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  1. Leong LH, Yap YC, Lo ZZ
    PMID: 37449275 DOI: 10.51866/cr.370
    Ischaemic heart disorders are among the leading causes of mortality worldwide. There has been a growing occurrence of heart disease among young adults. Thus, acute myocardial infarction (MI) should be considered in all patients with central chest pain. Herein, we report the case of a young, fit, active smoker with underlying dyslipidaemia presenting with acute MI, characterised by dynamic changes in lead aVL wherein T wave flattening progressed to inversion, suggestive of early reciprocal changes. Soon after, electrocardiogram (ECG) revealed ST elevation in leads III and aVF, indicative of acute inferior wall MI. Subsequently, coronary angiogram showed right coronary artery occlusion. This case report highlights the importance of serial ECGs in patients who present with chest pain and have a high clinical suspicion for acute MI with normal or inconclusive ECG findings. Measurement of highly sensitive serum troponin based on a 1- or 3-h protocol is important in diagnosing acute MI but not ST-elevation MI. An early sign of inferior wall MI may be a new T wave inversion in lead aVL.
  2. Khoo JJ, Pee S, Thevarajah B, Yap YC, Chin CK
    J Paediatr Child Health, 2005 Jan-Feb;41(1-2):31-5.
    PMID: 15670221 DOI: 10.1111/j.1440-1754.2005.00532.x
    OBJECTIVES: To determine the pattern of renal histology, clinical outcome of children with lupus nephritis and to identify any associated risk factors predicting renal failure in these children.
    METHODS: Retrospectively, 27 children under 16 years of age with lupus nephritis who had renal biopsies done at Sultanah Aminah Hospital Johor, Malaysia from 1994 to 2002 were studied. The renal histology was graded according to WHO classification system (1982). The medical records, laboratory data and the clinical outcome of the patients were studied.
    RESULTS: There were 24 cases of WHO Class IV, two cases of WHO Class II and a case of WHO Class V. Twenty children were in the good renal outcome group while six children progressed into the poor renal outcome group and required renal replacement. One child was lost to follow-up. All six children in the poor renal outcome group had WHO Class IV histology. The 5-year patient and renal survival rates were 84% and 75%, respectively. Age, sex, activity and chronicity indices in the renal histology, anaemia, elevated serum creatinine, depressed levels of C3 and C4, heavy proteinuria or presence of urinary active sediments were not associated with progression to renal failure.
    CONCLUSIONS: Presently, children with lupus nephritis appeared to have better patient and renal survival rates. Assessment of renal histology in these children was important for diagnosis, treatment and probably prognosis. In this study, there was a 25% incidence of loss of renal function over 5 years in children with WHO Class IV renal histology.
  3. Khoo JJ, Pee S, Thevarajah B, Yap YC, Chin CK
    Med J Malaysia, 2004 Jun;59(2):218-25.
    PMID: 15559173 MyJurnal
    Background: There has been no published study of biopsy proven childhood glomerulonephritis in Malaysia.
    Objectives: To determine the pattern of childhood glomerulonephritis in Johor, Malaysia from a histopathological perspective and the various indications used for renal biopsy in children.
    Materials and methods: Retrospective study was done of all renal biopsies from children under 16 years of age, received in Sultanah Aminah Hospital, Johor between 1994 and 2001. The histopathological findings were reviewed to determine the pattern of biopsy proven glomerulonephritis. The indications of biopsy, mode of therapy given after biopsy and the clinical outcome were studied.
    Results: 123 adequate biopsies were received, 9 children had repeated biopsies. Of the 113 biopsies, minimal change disease formed the most common histopathological diagnosis (40.7%) while lupus nephritis formed the most common secondary glomerulonephritis (23.0%). The main indications for biopsy were nephrotic syndrome (50.8%), lupus nephritis (25.4%) and renal impairment (13.1%). The mode of therapy was changed in 59.8% of the children. Of 106 patients followed up, 84 children were found to have normal renal function in remission or on treatment. 4 patients developed chronic renal impairment and 16 reached end stage renal disease. Five of the 16 children with end stage disease had since died while 11 were on renal replacement therapy. another 2 patients died of other complications.
