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Fulltext The Integrated Care Pathway for Managing Post Stroke (ICAPPS) Patients in the Community: A Cost -Effectiveness Analysis

Abdul AA, Muhammad Nur A, Sulong S, Aljunid S

Value Health, 2014 Nov;17(7):A761.
PMID: 27202786 DOI: 10.1016/j.jval.2014.08.259
Fulltext Care for post-stroke patients at Malaysian public health centres: self-reported practices of family medicine specialists

Abdul Aziz AF, Mohd Nordin NA, Abd Aziz N, Abdullah S, Sulong S, Aljunid SM

BMC Fam Pract, 2014;15:40.
PMID: 24580779 DOI: 10.1186/1471-2296-15-40

BACKGROUND: Provision of post stroke care in developing countries is hampered by discoordination of services and limited access to specialised care. Albeit shortcomings, primary care continues to provide post-stroke services in less than favourable circumstances. This paper aimed to review provision of post-stroke care and related problems among Family Medicine Specialists managing public primary health care services.
METHODS: A semi-structured questionnaire was distributed to 121 Family Physicians servicing public funded health centres in a pilot survey focused on improving post stroke care provision at community level. The questionnaire assessed respondents background and practice details i.e. estimated stroke care burden, current service provision and opinion on service improvement. Means and frequencies described quantitative data. For qualitative data, constant comparison method was used until saturation of themes was reached.
RESULTS: Response rate of 48.8% was obtained. For every 100 patients seen at public healthcentres each month, 2 patients have stroke. Median number of stroke patients seen per month is 5 (IQR 2-10). 57.6% of respondents estimated total stroke patients treated per year at each centre was less than 40 patients. 72.4% lacked a standard care plan although 96.6% agreed one was needed. Patients seen were: discharged from tertiary care (88.1%), shared care plan with specialists (67.8%) and patients who developed stroke during follow up at primary care (64.4%). Follow-ups were done at 8-12 weekly intervals (60.3%) with 3.4% on 'as needed' basis. Referrals ranked in order of frequency were to physiotherapy services, dietitian and speech and language pathologists in public facilities. The FMS' perceived 4 important 'needs' in managing stroke patients at primary care level; access to rehabilitation services, coordinated care between tertiary centres and primary care using multidisciplinary care approach, a standardized guideline and family and caregiver support.
CONCLUSIONS: Post discharge stroke care guidelines and access to rehabilitation services at primary care is needed for post stroke patients residing at home in the community.
Fulltext Profile and outcome of post stroke patients managed at selected public primary care health centres in Peninsular Malaysia: A retrospective observational study

Abdul Aziz AF, Ali MF, Yusof MF, Che' Man Z, Sulong S, Aljunid SM

Sci Rep, 2018 12 19;8(1):17965.
PMID: 30568180 DOI: 10.1038/s41598-018-36154-0

Data on post stroke outcomes in developing countries are scarce due to uncoordinated healthcare delivery systems. In Malaysia, the national stroke clinical practice guideline does not address transfer of care and longer term post stroke care beyond tertiary care. Hence, post stroke care delivery may be delivered at either tertiary or primary care facilities. This study aimed at describing patients' characteristics and outcomes of post stroke care delivered by the primary care teams at public primary care healthcentres across Peninsular Malaysia. Multi staged sampling was done to select public primary care health centres to recruit post stroke patients. At each health centre, convenience sampling was done to recruit adult patients (≥18 years) who received post stroke care between July-December 2012. Baseline measurements were recorded at recruitment and retrospective medical record review was done simultaneously, for details on medical and / or rehabilitation treatment at health centre. Changes in the measurements for post stroke care were compared using paired t-tests and Wilcoxon Rank test where appropriate. Total of 151 patients were recruited from ten public primary care healthcentres. The mean age at stroke presentation was 55.8 ± 9.8 years. Median duration of follow up was 2.3 (IQR 5.1) years. Majority co-resided with a relative (80.8%), and a family member was primary caregiver (75.%). Eleven percent were current smokers. Almost 71.0% of patients achieved BP ≤ 140/90 mmHg. Only 68.9% of the patients had been referred for neurorehabilitation. Percentage of recorded data was highest for blood pressure (88.1%) while lowest was HbA1c (43.0%). For clinical outcomes, systolic and diastolic blood pressure, triglyceride level and calculated GFR (eGFR) showed statistically significant changes during follow up (p
Fulltext The integrated care pathway for managing post stroke patients (iCaPPS©) in public primary care Healthcentres in Malaysia: impact on quality adjusted life years (QALYs) and cost effectiveness analysis

