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  1. Asher MI, Stewart AW, Wong G, Strachan DP, García-Marcos L, Anderson HR, et al.
    Allergol Immunopathol (Madr), 2012 Sep-Oct;40(5):267-74.
    PMID: 22297190 DOI: 10.1016/j.aller.2011.11.004
    BACKGROUND: The International Study of Asthma and Allergies in Childhood (ISAAC) identified trends in the prevalence of symptoms of asthma, rhinoconjunctivitis and eczema over a seven-year period. We hypothesised that environmental influences on the three diseases are different and therefore investigated the correlation over time between trends in the prevalence of these diseases and their combinations at centre and individual level.
    METHODS: Centre level analyses were correlations between time trends in the prevalence of symptoms. At an individual level, odds ratios were calculated for associations between symptoms between Phases One and Three. We also investigated potential effect modification in the younger versus older age group; male versus female; and by average Gross National Income per capita (GNI).
    RESULTS: Both phases were completed in 66 centres in 37 countries for the 6-7 year age group and in 106 centres in 56 countries for the 13-14 year age group. We found that the correlations in time trends were stronger for the older age group than the younger one. Between symptoms of diseases, correlations of time trends were the strongest for rhinoconjunctivitis with eczema and weakest for eczema with asthma. The relationship between the three diseases was generally consistent over the seven-year period, and there was little association found with average GNI.
    CONCLUSIONS: Despite some increase in the proportion of children with symptoms of asthma, rhinoconjunctivitis and eczema, the pattern between the three diseases has not changed much, suggesting that similar factors may be affecting them at a global level.
  2. Loh LC, Abdul Samah SZ, Zainudin A, Wong GLS, Gan WH, Yusuf WS, et al.
    Med J Malaysia, 2005 Mar;60(1):62-70.
    PMID: 16250282
    Pulmonary disease is sometimes treated empirically as tuberculosis (TB) in the absence of microbial confirmation if the clinical suspicion of active TB is high. In a country of relatively high TB and low HIV burden, we retrospectively studied 107 patients (69.2% male; mean age (SD): 45 (17) years) who received empirical anti-TB treatment for intrapulmonary opacities or pleural effusions suspected of active TB in our hospitals between 1998 and 2002. The diagnosis of definite or probable 'smear-negative' pulmonary TB was made based on treatment outcome at two months with rifampicin, isoniazid, pyrazinamide and ethambutol (or streptomycin). At this end-point, 81 patients (84.4%) had both clinical and radiological improvement (definite cases), 12 (12.5%) had clinical improvement alone and 3 (3.1%) had radiological improvement alone (probable cases). Confirmation of acid-fast bacilli was subsequently obtained in 12 patients (all definite cases) from culture of initial pulmonary specimens. Eleven patients (10.5%) were diagnosed as 'non-TB' based on absence of both clinical and radiological improvement or discovery of another cause for the pulmonary condition at or before this two-month study end-point. In the 'non-TB' group, 2 had carcinoma, 2 had HIV-related pulmonary diseases, 1 had bronchiectasis, while in 6 causes were indeterminate. Six (6.3%) and 3 (27.3%) patients reported adverse effects from anti-TB drugs from the 'TB' and 'non-TB' groups respectively. Our findings suggest that empirical anti-TB treatment is an acceptable practice if clinical suspicion is high in patients coming in our region.
  3. Wong GR, Ha KO, Himratul-Aznita WH, Yang YH, Wan Mustafa WM, Yuen KM, et al.
    Oral Dis, 2014 Nov;20(8):762-7.
    PMID: 24320099 DOI: 10.1111/odi.12218
    The objective of the study was to determine the prevalence of HPV seropositivity among patients with oral squamous cell carcinoma (OSCC) and healthy individuals and to correlate the association between HPV 16 seropositivity and risk of OSCC.
  4. Chisholm A, Price DB, Pinnock H, Lee TT, Roa C, Cho SH, et al.
    NPJ Prim Care Respir Med, 2017 Jan 05;27:16089.
    PMID: 28055000 DOI: 10.1038/npjpcrm.2016.89
    REALISE Asia-an online questionnaire-based study of Asian asthma patients-identified five patient clusters defined in terms of their control status and attitude towards their asthma (categorised as: 'Well-adjusted and at least partly controlled'; 'In denial about symptoms'; 'Tolerating with poor control'; 'Adrift and poorly controlled'; 'Worried with multiple symptoms'). We developed consensus recommendations for tailoring management of these attitudinal-control clusters. An expert panel undertook a three-round electronic Delphi (e-Delphi): Round 1: panellists received descriptions of the attitudinal-control clusters and provided free text recommendations for their assessment and management. Round 2: panellists prioritised Round 1 recommendations and met (or joined a teleconference) to consolidate the recommendations. Round 3: panellists voted and prioritised the remaining recommendations. Consensus was defined as Round 3 recommendations endorsed by >50% of panellists. Highest priority recommendations were those receiving the highest score. The multidisciplinary panellists (9 clinicians, 1 pharmacist and 1 health social scientist; 7 from Asia) identified consensus recommendations for all clusters. Recommended pharmacological (e.g., step-up/down; self-management; simplified regimen) and non-pharmacological approaches (e.g., trigger management, education, social support; inhaler technique) varied substantially according to each cluster's attitude to asthma and associated psychosocial drivers of behaviour. The attitudinal-control clusters defined by REALISE Asia resonated with the international panel. Consensus was reached on appropriate tailored management approaches for all clusters. Summarised and incorporated into a structured management pathway, these recommendations could facilitate personalised care. Generalisability of these patient clusters should be assessed in other socio-economic, cultural and literacy groups and nationalities in Asia.
  5. Vijayan K, Schroder HJ, Hameed A, Hitos K, Lo W, Laurence JM, et al.
    Transplantation, 2024 Feb 16.
    PMID: 38361237 DOI: 10.1097/TP.0000000000004937
    BACKGROUND: Uncontrolled donation after circulatory death (uDCD) is a potential additional source of donor kidneys. This study reviewed uDCD kidney transplant outcomes to determine if these are comparable to controlled donation after circulatory death (cDCD).

