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  1. Heery EC, Hoeksema BW, Browne NK, Reimer JD, Ang PO, Huang D, et al.
    Mar Pollut Bull, 2018 Oct;135:654-681.
    PMID: 30301085 DOI: 10.1016/j.marpolbul.2018.07.041
    Given predicted increases in urbanization in tropical and subtropical regions, understanding the processes shaping urban coral reefs may be essential for anticipating future conservation challenges. We used a case study approach to identify unifying patterns of urban coral reefs and clarify the effects of urbanization on hard coral assemblages. Data were compiled from 11 cities throughout East and Southeast Asia, with particular focus on Singapore, Jakarta, Hong Kong, and Naha (Okinawa). Our review highlights several key characteristics of urban coral reefs, including "reef compression" (a decline in bathymetric range with increasing turbidity and decreasing water clarity over time and relative to shore), dominance by domed coral growth forms and low reef complexity, variable city-specific inshore-offshore gradients, early declines in coral cover with recent fluctuating periods of acute impacts and rapid recovery, and colonization of urban infrastructure by hard corals. We present hypotheses for urban reef community dynamics and discuss potential of ecological engineering for corals in urban areas.
  2. Iwatate M, Hirata D, Francisco CPD, Co JT, Byeon JS, Joshi N, et al.
    Dig Endosc, 2022 Feb 04.
    PMID: 35122323 DOI: 10.1111/den.14244
    OBJECTIVE: Three high-risk flat and depressed lesions (FDLs), laterally spreading tumors non-granular type (LST-NG), depressed lesions, and large sessile serrated lesions (SSLs), are highly attributable to post-colonoscopy colorectal cancer (CRC). Efficient and organized educational programs on detecting high-risk FDLs are lacking. We aimed to explore whether a web-based educational intervention with training on FIND clues (fold deformation, intensive stool/mucus attachment, no vessel visibility, and demarcated reddish area) may improve the ability to detect high-risk FDLs.

    METHODS: This was an international web-based randomized control trial that enrolled non-expert endoscopists in 13 Asian countries. The participants were randomized into either education or non-education group. All participants took the pre-test and post-test to read 60 endoscopic images (40 high-risk FDL, 5 polypoid, 15 no lesions) and answered whether there was a lesion. Only the education group received a self-education program (video and training questions and answers) between the tests. The primary outcome was a detection rate of high-risk FDLs.

    RESULTS: In total, 284 participants were randomized. After excluding non-responders, the final data analyses were based on 139 participants in the education group and 130 in the non-education group. The detection rate of high-risk FDLs in the education group significantly improved by 14.7% (66.6% to 81.3%) compared with -0.8% (70.8% to 70.0%) in the non-education group. Similarly, the detection rate of LST-NG, depressed lesions, and large SSLs significantly increased only in the education group by 12.7%, 12.0%, and 21.6%, respectively.

    CONCLUSION: Short self-education focusing on detecting high-risk FDLs was effective for Asian non-expert endoscopists. (UMIN000042348).

  3. Teoh AYB, Dhir V, Kida M, Yasuda I, Jin ZD, Seo DW, et al.
    Gut, 2018 Jul;67(7):1209-1228.
    PMID: 29463614 DOI: 10.1136/gutjnl-2017-314341
    OBJECTIVES: Interventional endoscopic ultrasonography (EUS) procedures are gaining popularity and the most commonly performed procedures include EUS-guided drainage of pancreatic pseudocyst, EUS-guided biliary drainage, EUS-guided pancreatic duct drainage and EUS-guided celiac plexus ablation. The aim of this paper is to formulate a set of practice guidelines addressing various aspects of the above procedures.

    METHODS: Formulation of the guidelines was based on the best scientific evidence available. The RAND/UCLA appropriateness methodology (RAM) was used. Panellists recruited comprised experts in surgery, interventional EUS, interventional radiology and oncology from 11 countries. Between June 2014 and October 2016, the panellists met in meetings to discuss and vote on the clinical scenarios for each of the interventional EUS procedures in question.