Abdul Aziz AF, Mohd Nordin NA, Muhd Nur A, Sulong S, Aljunid SM

BMC Geriatr, 2020 02 18;20(1):70.
PMID: 32070291 DOI: 10.1186/s12877-020-1453-z

BACKGROUND: The delivery of post stroke care is fragmented even in advanced public healthcare systems, globally. Primary care teams are entrusted to provide longer term care for stroke survivors in most developing countries. The integrated Care Pathway for Post Stroke patients (iCaPPS©) was designed to guide primary care teams to incorporate further rehabilitation and regular screening for post stroke complications among patients residing at home in communities, using the shared-care approach, especially in areas with limited access to specialist stroke care services. The iCaPPS© addressed coordination of rehabilitation and screening for post stroke complications which were absent in the current conventional care of patients managed at public primary care healthcentres. This study aimed to evaluate the cost effectiveness and impact of iCaPPS© on quality-adjusted- life-years (QALY) compared with current conventional monitoring at public primary care healthcentres.
METHODS: A pragmatic healthcentre-based cluster randomised controlled trial-within trial on 151 post stroke patients from 10 public primary care facilities in Peninsular Malaysia was conducted to evaluate QALY of patients managed with iCaPPS© (n = 86) vs conventional care (n = 65) for 6 months. Costs from societal perspective were calculated, using combination of top down and activity-based costing methods. The 5-level EQ5D (EQ-5D-5 L) was used to calculate health state utility scores. Cost per QALY and incremental cost effectiveness ratio (ICER) were determined. Differences within groups were determined using Mann-Whitney tests.
RESULTS: Total costs for 6 months treatment with iCaPPS© was MYR790.34, while conventional care cost MYR527.22. Median QALY for iCaPPS© was 0.55 (0,1.65) compared to conventional care 0.32 (0, 0.73) (z = - 0.21, p = 0.84). Cost per QALY for iCaPPS© was MYR1436.98, conventional care was MYR1647.56. The ICER was MYR1144.00, equivalent to 3.7% of per capita GDP (2012 prices).
CONCLUSIONS: Management of post stroke patients in the community using iCaPPS© costs less per QALY compared to current conventional care and is very cost effective.
TRIAL REGISTRATION: Trial Registration number ACTRN12616001322426. Registered 21 September 2016. (Retrospectively registered).
Fulltext The integrated care pathway for post stroke patients (iCaPPS): a shared care approach between stakeholders in areas with limited access to specialist stroke care services

Abdul Aziz AF, Mohd Nordin NA, Ali MF, Abd Aziz NA, Sulong S, Aljunid SM

BMC Health Serv Res, 2017 Jan 13;17(1):35.
PMID: 28086871 DOI: 10.1186/s12913-016-1963-8

BACKGROUND: Lack of intersectoral collaboration within public health sectors compound efforts to promote effective multidisciplinary post stroke care after discharge following acute phase. A coordinated, primary care-led care pathway to manage post stroke patients residing at home in the community was designed by an expert panel of specialist stroke care providers to help overcome fragmented post stroke care in areas where access is limited or lacking.

METHODS: Expert panel discussions comprising Family Medicine Specialists, Neurologists, Rehabilitation Physicians and Therapists, and Nurse Managers from Ministry of Health and acadaemia were conducted. In Phase One, experts chartered current care processes in public healthcare facilities, from acute stroke till discharge and also patients who presented late with stroke symptoms to public primary care health centres. In Phase Two, modified Delphi technique was employed to obtain consensus on recommendations, based on current evidence and best care practices. Care algorithms were designed around existing work schedules at public health centres.

RESULTS: Indication for patients eligible for monitoring by primary care at public health centres were identified. Gaps in transfer of care occurred either at post discharge from acute care or primary care patients diagnosed at or beyond subacute phase at health centres. Essential information required during transfer of care from tertiary care to primary care providers was identified. Care algorithms including appropriate tools were summarised to guide primary care teams to identify patients requiring further multidisciplinary interventions. Shared care approaches with Specialist Stroke care team were outlined. Components of the iCaPPS were developed simultaneously: (i) iCaPPS-Rehab© for rehabilitation of stroke patients at community level (ii) iCaPPS-Swallow© guided the primary care team to screen and manage stroke related swallowing problems.

CONCLUSION: Coordinated post stroke care monitoring service for patients at community level is achievable using the iCaPPS and its components as a guide. The iCaPPS may be used for post stroke care monitoring of patients in similar fragmented healthcare delivery systems or areas with limited access to specialist stroke care services.

