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Fulltext Malaysian children with spina bifida: relationship between functional outcome and level of lesion

Ong LC, Lim YN, Sofiah A

Singapore Med J, 2002 Jan;43(1):12-7.
PMID: 12008770

To determine the relationship between spinal lesion level and functional outcome in children with spina bifida.
Review article: Use of renal registry data for research, health-care planning and quality improvement: what can we learn from registry data in the Asia-Pacific region?

Lim TO, Goh A, Lim YN, Morad Z

Nephrology (Carlton), 2008 Dec;13(8):745-52.
PMID: 19154324 DOI: 10.1111/j.1440-1797.2008.01044.x

We review renal registry data from the Asia-Pacific region with an emphasis on their uses in health care and in dialysis care in particular. The review aims to demonstrate the information value of registry data. While renal registry provides a useful data resource for epidemiological research, there are severe methodological limitations in its application for analytical or therapeutic research. However, it is the use of renal registry data for public health and health-care management purposes that registry really comes into its own, and it is primarily for these that governments have invested in national patient and disease registries. We apply data from several renal registries in the Asia-Pacific region to illustrate its wide application for planning dialysis services, for evaluating dialysis practices and health outcomes, with a view to improving the quality of dialysis care. In the course of preparing the review, we have found that the quality and accessibility of renal registry data were highly variable across the region. Given the value of renal registry, every country in the Asia-Pacific region should establish one or should ensure that their current registries are better resourced and developed. Greater data sharing and collaboration among registries in the region could help advance the nephrology to serve our patients better.
Peritoneal dialysis in Malaysia

Morad Z, Lee DG, Lim YN, Tan PC

Perit Dial Int, 2005 9 24;25(5):426-31.
PMID: 16178472
Anthropometric and growth assessment of children receiving renal replacement therapy in Malaysia

Karupaiah T, Chooi CH, Lim YN, Morad Z

J Ren Nutr, 2002 Apr;12(2):113-21.
PMID: 11953925

To report on the anthropometric and growth status of children receiving renal replacement therapy (RRT) in Malaysia.
Fulltext Neurological manifestations of children with systemic lupus erythematosus

Loh WF, Hussain IMI, Soffiah A, Lim YN

Med J Malaysia, 2000 Dec;55(4):459-63.
PMID: 11221157

In a cross-sectional study of 21 children with Systemic Lupus Erythematosus, 15 (71%) were found to have neuropsychiatric manifestations. The most common finding was generalised seizures (42.8%) followed by encephalopathy (19%) and hallucinations (19%). One child (4.76%) had hemichorea. In 3 children neurological manifestations were the first symptom of SLE. Computerised Axial Tomograms (CAT scans) showed cerebral atrophy in 7 of 12 scans available for review. Ten children had abnormal EEGs. Although none of the children had clinical evidence of a peripheral neuropathy, 8 had neurophysiological evidence of a neuropathy. One child died of intracranial haemorrhage. Six children had residual neuropsychiatric sequalae.
Fulltext How public and private reforms dramatically improved access to dialysis therapy in Malaysia

Lim TO, Goh A, Lim YN, Mohamad Zaher ZM, Suleiman AB

Health Aff (Millwood), 2010 Dec;29(12):2214-22.
PMID: 21134922 DOI: 10.1377/hlthaff.2009.0135

Between 1990 and 2005, dialysis treatment rates in Malaysia increased more than eightfold. Dialysis treatment reached a level comparable to rates in developed countries. This remarkable transformation was brought about in large part by the Malaysian government's large-scale purchase of dialysis services from the highly competitive private sector. This paper traces a series of public- and private-sector reforms that dramatically increased access to dialysis for patients with kidney failure from 13 per million people in the population in 1990 to 119 per million in 2005. Not all developing countries have had uniformly positive experiences with private-sector participation in health care. However, our data suggest that strong participation by the private sector in Malaysia has helped make for a stronger health care system as well as healthier patients. Yet the policy decisions that enabled the private sector to participate fully in providing dialysis have not been repeated with other medical services.
Fulltext A report of the Malaysian dialysis registry of the National Renal Registry, Malaysia

Lim YN, Lim TO, Lee DG, Wong HS, Ong LM, Shaariah W, et al.

