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  1. Man KKC, Shao SC, Chaiyakunapruk N, Dilokthornsakul P, Kubota K, Li J, et al.
    Eur Child Adolesc Psychiatry, 2022 Jan;31(1):99-120.
    PMID: 33185773 DOI: 10.1007/s00787-020-01674-6
    It is known that younger patients treated with antipsychotics are at increased risk of metabolic events; however, it is unknown how this risk varies according to ethnicity, the class of antipsychotic and the specific product used, and by age group. We conducted a multinational sequence symmetry study in Asian populations (Hong Kong, Japan, Korea, Taiwan and Thailand) and non-Asian populations (Australia and Denmark) to evaluate the metabolic events associated with antipsychotics in both Asian and non-Asian populations, for typical and atypical antipsychotics, and by the subgroups of children and adolescents, and young adults. Patients aged 6-30 years newly initiating oral antipsychotic drugs were included. We defined a composite outcome for metabolic events which included dyslipidemia, hypertension and hyperglycemia. We calculated the sequence ratio (SR) by dividing the number of people for whom a medicine for one of the outcome events was initiated within a 12-month period after antipsychotic initiation by the number before antipsychotic initiation. This study included 346,904 antipsychotic initiators across seven countries. Antipsychotic use was associated with an increased risk of composite metabolic events with a pooled adjusted SR (ASR) of 1.22 (95% CI 1.00-1.50). Pooled ASRs were similar between Asian (ASR, 1.22; 95% CI 0.88-1.70) and non-Asian populations (ASR, 1.22; 95% CI 1.04-1.43). The pooled ASR for typical and atypical antipsychotics was 0.98 (95% CI 0.85-1.12) and 1.24 (95% CI 0.97-1.59), respectively. No difference was observed in the relative effect in children and adolescents compared to young adults. The risk of metabolic events associated with antipsychotics use was similar in magnitude in Asian and non-Asian populations despite the marked difference in drug utilization patterns.
  2. Kongpakwattana K, Dilokthornsakul P, Dhippayom T, Chaiyakunapruk N
    J Med Econ, 2020 Oct;23(10):1046-1052.
    PMID: 32580609 DOI: 10.1080/13696998.2020.1787420
    BACKGROUND: This study aimed to understand the clinical and economic burden associated with postsurgical complications in high-risk surgeries in Thailand.

    METHODS: A cost and outcome study was conducted using a retrospective cohort database from four tertiary hospitals. All patients with high-risk surgeries visiting the hospitals from 2011 to 2017 were included. Outcomes included major postsurgical complications, length of stay (LOS), in-hospital death, and total healthcare costs. Multivariate regression analyses were performed to identify risk factors of postsurgical outcomes.

    RESULTS: A total of 14,930 patients were identified with an average age of 57.7 ± 17.0 years and 34.9% being male. Gastrointestinal (GI) procedures were the most common high-risk procedures, accounting for 54.9% of the patients, followed by cardiovascular (CV) procedures (25.2%). Approximately 27.2% of the patients experienced major postsurgical complications. The top three complications were respiratory failure (14.0%), renal failure (3.5%), and myocardial infarction (3.4%). In-hospital death was 10.0%. The median LOS was 9 days. The median total costs of all included patients were 2,592 US$(IQR: 1,399-6,168 US$). The patients, who received high-risk GI surgeries and experienced major complications, had significantly increased risk of in-hospital death (OR: 4.53; 95%CI: 3.81-5.38), longer LOS (6.53 days; 95%CI: 2.60-10.46 days) and higher median total costs (2,465 US$; 95%CI: 1,945-2,984 US$), compared to those without major complications. Besides, the patients, who underwent high-risk CV surgeries and developed major complications, resulted in significantly elevated risk of in-hospital death (OR: 2.22; 95%CI: 1.74-2.84) and increased median total costs (2,719 US$; 95%CI: 2,129-3,310 US$), compared to those without major complications.

    CONCLUSIONS: Postsurgical complications are a serious problem in Thailand, as they are associated with worsening mortality risk, LOS, and healthcare costs. Clinicians should develop interventions to prevent or effectively treat postsurgical complications to mitigate such burdens.