TRIAL REGISTRATION: No.: ACTRN12616001322426 (Registration Date: 21st September 2016).
The role of social media in primary care

Abdul Rashid A, Kamarulzaman A, Sulong S, Abdullah S

Malays Fam Physician, 2021 Jul 22;16(2):14-18.
PMID: 34386159 DOI: 10.51866/rv1048

Online activities have become the norm. From searching for new information to conducting business meetings, social media's role in daily life continues to grow in prominence. It is estimated that the majority of the population uses social media, and users include doctors and other healthcare professionals. It is critical for primary care doctors to note how social media can substantially influence one's healthcare behaviour and decision making. Because primary care doctors are usually the first line of contact for patients, they are the most easily accessible and most instrumental in using social media to steer the public toward proper information on healthcare.
Molecular genetic analysis of phosphatase and tensin homolog and p16 tumor suppressor genes in patients with malignant glioma

Abdullah JM, Zainuddin N, Sulong S, Jaafar H, Isa MN

Neurosurg Focus, 2003 Apr 15;14(4):e6.
PMID: 15679305

Several genes have been shown to carry mutations in human malignant gliomas, including the phosphatase and tensin homolog (PTEN) deleted on chromosome 10 and p16 tumor suppressor genes. Alterations of this gene located on chromosome 10 q23 and 9p21, respectively, may contribute to gliomagenesis. In this study, the authors analyzed 20 cases of malignant gliomas obtained in patients living on the east coast of Malaysia to investigate the possibilities of involvement of the PTEN and p16 genes.
Fulltext Identification of AOC3 and LRRC17 as Colonic Fibroblast Activation Markers and Their Potential Roles in Colorectal Cancer Progression

Ahmad Zawawi SS, Mohd Azram NAS, Sulong S, Zakaria AD, Lee YY, Che Jalil NA, et al.

Asian Pac J Cancer Prev, 2023 Sep 01;24(9):3099-3107.
PMID: 37774061 DOI: 10.31557/APJCP.2023.24.9.3099

BACKGROUND: Accumulation of cancer-associated fibroblasts (CAFs) in the tumor stroma is linked to poor prognosis in colorectal cancer (CRC). CAF-cancer cell interplay, facilitated by secretomes including transforming growth factor-beta 1 (TGF-β1), supports fibroblast activation, drives colorectal carcinogenesis, and contributes to CRC aggressive phenotypes. Although widely used, traditional CAF biomarkers are found to have heterogeneous and non-specific expression. Amine oxidase copper containing 3 (AOC3) and leucine-rich repeat-containing 17 (LRRC17) have been reported to be emerging markers of myofibroblasts.
AIM: Our objective was to investigate the potential of AOC3 and LRRC17 as biomarkers for fibroblast activation thus predicting their roles in CRC progression.
METHODS: Immunofluorescence (IF) staining of AOC3 and LRRC17 was performed on myofibroblast line (CCD-112CoN), primary fibroblasts from colorectal tumor (CAFs), and adjacent normal tissue (normal fibroblasts-NFs). SW620 (epithelial CRC cell line) was used as a control. Conventional CAF biomarker (alpha-smooth muscle actin - α-SMA) was included in the IF analysis. Fluorescence intensity was compared between groups using ImageJ software. Proliferation and contractility of treated cells were assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) and collagen gel contraction assays, respectively. Fibroblast contraction under TGF-β1 treatment was compared to those treated with complete medium (addition of 10% serum) and serum free (SF) medium.
RESULTS: Positive AOC3, LRRC17, and α-SMA expression were observed in colonic fibroblasts, more prominent in CAFs, whereas negative staining was found in SW620. Significant downregulation of AOC3, and upregulations in LRRC17 and α-SMA expression was found in TGF-β1-treated fibroblasts compared to SF medium treatment (p-value<0.05). All fibroblasts exhibited higher proliferation in complete medium and under treatment with conditioned medium from SW620 than SF medium. Significant contraction of NFs was recorded in complete medium and TGF-β1 (p-value<0.01).
CONCLUSION: Our results demonstrate AOC3 and LRRC17 as the potential markers of CAF activation which promote CRC progression.
Fulltext Impact of routine PCV7 (Prevenar) vaccination of infants on the clinical and economic burden of pneumococcal disease in Malaysia

