Displaying publications 1 - 20 of 29 in total

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  1. Chong HY, Leow CY, Abdul Majeed AB, Leow CH
    Virus Res, 2019 12;274:197770.
    PMID: 31626874 DOI: 10.1016/j.virusres.2019.197770
    Flaviviruses are group of single stranded RNA viruses that cause severe endemic infection and epidemics on a global scale. It presents a significant health impact worldwide and the viruses have the potential to emerge and outbreak in a non-endemic geographical region. Effective vaccines for prophylaxis are only available for several flaviviruses such as Yellow Fever virus, Tick-borne Encephalitis Virus, Dengue Virus and Japanese Encephalitis Virus and there is no antiflaviviral agent being marketed. This review discusses the flavivirus genome, replication cycle, epidemiology, clinical presentation and pathogenesis upon infection. Effective humoral response is critical to confer protective immunity against flaviviruses. Hence, we have also highlighted the immune responses elicited upon infection, various diagnostic facilities available for flaviviral disease and monoclonal antibodies available to date against flavivirus infection.
  2. Chong HY, Saokaew S, Dumrongprat K, Permsuwan U, Sritara P, Chaiyakunapruk N
    Value Health, 2014 Nov;17(7):A760.
    PMID: 27202779 DOI: 10.1016/j.jval.2014.08.254
  3. Wu DB, Chaiyakunapruk N, Chong HY, Beutels P
    Vaccine, 2015 Mar 30;33(14):1633-58.
    PMID: 25681663 DOI: 10.1016/j.vaccine.2015.01.081
    BACKGROUND: Seven-valent pneumococcal conjugate vaccines (PCV7) have been used in children for more than a decade. Given the observed increase in disease caused by pneumococcal serotypes not covered by PCV7, an increasing number of countries are switching from 7-valent to 10- and 13-valent PCVs ("PCV10" and "PCV13"). Economic evaluations are important tools to inform decisions and price negotiations to make such a switch.
    OBJECTIVE: This review aims to provide a critical assessment of economic evaluations involving PCV10 or PCV13, published since 2006.
    METHODS: We searched Scopus, ISI Web of Science (SCI and SSCI) and Pubmed to retrieve, select and review relevant studies, which were archived between 1st January 2006 and 31st January 2014. The review protocol involved standard extraction of assumptions, methods, results and sponsorships from the original studies.
    RESULTS: Sixty-three economic evaluations on PCVs published since January 2006 were identified. About half of these evaluated PCV10 and/or PCV13, the subject of this review. At current prices, both PCV13 and PCV10 were likely judged preferable to PCV7. However, the combined uncertainty related to price differences, burden of disease, vaccine effectiveness, herd and serotype replacement effects determine the preference base for either PCV10 or PCV13. The pivotal assumptions and results of these analyses also depended on which manufacturer sponsored the study.
    CONCLUSION: A more thorough exploration of uncertainty should be made in future analyses on this subject, as we lack understanding to adequately model herd and serotype replacement effects to reliably predict the population impact of PCVs. The introduction of further improved PCVs in an environment of evolving antibiotic resistance and under the continuing influence of previous PCVs implies that the complexity and data requirements for relevant analyses will further increase. Decision makers using these analyses should not just rely on an analysis from a single manufacturer.
    KEYWORDS: Cost-effectiveness; Cost–benefit; Pneumococcal conjugate vaccine; Streptococcus pneumoniae
  4. Chong HY, Saokaew S, Dumrongprat K, Permsuwan U, Wu DB, Sritara P, et al.
    Thromb Res, 2014 Dec;134(6):1278-84.
    PMID: 25456732 DOI: 10.1016/j.thromres.2014.10.006
    Pharmacogenetic (PGx) test is a useful tool for guiding physician on an initiation of an optimal warfarin dose. To implement of such strategy, the evidence on the economic value is needed. This study aimed to determine the cost-effectiveness of PGx-guided warfarin dosing compared with usual care (UC).
  5. Chong HY, Roslani AC, Law CW
    Med J Malaysia, 2013;68(1):30-3.
    PMID: 23466763 MyJurnal
    BACKGROUND: Screening for colorectal cancer (CRC) improves outcomes and reduces its incidence. However, population-based screening in Malaysia continues to be a challenge, in view of cost and limited availability of colonoscopic skills and facilities. Conventional qualitative faecal occult blood tests help to prioritize those who require earlier colonoscopies, but cannot distinguish between benign and malignant causes. Recently, quantitative immunochemical faecal occult blood tests (qFOBT) have demonstrated some discriminatory ability in distinguishing benign and malignant causes. We aim to assess feasibility of qFOBT as a tool for stratification of colonoscopic priority in asymptomatic patients.
    METHODS: A health awareness exhibition was held in a major shopping complex in Kuala Lumpur on 6 and 7 Feb 2010. All asymptomatic individuals> 40 years, and those < 40 with family history of CRC, were invited to participate. Eligible participants were given a questionnaire and screened using a qFOBT. A faecal haemoglobin level of 100 - 199 ng/mL was considered moderately positive, while a level of 200 ng/mL or more was strongly positive. Participants with a strongly positive qFOBT result were scheduled for a colonoscopy within the month, while those who were moderately positive were scheduled within 3 months.
    RESULTS: A total of 125 (82%) participants returned the qFOBT kit, of which 70 (56%) were male. The median age was 54 years. Majority of the participants were Chinese (60%), followed by Malay (25%), Indian (12%) and others (3%). Twelve (10%) participants were tested positive and were advised to undergo colonoscopy but 9 (75%) declined colonoscopy and further investigations citing lack of time as the reason. Of the 3 participants (all in the moderately positive group) who underwent colonoscopy, 2 had a family history of CRC. Colonoscopic findings revealed haemorrhoids in one participant and two participants had histologically proven benign sigmoid colonic polyps.
    CONCLUSION: The use of qFOBT as a tool to screen and prioritize asymptomatic patients for early colonoscopy in CRC screening is logistically feasible. However, in order for it to be effective, measures to improve compliance to colonoscopy need to be taken.
  6. Chong HY, Mohamed Z, Tan LL, Wu DBC, Shabaruddin FH, Dahlui M, et al.
    Br J Dermatol, 2017 Oct;177(4):1102-1112.
    PMID: 28346659 DOI: 10.1111/bjd.15498
    BACKGROUND: A strong association has been documented between HLA-B*15:02 and carbamazepine-induced severe cutaneous adverse reactions (SCARs) in Asians. Human leucocyte antigen testing is potentially valuable in many countries to facilitate early recognition of patient susceptibility to SCARs.