    Conclusions: The pattern of childhood GN in our study tended to reflect the more severe renal parenchymal diseases in children and those requiring more aggressive treatment. This was because of our criteria of selection (indication) for renal biopsy. Renal biopsy where performed appropriately in selected children may not only be a useful investigative tool for histological diagnosis and prognosis but may help clinicians plan the optimal therapy for these children.
  4. Karmila AB, Yap YC, Appadurai M, Oh L, Fazarina M, Abd Ghani F, et al.
    Fetal Pediatr Pathol, 2021 Apr;40(2):113-120.
    PMID: 31707902 DOI: 10.1080/15513815.2019.1686788
    Introduction: Denys-Drash Syndrome (DDS) consists of a triad of pseudohermaphroditism, Wilms'tumor and nephropathy. This condition may manifest as a complete triad or in an incomplete form; with either one or a combination of the above features. The characteristic glomerular abnormality in DDS is diffuse mesangial sclerosis (DMS).Case report: We report two cases of DDS with focal membranoproliferative glomerulonephritis (MPGN). Both of our cases were males with ambiguous genitalia. They had a similar heterozygous germline mutation in exon 9 of WT1, c.1180C>T, p.R394W; a known mutation hotspot for DDS. Case 1 had nephropathy at the age of 4 years and Case 2 at 2.5 years with different rates of progression to end-stage renal failure. Conclusion: Our findings, in combination with other reports, illustrate the clinicopathological heterogeneity of DDS. There are no universal recommendations for optimal management of patients with DDS due to the inability to accurately predict affected individuals' progress.
  5. Yahya R, Bavanandan S, Yap YC, Jazilah W, Shaariah W, Wong HS, et al.
    Med J Malaysia, 2008 Sep;63 Suppl C:18-9.
    PMID: 19230242
  6. Lim SC, Yap YC, Barmania S, Govender V, Danhoundo G, Remme M
    Sex Reprod Health Matters, 2020 Dec;28(2):1842153.
    PMID: 33236973 DOI: 10.1080/26410397.2020.1842153
    Despite increasing calls to integrate and prioritise sexual and reproductive health (SRH) services in universal health coverage (UHC) processes, several SRH services have remained a low priority in countries' UHC plans. This study aims to understand the priority-setting process of SRH interventions in the context of UHC, drawing on the Malaysian experience. A realist evaluation framework was adopted to examine the priority-setting process for three SRH tracer interventions: pregnancy, safe delivery and post-natal care; gender-based violence (GBV) services; and abortion-related services. The study used a qualitative multi-method design, including a literature and document review, and 20 in-depth key informant interviews, to explore the context-mechanism-outcome configurations that influenced and explained the priority-setting process. Four key advocacy strategies were identified for the effective prioritisation of SRH services, namely: (1) generating public demand and social support, (2) linking SRH issues with public agendas or international commitments, (3) engaging champions that are internal and external to the public health sector, and (4) reframing SRH issues as public health issues. While these strategies successfully triggered mechanisms, such as mutual understanding and increased buy-in of policymakers to prioritise SRH services, the level and extent of prioritisation was affected by both inner and outer contextual factors, in particular the socio-cultural and political context. Priority-setting is a political decision-making process that reflects societal values and norms. Efforts to integrate SRH services in UHC processes need both to make technical arguments and to find strategies to overcome barriers related to societal values (including certain socio-cultural and religious norms). This is particularly important for sensitive SRH services, like GBV and safe abortion, and for certain populations.
  7. Bavanandan S, Yap YC, Ahmad G, Wong HS, Azmi S, Goh A
    Transplant Direct, 2015 Nov;1(10):e45.
    PMID: 27500211 DOI: 10.1097/TXD.0000000000000553
    Kidney transplantation is the optimal therapy for the majority of patients with end-stage renal disease. However, the cost and health outcomes of transplantation have not been assessed in a middle-income nation with a low volume of transplantation, such as Malaysia.