    METHODS: MEDLINE, Cochrane, and Embase databases were searched. Data on demographic information and transplant outcomes were extracted from included studies. Meta-analyses were performed, and risk ratios (RR) were estimated to compare transplant outcomes from uDCD to cDCD.

    RESULTS: Nine cohort studies were included, from 2178 uDCD kidney transplants. There was a moderate degree of bias, as 4 studies did not account for potential confounding factors. The median incidence of primary nonfunction in uDCD was 12.3% versus 5.7% for cDCD (RR, 1.85; 95% confidence intervals, 1.06-3.23; P = 0.03, I2 = 75). The median rate of delayed graft function was 65.1% for uDCD and 52.0% for cDCD. The median 1-y graft survival for uDCD was 82.7% compared with 87.5% for cDCD (RR, 1.43; 95% confidence intervals, 1.02-2.01; P = 0.04; I2 = 71%). The median 5-y graft survival for uDCD and cDCD was 70% each. Notably, the use of normothermic regional perfusion improved primary nonfunction rates in uDCD grafts.

    CONCLUSIONS: Although uDCD outcomes may be inferior in the short-term, the long-term outcomes are comparable to cDCD.

  6. Lu M, Yao Y, Liu H, Zhang X, Li X, Liu Y, et al.
    JCI Insight, 2023 Dec 08;8(23).
    PMID: 37917215 DOI: 10.1172/jci.insight.175461
    Nipah virus (NiV), a bat-borne paramyxovirus, results in neurological and respiratory diseases with high mortality in humans and animals. Developing vaccines is crucial for fighting these diseases. Previously, only a few studies focused on the fusion (F) protein alone as the immunogen. Numerous NiV strains have been identified, including 2 representative strains from Malaysia (NiV-M) and Bangladesh (NiV-B), which differ significantly from each other. In this study, an F protein sequence with the potential to prevent different NiV strain infections was designed by bioinformatics analysis after an in-depth study of NiV sequences in GenBank. Then, a chimpanzee adenoviral vector vaccine and a DNA vaccine were developed. High levels of immune responses were detected after AdC68-F, pVAX1-F, and a prime-boost strategy (pVAX1-F/AdC68-F) in mice. After high titers of humoral responses were induced, the hamsters were challenged by the lethal NiV-M and NiV-B strains separately. The vaccinated hamsters did not show any clinical signs and survived 21 days after infection with either strain of NiV, and no virus was detected in different tissues. These results indicate that the vaccines provided complete protection against representative strains of NiV infection and have the potential to be developed as a broad-spectrum vaccine for human use.
  7. Kared H, Tan SW, Lau MC, Chevrier M, Tan C, How W, et al.
    Nat Commun, 2020 02 10;11(1):821.
    PMID: 32041953 DOI: 10.1038/s41467-020-14442-6
    The diversity of the naïve T cell repertoire drives the replenishment potential and capacity of memory T cells to respond to immune challenges. Attrition of the immune system is associated with an increased prevalence of pathologies in aged individuals, but whether stem cell memory T lymphocytes (TSCM) contribute to such attrition is still unclear. Using single cells RNA sequencing and high-dimensional flow cytometry, we demonstrate that TSCM heterogeneity results from differential engagement of Wnt signaling. In humans, aging is associated with the coupled loss of Wnt/β-catenin signature in CD4 TSCM and systemic increase in the levels of Dickkopf-related protein 1, a natural inhibitor of the Wnt/β-catenin pathway. Functional assays support recent thymic emigrants as the precursors of CD4 TSCM. Our data thus hint that reversing TSCM defects by metabolic targeting of the Wnt/β-catenin pathway may be a viable approach to restore and preserve immune homeostasis in the context of immunological history.