Aljunid S, Abuduxike G, Ahmed Z, Sulong S, Nur AM, Goh A

BMC Infect Dis, 2011;11:248.
PMID: 21936928 DOI: 10.1186/1471-2334-11-248

BACKGROUND: Pneumococcal disease is the leading cause of vaccine-preventable death in children younger than 5 years of age worldwide. The World Health Organization recommends pneumococcal conjugate vaccine as a priority for inclusion into national childhood immunization programmes. Pneumococcal vaccine has yet to be included as part of the national vaccination programme in Malaysia although it has been available in the country since 2005. This study sought to estimate the disease burden of pneumococcal disease in Malaysia and to assess the cost effectiveness of routine infant vaccination with PCV7.
METHODS: A decision model was adapted taking into consideration prevalence, disease burden, treatment costs and outcomes for pneumococcal disease severe enough to result in a hospital admission. Disease burden were estimated from the medical records of 6 hospitals. Where local data was unavailable, model inputs were obtained from international and regional studies and from focus group discussions. The model incorporated the effects of herd protection on the unvaccinated adult population.
RESULTS: At current vaccine prices, PCV7 vaccination of 90% of a hypothetical 550,000 birth cohort would incur costs of RM 439.6 million (US$128 million). Over a 10 year time horizon, vaccination would reduce episodes of pneumococcal hospitalisation by 9,585 cases to 73,845 hospitalisations with cost savings of RM 37.5 million (US$10.9 million) to the health system with 11,422.5 life years saved at a cost effectiveness ratio of RM 35,196 (US$10,261) per life year gained.
CONCLUSIONS: PCV7 vaccination of infants is expected to be cost-effective for Malaysia with an incremental cost per life year gained of RM 35,196 (US$10,261). This is well below the WHO's threshold for cost effectiveness of public health interventions in Malaysia of RM 71,761 (US$20,922).
Economic Impact of Pneumococcal Protein-D Conjugate Vaccine (PHiD-CV) on the Malaysian National Immunization Programme

Aljunid S, Maimaiti N, Ahmed Z, Muhammad Nur A, Md Isa Z, Azmi S, et al.

Value Health Reg Issues, 2014 May;3:146-155.
PMID: 29702920 DOI: 10.1016/j.vhri.2014.04.008

OBJECTIVE: To assess the cost-effectiveness of introducing pneumococcal polysaccharide and nontypeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) in the National Immunization Programme of Malaysia. This study compared introducing PHiD-CV (10 valent vaccine) with current no vaccination, as well as against the alternative 13-valent pneumococcal conjugate vaccine (PCV13).

METHODS: A lifetime Markov cohort model was adapted using national estimates of disease burden, outcomes of pneumococcal disease, and treatment costs of disease manifestations including pneumonia, acute otitis media, septicemia, and meningitis for a hypothetical birth cohort of 550,000 infants. Clinical information was obtained by review of medical records from four public hospitals in Malaysia from the year 2008 to 2009. Inpatient cost from the four study hospitals was obtained from a diagnostic-related group-based costing system. Outpatient cost was estimated using clinical pathways developed by an expert panel. The perspective assessed was that of the Ministry of Health, Malaysia.

RESULTS: The estimated disease incidence was 1.2, 3.7, 70, and 6.9 per 100,000 population for meningitis, bacteremia, pneumonia, and acute otitis media, respectively. The Markov model predicted medical costs of Malaysian ringgit (RM) 4.86 billion (US $1.51 billion) in the absence of vaccination. Vaccination with PHiD-CV would be highly cost-effective against no vaccination at RM30,290 (US $7,407) per quality-adjusted life-year gained. On comparing PHiD-CV with PCV13, it was found that PHiD-CV dominates PCV13, with 179 quality-adjusted life-years gained while saving RM35 million (US $10.87 million).

CONCLUSIONS: It is cost-effective to incorporate pneumococcal vaccination in the National Immunization Programme of Malaysia. Our model suggests that PHiD-CV would be more cost saving than PCV13 from the perspective of the Ministry of Health of Malaysia.

Study site: UKM Medical Centre, Hospital Kuala Lumpur, Hospital
Alor Setar, and Hospital Queen Elizabeth, Kota Kinabalu
Fulltext Genomic Alterations, Gene Expression Profiles and Functional Enrichment of Normal-Karyotype Acute Myeloid Leukaemia Based on Targeted Next-Generation Sequencing

Ambayya A, Razali R, Sulong S, Zulkefli ES, Yap YY, Sathar J, et al.

Cancers (Basel), 2023 Feb 22;15(5).
PMID: 36900179 DOI: 10.3390/cancers15051386

Characterising genomic variants is paramount in understanding the pathogenesis and heterogeneity of normal-karyotype acute myeloid leukaemia (AML-NK). In this study, clinically significant genomic biomarkers were ascertained using targeted DNA sequencing and RNA sequencing on eight AML-NK patients' samples collected at disease presentation and after complete remission. In silico and Sanger sequencing validations were performed to validate variants of interest, and they were followed by the performance of functional and pathway enrichment analyses for overrepresentation analysis of genes with somatic variants. Somatic variants involving 26 genes were identified and classified as follows: 18/42 (42.9%) as pathogenic, 4/42 (9.5%) as likely pathogenic, 4/42 (9.5%) as variants of unknown significance, 7/42 (16.7%) as likely benign and 9/42 (21.4%) as benign. Nine novel somatic variants were discovered, of which three were likely pathogenic, in the CEBPA gene with significant association with its upregulation. Transcription misregulation in cancer tops the affected pathways involving upstream genes (CEBPA and RUNX1) that were deregulated in most patients during disease presentation and were closely related to the most enriched molecular function gene ontology category, DNA-binding transcription activator activity RNA polymerase II-specific (GO:0001228). In summary, this study elucidated putative variants and their gene expression profiles along with functional and pathway enrichment in AML-NK patients.
Clinical implications of conventional cytogenetics, fluorescence in situ hybridization (FISH) and molecular testing in chronic myeloid leukaemia patients in the tyrosine kinase inhibitor era - A review