Med J Malaysia, 2008 Sep;63 Suppl C:5-8.
PMID: 19230240

The Malaysian National Renal Registry was set up in 1992 to collect data for patients on renal replacement therapy (RRT). We present here the report of the Malaysian dialysis registry. The objectives of this papar are: (1) To examine the overall provision of dialysis treatment in Malaysia and its trend from 1980 to 2006. (2) To assess the treatment rate according to the states in the country. (3) To describe the method, location and funding of dialysis. (4) To characterise the patients accepted for dialysis treatment. (5) To analyze the outcomes of the dialysis treatment. Data on patients receiving dialysis treatment were collected at initiation of dialysis, at the time of any significant outcome, as well as yearly. The number of dialysis patients increased from 59 in 1980 to almost 15,000 in 2006. The dialysis acceptance rate increased from 3 per million population in 1980 to 116 per million population in 2006, and the prevalence rate from 4 to 550 per million population over the same period. The economically advantaged states of Malaysia had much higher dialysis treatment rates compared to the less economically advanced states. Eighty to 90% of new dialysis patients were accepted into centre haemodialysis (HD), and the rest into the chronic ambulatory peritoneal dialysis (CAPD) programme. The government provided about half of the funding for dialysis treatment. Patients older than 55 years accounted for the largest proportion of new patients on dialysis since the 1990s. Diabetes mellitus has been the main cause of ESRD and accounted for more than 50% of new ESRD since 2002. Annual death rate averaged about 10% on HD and 15% on CAPD. The unadjusted 5-year patient survival on both HD and CAPD was about 80%. Fifty percent of dialysis patients reported very good median QoL index score. About 70% of dialysis patients were about to work full or part time. There has been a very rapid growth of dialysis provision in Malaysia particularly in the older age groups. ESRD caused by diabetes mellitus, despite being a preventable and treatable cause of ESRD--has increased and accounted for more than 50% of incident dialysis patients. Death and survival rates on dialysis are comparable to those from other countries.
Fulltext Adrenal Insufficiency in Children With Nephrotic Syndrome on Corticosteroid Treatment

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.
A randomized, multicenter, open-label trial to establish therapeutic equivalence between the Carex and ultra disconnect systems in patients on continuous ambulatory peritoneal dialysis

Ong LM, Lim TO, Hooi LS, Morad Z, Tan PC, Wong HS, et al.

Perit Dial Int, 2003 Dec;23 Suppl 2:S139-43.
PMID: 17986534

OBJECTIVE: In the present study, we undertook to establish therapeutic equivalence with respect to peritonitis and technique failure between the Carex disconnect system (B. Braun Carex, Mirandola, Italy) and the standard Ultra system (Baxter Healthcare, Tokyo, Japan) in patients on continuous ambulatory peritoneal dialysis (CAPD).
DESIGN: This multicenter, parallel group, randomized controlled trial involved 363 prevalent CAPD patients from 8 centers. The primary endpoint was peritonitis rate; secondary endpoints were technique failure and technical problems encountered. The duration of the evaluation was 1 year.
RESULTS: The risk of peritonitis on Carex varied between the centers. We found a significant treatment-center interaction effect (likelihood ratio test: p = 0.03). The incidence rate ratio (IRR) of peritonitis on Carex as compared with Ultra ranged from 0.4 to 7.2. In two centers, Carex was inferior to Ultra with regard to peritonitis; but, in five centers, the results were inconclusive. Equivalence was not demonstrated in any center. The overall rate of peritonitis in the Carex group was twice that in the Ultra group [IRR: 2.18; 95% confidence interval (CI): 1.51 to 3.14]. Technique failure and technical problems were more common with the Carex system. Technique failure rate at 1 year was 44% in the Carex group and 22% in the Ultra group.
CONCLUSIONS: Equivalence between the Carex disconnect system and the Ultra disconnect system could not be demonstrated. The risk of peritonitis on Carex varied significantly between centers.
Fulltext Cost effectiveness evaluation of the Ministry of Health Malaysia dialysis programme

Lim TO, Lim YN, Wong HS, Ahmad G, Singam TS, Morad Z, et al.