  8. Lau G, Yu ML, Wong G, Thompson A, Ghazinian H, Hou JL, et al.
    Hepatol Int, 2021 Oct;15(5):1031-1048.
    PMID: 34427860 DOI: 10.1007/s12072-021-10239-x
    BACKGROUND & AIM: Hepatitis B reactivation related to the use of immunosuppressive therapy remains a major cause of liver-related morbidity and mortality in hepatitis B endemic Asia-Pacific region. This clinical practice guidelines aim to assist clinicians in all disciplines involved in the use of immunosuppressive therapy to effectively prevent and manage hepatitis B reactivation.

    METHODS: All publications related to hepatitis B reactivation with the use of immunosuppressive therapy since 1975 were reviewed. Advice from key opinion leaders in member countries/administrative regions of Asian-Pacific Association for the study of the liver was collected and synchronized. Immunosuppressive therapy was risk-stratified according to its reported rate of hepatitis B reactivation.

    RECOMMENDATIONS: We recommend the necessity to screen all patients for hepatitis B prior to the initiation of immunosuppressive therapy and to administer pre-emptive nucleos(t)ide analogues to those patients with a substantial risk of hepatitis and acute-on-chronic liver failure due to hepatitis B reactivation.

  9. Karlas T, Petroff D, Sasso M, Fan JG, Mi YQ, de Lédinghen V, et al.
    Aliment Pharmacol Ther, 2018 Apr;47(7):989-1000.
    PMID: 29446106 DOI: 10.1111/apt.14529
    BACKGROUND: Liver fibrosis is often accompanied by steatosis, particularly in patients with non-alcoholic fatty liver disease (NAFLD), and its non-invasive characterisation is of utmost importance. Vibration-controlled transient elastography is the non-invasive method of choice; however, recent research suggests that steatosis may influence its diagnostic performance. Controlled Attenuation Parameter (CAP) added to transient elastography enables simultaneous assessment of steatosis and fibrosis.

    AIM: To determine how to use CAP in interpreting liver stiffness measurements.

    METHODS: This is a secondary analysis of data from an individual patient data meta-analysis on CAP. The main exclusion criteria for the current analysis were unknown aetiology, unreliable elastography measurement and data already used for the same research question. Aetiology-specific liver stiffness measurement cut-offs were determined and used to estimate positive and negative predictive values (PPV/NPV) with logistic regression as functions of CAP.

    RESULTS: Two thousand and fifty eight patients fulfilled the inclusion criteria (37% women, 18% NAFLD/NASH, 42% HBV, 40% HCV, 51% significant fibrosis ≥ F2). Youden optimised cut-offs were only sufficient for ruling out cirrhosis (NPV of 98%). With sensitivity and specificity-optimised cut-offs, NPV for ruling out significant fibrosis was moderate (70%) and could be improved slightly through consideration of CAP. PPV for significant fibrosis and cirrhosis were 68% and 55% respectively, despite specificity-optimised cut-offs for cirrhosis.