    OBJECTIVES: To determine the cost-effectiveness of universal HLA-B*15:02 screening in preventing carbamazepine-induced Stevens-Johnson syndrome/toxic epidermal necrolysis in an ethnically diverse Malaysian population.

    METHODS: A hybrid model of a decision tree and Markov model was developed to evaluate three strategies for treating newly diagnosed epilepsy among adults: (i) carbamazepine initiation without HLA-B*15:02 screening (current practice); (ii) universal HLA-B*15:02 screening prior to carbamazepine initiation; and (iii) alternative treatment [sodium valproate (VPA)] prescribing without HLA-B*15:02 screening. Base-case analysis and sensitivity analyses were performed over a lifetime time horizon. Incremental cost-effectiveness ratios were calculated.

    RESULTS: Both universal HLA-B*15:02 screening and VPA prescribing were dominated by current practice. Compared with current practice, universal HLA-B*15:02 screening resulted in a loss of 0·0255 quality-adjusted life years (QALYs) at an additional cost of 707 U.S. dollars (USD); VPA prescribing resulted in a loss of 0·2622 QALYs at an additional cost of USD 4127, owing to estimated differences in antiepileptic treatment efficacy.

    CONCLUSIONS: Universal HLA-B*15:02 screening is unlikely to be a cost-effective intervention in Malaysia. However, with the emergence of an ethnically diverse population in many other countries, this may render HLA-B*15:02 screening a viable intervention when an increasing proportion of the population is at risk and an equally effective yet safer antiepileptic drug is available.

  7. Snyder SR, Hao J, Cavallari LH, Geng Z, Elsey A, Johnson JA, et al.
    Public Health Genomics, 2018;21(5-6):217-227.
    PMID: 31189173 DOI: 10.1159/000500725
    BACKGROUND/AIMS: Economic evaluation is integral to informed public health decision-making in the rapidly growing field of precision and personalized medicine (PM); however, this research requires specialized expertise and significant resources. Generic models are a novel innovation to efficiently address a critical PM evidence shortage and implementation barrier by enabling use of population-specific input values. This is a generic PM economic evaluation model proof-of-concept study for a pharmacogenomic use case.