    RESULTS: A total of 15 statements on EUS-guided drainage of pancreatic pseudocyst, 15 statements on EUS-guided biliary drainage, 12 statements on EUS-guided pancreatic duct drainage and 14 statements on EUS-guided celiac plexus ablation were formulated. The statements addressed the indications for the procedures, technical aspects, pre- and post-procedural management, management of complications, and competency and training in the procedures. All statements except one were found to be appropriate. Randomised studies to address clinical questions in a number of aspects of the procedures are urgently required.

    CONCLUSIONS: The current guidelines on interventional EUS procedures are the first published by an endoscopic society. These guidelines provide an in-depth review of the current evidence and standardise the management of the procedures.

  4. Kunaviktikul W, Ang E, Baridwan NS, Bernal AB, Dones LBP, Flores JL, et al.
    Nurse Educ Today, 2022 Apr;111:105307.
    PMID: 35217457 DOI: 10.1016/j.nedt.2022.105307
    BACKGROUND: The COVID-19 pandemic has caused extraordinary disruptions to education systems globally, forcing a rapid switch from conventional to online education. Although some qualitative studies have been carried out exploring the online education experiences of nursing students and faculty members during the COVID-19 pandemic, to our knowledge, no study has used the Photovoice approach.

    OBJECTIVES: To explore the experiences of nursing students and faculty members as related to online education during the COVID-19 pandemic.

    DESIGN: A descriptive qualitative design using Photovoice was adopted.

    SETTING: The study took place across five countries and one city in Southeast Asia (Indonesia, Malaysia, the Philippines, Thailand, Vietnam, and Hong Kong).

    PARTICIPANTS: Fifty-two nursing students and twenty-eight nursing faculty members who participated in online education during the COVID-19 pandemic.

    METHODS: Each participant submitted one photo substantiated with written reflections. Data were analysed using thematic analysis. Ethical approval was obtained from institution-specific ethics boards.

    RESULTS: Three themes and eleven sub-themes emerged from the data. The three main themes were: 1) Psychological roadblocks to online education; 2) Developing resilience despite adversities; and 3) Online education: What worked and what did not.

    CONCLUSION: Through Photovoice, the reflections revealed that nursing students and faculty members were generally overwhelmed with the online education experience. At the same time, participants were satisfied with the flexibility and convenience, opportunities for professional and personal development and safety afforded by online education. However, concerns over academic integrity, practical skills and clinical competencies, engagement and participation, the duality of technology and social isolation out-shadowed the advantages. It is worthwhile to explore the concerns raised to enhance online education across the nursing curriculum.

  5. Shorey S, Ang E, Baridwan NS, Bonito SR, Dones LBP, Flores JLA, et al.
    Nurse Educ Today, 2022 Mar;110:105277.
    PMID: 35101809 DOI: 10.1016/j.nedt.2022.105277
    BACKGROUND: The COVID-19 pandemic has disrupted the lives of many. Particularly, nursing students experience greater stress as their normal curriculum is interrupted and some of them face the risk of being infected as frontline workers. Nursing faculty members may face similar struggles, in addition to developing teaching materials for online learning. Thus, it is important to examine the faculty members' and students' views on their ability to adapt during the pandemic to obtain a holistic view of how learning and training has been affected.

    DESIGN: The descriptive cross-sectional quantitative design was used.

    SETTINGS: Data were collected from Southeast and East Asian Nursing Education and Research Network (SEANERN) affiliated nursing institutions from January 2021 to August 2021.

    PARTICIPANTS: A total of 1897 nursing students and 395 faculty members from SEANERN-affiliated nursing institutions in Cambodia, Hong Kong, Indonesia, Japan, Laos, Malaysia, Philippines, Singapore, Thailand and Vietnam were recruited for this study.

    METHODS: Quantitative surveys were used to explore the satisfaction levels in education modalities, confidence levels, psychosocial well-being, sense of coherence and stress levels of nursing students and faculty members during the COVID-19 pandemic.

    RESULTS: Participants were mostly satisfied with the new education modalities, although most students felt that their education was compromised. Both groups showed positive levels of psychosocial well-being, despite scoring low to medium on the sense of coherence scale and experiencing great stress. The participants' sense of coherence was positively correlated with their psychosocial well-being and negatively correlated with stress levels.