    AIM AND METHODS: This study used microcosting methods to determine the cost and health outcomes of living and deceased donor kidney transplantation in adult and pediatric recipients. The perspective used was from the Ministry of Health Malaysia. Cost-effectiveness measures were cost per life year (LY) and cost per quality-adjusted LYs. The time horizon was the lifetime of the transplant recipient from transplant to death.

    RESULTS: Records of 206 KT recipients (118 adults and 88 children) were obtained for microcosting. In adults, discounted cost per LY was US $8609(Malaysian Ringgit [RM]29 482) and US $13 209(RM45 234) for living-donor kidney transplant (LKT) and deceased donor kidney transplant (DKT), respectively, whereas in children, it was US $10 485(RM35 905) and US $14 985(RM51 317), respectively. Cost per quality-adjusted LY in adults was US $8826 (RM30 224) for LKT and US $13 592(RM46 546) for DKT. Total lifetime discounted costs of adult transplants were US $119 702 (RM409 921) for LKT, US $147 152 (RM503 922) for DKT. Total costs for pediatric transplants were US $154 841(RM530 252) and US $159 313(RM545 566) for the 2 categories respectively.

    CONCLUSIONS: Both LKT and DKT are economically favorable for Malaysian adult and pediatric patients with ESRD and result in improvement in quality of life.

  8. Abu Bakar K, Khalil K, Lim YN, Yap YC, Appadurai M, Sidhu S, et al.
    Front Pediatr, 2020;8:164.
    PMID: 32351921 DOI: 10.3389/fped.2020.00164
    Background: Adrenal insufficiency can result from impaired functions at all levels of hypothalamic-pituitary-adrenal (HPA) axis. We here studied risk factors associated with adrenal insufficiency in children receiving prolonged exogenous steroid treatment for nephrotic syndrome. Method:We performed low-dose Synacthen tests (LDSTs, 0.5 μg/m2) in children with steroid-sensitive nephrotic syndrome 4-6 weeks after discontinuation of the corticosteroid therapy. We measured early morning serum cortisol levels at baseline and at intervals of 10, 20, 30, and 60 min following the stimulation test. We defined normal HPA axis stimulation responses as those with peak cortisol cut-off values >550 nmol/L. Result:We enrolled 37 children for this study research. All children enrolled had normal early morning cortisol levels. However, 13 (35.1%) demonstrated HPA axis suppression (by LDST) 4-+6 weeks after discontinuation of oral prednisolone. Nephrotic syndrome diagnosed before 5 years of age (OR, 0.75; 95% CI, 0.57-0.99; p = 0.043), and steroid-dependence [OR, 5.58; 95% confidence interval (CI), 1.06-29.34; p = 0.042] were associated with increased risk of developing adrenal suppression after steroid discontinuation. Conclusion:HPA axis suppression, may go unnoticed without proper screening. A normal early morning cortisol level (275-555 nmol/L) does not exclude adrenal insufficiency in children with steroid-sensitive nephrotic syndrome. Further screening with LDSTs, particularly in children younger than 5 years at diagnosis, may be warranted.
  9. Kamath N, Borzych-Dużałka D, Kaur A, Neto G, Arbeiter K, Yap YC, et al.
    Pediatr Nephrol, 2023 Dec;38(12):4111-4118.
    PMID: 37405492 DOI: 10.1007/s00467-023-05995-x
    BACKGROUND: The guidelines for training of patients and caregivers to perform home peritoneal dialysis (PD) uniformly include recommendations pertaining to the prevention of peritonitis. The objective of this study conducted by the International Pediatric Peritoneal Dialysis Network (IPPN) was to investigate the training practices for pediatric PD and to evaluate the impact of these practices on the peritonitis and exit-site infection (ESI) rate.

    METHODS: A questionnaire regarding details of the PD program and training practices was distributed to IPPN member centers, while peritonitis and ESI rates were either derived from the IPPN registry or obtained directly from the centers. Poisson univariate and multivariate regression was used to determine the training-related peritonitis and ESI risk factors.