Ankathil R, Ismail SM, Mohd Yunus N, Sulong S, Husin A, Abdullah AD, et al.

Malays J Pathol, 2020 Dec;42(3):307-321.
PMID: 33361712

Chronic myeloid leukaemia (CML) provides an illustrative disease model for both molecular pathogenesis of cancer and rational drug therapy. Imatinib mesylate (IM), a BCR-ABL1 targeted tyrosine kinase inhibitor (TKI) drug, is the first line gold standard drug for CML treatment. Conventional cytogenetic analysis (CCA) can identify the standard and variant Philadelphia (Ph) chromosome, and any additional complex chromosome abnormalities at diagnosis as well as during treatment course. Fluorescence in situ hybridization (FISH) is especially important for cells of CML patients with inadequate or inferior quality metaphases or those with variant Ph translocations. CCA in conjunction with FISH can serve as powerful tools in all phases of CML including the diagnosis, prognosis, risk stratification and monitoring of cytogenetic responses to treatment. Molecular techniques such as reverse transcriptase-polymerase chain reaction (RT-PCR) is used for the detection of BCR-ABL1 transcripts at diagnosis whereas quantitative reverse transcriptase-polymerase chain reaction (qRTPCR) is used at the time of diagnosis as well as during TKI therapy for the quantitation of BCR-ABL1 transcripts to evaluate the molecular response and minimal residual disease (MRD). Despite the excellent treatment results obtained after the introduction of TKI drugs, especially Imatinib mesylate (IM), resistance to TKIs develops in approximately 35% - 40% of CML patients on TKI therapy. Since point mutations in BCR-ABL1 are a common cause of IM resistance, mutation analysis is important in IM resistant patients. Mutations are reliably detected by nested PCR amplification of the translocated ABL1 kinase domain followed by direct sequencing of the entire amplified kinase domain. The objective of this review is to highlight the importance of regular and timely CCA, FISH analysis and molecular testing in the diagnosis, prognosis, assessment of therapeutic efficacy, evaluation of MRD and in the detection of BCR-ABL1 kinase mutations which cause therapeutic resistance in adult CML patients.
Fulltext Impact of Fas/Fasl Gene Polymorphisms on Susceptibility Risk and Imatinib Mesylate Treatment Response in Chronic Myeloid Leukaemia Patients

Annuar AA, Ankathil R, Mohd Yunus N, Husin A, Ab Rajab NS, Abdul Aziz AA, et al.

Asian Pac J Cancer Prev, 2021 Feb 01;22(2):565-571.
PMID: 33639675 DOI: 10.31557/APJCP.2021.22.2.565

BACKGROUND: The FAS mediated apoptosis pathway involving the FAS and FASL genes plays a crucial role in the regulation of apoptotic cell death and imatinib mesylate (IM) mechanism of action. Promoter polymorphisms FAS-670 A>G and FAS-844 T>C which alter the transcriptional activity of these genes may grant a risk to develop cancer and revamp the drug activities towards the cancer cell. We investigated the association of these two polymorphisms with the susceptibility risk and IM treatment response in Malaysian chronic myeloid leukaemia (CML) patients.
METHODS: This is a retrospective study, which included 93 CML patients and 98 controls. The polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) method was used to genotype the FAS and FASL polymorphisms. Data nanlysis was done using SPSS Version 22. The associations of the genotypes with susceptibility risk and IM response in CML patients were assessed by means of logistic regression analysis and deriving odds ratio with 95% CI.
RESULTS: We observed a significant association between FASL-844T>C polymorphism and CML susceptibility risk and IM response. Variant C allele and FASL-844 CC variant genotype carriers had significantly higher risk for CML susceptibility (OR 1.756, CI 1.163-2.652, p=0.007 and OR 2.261, CI 1.013-5.047, p=0.047 respectively). Conversely, the heterozygous genotype FASL-844 TC conferred lower risk for CML susceptibility (OR 0.379, CI 0.176-0.816, p=0.013). The heterozygous and homozygous variant genotypes and variant C alleles were found to confer a lower risk for the development of IM resistance with OR 0.129 (95% CI: 0.034-0.489 p=0.003), OR 0.257 (95% CI: 0.081-0.818, p=0.021), and OR 0.486 (95% CI: 0.262-0.899, p=0.021) respectively. We also found that FAS-670 A>G polymorphism was not associated with CML susceptibility risk or IM response.
CONCLUSION: The genetic polymorphism FASL-844 T>C may contribute to the CML susceptibility risk and also IM treatment response in CML patients. Accodringly, it may be useful as a biomarker for predicting CML susceptibility risk and IM resistance.
Fulltext Direct Medical Cost of Stroke and the Cost-Effectiveness of Direct Oral Anticoagulants in Atrial Fibrillation-Related Stroke: A Cross-Sectional Study