  3. Sawangjit R, Dilokthornsakul P, Lloyd-Lavery A, Lai NM, Dellavalle R, Chaiyakunapruk N
    Cochrane Database Syst Rev, 2020 Sep 14;9(9):CD013206.
    PMID: 32927498 DOI: 10.1002/14651858.CD013206.pub2
    BACKGROUND: Eczema is a common and chronic, relapsing, inflammatory skin disorder. It seriously impacts quality of life and economic outcomes, especially for those with moderate to severe eczema. Various treatments allow sustained control of the disease; however, their relative benefit remains unclear due to the limited number of trials directly comparing treatments.

    OBJECTIVES: To assess the comparative efficacy and safety of different types of systemic immunosuppressive treatments for moderate to severe eczema using NMA and to generate rankings of available systemic immunosuppressive treatments for eczema according to their efficacy and safety.

    SEARCH METHODS: We searched the following databases up to August 2019: the Cochrane Skin Specialised Register, CENTRAL, MEDLINE, and Embase.

    SELECTION CRITERIA: All randomised controlled trials (RCTs) of systemic immunosuppressive agents for moderate to severe atopic eczema when compared against placebo or any other eligible eczema treatment.

    DATA COLLECTION AND ANALYSIS: We synthesised data using pair-wise analysis and NMA to compare treatments and rank them according to their effectiveness. Effectiveness was assessed primarily by determining the proportion of participants who achieved at least 75% improvement in the Eczema Area and Severity Index (EASI75) and improvement in the Patient-Oriented Eczema Measure (POEM). Safety was evaluated primarily by considering the proportion of participants with serious adverse events (SAEs) and infection. We deemed short-term follow-up as ≤ 16 weeks and long-term follow-up as > 16 weeks. We assessed the certainty of the body of evidence from the NMA for these primary outcomes using six domains of CiNEMA grading.

    MAIN RESULTS: We included a total of 74 studies, with 8177 randomised participants. Approximately 55% of participants were male, with average age of 32 years (range 2 to 84 years), although age and gender were unreported for 419 and 902 participants, respectively. Most of the included trials were placebo controlled (65%), 34% were head-to-head studies (15% assessed the effects of different doses of the same drug), and 1% were multi-armed studies with both an active comparator and a placebo. All trials included participants with moderate to severe eczema, but 62% of studies did not separate data by severity; 38% of studies assessed only severe eczema. The total duration of included trials ranged from 2 weeks to 60 months, whereas treatment duration varied from a single dose (CIM331, KPL-716) to 60 months (methotrexate (MTX)). Seventy studies were available for quantitative synthesis; this review assessed 29 immunosuppressive agents from three classes of interventions. These included (1) conventional treatments, with ciclosporin assessed most commonly; (2) small molecule treatments, including phosphodiesterase (PDE)-4 inhibitors, tyrosine kinase inhibitors, and Janus kinase (JAK) inhibitors; and (3) biological treatments, including anti-CD31 receptors, anti-interleukin (IL)-22, anti-IL-31, anti-IL-13, anti-IL-12/23p40, anti-OX40, anti-TSLP, anti-CRTH2, and anti-immunoglobulin E (IgE) monoclonal antibodies, but most commonly dupilumab. Most trials (73) assessed outcomes at a short-term duration ranging from 2 to 16 weeks, whereas 33 trials assessed long-term outcomes, with duration ranging from 5 to 60 months. All participants were from a hospital setting. Fifty-two studies declared a source of funding, and of these, pharmaceutical companies funded 88%. We rated 37 studies as high risk; 21, unclear risk, and 16, low risk of bias, with studies most commonly at high risk of attrition bias. Network meta-analysis suggests that dupilumab ranks first for effectiveness when compared with other biological treatments. Dupilumab is more effective than placebo in achieving EASI75 (risk ratio (RR) 3.04, 95% confidence interval (CI) 2.51 to 3.69) and improvement in POEM score (mean difference 7.30, 95% CI 6.61 to 8.00) at short-term follow-up (high-certainty evidence). Very low-certainty evidence means we are uncertain of the effects of dupilumab when compared with placebo, in terms of the proportion of participants who achieve EASI75 (RR 2.59, 95% CI 1.87 to 3.60) at longer-term follow-up. Low-certainty evidence indicates that tralokinumab may be more effective than placebo in achieving short-term EASI75 (RR 2.54, 95% CI 1.21 to 5.34), but there was no evidence for tralokinumab to allow us to assess short-term follow-up of POEM or long-term follow-up of EASI75. We are uncertain of the effect of ustekinumab compared with placebo in achieving EASI75 (long-term follow-up: RR 1.17, 95% CI 0.40 to 3.45; short-term follow-up: RR 0.91, 95% CI 0.28 to 2.97; both very low certainty). We found no evidence on ustekinumab for the POEM outcome. We are uncertain whether other immunosuppressive agents that targeted our key outcomes influence the achievement of short-term EASI75 compared with placebo due to low- or very low-certainty evidence. Dupilumab and ustekinumab were the only immunosuppressive agents evaluated for longer-term EASI75. Dupilumab was the only agent evaluated for improvement in POEM during short-term follow-up. Low- to moderate-certainty evidence indicates a lower proportion of participants with SAEs after treatment with QAW039 and dupilumab compared to placebo during short-term follow-up, but low- to very low-certainty evidence suggests no difference in SAEs during short-term follow-up of other immunosuppressive agents compared to placebo. Evidence for effects of immunosuppressive agents on risk of any infection during short-term follow-up and SAEs during long-term follow-up compared with placebo was of low or very low certainty but did not indicate a difference. We did not identify differences in other adverse events (AEs), but dupilumab is associated with specific AEs, including eye inflammation and eosinophilia.