    RESULTS: Sixty-two of 137 centers responded. Information on peritonitis and ESI rates were available from fifty centers. Training was conducted by a PD nurse in 93.5% of centers, most commonly (50%) as an in-hospital program. The median total training time was 24 hours, with a formal assessment conducted in 88.7% and skills demonstration in 71% of centers. Home visits were performed by 58% of centers. Shorter (

  10. Borzych-Duzalka D, Shroff R, Ariceta G, Yap YC, Paglialonga F, Xu H, et al.
    Am J Kidney Dis, 2019 08;74(2):193-202.
    PMID: 31010601 DOI: 10.1053/j.ajkd.2019.02.014
    RATIONALE & OBJECTIVE: Arteriovenous fistulas (AVFs) have been recommended as the preferred vascular access for pediatric patients on maintenance hemodialysis (HD), but data comparing AVFs with other access types are scant. We studied vascular access choice, placement, complications, and outcomes in children.

    STUDY DESIGN: Prospective observational cohort study.

    SETTING & PARTICIPANTS: 552 children and adolescents from 27 countries on maintenance HD followed up prospectively by the International Pediatric HD Network (IPHN) Registry between 2012 and 2017.

    PREDICTOR: Type of vascular access: AVF, central venous catheter (CVC), or arteriovenous graft.

    OUTCOME: Infectious and noninfectious vascular access complication rates, dialysis performance, biochemical and hematologic parameters, and clinical outcomes.

    ANALYTICAL APPROACH: Univariate and multivariable linear mixed models, generalized linear mixed models, and proportional hazards models; cumulative incidence functions.

    RESULTS: During 314 cumulative patient-years, 628 CVCs, 225 AVFs, and 17 arteriovenous grafts were placed. One-third of the children with an AVF required a temporary CVC until fistula maturation. Vascular access choice was associated with age and expectations for early transplantation. There was a 3-fold higher living related transplantation rate and lower median time to transplantation of 14 (IQR, 6-23) versus 20 (IQR, 14-36) months with CVCs compared with AVFs. Higher blood flow rates and Kt/Vurea were achieved with AVFs than with CVCs. Infectious complications were reported only with CVCs (1.3/1,000 catheter-days) and required vascular access replacement in 47%. CVC dysfunction rates were 2.5/1,000 catheter-days compared to 1.2/1,000 fistula-days. CVCs required 82% more revisions and almost 3-fold more vascular access replacements to a different site than AVFs (P<0.001).

    LIMITATIONS: Clinical rather than population-based data.

    CONCLUSIONS: CVCs are the predominant vascular access choice in children receiving HD within the IPHN. Age-related anatomical limitations and expected early living related transplantation were associated with CVC use. CVCs were associated with poorer dialysis efficacy, higher complication rates, and more frequent need for vascular access replacement. Such findings call for a re-evaluation of pediatric CVC use and practices.

  11. Ploos van Amstel S, Noordzij M, Borzych-Duzalka D, Chesnaye NC, Xu H, Rees L, et al.
    Am J Kidney Dis, 2021 09;78(3):380-390.
    PMID: 33549627 DOI: 10.1053/j.ajkd.2020.11.031
    RATIONALE & OBJECTIVE: Research on pediatric kidney replacement therapy (KRT) has primarily focused on Europe and North America. In this study, we describe the mortality risk of children treated with maintenance peritoneal dialysis (MPD) in different parts of the world and characterize the associated demographic and macroeconomic factors.

    STUDY DESIGN: Prospective cohort study.

    SETTING & PARTICIPANTS: Patients younger than 19 years at inclusion into the International Pediatric Peritoneal Dialysis Network registry, who initiated MPD between 1996 and 2017.

    EXPOSURE: Region as primary exposure (Asia, Western Europe, Eastern Europe, Latin America, North America, and Oceania). Other demographic, clinical, and macroeconomic (4 income groups based on gross national income) factors also were studied.

    OUTCOME: All-cause MPD mortality.