    CONCLUSIONS: While the COVID-19 pandemic had negatively impacted the lives of nursing students and faculty members, most of them had a healthy level of psychosocial well-being. Having a strong sense of coherence was associated with better psychosocial health and lower stress levels. As such, it may be helpful to develop interventions aimed at improving the sense of coherence of nursing students and staff to help them manage stressors better.

  6. Ng KKS, Kobayashi MJ, Fawcett JA, Hatakeyama M, Paape T, Ng CH, et al.
    Commun Biol, 2021 Oct 07;4(1):1166.
    PMID: 34620991 DOI: 10.1038/s42003-021-02682-1
    Hyperdiverse tropical rainforests, such as the aseasonal forests in Southeast Asia, are supported by high annual rainfall. Its canopy is dominated by the species-rich tree family of Dipterocarpaceae (Asian dipterocarps), which has both ecological (e.g., supports flora and fauna) and economical (e.g., timber production) importance. Recent ecological studies suggested that rare irregular drought events may be an environmental stress and signal for the tropical trees. We assembled the genome of a widespread but near threatened dipterocarp, Shorea leprosula, and analyzed the transcriptome sequences of ten dipterocarp species representing seven genera. Comparative genomic and molecular dating analyses suggested a whole-genome duplication close to the Cretaceous-Paleogene extinction event followed by the diversification of major dipterocarp lineages (i.e. Dipterocarpoideae). Interestingly, the retained duplicated genes were enriched for genes upregulated by no-irrigation treatment. These findings provide molecular support for the relevance of drought for tropical trees despite the lack of an annual dry season.
  7. Schee JP, Ang CL, Crystal Teoh SC, Tan HJ, Chew SH, Steven A, et al.
    Med J Malaysia, 2023 Sep;78(5):594-601.
    PMID: 37775485
    INTRODUCTION: Intravenous thrombolysis (IVT) with recombinant tissue plasminogen activator is beneficial in acute ischaemic stroke (AIS). We aim to compare the realworld clinical outcomes and service efficiency of IVT in Malaysian primary stroke centres (PSCs) versus acute stroke ready hospitals (ASRHs).

    MATERIALS AND METHODS: We conducted a multi-centre cohort study involving 5 PSCs and 7 ASRHs in Malaysia. Through review of medical records of AIS patients who received IVT from 01 January 2014 to 30 June 2021, real-world data was extracted for analysis. Univariate and multivariate regression models were employed to evaluate the role of PSCs versus ASRHs in post-IVT outcomes and complications. Statistical significance was set at p<0.05.

    RESULTS: A total of 313 multi-ethnic Asians, namely 231 from PSCs and 82 from ASRHs, were included. Both groups were comparable in baseline demographic, clinical, and stroke characteristics. The efficiency of IVT delivery (door-toneedle time), functional outcomes (mRS at 3 months post- IVT), and rates of adverse events (intracranial haemorrhages and mortality) following IVT were comparable between the 2 groups. Notably, 46.8% and 48.8% of patients in PSCs and ASRHs group respectively (p=0.752) achieved favourable functional outcome (mRS≤1 at 3 months post-IVT). Regression analyses demonstrated that post-IVT functional outcomes and adverse events were independent of the role of PSCs or ASRHs.

    CONCLUSION: Our study provides real-world evidence which suggests that IVT can be equally safe, effective, and efficiently delivered in ASRHs. This may encourage the establishment of more ASRHs to extend the benefits of IVT to a greater proportion of stroke populations and enhance the regional stroke care.