Med J Malaysia, 1999 Dec;54(4):442-52.
PMID: 11072461

We determine the cost effectiveness of centre and home haemodialysis (HD), continuous ambulatory peritoneal dialysis (CAPD) and intermittent peritoneal dialysis (IPD) treatment in the Ministry of Health (MOH) programme. The viewpoint taken for this evaluation is that of MOH. Cost categories identified were capital cost, dialysis operational cost, medical cost and general hospital cost. Cost estimates were mostly based on actual resource utilisation. Life years saved were estimated based on Dialysis Registry data on 2480 HD and 732 CAPD patients. Overall, the cost-effectiveness ratio (CER) of centre HD was RM21620/life year saved. Those of home HD, CAPD and IPD were RM23375, RM30469 and RM36016 respectively. Sensitivity analyses did not change the ranking of the CER. We conclude the MOH dialysis programme was cost-effective, and among the various dialysis modalities centre HD was the most cost-effective.
Fulltext Outcome assessment of the Ministry of Health Malaysia dialysis programme

Lim TO, Lim YN, Wong HS, Ahmad G, Singam TS, Morad Z, et al.

Med J Malaysia, 1999 Dec;54(4):459-70.
PMID: 11072463

We describe the outcomes on haemodialysis (HD) and continuous ambulatory peritoneal dialysis (CAPD) provided by the Ministry of Health (MOH). The assessment was based on data from the Malaysian Dialysis Registry on 2480 HD and 732 CAPD patients who commenced dialysis between 1980 and 1996. Young patients (age < 40) have remarkable long term survival (life expectancies of 16 years on HD, 18 years on CAPD). Adjusting for background mortality, relative survival of older patients was as good as younger ones. Diabetics did poorly. 52% of HD and 26% of CAPD patients were employed in 1996. 71% of HD patients scored 10(normal) on QL index (a measure of quality of life) while 60% of CAPD patients have similar score. Differences in rehabilitation and QL index scores by age, gender and diabetes were also observed. Outcomes of dialysis in the MOH programme are reassuring.
Fulltext IPNA clinical practice recommendations for the diagnosis and management of children with steroid-resistant nephrotic syndrome

Trautmann A, Vivarelli M, Samuel S, Gipson D, Sinha A, Schaefer F, et al.

Pediatr Nephrol, 2020 Aug;35(8):1529-1561.
PMID: 32382828 DOI: 10.1007/s00467-020-04519-1

Idiopathic nephrotic syndrome newly affects 1-3 per 100,000 children per year. Approximately 85% of cases show complete remission of proteinuria following glucocorticoid treatment. Patients who do not achieve complete remission within 4-6 weeks of glucocorticoid treatment have steroid-resistant nephrotic syndrome (SRNS). In 10-30% of steroid-resistant patients, mutations in podocyte-associated genes can be detected, whereas an undefined circulating factor of immune origin is assumed in the remaining ones. Diagnosis and management of SRNS is a great challenge due to its heterogeneous etiology, frequent lack of remission by further immunosuppressive treatment, and severe complications including the development of end-stage kidney disease and recurrence after renal transplantation. A team of experts including pediatric nephrologists and renal geneticists from the International Pediatric Nephrology Association (IPNA), a renal pathologist, and an adult nephrologist have now developed comprehensive clinical practice recommendations on the diagnosis and management of SRNS in children. The team performed a systematic literature review on 9 clinically relevant PICO (Patient or Population covered, Intervention, Comparator, Outcome) questions, formulated recommendations and formally graded them at a consensus meeting, with input from patient representatives and a dietician acting as external advisors and a voting panel of pediatric nephrologists. Research recommendations are also given.
Fulltext Lazertinib Versus Gefitinib Tyrosine Kinase Inhibitors in Treatment-Naíve Patients With EGFR-Mutated Advanced NSCLC: Analysis of the Asian Subpopulation in LASER301

Reungwetwattana T, Cho BC, Lee KH, Pang YK, Fong CH, Kang JH, et al.