Azahar SN, Sulong S, Wan Zaidi WA, Muhammad N, Kamisah Y, Masbah N

Int J Environ Res Public Health, 2022 Jan 19;19(3).
PMID: 35162102 DOI: 10.3390/ijerph19031078

BACKGROUND: Stroke has significant direct medical costs, and direct oral anticoagulants (DOACs) are better alternatives to warfarin for stroke prevention in atrial fibrillation (AF). This study aimed to determine the direct medical costs of stroke, with emphasis on AF stroke and the cost-effectiveness of DOACs among stroke patients in a tertiary hospital in Malaysia.
METHODS: This study utilised in-patient data from the case mix unit of Universiti Kebangsaan Malaysia Medical Centre (UKMMC) between 2011 and 2018. Direct medical costs of stroke were determined using a top-down costing approach and factors associated with costs were identified. Incremental cost effectiveness ratio (ICER) was calculated to compare the cost-effectiveness between DOACs and warfarin.
RESULTS: The direct medical cost of stroke was MYR 11,669,414.83 (n = 3689). AF-related stroke cases had higher median cost of MYR 2839.73 (IQR 2269.79-3101.52). Regression analysis showed that stroke type (AF versus non-AF stroke) (p = 0.013), stroke severity (p = 0.010) and discharge status (p < 0.001) significantly influenced stroke costs. DOACs were cost-effective compared to warfarin with an ICER of MYR 19.25.
CONCLUSIONS: The direct medical cost of stroke is substantial, with AF-stroke having a higher median cost per stroke care. DOACs were cost effective in the treatment of AF-related stroke in UKMMC.
Fulltext What is next after transfer of care from hospital to home for stroke patients? Evaluation of a community stroke care service based in a primary care clinic

Aziz AF, Aziz NA, Nordin NA, Ali MF, Sulong S, Aljunid SM

J Neurosci Rural Pract, 2013 Oct;4(4):413-20.
PMID: 24347948 DOI: 10.4103/0976-3147.120243

CONTEXT: Poststroke care in developing countries is inundated with poor concordance and scarce specialist stroke care providers. A primary care-driven health service is an option to ensure optimal care to poststroke patients residing at home in the community.
AIMS: We assessed outcomes of a pilot long-term stroke care clinic which combined secondary prevention and rehabilitation at community level.
SETTINGS AND DESIGN: A prospective observational study of stroke patients treated between 2008 and 2010 at a primary care teaching facility.
SUBJECTS AND METHODS: Analysis of patients was done at initial contact and at 1-year post treatment. Clinical outcomes included stroke risk factor(s) control, depression according to Patient Health Questionnaire (PHQ9), and level of independence using Barthel Index (BI).
STATISTICAL ANALYSIS USED: Differences in means between baseline and post treatment were compared using paired t-tests or Wilcoxon-signed rank test. Significance level was set at 0.05.
RESULTS: Ninety-one patients were analyzed. Their mean age was 62.9 [standard deviation (SD) 10.9] years, mean stroke episodes were 1.30 (SD 0.5). The median interval between acute stroke and first contact with the clinic 4.0 (interquartile range 9.0) months. Mean systolic blood pressure decreased by 9.7 mmHg (t = 2.79, P = 0.007), while mean diastolic blood pressure remained unchanged at 80mmHg (z = 1.87, P = 0.06). Neurorehabilitation treatment was given to 84.6% of the patients. Median BI increased from 81 (range: 2-100) to 90.5 (range: 27-100) (Z = 2.34, P = 0.01). Median PHQ9 scores decreased from 4.0 (range: 0-22) to 3.0 (range: 0-19) though the change was not significant (Z= -0.744, P = 0.457).
CONCLUSIONS: Primary care-driven long-term stroke care services yield favorable outcomes for blood pressure control and functional level.
Fulltext Cost-Effectiveness Analysis of Psoriasis Treatment Modalities in Malaysia