    AUTHORS' CONCLUSIONS: Our findings indicate that dupilumab is the most effective biological treatment for eczema. Compared to placebo, dupilumab reduces eczema signs and symptoms in the short term for people with moderate to severe atopic eczema. Short-term safety outcomes from clinical trials did not reveal new safety concerns with dupilumab. Overall, evidence for the efficacy of most other immunosuppressive treatments for moderate to severe atopic eczema is of low or very low certainty. Given the lack of data comparing conventional with newer biological treatments for the primary outcomes, there remains high uncertainty for ranking the efficacy and safety of conventional treatments such as ciclosporin and biological treatments such as dupilumab. Most studies were placebo-controlled and assessed only short-term efficacy of immunosuppressive agents. Further adequately powered head-to-head RCTs should evaluate comparative long-term efficacy and safety of available treatments for moderate to severe eczema.

  4. Ounsirithupsakul T, Dilokthornsakul P, Kongpakwattana K, Ademi Z, Liew D, Chaiyakunapruk N
    Appl Health Econ Health Policy, 2020 08;18(4):579-587.
    PMID: 32009211 DOI: 10.1007/s40258-020-00553-0
    BACKGROUND: Pneumococcal diseases were estimated to cause 1.6 million deaths annually worldwide in 2008, with approximately half of these occurring in children aged under 5 years. The consequences and deaths adversely impact individuals' and caregivers' work productivity.

    OBJECTIVES: This study aimed to quantify the potential lifetime productivity loss due to pneumococcal diseases among the pediatric population in Thailand using productivity-adjusted life years (PALYs).

    METHODS: A decision analytic model was used to estimate the burden of pneumococcal diseases among the current Thai population aged 0-5 years and followed up until aged 99 years or death. Base-case analysis compared years of life and PALYs lost to pneumococcal diseases. Scenario analyses investigated the benefits of prevention with pneumococcal conjugated vaccine 13 (PCV 13). All health outcomes were discounted at 3% per annum.

    RESULTS: The base-case analysis estimated that 453,401 years of life and 457,598 PALYs would be lost to pneumococcal diseases, equating to a loss of US$5586 (95% CI 3338-10,302) million. Vaccination with PCV13 at birth was estimated to save 82,609 years of life and 93,759 PALYs, which equated to US$1144 (95% CI 367-2591) million in economic benefits. The incidence of pneumonia in those aged 0-4 years, vaccine efficacy, and the assumed period of protection were key determinants of the health economic outputs.

    CONCLUSIONS: The disease and financial burden of pneumococcal diseases in Thailand is significant, but a large proportion of this is potentially preventable with vaccination.