    METHODS: An 8-step generic economic model development process was applied to the use case of human leukocyte antigen (HLA)-B*15:02genotyping for prediction of carbamazepine-induced cutaneous reactions, with a user-friendly decision-making tool relying on user-provided input values. This generic model was transparently documented and validated, including cross-validation comparing cost-effectiveness results with 3 country-specific models.

    RESULTS: A generic pharmacogenomic use case cost-effectiveness model with decision-making tool was successfully developed and cross-validated using input values for 6 populations which produced consistent results for HLA-B*15:02 screening at country-specific cost-effectiveness threshold values. Differences between the generic and country-specific model results were largely due to differences in model structure and assumptions.

    CONCLUSION: This proof on concept demonstrates the feasibility of generic models to provide useful PM economic evidence, supporting their use as a pragmatic and timely approach to address a growing need.

  8. Bo ZM, Tan WK, Chong CSC, Lye MS, Parmasivam S, Pang ST, et al.
    PLoS One, 2022;17(11):e0277802.
    PMID: 36395327 DOI: 10.1371/journal.pone.0277802
    Acute pharyngitis (AP) is a common reason for private primary care consultations, thus providing an avenue for widespread antibiotic intake among the community. However, there is limited data on the antibiotic prescription appropriateness and resistance information in the Malaysian private primary care setting, therefore, this study aimed to investigate the prevalence of isolated viruses and bacteria, antibiotic resistance patterns, antibiotic prescription patterns and appropriateness by general practitioners (GPs) and factors affecting antibiotic resistance and antibiotic prescription patterns. To investigate, a cross-sectional study was conducted among 205 patients presenting with AP symptoms at private primary care clinics in central Malaysia from 3rd January 2016 to 30th November 2016. Throat swabs were collected from 205 AP patients for two purposes: (i) the detection of four common respiratory viruses associated with AP via reverse-transcription real-time PCR (qRT-PCR); and (ii) bacterial identification using matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF MS). Bacterial isolates were then subjected to antibiotic susceptibility screening and McIsaac scoring was calculated post-prescription based on GP selection of criteria. Generalized estimating equations analysis with multiple logistic regression was conducted to identify factors associated with presence of virus and antibiotic prescription. The results showed that 95.1% (195/205) of patients had at least one of the four viruses, with rhinovirus (88.5%) being the most prevalent, followed by adenovirus (74.9%), influenza A virus (4.6%) and enterovirus (2.1%). A total of 862 non-repetitive colonies were isolated from the culture of throat swabs from 205 patients who were positive for bacteria. From a total of 22 genera, Streptococcus constitutes the most prevalent bacteria genus (40.9%), followed by Neisseria (20%), Rothia (13.0%), Staphylococcus (11%) and Klebsiella (4.9%). Only 5 patients carried group A beta-hemolytic streptococci (GABHS). We also report the presence of vancomycin-resistant S. aureus or VRSA (n = 9, 10.1%) among which one isolate is a multidrug-resistant methicillin-resistant S. aureus (MDR-MRSA), while 54.1% (n = 111) were found to carry at least one antibiotic-resistant bacteria species. Application of the McIsaac scoring system indicated that 87.8% (n = 180) of patients should not be prescribed antibiotics as the majority of AP patients in this study had viral pharyngitis. The antibiotic prescription appropriateness by applying post-prescription McIsaac scoring was able to rule out GABHS pharyngitis in this sample with a GABHS culture-positive sensitivity of 40% (n = 2/5) and specificity of 90% (180/200). In conclusion, antibiotic-resistant throat isolates and over-prescription of antibiotics were observed and McIsaac scoring system is effective in guiding GPs to determine occurrences of viral pharyngitis to reduce unnecessary antibiotic prescription.
  9. Chong HY, Lim YH, Prawjaeng J, Tassaneeyakul W, Mohamed Z, Chaiyakunapruk N
    Pharmacogenet Genomics, 2018 02;28(2):56-67.
    PMID: 29176400 DOI: 10.1097/FPC.0000000000000319
    OBJECTIVE: Studies found a strong association between allopurinol-induced Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) and the HLA-B*58:01 allele. HLA-B*58:01 screening-guided therapy may mitigate the risk of allopurinol-induced SJS/TEN. This study aimed to evaluate the cost-effectiveness of HLA-B*58:01 screening before allopurinol therapy initiation compared with the current practice of no screening for Malaysian patients with chronic gout in whom a hypouricemic agent is indicated.