Azizam NA, Ismail A, Sulong S, Nor NM

Int J Health Policy Manag, 2019 07 01;8(7):394-402.
PMID: 31441276 DOI: 10.15171/ijhpm.2019.17

BACKGROUND: There is limited evidence detailing the cost-effectiveness of psoriasis treatments in the Asian region. Therefore, this study is aimed to evaluate the cost-effectiveness of 3 psoriasis treatments tailored for moderate to severe psoriasis, namely topical and phototherapy (TP), topical and systemic (TS), and topical and biologic (TB) regimens, respectively.
METHODS: This has been achieved by the participation of a prospective cohort involving a total of 90 moderate to severe psoriasis patients, which has been conducted at 5 public hospitals in Malaysia. The main outcome measures have been evaluated via cost and effectiveness psoriasis area severity index (PASI)-75 and/or body surface area (BSA) <5 and/or dermatology life quality index (DLQI) ≤5), estimated from the societal perspective over a 6-months duration. All costs are based on 2015's recorded Malaysian Ringgit (RM) currency.
RESULTS: Consequently, TS has been found to be the most cost-effective treatment with the lowest cost/PASI-75/and/or BSA <5 and/or DLQI ≤5, valued at RM9034.56 (US$2582.55). This is followed by TP, which is valued at RM28 080.71 (US$8026.93) and TB, valued at RM54 287.02 (US$15 518.06). Furthermore, one-way sensitivity analysis has highlighted the cost of medication as the most sensitive parameter.
CONCLUSION: Thus, the input from this study is helpful for policy-makers in determining the first line treatment for moderate to severe psoriasis with consideration of the costs and its effectiveness in Malaysia. This will consequently allow hospitals to justify and provide the essential resources for further research and development, as well as the adoption of better treatment options.
Microvascular endothelial function and severity of primary open angle glaucoma

Bukhari SM, Kiu KY, Thambiraja R, Sulong S, Rasool AH, Liza-Sharmini AT

Eye (Lond), 2016 Dec;30(12):1579-1587.
PMID: 27540832 DOI: 10.1038/eye.2016.185

PurposeThe role of microvascular endothelial dysfunction on severity of primary open angle glaucoma (POAG) was investigated in this study.Patients and methodsA prospective cohort study was conducted. One hundred and fourteen ethnically Malay patients (114 eyes) with POAG treated at the eye clinic of Hospital University Sains Malaysia between April 2012 and December 2014 were recruited. Patients aged between 40 and 80 years with two consecutive reliable and reproducible Humphrey visual field 24-2 analyses were selected. Patients who were diagnosed with any other type of glaucoma, previous glaucoma-filtering surgery, or other surgeries except uncomplicated cataract and pterygium surgery were excluded. Humphrey visual field analysis 24-2 was used to stratify the severity of glaucoma using Advanced Glaucoma Intervention Study (AGIS) score at the time of recruitment. Microvascular endothelial function was assessed using Laser Doppler fluximetry and iontophoresis. Iontophoresis process with acetylcholine (ACh) and sodium nitroprusside (SNP) was used to measure microvascular endothelium-dependent and -independent vasodilatation, respectively.ResultsBased on the AGIS score, 55 patients showed mild glaucoma, with 29 moderate and 30 severe. There was statistically significant difference in microvascular endothelial function (ACh% and AChmax) between mild and moderate POAG cases (P=0.023) and between mild and severe POAG cases (P<0.001). There was negative correlation between microvascular endothelial function and severity of POAG (r=-0.457, P<0.001).ConclusionMicrovascular endothelial dysfunction may have a role in influencing the severity of POAG in Malay patients.

Study site: Eye clinic Hospital Universiti Sains Malaysia (HUSM)
Fulltext Clastogenicity and Aneugenicity of 1,4-Benzoquinone in Different Lineages of Mouse Hematopoietic Stem/Progenitor Cells