  8. Chan YKS, Affendi YA, Ang PO, Baria-Rodriguez MV, Chen CA, Chui APY, et al.
    Commun Biol, 2023 Jun 10;6(1):630.
    PMID: 37301948 DOI: 10.1038/s42003-023-05000-z
    Coral reefs in the Central Indo-Pacific region comprise some of the most diverse and yet threatened marine habitats. While reef monitoring has grown throughout the region in recent years, studies of coral reef benthic cover remain limited in spatial and temporal scales. Here, we analysed 24,365 reef surveys performed over 37 years at 1972 sites throughout East Asia by the Global Coral Reef Monitoring Network using Bayesian approaches. Our results show that overall coral cover at surveyed reefs has not declined as suggested in previous studies and compared to reef regions like the Caribbean. Concurrently, macroalgal cover has not increased, with no indications of phase shifts from coral to macroalgal dominance on reefs. Yet, models incorporating socio-economic and environmental variables reveal negative associations of coral cover with coastal urbanisation and sea surface temperature. The diversity of reef assemblages may have mitigated cover declines thus far, but climate change could threaten reef resilience. We recommend prioritisation of regionally coordinated, locally collaborative long-term studies for better contextualisation of monitoring data and analyses, which are essential for achieving reef conservation goals.
  9. Ang BH, Ho WK, Wijaya E, Kwan PY, Ng PS, Yoon SY, et al.
    J Clin Oncol, 2022 May 10;40(14):1542-1551.
    PMID: 35143328 DOI: 10.1200/JCO.21.01647
    PURPOSE: With the development of poly (ADP-ribose) polymerase inhibitors for treatment of patients with cancer with an altered BRCA1 or BRCA2 gene, there is an urgent need to ensure that there are appropriate strategies for identifying mutation carriers while balancing the increased demand for and cost of cancer genetics services. To date, the majority of mutation prediction tools have been developed in women of European descent where the age and cancer-subtype distributions are different from that in Asian women.

    METHODS: In this study, we built a new model (Asian Risk Calculator) for estimating the likelihood of carrying a pathogenic variant in BRCA1 or BRCA2 gene, using germline BRCA genetic testing results in a cross-sectional population-based study of 8,162 Asian patients with breast cancer. We compared the model performance to existing mutation prediction models. The models were evaluated for discrimination and calibration.

    RESULTS: Asian Risk Calculator included age of diagnosis, ethnicity, bilateral breast cancer, tumor biomarkers, and family history of breast cancer or ovarian cancer as predictors. The inclusion of tumor grade improved significantly the model performance. The full model was calibrated (Hosmer-Lemeshow P value = .614) and discriminated well between BRCA and non-BRCA pathogenic variant carriers (area under receiver operating curve, 0.80; 95% CI, 0.75 to 0.84). Addition of grade to the existing clinical genetic testing criteria targeting patients with breast cancer age younger than 45 years reduced the proportion of patients referred for genetic counseling and testing from 37% to 33% (P value = .003), thereby improving the overall efficacy.

    CONCLUSION: Population-specific customization of mutation prediction models and clinical genetic testing criteria improved the accuracy of BRCA mutation prediction in Asian patients.

  10. Tan TT, Tan MP, Lam CL, Loh EC, Capelle DP, Zainuddin SI, et al.
    BMJ Support Palliat Care, 2023 Dec 07;13(e2):e389-e396.
    PMID: 34244182 DOI: 10.1136/bmjspcare-2021-003068
    CONTEXT: Numerous studies have shown that gratitude can reduce stress and improve quality of life.

    OBJECTIVE: Our study aimed to examine the effect of mindful gratitude journaling on suffering, psychological distress and quality of life of patients with advanced cancer.

    METHODS: We conducted a parallel-group, blinded, randomised controlled trial at the University of Malaya Medical Centre, Malaysia. Ninety-two adult patients with advanced cancer, and an overall suffering score ≥4/10 based on the Suffering Pictogram were recruited and randomly assigned to either a mindful gratitude journaling group (N=49) or a routine journaling group (N=43).

    RESULTS: After 1 week, there were significant reductions in the overall suffering score from the baseline in both the intervention group (mean difference in overall suffering score=-2.0, 95% CI=-2.7 to -1.4, t=-6.125, p=0.000) and the control group (mean difference in overall suffering score=-1.6, 95% CI=-2.3 to -0.8, t=-4.106, p=0.037). There were also significant improvements in the total Hospital Anxiety and Depression Scale score (mean difference=-3.4, 95% CI=-5.3 to -1.5, t=-3.525, p=0.000) and the total Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being score (mean difference=7.3, 95% CI=1.5 to 13.1, t=2.460, p=0.014) in the intervention group after 7 days, but not in the control group.

    CONCLUSION: The results provide evidence that 7 days of mindful gratitude journaling could positively affect the state of suffering, psychological distress and quality of life of patients with advanced cancer.