    METHODS: This cost-effectiveness analysis adopted a societal perspective with a lifetime horizon. A decision tree model coupled with Markov models were developed to estimate the costs and outcomes, represented by quality-adjusted life years (QALYs) gained, of three treatment strategies: (a) current practice (allopurinol initiation without HLA-B*58:01 screening); (b) HLA-B*58:01 screening before allopurinol initiation; and (c) alternative treatment (probenecid) without HLA-B*58:01 screening. The model was populated with data from literature review, meta-analysis, and published government documents. Cost values were adjusted for the year 2016, with costs and health outcomes discounted at 3% per annum. A series of sensitivity analysis including probabilistic sensitivity analysis were carried out to determine the robustness of the findings.

    RESULTS: Both HLA-B*58:01 screening and probenecid prescribing were dominated by current practice. Compared with current practice, HLA-B*58:01 screening resulted in 0.252 QALYs loss per patient at an additional cost of USD 322, whereas probenecid prescribing resulted in 1.928 QALYs loss per patient at an additional cost of USD 2203. One SJS/TEN case would be avoided for every 556 patients screened. At the cost-effectiveness threshold of USD 8695 per QALY, the probability of current practice being the best choice is 99.9%, in contrast with 0.1 and 0% in HLA-B*58:01 screening and probenecid prescribing, respectively. This is because of the low incidence of allopurinol-induced SJS/TEN in Malaysia and the lower efficacy of probenecid compared with allopurinol in gout control.

    CONCLUSION: This analysis showed that HLA-B*58:01 genetic testing before allopurinol initiation is unlikely to be a cost-effective intervention in Malaysia.
  10. Chong HY, Teoh SL, Wu DB, Kotirum S, Chiou CF, Chaiyakunapruk N
    Neuropsychiatr Dis Treat, 2016;12:357-73.
    PMID: 26937191 DOI: 10.2147/NDT.S96649
    BACKGROUND: Schizophrenia is one of the top 25 leading causes of disability worldwide in 2013. Despite its low prevalence, its health, social, and economic burden has been tremendous, not only for patients but also for families, caregivers, and the wider society. The magnitude of disease burden investigated in an economic burden study is an important source to policymakers in decision making. This study aims to systematically identify studies focusing on the economic burden of schizophrenia, describe the methods and data sources used, and summarize the findings of economic burden of schizophrenia.

    METHODS: A systematic review was performed for economic burden studies in schizophrenia using four electronic databases (Medline, EMBASE, PsycINFO, and EconLit) from inception to August 31, 2014.

    RESULTS: A total of 56 articles were included in this review. More than 80% of the studies were conducted in high-income countries. Most studies had undertaken a retrospective- and prevalence-based study design. The bottom-up approach was commonly employed to determine cost, while human capital method was used for indirect cost estimation. Database and literature were the most commonly used data sources in cost estimation in high-income countries, while chart review and interview were the main data sources in low and middle-income countries. Annual costs for the schizophrenia population in the country ranged from US$94 million to US$102 billion. Indirect costs contributed to 50%-85% of the total costs associated with schizophrenia. The economic burden of schizophrenia was estimated to range from 0.02% to 1.65% of the gross domestic product.

    CONCLUSION: The enormous economic burden in schizophrenia is suggestive of the inadequate provision of health care services to these patients. An informed decision is achievable with the increasing recognition among public and policymakers that schizophrenia is burdensome. This results in better resource allocation and the development of policy-oriented research for this highly disabling yet under-recognized mental health disease.

  11. Teoh SL, Chong HY, Abdul Aziz S, Chemi N, Othman AR, Md Zaki N, et al.
    Neuropsychiatr Dis Treat, 2017;13:1979-1987.
    PMID: 28814869 DOI: 10.2147/NDT.S137140
    INTRODUCTION: Schizophrenia (SCZ) is a highly debilitating disease despite its low prevalence. The economic burden associated with SCZ is substantial and mainly attributed to productivity loss. To improve the understanding of economic burden of SCZ in the low- and middle-income country regions, we aimed to determine the economic burden of SCZ in Malaysia.