    CONCLUSIONS: Liver stiffness measurement values below aetiology-specific cut-offs are very useful for ruling out cirrhosis, and to a lesser extent for ruling out significant fibrosis. In the case of the latter, Controlled Attenuation Parameter can improve interpretation slightly. Even if cut-offs are very high, liver stiffness measurements are not very reliable for ruling in fibrosis or cirrhosis.

  10. Zhang S, Chen WJ, Sankardas MA, Ahmed WH, Liew HB, Gwon HC, et al.
    JACC Asia, 2022 Oct;2(5):559-571.
    PMID: 36518723 DOI: 10.1016/j.jacasi.2022.06.006
    BACKGROUND: Implantable cardioverter-defibrillator (ICD) implantation to prevent sudden cardiac death (SCD) in post-myocardial infarction (MI) patients varies by geography but remains low in many regions despite guideline recommendations.

    OBJECTIVES: This study aimed to characterize the care pathway of post-MI patients and understand barriers to referral for further SCD risk stratification and management in patients meeting referral criteria.

    METHODS: This prospective, nonrandomized, multi-nation study included patients ≥18 years of age, with an acute MI ≤30 days and left ventricular ejection fraction <50% ≤14 days post-MI. The primary endpoint was defined as the physician's decision to refer a patient for SCD stratification and management.

    RESULTS: In total, 1,491 post-MI patients were enrolled (60.2 ± 12.0 years of age, 82.4% male). During the study, 26.7% (n = 398) of patients met criteria for further SCD risk stratification; however, only 59.3% of those meeting criteria (n = 236; 95% CI: 54.4%-64.0%) were referred for a visit. Of patients referred for SCD risk stratification and management, 94.9% (n = 224) attended the visit of which 56.7% (n =127; 95% CI: 50.1%-63.0%) met ICD indication criteria. Of patients who met ICD indication criteria, 14.2% (n = 18) were implanted.

    CONCLUSIONS: We found that ∼40% of patients meeting criteria were not referred for further SCD risk stratification and management and ∼85% of patients who met ICD indications did not receive a guideline-directed ICD. Physician and patient reasons for refusing referral to SCD risk stratification and management or ICD implant varied by geography suggesting that improvement will require both physician- and patient-focused approaches. (Improve Sudden Cardiac Arrest [SCA] Bridge Study; NCT03715790).

  11. Yelamanchi SD, Tyagi A, Mohanty V, Dutta P, Korbonits M, Chavan S, et al.
    OMICS, 2018 12;22(12):759-769.
    PMID: 30571610 DOI: 10.1089/omi.2018.0160
    The pituitary function is regulated by a complex system involving the hypothalamus and biological networks within the pituitary. Although the hormones secreted from the pituitary have been well studied, comprehensive analyses of the pituitary proteome are limited. Pituitary proteomics is a field of postgenomic research that is crucial to understand human health and pituitary diseases. In this context, we report here a systematic proteomic profiling of human anterior pituitary gland (adenohypophysis) using high-resolution Fourier transform mass spectrometry. A total of 2164 proteins were identified in this study, of which 105 proteins were identified for the first time compared with high-throughput proteomic-based studies from human pituitary glands. In addition, we identified 480 proteins with secretory potential and 187 N-terminally acetylated proteins. These are the first region-specific data that could serve as a vital resource for further investigations on the physiological role of the human anterior pituitary glands and the proteins secreted by them. We anticipate that the identification of previously unknown proteins in the present study will accelerate biomedical research to decipher their role in functioning of the human anterior pituitary gland and associated human diseases.
  12. Ji F, Tran S, Ogawa E, Huang CF, Suzuki T, Wong YJ, et al.
    J Clin Transl Hepatol, 2024 Jul 28;12(7):646-658.
    PMID: 38993510 DOI: 10.14218/JCTH.2024.00089
    BACKGROUND AND AIMS: As practice patterns and hepatitis C virus (HCV) genotypes (GT) vary geographically, a global real-world study from both East and West covering all GTs can help inform practice policy toward the 2030 HCV elimination goal. This study aimed to assess the effectiveness and tolerability of DAA treatment in routine clinical practice in a multinational cohort for patients infected with all HCV GTs, focusing on GT3 and GT6.