    TRIAL REGISTRATION NUMBER: The trial was registered with the Australian and New Zealand Clinical Trials Registry (ACTRN1261800172191) and conducted in accordance with the Declaration of Helsinki.

  11. Feliciano EJG, Ho FDV, Yee K, Paguio JA, Eala MAB, Robredo JPG, et al.
    Lancet Reg Health West Pac, 2023 Dec;41:100971.
    PMID: 38053740 DOI: 10.1016/j.lanwpc.2023.100971
  12. Linn KZ, Sutjipto S, Ng OT, Teo J, Cherng BPZ, Tan TY, et al.
    PMID: 38156208 DOI: 10.1017/ash.2023.477
    The COVID-19 pandemic led to an initial increase in the incidence of carbapenem-resistant Enterobacterales (CRE) from clinical cultures in South-East Asia hospitals, which was unsustained as the pandemic progressed. Conversely, there was a decrease in CRE incidence from surveillance cultures and overall combined incidence. Further studies are needed for future pandemic preparedness.
  13. Huang CF, Chen JF, Reid IR, Chan WP, Ebeling PR, Langdahl B, et al.
    J Formos Med Assoc, 2023;122 Suppl 1:S14-S20.
    PMID: 36775679 DOI: 10.1016/j.jfma.2023.01.013
    Postmenopausal women are at significant risk for osteoporotic fractures due to their rapid bone loss. Half of all postmenopausal women will get an osteoporosis-related fracture over their lifetime, with 25% developing a spine deformity and 15% developing a hip fracture. By 2050, more than half of all osteoporotic fractures will occur in Asia, with postmenopausal women being the most susceptible. Early management can halt or even reverse the progression of osteoporosis. Consequently, on October 31, 2020, the Taiwanese Osteoporosis Association hosted the Asia-Pacific (AP) Postmenopausal Osteoporotic Fracture Prevention (POFP) consensus meeting, which was supported by the Asian Federation of Osteoporosis Societies (AFOS) and the Asia Pacific Osteoporosis Foundation (APOF). International and domestic experts developed ten applicable statements for the prevention of osteoporotic fractures in postmenopausal women with low bone mass or osteoporosis but no fragility fractures in the AP region. The experts advocated, for example, that postmenopausal women with a high fracture risk be reimbursed for pharmaceutical therapy to prevent osteoporotic fractures. More clinical experience and data are required to modify intervention tactics.
  14. Lee JK, Mitchell PJ, Ang SB, Mercado-Asis LB, Rey-Matias R, Li J, et al.
    Arch Osteoporos, 2024 Apr 02;19(1):24.
    PMID: 38565791 DOI: 10.1007/s11657-024-01375-6
    A survey of awareness and attitudes to the management of fragility fractures among the membership of the Asia Pacific Orthopaedic Association conducted in 2022 found considerable variation in care across the region. A Call to Action is proposed to improve acute care, rehabilitation and secondary fracture prevention across Asia Pacific.

    PURPOSE: Fragility fractures impose a substantial burden on older people and their families, healthcare systems and national economies. The current incidence of hip and other fragility fractures across the Asia Pacific region is enormous and set to escalate rapidly in the coming decades. This publication describes findings of a survey of awareness and attitudes to the management of fragility fractures among the membership of the Asia Pacific Orthopaedic Association (APOA) conducted in 2022.

    METHODS: The survey was developed as a collaboration between the Asia Pacific Osteoporosis and Fragility Fracture Society and the Asia Pacific Fragility Fracture Alliance, and included questions relating to aspects of care upon presentation, during surgery and mobilisation, secondary fracture prevention, and access to specific services.

    RESULTS: In total, 521 APOA members completed the survey and marked variation in delivery of care was evident. Notable findings included: Fifty-nine percent of respondents indicated that analgesia was routinely initiated in transit (by paramedics) or within 30 minutes of arrival in the Emergency Department. One-quarter of respondents stated that more than 80% of their patients underwent surgery within 48 hours of admission. One-third of respondents considered non-hip, non-vertebral fractures to merit assessment of future fracture risk. One-third of respondents reported the presence of an Orthogeriatric Service in their hospital, and less than a quarter reported the presence of a Fracture Liaison Service.