  5. Nagendrababu V, Dilokthornsakul P, Jinatongthai P, Veettil SK, Pulikkotil SJ, Duncan HF, et al.
    Int Endod J, 2020 Feb;53(2):232-249.
    PMID: 31520403 DOI: 10.1111/iej.13217
    A systematic review aims to answer a focussed research question through a structured review of the evidence, using a predefined methodology, which often includes a meta-analysis. A meta-analysis is a statistical method used to combine the effect estimates from the individual studies included in a systematic review. Systematic reviews and meta-analyses are positioned at the highest level in the hierarchy of clinical evidence. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement was introduced in 2009 to help authors improve the quality and reliability of systematic reviews and meta-analyses. Recently, the volume of systematic reviews and meta-analyses in the field of Endodontology has increased; however, the quality of the published manuscripts has been reported to be sub-optimal, which does not take account of the systematic reviews that were rejected because of more obvious deficiencies. The aim of this paper is to present a comprehensive glossary of terminology commonly used in systematic reviews and meta-analyses in an attempt to provide easily understood definitions and explanations to assist authors when reporting systematic reviews and meta-analyses and to allow those wishing to read them to become better informed.
  6. Ng SS, Lai NM, Nathisuwan S, Jahan NK, Dilokthornsakul P, Kongpakwattana K, et al.
    Sci Rep, 2020 01 20;10(1):662.
    PMID: 31959803 DOI: 10.1038/s41598-019-57370-2
    Warfarin care bundles (e.g. genotype-guided warfarin dosing, patient's self-testing [PST] or patient's self-management [PSM] and left atrial appendage closure) are based on the concept of combining several interventions to improve anticoagulation care. NOACs are also introduced for stroke prevention in atrial fibrillation (SPAF). However, these interventions have not been compared in head-to-head trials yet. We did a network meta-analysis based on a systematic review of randomized controlled trials comparing anticoagulant interventions for SPAF. Studies comparing these interventions in adults, whether administered alone or as care bundles were included in the analyses. The primary efficacy outcome was stroke and the primary safety outcome was major bleeding. Thirty-seven studies, involving 100,142 patients were assessed. Compared to usual care, PSM significantly reduced the risk of stroke (risk ratio [RR] 0.24, 95% CI 0.08-0.68). For major bleeding, edoxaban 60 mg (0.80, 0.71-0.90), edoxaban 30 mg (0.48, 0.42-0.56), and dabigatran 110 mg (0.81, 0.71-0.94) significantly reduced the risk of major bleeding compared with usual warfarin care. Cluster rank plot incorporating stroke and major bleeding outcomes indicates that some warfarin care bundles perform as well as NOACs. Both interventions are therefore viable options to be considered for SPAF. Additional studies including head-to-head trials and cost-effectiveness evaluation are still warranted.
  7. Kongpakwattana K, Dejthevaporn C, Krairit O, Dilokthornsakul P, Mohan D, Chaiyakunapruk N
    Value Health, 2019 10;22(10):1137-1145.
    PMID: 31563256 DOI: 10.1016/j.jval.2019.04.1937
    BACKGROUND: Although an increase in the burden of Alzheimer's disease (AD) is evident worldwide, knowledge of costs and health-related quality of life (HRQOL) associated with AD in low- and middle-income countries is still lacking.

    OBJECTIVES: This study aimed to collect real-world cost and HRQOL data, and investigate their associations with multiple disease-severity indicators among AD patients in Thailand.

    METHODS: We recruited AD patients aged ≥60 years accompanied by their caregivers at a university-affiliated tertiary hospital. A one-time structured interview was conducted to collect disease-severity indicators, HRQOL, and caregiving information using standardized tools. The hospital's database was used to retrieve healthcare resource utilization occurred over 6 months preceding the interview date. Costs were annualized and stratified based on cognitive status. Generalized linear models were employed to evaluate determinants of costs and HRQOL.

    RESULTS: Among 148 community-dwelling patients, average annual total societal costs of AD care were $8014 (95% confidence interval [CI]: $7295-$8844) per patient. Total costs of patients with severe stage ($9860; 95% CI: $8785-$11 328) were almost twice as high as those of mild stage ($5524; 95% CI: $4649-$6593). The major cost driver was direct medical costs, particularly those incurred by AD prescriptions. Functional status was the strongest determinant for both total costs and patient's HRQOL (P value