    METHODS: A retrospective study was conducted using a prevalence-based approach from a societal perspective in Malaysia with a 1 year period from 2013. We used micro-costing technique with bottom-up method and included direct medical cost, direct non-medical cost, and indirect cost. The main data source was medical chart review which was conducted in Hospital Kuala Lumpur (HKL). The medical charts were identified electronically by matching the unique patient's identification number registered under the National Mental Health Schizophrenia Registry and the list of patients in HKL in 2013. Other data sources were government documents, literatures, and local websites. To ensure robustness of result, probabilistic sensitivity analysis was conducted.

    RESULTS: The total estimated number of treated SCZ cases in Malaysia in 2015 was 15,104 with the total economic burden of USD 100 million (M) which was equivalent to 0.04% of the national gross domestic product. On average, the mean cost per patient was USD 6,594. Of the total economic burden of SCZ, 72% was attributed to indirect cost, costing at USD 72M, followed by direct medical cost (26%), costing at USD 26M, and direct non-medical cost (2%), costing at USD 1.7M.

    CONCLUSION: This study highlights the magnitude of economic burden of SCZ and informs the policy-makers that there is an inadequate support for SCZ patients. More resources should be allocated to improve the condition of SCZ patients and to reduce the economic burden.

  12. Drewes JL, White JR, Dejea CM, Fathi P, Iyadorai T, Vadivelu J, et al.
    NPJ Biofilms Microbiomes, 2019 01 09;5(1):2.
    PMID: 30652010 DOI: 10.1038/s41522-018-0078-x
    [This corrects the article DOI: 10.1038/s41522-017-0040-3.].
  13. Drewes JL, White JR, Dejea CM, Fathi P, Iyadorai T, Vadivelu J, et al.
    PMID: 29214046 DOI: 10.1038/s41522-017-0040-3
    Colorectal cancer (CRC) remains the third most common cancer worldwide, with a growing incidence among young adults. Multiple studies have presented associations between the gut microbiome and CRC, suggesting a link with cancer risk. Although CRC microbiome studies continue to profile larger patient cohorts with increasingly economical and rapid DNA sequencing platforms, few common associations with CRC have been identified, in part due to limitations in taxonomic resolution and differences in analysis methodologies. Complementing these taxonomic studies is the newly recognized phenomenon that bacterial organization into biofilm structures in the mucus layer of the gut is a consistent feature of right-sided (proximal), but not left-sided (distal) colorectal cancer. In the present study, we performed 16S rRNA gene amplicon sequencing and biofilm quantification in a new cohort of patients from Malaysia, followed by a meta-analysis of eleven additional publicly available data sets on stool and tissue-based CRC microbiota using Resphera Insight, a high-resolution analytical tool for species-level characterization. Results from the Malaysian cohort and the expanded meta-analysis confirm that CRC tissues are enriched for invasive biofilms (particularly on right-sided tumors), a symbiont with capacity for tumorigenesis (Bacteroides fragilis), and oral pathogens including Fusobacterium nucleatum, Parvimonas micra, and Peptostreptococcus stomatis. Considered in aggregate, species from the Human Oral Microbiome Database are highly enriched in CRC. Although no detected microbial feature was universally present, their substantial overlap and combined prevalence supports a role for the gut microbiota in a significant percentage (>80%) of CRC cases.
  14. Choon JWY, Wu DBC, Chong HY, Lo WTL, Chong CSY, Chung WS, et al.
    J Med Econ, 2019 Mar;22(3):273-279.
    PMID: 30561238 DOI: 10.1080/13696998.2018.1560749
    BACKGROUND: Very few data are available to demonstrate the economic benefit of early paliperidone palmitate once-monthly long-acting injectable (PP1M) treatment in patients with schizophrenia or schizoaffective disorder.

    METHODS AND MATERIALS: This study has retrospectively compared the healthcare utilization and associated costs of pre- and post-PPIM treatment in 413 patients with schizophrenia or schizoaffective disorder recruited from three major public hospitals providing psychiatric services in Hong Kong. Patients were categorized into early treatment (≤3 years since diagnosis) and chronic (>3 years) groups, and also whether they were receiving polypharmacy (POP).