    CONCLUSION: A Call to Action for all National Orthopaedic Associations affiliated with APOA is proposed to improve the care of fragility fracture patients across the region.

  15. Jaganathan M, Ang BH, Ali A, Sharif SZ, Mohamad M, Mohd Khairy A, et al.
    JCO Glob Oncol, 2024 Mar;10:e2300297.
    PMID: 38484197 DOI: 10.1200/GO.23.00297
    PURPOSE: Breast cancer deaths disproportionately affect women living in low- and middle-income countries (LMICs). Patient navigation has emerged as a cost-effective and impactful approach to enable women with symptoms or suspicious mammogram findings to access timely diagnosis and patients with breast cancer to access timely and appropriate multimodality treatment. However, few studies have systematically evaluated the impact of patient navigation on timeliness of diagnosis and treatment in LMICs.

    METHODS: We established a nurse- and community-navigator-led navigation program in breast clinics of four public hospitals located in Peninsular and East Malaysia and evaluated the impact of navigation on timeliness of diagnosis and treatment.

    RESULTS: Patients with breast cancer treated at public hospitals reported facing barriers to accessing care, including having a poor recognition of breast cancer symptoms and low awareness of screening methods, and facing financial and logistics challenges. Compared with patients diagnosed in the previous year, patients receiving navigation experienced timely ultrasound (84.0% v 65.0%; P < .001), biopsy (84.0% v 78.0%; P = .012), communication of news (63.0% v 40.0%; P < .001), surgery (46% v 36%; P = .008), and neoadjuvant therapy (59% v 42%, P = .030). Treatment adherence improved significantly (98.0% v 87.0%, P < .001), and this was consistent across the network of four breast clinics.

    CONCLUSION: Patient navigation improves access to timely diagnosis and treatment for women presenting at secondary and tertiary hospitals in Malaysia.

  16. Hunter E, Salter M, Powell R, Dring A, Naithani T, Chatziioannou ME, et al.
    Cancers (Basel), 2023 May 10;15(10).
    PMID: 37345033 DOI: 10.3390/cancers15102696
    BACKGROUND: Unprecedented advantages in cancer treatment with immune checkpoint inhibitors (ICIs) remain limited to only a subset of patients. Systemic analyses of the regulatory 3D genome architecture linked to individual epigenetic and immunogenetic controls associated with tumour immune evasion mechanisms and immune checkpoint pathways reveal a highly prevalent molecular profile predictive of response to PD-1/PD-L1 ICIs. A clinical blood test based on a set of eight (8) 3D genomic biomarkers has been developed and validated on the basis of an observational trial to predict response to ICI therapy.

    METHODS: The predictive eight biomarker set is derived from prospective observational clinical trials, representing 280 treatments with Pembrolizumab, Atezolizumab, Durvalumab, Nivolumab, and Avelumab in a broad range of indications: melanoma, lung, hepatocellular, renal, breast, bladder, colon, head and neck, bone, brain, lymphoma, prostate, vulvar, and cervical cancers.

    RESULTS: The 3D genomic eight biomarker panel for response to immune checkpoint therapy achieved a high accuracy of 85%, sensitivity of 93%, and specificity of 82%.

    CONCLUSIONS: This study demonstrates that a 3D genomic approach can be used to develop a predictive clinical assay for response to PD-1/PD-L1 checkpoint inhibition in cancer patients.

  17. Lee YY, Izham N, Mohd Zulkifly MF, Mohamed Mustafar MF, Ismail AK, Mohamed Shah NFFN, et al.
    Malays J Med Sci, 2023 Jun;30(3):1-7.
    PMID: 37425382 DOI: 10.21315/mjms2023.30.3.1
    Neurogastroenterology and motility is a new but advanced subspecialty within gasteroenterology that cater to difficult, persistent and refractory gut-brain symptoms. Hospital USM has the country's first and new state-of-the art motility lab that was recently launched on the 25 May 2023, and is covered in nationwide media. Another first is the Brain-Gut Clinic, established on the 16 November 2022. The clinic is a new concept that builds on unique multiple disciplines in relation to the gut-brain axis. It is hoped that there will be more awareness on the existence of neurogastroenterology and motility among doctors and community, and that more research can be forthcoming to reduce the disease burden.
  18. Luk ADW, Lee PP, Mao H, Chan KW, Chen XY, Chen TX, et al.
    Front Immunol, 2017;8:808.
    PMID: 28747913 DOI: 10.3389/fimmu.2017.00808
    BACKGROUND: Severe combined immunodeficiency (SCID) is fatal unless treated with hematopoietic stem cell transplant. Delay in diagnosis is common without newborn screening. Family history of infant death due to infection or known SCID (FH) has been associated with earlier diagnosis.