    METHODS: We analyzed the sustained virological response (SVR12) of 15,849 chronic hepatitis C patients from 39 Real-World Evidence from the Asia Liver Consortium for HCV clinical sites in Asia Pacific, North America, and Europe between 07/01/2014-07/01/2021.

    RESULTS: The mean age was 62±13 years, with 49.6% male. The demographic breakdown was 91.1% Asian (52.9% Japanese, 25.7% Chinese/Taiwanese, 5.4% Korean, 3.3% Malaysian, and 2.9% Vietnamese), 6.4% White, 1.3% Hispanic/Latino, and 1% Black/African-American. Additionally, 34.8% had cirrhosis, 8.6% had hepatocellular carcinoma (HCC), and 24.9% were treatment-experienced (20.7% with interferon, 4.3% with direct-acting antivirals). The largest group was GT1 (10,246 [64.6%]), followed by GT2 (3,686 [23.2%]), GT3 (1,151 [7.2%]), GT6 (457 [2.8%]), GT4 (47 [0.3%]), GT5 (1 [0.006%]), and untyped GTs (261 [1.6%]). The overall SVR12 was 96.9%, with rates over 95% for GT1/2/3/6 but 91.5% for GT4. SVR12 for GT3 was 95.1% overall, 98.2% for GT3a, and 94.0% for GT3b. SVR12 was 98.3% overall for GT6, lower for patients with cirrhosis and treatment-experienced (TE) (93.8%) but ≥97.5% for treatment-naive patients regardless of cirrhosis status. On multivariable analysis, advanced age, prior treatment failure, cirrhosis, active HCC, and GT3/4 were independent predictors of lower SVR12, while being Asian was a significant predictor of achieving SVR12.

    CONCLUSIONS: In this diverse multinational real-world cohort of patients with various GTs, the overall cure rate was 96.9%, despite large numbers of patients with cirrhosis, HCC, TE, and GT3/6. SVR12 for GT3/6 with cirrhosis and TE was lower but still excellent (>91%).

  13. Bousquet J, Schünemann HJ, Sousa-Pinto B, Zuberbier T, Togias A, Samolinski B, et al.
    PMID: 38971567 DOI: 10.1016/j.jaip.2024.06.040
    The traditional healthcare model is focused on diseases (medicine and natural science) and does not acknowledge patients' resources and abilities to be experts in their own life based on their lived experiences. Improving healthcare safety, quality and coordination, as well as quality of life, are important aims in the care of patients with chronic conditions. Person-centred care needs to ensure that people's values and preferences guide clinical decisions. This paper reviews current knowledge to develop (i) digital care pathways for rhinitis and asthma multimorbidity and (ii) digitally-enabled person-centred care (1). It combines all relevant research evidence, including the so-called real-world evidence, with the ultimate goal to develop digitally-enabled, patient-centred care. The paper includes (i) Allergic Rhinitis and its Impact on Asthma (ARIA), a two-decade journey, (ii) Grading of Recommendations, Assessment, Development and Evaluation (GRADE), the evidence-based model of guidelines in airway diseases, (iii) mHealth impact on airway diseases, (iv) from guidelines to digital care pathways, (v) embedding Planetary Health, (vi) novel classification of rhinitis and asthma, (vi) embedding real-life data with population-based studies, (vii) the ARIA-EAACI strategy for the management of airway diseases using digital biomarkers, (viii) Artificial Intelligence, (ix) the development of digitally-enabled ARIA Person-Centred Care and (x) the political agenda. The ultimate goal is to propose ARIA 2024 guidelines centred around the patient in order to make them more applicable and sustainable.
  14. Klionsky DJ, Abdelmohsen K, Abe A, Abedin MJ, Abeliovich H, Acevedo Arozena A, et al.
    Autophagy, 2016;12(1):1-222.
    PMID: 26799652 DOI: 10.1080/15548627.2015.1100356
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