    RESULTS: It was found that patients who were started on early therapy with no POP had the most favourable outcomes. Overall results of the entire cohort, including both early and late treatments, indicate that there was a slight increase in annual in-patient days (IP) per patient and outpatient visit (OP) by 3.18 and 1.87, respectively, and a decrease in emergency room visit (ER) of 0.9 (p 

  15. Ho SC, Chong HY, Chaiyakunapruk N, Tangiisuran B, Jacob SA
    J Affect Disord, 2016 Mar 15;193:1-10.
    PMID: 26748881 DOI: 10.1016/j.jad.2015.12.029
    Medication non-adherence is one of the major challenges in treating patients with depression. This systematic review aims to determine the clinical and economic outcomes of non-adherence in depression.
  16. Chong HY, Low TS
    Int J Occup Saf Ergon, 2014;20(3):503-13.
    PMID: 25189753
    Safety and health issues remain critical to the construction industry due to its working environment and the complexity of working practises. This research attempts to adopt 2 research approaches using statistical data and court cases to address and identify the causes and behavior underlying construction safety and health issues in Malaysia. Factual data on the period of 2000-2009 were retrieved to identify the causes and agents that contributed to health issues. Moreover, court cases were tabulated and analyzed to identify legal patterns of parties involved in construction site accidents. Approaches of this research produced consistent results and highlighted a significant reduction in the rate of accidents per construction project in Malaysia.
  17. Chong HY, Leow CY, Leow CH
    Int J Biol Macromol, 2021 Aug 31;185:485-493.
    PMID: 34174313 DOI: 10.1016/j.ijbiomac.2021.06.146
    Co-existence of Japanese Encephalitis virus (JEV) with highly homologous antigenic epitopes results in antibody-based serodiagnosis being inaccurate at detecting and distinguishing JEV from other flaviviruses. This often causes misdiagnosis and inefficient treatments of flavivirus infection. Generation of JEV NS1 protein remains a challenge as it is notably expressed in the form of inactive aggregates known as inclusion bodies using bacterial expression systems. This study evaluated two trxB and gor E. coli strains in producing soluble JEV NS1 via a cold-shock expression system. High yield of JEV NS1 inclusion bodies was produced using cold-shocked expression system. Subsequently, a simplified yet successful approach in generating soluble, active JEV NS1 protein through solubilization, purification and in vitro refolding of JEV NS1 protein from inclusion bodies was developed. A step-wise dialysis refolding approach was used to facilitate JEV NS1 refolding. The authenticity of the refolded JEV NS1 was confirmed by specific antibody binding on indirect ELISA commercial anti-NS1 antibodies which showed that the refolded JEV NS1 was highly immunoreactive. This presented approach is cost-effective, and negates the need for mammalian or insect cell expression systems in order to synthesize this JEV NS1 protein of important diagnostic and therapeutic relevance in Japanese Encephalitis disease.
  18. Chong CS, Chong HY, Fun HK, Leong LS
    Health Phys, 1985 Nov;49(5):1008-10.
    PMID: 4066326
  19. Wu DBC, Chaiyakunapruk N, Pratoomsoot C, Lee KKC, Chong HY, Nelson RE, et al.
    Epidemiol Infect, 2018 03;146(4):496-507.
    PMID: 29446343 DOI: 10.1017/S0950268818000158
    Simulation models are used widely in pharmacology, epidemiology and health economics (HEs). However, there have been no attempts to incorporate models from these disciplines into a single integrated model. Accordingly, we explored this linkage to evaluate the epidemiological and economic impact of oseltamivir dose optimisation in supporting pandemic influenza planning in the USA. An HE decision analytic model was linked to a pharmacokinetic/pharmacodynamics (PK/PD) - dynamic transmission model simulating the impact of pandemic influenza with low virulence and low transmissibility and, high virulence and high transmissibility. The cost-utility analysis was from the payer and societal perspectives, comparing oseltamivir 75 and 150 mg twice daily (BID) to no treatment over a 1-year time horizon. Model parameters were derived from published studies. Outcomes were measured as cost per quality-adjusted life year (QALY) gained. Sensitivity analyses were performed to examine the integrated model's robustness. Under both pandemic scenarios, compared to no treatment, the use of oseltamivir 75 or 150 mg BID led to a significant reduction of influenza episodes and influenza-related deaths, translating to substantial savings of QALYs. Overall drug costs were offset by the reduction of both direct and indirect costs, making these two interventions cost-saving from both perspectives. The results were sensitive to the proportion of inpatient presentation at the emergency visit and patients' quality of life. Integrating PK/PD-EPI/HE models is achievable. Whilst further refinement of this novel linkage model to more closely mimic the reality is needed, the current study has generated useful insights to support influenza pandemic planning.
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