interquartile range [IQR] 1.7-7.8) to 6.6 (IQR 2.2-13.3), and that for high-income economies increased from 11.4 (IQR 7.3-22.8) to 13.9 (IQR 10.7-21.7). Only 3 countries did not see a rise in bed capacity. Where data were available in 2022, 10.9% of critical care beds were in single rooms (median 5.0% in middle-income and 20.3% in high-income economies), and 5.3% had negative pressure (median 0.7% in middle-income and 18.5% in high-income economies).

    INTERPRETATION: Critical care bed capacity in the studied Asian countries and regions increased close to three-fold from 2017 to 2022. Much of this increase was attributed to middle-income economies, but substantial heterogeneity exists.

    FUNDING: None.

  8. Nam KH, Phua J, Du B, Ohshimo S, Kim HJ, Lim CM, et al.
    J Crit Care, 2024 Feb;79:154452.
    PMID: 37948944 DOI: 10.1016/j.jcrc.2023.154452
    PURPOSE: This study investigated current practices of mechanical ventilation in Asian intensive care units, focusing on tidal volume, plateau pressure, and positive end-expiratory pressure (PEEP).

    MATERIALS AND METHODS: In this multicenter cross-sectional study, data on mechanical ventilation and clinical outcomes were collected. Predictors of mortality were analyzed by univariate and multivariable logistic regression. A scoring system was generated to predict 28-day mortality.

    RESULTS: A total of 1408 patients were enrolled. In 138 patients with acute respiratory distress syndrome (ARDS), 65.9% were on a tidal volume ≤ 8 ml/kg predicted body weight (PBW), and 71.3% were on sufficient PEEP. In 1270 patients without ARDS, 88.8% were on a tidal volume ≤ 10 ml/kg PBW. A plateau pressure 

  9. Li A, Ling L, Qin H, Arabi YM, Myatra SN, Egi M, et al.
    Am J Respir Crit Care Med, 2022 Nov 01;206(9):1107-1116.
    PMID: 35763381 DOI: 10.1164/rccm.202112-2743OC
    Rationale: Directly comparative data on sepsis epidemiology and sepsis bundle implementation in countries of differing national wealth remain sparse. Objectives: To evaluate across countries/regions of differing income status in Asia 1) the prevalence, causes, and outcomes of sepsis as a reason for ICU admission and 2) sepsis bundle (antibiotic administration, blood culture, and lactate measurement) compliance and its association with hospital mortality. Methods: A prospective point prevalence study was conducted among 386 adult ICUs from 22 Asian countries/regions. Adult ICU participants admitted for sepsis on four separate days (representing the seasons of 2019) were recruited. Measurements and Main Results: The overall prevalence of sepsis in ICUs was 22.4% (20.9%, 24.5%, and 21.3% in low-income countries/regions [LICs]/lower middle-income countries/regions [LMICs], upper middle-income countries/regions, and high-income countries/regions [HICs], respectively; P 
  10. Li A, Ling L, Qin H, Arabi YM, Myatra SN, Egi M, et al.
    Crit Care, 2024 Jan 23;28(1):30.
    PMID: 38263076 DOI: 10.1186/s13054-024-04804-7
    BACKGROUND: There is conflicting evidence on association between quick sequential organ failure assessment (qSOFA) and sepsis mortality in ICU patients. The primary aim of this study was to determine the association between qSOFA and 28-day mortality in ICU patients admitted for sepsis. Association of qSOFA with early (3-day), medium (28-day), late (90-day) mortality was assessed in low and lower middle income (LLMIC), upper middle income (UMIC) and high income (HIC) countries/regions.

    METHODS: This was a secondary analysis of the MOSAICS II study, an international prospective observational study on sepsis epidemiology in Asian ICUs. Associations between qSOFA at ICU admission and mortality were separately assessed in LLMIC, UMIC and HIC countries/regions. Modified Poisson regression was used to determine the adjusted relative risk (RR) of qSOFA score on mortality at 28 days with adjustments for confounders identified in the MOSAICS II study.

    RESULTS: Among the MOSAICS II study cohort of 4980 patients, 4826 patients from 343 ICUs and 22 countries were included in this secondary analysis. Higher qSOFA was associated with increasing 28-day mortality, but this was only observed in LLMIC (p 

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