Chow PW, Abd Hamid Z, Mathialagan RD, Rajab NF, Shuib S, Sulong S

Toxics, 2021 May 12;9(5).
PMID: 34065823 DOI: 10.3390/toxics9050107

Previous reports on hematotoxicity and leukemogenicity related to benzene exposure highlighted its adverse effects on hematopoiesis. Despite the reported findings, studies concerning the mechanism of benzene affecting chromosomal integrity in lineage-committed hematopoietic stem/progenitor cells (HSPCs) remain unclear. Here, we studied the clastogenicity and aneugenicity of benzene in lineage-committed HSPCs via karyotyping. Isolated mouse bone marrow cells (MBMCs) were exposed to the benzene metabolite 1,4-benzoquinone (1,4-BQ) at 1.25, 2.5, 5, 7, and 12 μM for 24 h, followed by karyotyping. Then, the chromosomal aberration (CA) in 1,4-BQ-exposed hematopoietic progenitor cells (HPCs) comprising myeloid, Pre-B lymphoid, and erythroid lineages were evaluated following colony-forming cell (CFC) assay. Percentage of CA, predominantly via Robertsonian translocation (Rb), was increased significantly (p < 0.05) in MBMCs and all progenitors at all concentrations. As a comparison, Pre-B lymphoid progenitor demonstrated a significantly higher percentage of CA (p < 0.05) than erythroid progenitor at 1.25, 2.5, and 7 μM as well as a significantly higher percentage (p < 0.05) than myeloid progenitor at 7 μM of 1,4-BQ. In conclusion, 1,4-BQ induced CA, particularly via Rb in both MBMCs and HPCs, notably via a lineage-dependent response. The role of lineage specificity in governing the clastogenicity and aneugenicity of 1,4-BQ deserves further investigation.
Fulltext HOXA4 gene promoter hypermethylation as an epigenetic mechanism mediating resistance to imatinib mesylate in chronic myeloid leukemia patients

Elias MH, Baba AA, Husin A, Sulong S, Hassan R, Sim GA, et al.

Biomed Res Int, 2013;2013:129715.
PMID: 23484077 DOI: 10.1155/2013/129715

Development of resistance to imatinib mesylate (IM) in chronic myeloid leukemia (CML) patients has emerged as a significant clinical problem. The observation that increased epigenetic silencing of potential tumor suppressor genes correlates with disease progression in some CML patients treated with IM suggests a relationship between epigenetic silencing and resistance development. We hypothesize that promoter hypermethylation of HOXA4 could be an epigenetic mechanism mediating IM resistance in CML patients. Thus a study was undertaken to investigate the promoter hypermethylation status of HOXA4 in CML patients on IM treatment and to determine its role in mediating resistance to IM. Genomic DNA was extracted from peripheral blood samples of 95 CML patients (38 good responders and 57 resistant) and 12 normal controls. All samples were bisulfite treated and analysed by methylation-specific high-resolution melt analysis. Compared to the good responders, the HOXA4 hypermethylation level was significantly higher (P = 0.002) in IM-resistant CML patients. On comparing the risk, HOXA4 hypermethylation was associated with a higher risk for IM resistance (OR 4.658; 95% CI, 1.673-12.971; P = 0.003). Thus, it is reasonable to suggest that promoter hypermethylation of HOXA4 gene could be an epigenetic mechanism mediating IM resistance in CML patients.
Fulltext Aberrant DNA methylation at HOXA4 and HOXA5 genes are associated with resistance to imatinib mesylate among chronic myeloid leukemia patients

Elias MH, Azlan H, Sulong S, Baba AA, Ankathil R

Cancer Rep (Hoboken), 2018 08;1(2):e1111.
PMID: 32721103 DOI: 10.1002/cnr2.1111

BACKGROUND: Imatinib mesylate is a molecularly targeted tyrosine kinase inhibitor drug. It is effectively used in the treatment of chronic myeloid leukemia (CML) patients. However, development of resistance to imatinib mesylate as a result of BCR-ABL dependent and BCR-ABL independent mechanisms has emerged as a daunting problem in the management of CML patients. Between these mechanisms, BCR-ABL independent mechanisms are still not robustly understood.
AIM: To investigate the correlation of HOXA4 and HOXA5 promoter DNA hypermethylation with imatinib resistance among CML patients.
METHODS AND RESULTS: Samples from 175 Philadelphia positive CML patients (83 good response and 92 BCR-ABL non-mutated imatinib resistant patients) were subjected to Methylation Specific High Resolution Melt Analysis for methylation levels quantification of the HOXA4 and HOXA5 promoter regions. Receiver operating characteristic curve analysis was done to elucidate the optimal methylation cut-off point followed by multiple logistic regression analysis. Log-Rank analysis was done to measure the overall survival difference between CML groups. The optimal methylation cut-off point was found to be at 62.5% for both HOXA4 and HOXA5. Chronic myeloid leukemia patients with ≥63% HOXA4 and HOXA5 methylation level were shown to have 3.78 and 3.95 times the odds, respectively, to acquire resistance to imatinib. However, overall survival of CML patients that have ≤62% and ≥ 63% methylation levels of HOXA4 and HOXA5 genes were found to be not significant (P-value = 0.126 for HOXA4; P-value = 0.217 for HOXA5).
CONCLUSION: Hypermethylation of the HOXA4 and HOXA5 promoter is correlated with imatinib resistance and with further investigation, it could be a potential epigenetic biomarker in supplement to the BCR-ABL gene mutation in predicting imatinib treatment response among CML patients but could not be considered as a prognostic marker.

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