    ANALYTICAL APPROACH: Patients were observed for 3 years, and the mortality rates in different regions and income groups were calculated. Cause-specific hazards models with random effects were fit to calculate the proportional change in variance for factors that could explain variation in mortality rates.

    RESULTS: A total of 2,956 patients with a median age of 7.8 years at the start of KRT were included. After 3 years, the overall probability of death was 5%, ranging from 2% in North America to 9% in Eastern Europe. Mortality rates were higher in low-income countries than in high-income countries. Income category explained 50.1% of the variance in mortality risk between regions. Other explanatory factors included peritoneal dialysis modality at start (22.5%) and body mass index (11.1%).

    LIMITATIONS: The interpretation of interregional survival differences as found in this study may be hampered by selection bias.

    CONCLUSIONS: This study shows that the overall 3-year patient survival on pediatric MPD is high, and that country income is associated with patient survival.

  12. Lu L, Yap YC, Nguyen DQ, Chan YH, Ng JL, Zhang YC, et al.
    Clin Genet, 2022 Jan 22.
    PMID: 35064937 DOI: 10.1111/cge.14116
    Multinational studies have reported monogenic etiologies in 25%-30% of children with steroid-resistant nephrotic syndrome. Such large studies are lacking in Asia. We established Deciphering Diversities: Renal Asian Genetics Network (DRAGoN) and aimed to describe the genetic and clinical spectrums in Asians. We prospectively studied a cohort of 183 probands with suspected genetic glomerulopathies from South and Southeast Asia, of whom 17% had positive family history. Using multi-gene panel sequencing, we detected pathogenic variants in 26 (14%) probands, of whom one-third had COL4A4 or COL4A5 variants (n = 9, 5%). Of those with COL4A5 defects, only 25% had features suggestive of Alport syndrome. Besides traditional predictors for genetic disease (positive family history and extrarenal malformations), we identified novel predictors, namely older age (6.2 vs. 2.4 years; p = 0.001), hematuria (OR 5.6; 95% CI 2.1-14.8; p 60% when a second risk factor (positive family history or extrarenal manifestation) co-existed. The genetic spectrum of glomerulopathies appears different in Asia. Collagen IV genes may be included in sequencing panels even when suggestive clinical features are absent.
  13. Rohner K, Marlais M, Ahn YH, Ali A, Alsharief A, Novak AB, et al.
    PMID: 38211969 DOI: 10.1093/ndt/gfae009
    BACKGROUND AND HYPOTHESIS: IgA vasculitis with nephritis (IgAVN) is the most common vasculitis in children. Treatment recommendations are, due to a lack of evidence, based on expert opinion resulting in variation. The aim of this study was to describe clinical presentation, treatment and outcome of an extremely large cohort of children with biopsy proven IgAVN to identify prognostic risk factors and signals of treatment efficacy.

    METHODS: Retrospective data were collected on 1148 children with biopsy proven IgAVN between 2005 and 2019 from 41 international paediatric nephrology centres across 25 countries and analyzed using multivariate analysis. The primary outcome was estimated glomerular filtration rate (eGFR) and persistent proteinuria at last follow up.

    RESULTS: The median follow up was 3.7 years (IQR 2-6.2). At last follow up, 29% of patients had an eGFR 

  14. Aad G, Abbott B, Abeling K, Abicht NJ, Abidi SH, Aboulhorma A, et al.
    Phys Rev Lett, 2024 Jan 12;132(2):021803.
    PMID: 38277607 DOI: 10.1103/PhysRevLett.132.021803
    The first evidence for the Higgs boson decay to a Z boson and a photon is presented, with a statistical significance of 3.4 standard deviations. The result is derived from a combined analysis of the searches performed by the ATLAS and CMS Collaborations with proton-proton collision datasets collected at the CERN Large Hadron Collider (LHC) from 2015 to 2018. These correspond to integrated luminosities of around 140  fb^{-1} for each experiment, at a center-of-mass energy of 13 TeV. The measured signal yield is 2.2±0.7 times the standard model prediction, and agrees with the theoretical expectation within 1.9 standard deviations.
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