    OBJECTIVE: The aim of this study was to identify the clinical features that affect age at diagnosis (AD) and time to the diagnosis of SCID.

    METHODS: From 2005 to 2016, 147 SCID patients were referred to the Asian Primary Immunodeficiency Network. Patients with genetic diagnosis, age at presentation (AP), and AD were selected for study.

    RESULTS: A total of 88 different SCID gene mutations were identified in 94 patients, including 49 IL2RG mutations, 12 RAG1 mutations, 8 RAG2 mutations, 7 JAK3 mutations, 4 DCLRE1C mutations, 4 IL7R mutations, 2 RFXANK mutations, and 2 ADA mutations. A total of 29 mutations were previously unreported. Eighty-three of the 94 patients fulfilled the selection criteria. Their median AD was 4 months, and the time to diagnosis was 2 months. The commonest SCID was X-linked (n = 57). A total of 29 patients had a positive FH. Candidiasis (n = 27) and bacillus Calmette-Guérin (BCG) vaccine infection (n = 19) were the commonest infections. The median age for candidiasis and BCG infection documented were 3 months and 4 months, respectively. The median absolute lymphocyte count (ALC) was 1.05 × 10(9)/L with over 88% patients below 3 × 10(9)/L. Positive FH was associated with earlier AP by 1 month (p = 0.002) and diagnosis by 2 months (p = 0.008), but not shorter time to diagnosis (p = 0.494). Candidiasis was associated with later AD by 2 months (p = 0.008) and longer time to diagnosis by 0.55 months (p = 0.003). BCG infections were not associated with age or time to diagnosis.

    CONCLUSION: FH was useful to aid earlier diagnosis but was overlooked by clinicians and not by parents. Similarly, typical clinical features of SCID were not recognized by clinicians to shorten the time to diagnosis. We suggest that lymphocyte subset should be performed for any infant with one or more of the following four clinical features: FH, candidiasis, BCG infections, and ALC below 3 × 10(9)/L.

  19. Vitamin E in Neuroprotection Study (VENUS) Investigators, Hor CP, Fung WY, Ang HA, Lim SC, Kam LY, et al.
    JAMA Neurol, 2018 04 01;75(4):444-452.
    PMID: 29379943 DOI: 10.1001/jamaneurol.2017.4609
    Importance: Management of painful diabetic peripheral neuropathy remains challenging. Most therapies provide symptomatic relief with varying degrees of efficacy. Tocotrienols have modulatory effects on the neuropathy pathway and may reduce neuropathic symptoms with their antioxidative and anti-inflammatory activities.

    Objective: To evaluate the efficacy of oral mixed tocotrienols for patients with diabetic peripheral neuropathy.

    Design, Setting, and Participants: The Vitamin E in Neuroprotection Study (VENUS) was a parallel, double-blind, placebo-controlled trial that recruited participants from January 30, 2011, to December 7, 2014, with 12 months of follow-up. This trial screened 14 289 patients with diabetes from 6 health clinics and ambulatory care units from 5 public hospitals in Malaysia. A total of 391 patients who reported neuropathic symptoms were further assessed with Total Symptom Score (TSS) and Neuropathy Impairment Score (NIS). Patients 20 years or older with a TSS of 3 or higher and an NIS of 2 or higher were recruited.

    Interventions: Patients were randomized to receive 200 mg of mixed tocotrienols twice daily or matching placebo for 12 months. Patients with hyperhomocysteinemia (homocysteine level ≥2.03 mg/L) received oral folic acid, 5 mg once daily, and methylcobalamin, 500 μg thrice daily, in both groups.