J Thorac Oncol, 2023 Oct;18(10):1351-1361.
PMID: 37702629 DOI: 10.1016/j.jtho.2023.06.016

INTRODUCTION: Lazertinib is a third-generation central nervous system-penetrant tyrosine kinase inhibitor targeting mutant EGFR in NSCLC. Lazertinib exhibited improved efficacy versus gefitinib in the LASER301 study; this subset analysis compared lazertinib with gefitinib among Asian patients.
METHODS: The phase 3 LASER301 study evaluated lazertinib efficacy and safety in treatment-naive patients with EGFR-mutated (exon 19 deletion or L858R) locally advanced or metastatic NSCLC. Patients were randomized one-to-one and received either lazertinib or gefitinib. The primary end point was investigator-assessed progression-free survival using Response Evaluation Criteria in Solid Tumors version 1.1. Secondary end points included overall survival, objective response rate, duration of response, and safety.
RESULTS: Between February 13, 2020, and July 29, 2022, among 258 patients of Asian descent, the median progression-free survival was significantly longer with lazertinib than gefitinib (20.6 versus 9.7 mo; hazard ratio: 0.46; 95% confidence interval [CI]: 0.34-0.63, p < 0.001), and the benefit was consistent across predefined subgroups (exon 19 deletion, L858R, baseline central nervous system metastases). Objective response rate and disease control rates were similar between treatment groups. The median duration of response was 19.4 months (95% CI: 16.6-24.9) versus 9.6 months (95% CI: 6.9-12.4) in the lazertinib versus gefitinib group. Adverse event rates in Asian patients were comparable with the overall LASER301 population. Adverse events leading to discontinuation in the lazertinib and gefitinib groups were 13% and 12%, respectively.
CONCLUSIONS: In LASER301, efficacy and safety results in Asian patients were consistent with the overall population. Lazertinib exhibited better efficacy than gefitinib in Asian patients with a tolerable safety profile.
Fulltext Central Nervous System Outcomes of Lazertinib Versus Gefitinib in EGFR-Mutated Advanced NSCLC: A LASER301 Subset Analysis

Soo RA, Cho BC, Kim JH, Ahn MJ, Lee KH, Zimina A, et al.

J Thorac Oncol, 2023 Dec;18(12):1756-1766.
PMID: 37865896 DOI: 10.1016/j.jtho.2023.08.017

INTRODUCTION: Lazertinib, a third-generation mutant-selective EGFR tyrosine kinase inhibitor, improved progression-free survival compared with gefitinib in the phase 3 LASER301 study (ClinicalTrials.gov Identifier: NCT04248829). Here, we report the efficacy of lazertinib and gefitinib in patients with baseline central nervous system (CNS) metastases.
METHODS: Treatment-naive patients with EGFR-mutated advanced NSCLC were randomized one-to-one to lazertinib (240 mg/d) or gefitinib (250 mg/d). Patients with asymptomatic or stable CNS metastases were included if any planned radiation, surgery, or steroids were completed more than 2 weeks before randomization. For patients with CNS metastases confirmed at screening or subsequently suspected, CNS imaging was performed every 6 weeks for 18 months, then every 12 weeks. End points assessed by blinded independent central review and Response Evaluation Criteria in Solid Tumors version 1.1 included intracranial progression-free survival, intracranial objective response rate, and intracranial duration of response.
RESULTS: Of the 393 patients enrolled in LASER301, 86 (lazertinib, n = 45; gefitinib, n = 41) had measurable and or non-measurable baseline CNS metastases. The median intracranial progression-free survival in the lazertinib group was 28.2 months (95% confidence interval [CI]: 14.8-28.2) versus 8.4 months (95% CI: 6.7-not reached [NR]) in the gefitinib group (hazard ratio = 0.42, 95% CI: 0.20-0.89, p = 0.02). Among patients with measurable CNS lesions, the intracranial objective response rate was numerically higher with lazertinib (94%; n = 17) versus gefitinib (73%; n = 11, p = 0.124). The median intracranial duration of response with lazertinib was NR (8.3-NR) versus 6.3 months (2.8-NR) with gefitinib. Tolerability was similar to the overall LASER301 population.
CONCLUSIONS: In patients with CNS metastases, lazertinib significantly improved intracranial progression-free survival compared with gefitinib, with more durable responses.

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