    Main Outcomes and Measures: The primary outcome was patient-reported neuropathy TSS (lancinating pain, burning pain, paresthesia, and asleep numbness) changes at 12 months. The secondary outcomes were NIS and sensory nerve conduction test result.

    Results: Of 391 eligible patients, 300 were recruited (130 [43.3%] male; mean [SD] age, 57.6 [8.9] years; mean [SD] duration of diabetes, 11.4 [7.8] years) and 229 (76.3%) completed the trial. The TSS changes between the tocotrienols and placebo groups at 12 months (-0.30; 95% CI, -1.16 to 0.56; P = .49) were similar. No significant differences in NIS (0.60; 95% CI, -1.37 to 2.65; P = .53) and sensory nerve conduction test assessments were found between both groups. In post hoc subgroup analyses, tocotrienols reduced lancinating pain among patients with hemoglobin A1C levels greater than 8% (P = .03) and normohomocysteinemia (homocysteine level <2.03 mg/L; P = .008) at 1 year. Serious adverse events in both groups were similar, except more infections were observed in the tocotrienols group (6.7% vs 0.7%, P = .04). Results reported were of modified intention-to-treat analyses.

    Conclusions and Relevance: Supplementation of oral mixed tocotrienols, 400 mg/d for 1 year, did not improve overall neuropathic symptoms. The preliminary observations on lancinating pain among subsets of patients require further exploration.

    Trial Registration: National Medical Research Registry Identifier: NMRR-10-948-7327 and clinicaltrials.gov Identifier: NCT01973400.

  20. Gunasekeran DV, Zheng F, Lim GYS, Chong CCY, Zhang S, Ng WY, et al.
    Front Med (Lausanne), 2022;9:875242.
    PMID: 36314006 DOI: 10.3389/fmed.2022.875242
    BACKGROUND: Many artificial intelligence (AI) studies have focused on development of AI models, novel techniques, and reporting guidelines. However, little is understood about clinicians' perspectives of AI applications in medical fields including ophthalmology, particularly in light of recent regulatory guidelines. The aim for this study was to evaluate the perspectives of ophthalmologists regarding AI in 4 major eye conditions: diabetic retinopathy (DR), glaucoma, age-related macular degeneration (AMD) and cataract.

    METHODS: This was a multi-national survey of ophthalmologists between March 1st, 2020 to February 29th, 2021 disseminated via the major global ophthalmology societies. The survey was designed based on microsystem, mesosystem and macrosystem questions, and the software as a medical device (SaMD) regulatory framework chaired by the Food and Drug Administration (FDA). Factors associated with AI adoption for ophthalmology analyzed with multivariable logistic regression random forest machine learning.

    RESULTS: One thousand one hundred seventy-six ophthalmologists from 70 countries participated with a response rate ranging from 78.8 to 85.8% per question. Ophthalmologists were more willing to use AI as clinical assistive tools (88.1%, n = 890/1,010) especially those with over 20 years' experience (OR 3.70, 95% CI: 1.10-12.5, p = 0.035), as compared to clinical decision support tools (78.8%, n = 796/1,010) or diagnostic tools (64.5%, n = 651). A majority of Ophthalmologists felt that AI is most relevant to DR (78.2%), followed by glaucoma (70.7%), AMD (66.8%), and cataract (51.4%) detection. Many participants were confident their roles will not be replaced (68.2%, n = 632/927), and felt COVID-19 catalyzed willingness to adopt AI (80.9%, n = 750/927). Common barriers to implementation include medical liability from errors (72.5%, n = 672/927) whereas enablers include improving access (94.5%, n = 876/927). Machine learning modeling predicted acceptance from participant demographics with moderate to high accuracy, and area under the receiver operating curves of 0.63-0.83.

    CONCLUSION: Ophthalmologists are receptive to adopting AI as assistive tools for DR, glaucoma, and AMD. Furthermore, ML is a useful method that can be applied to evaluate predictive factors on clinical qualitative questionnaires. This study outlines actionable insights for future research and facilitation interventions to drive adoption and operationalization of AI tools for Ophthalmology.

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