  8. Chongmelaxme B, Chaiyakunapruk N, Dilokthornsakul P
    J Med Econ, 2019 Jun;22(6):554-566.
    PMID: 30663455 DOI: 10.1080/13696998.2019.1572014
    Aims: Non-adherence is associated with poor clinical outcomes among patients with asthma. While cost-effectiveness analysis (CEA) is increasingly used to inform value assessment of the interventions, most do not take into account adherence in the analyses. This study aims to: (1) Understand the extent of studies considering adherence as part of the economic analyses, and (2) summarize the methods of incorporating adherence in the economic models. Materials and methods: A literature search was performed from the inception to February 2018 using four databases: PubMed, EMBASE, NHS EED, and the Tufts CEA registry. Decision model-based CEA of asthma were identified. Outcomes of interest were the number of studies incorporating adherence in the economic models, and the incorporating methods. All data were extracted using a standardized data collection form. Results: From 1,587 articles, 23 studies were decision model-based CEA of asthma, of which four CEA (17.4%) incorporated adherence in the analyses. Only the method of incorporating adherence by adjusting treatment effectiveness according to adherence levels was demonstrated in this review. Two approaches were used to derive the associations between adherence and effectiveness. The first approach was to apply a mathematical formula, developed by an expert panel, and the second was to extrapolate the associations from previous published studies. The adherence-adjusted effectiveness was then incorporated in the economic models. Conclusions: A very low number of CEA of asthma incorporated adherence in the analyses. All the CEA adjusted treatment effectiveness according to adherence levels, applied to the economic models.
  9. Chongmelaxme B, Phisalprapa P, Manthaisong R, Dilokthornsakul P, Chaiyakunapruk N
    Pharmacoeconomics, 2019 Feb;37(2):291.
    PMID: 30547370 DOI: 10.1007/s40273-018-0754-y
    Weight Reduction is Cost-Effective for the Treatment of Non-alcoholic Fatty Liver Disease in Thailand.
  10. Chongmelaxme B, Phisalprapa P, Sawangjit R, Dilokthornsakul P, Chaiyakunapruk N
    Pharmacoeconomics, 2019 02;37(2):267-278.
    PMID: 30430467 DOI: 10.1007/s40273-018-0736-0
    INTRODUCTION: This study evaluated lifetime liver-related clinical outcomes, costs of treatment, and the cost-effectiveness of treatment options for non-alcoholic fatty liver disease (NAFLD) in Thailand.

    METHODS: A cost-utility analysis using a lifetime Markov model was conducted among Thai patients with NAFLD, from a societal perspective. Pioglitazone, vitamin E, a weight reduction program, and usual care were investigated, with the outcomes of interest being the number of cirrhosis and hepatocellular carcinoma (HCC) cases, life expectancy, quality-adjusted life-years (QALYs), lifetime costs, and the incremental cost-effectiveness ratios (ICERs). One-way and probabilistic sensitivity analyses were performed.

    RESULTS: When compared with usual care, a weight reduction program can prevent cirrhosis and HCC cases by 13.91% (95% credible interval [CrI] 0.97, 20.59) and 2.12% (95% CrI 0.43, 4.56), respectively; pioglitazone can prevent cirrhosis and HCC cases by 9.30% (95% CrI -2.52, 15.24) and 1.42% (95% CrI -0.18, 3.74), respectively; and vitamin E can prevent cirrhosis and HCC cases by 7.32% (95% CrI -4.64, 15.56) and 1.12% (95% CrI -0.81, 3.44), respectively. Estimated incremental life expectancy and incremental QALYs for all treatment options compared with usual care were approximately 0.06 years and 0.07 QALYs, respectively. The lifetime costs of both a weight reduction program and pioglitazone were less than usual care, while vitamin E was $3050 (95% CrI 2354, 3650). The weight reduction program dominated all other treatment options. The probability of being cost-effective in Thailand's willingness-to-pay threshold ($4546/QALY gained) was 76% for the weight reduction program, 22% for pioglitazone, 2% for usual care, and 0% for vitamin E.

    CONCLUSIONS: A weight reduction program can prevent cirrhosis and HCC occurrences, and dominates all other treatment options. Pioglitazone and vitamin E demonstrated a trend towards decreasing the number of cirrhosis and HCC cases.

  11. Chongmelaxme B, Lee S, Dhippayom T, Saokaew S, Chaiyakunapruk N, Dilokthornsakul P
    J Allergy Clin Immunol Pract, 2019 01;7(1):199-216.e11.
    PMID: 30055283 DOI: 10.1016/j.jaip.2018.07.015
    BACKGROUND: Telemedicine is increasingly used to improve health outcomes in asthma. However, it is still inconclusive which telemedicine works effectively.

    OBJECTIVE: This study aimed to determine the effects of telemedicine on asthma control and the quality of life in adults.

    METHODS: An electronic search was performed from the inception to March 2018 on the following databases: Cochrane CENTRAL, CINAHL, ClinicalTrials.gov, EMBASE, PubMed, and Scopus. Randomized controlled trials that assessed the effects of telemedicine in adults with asthma were included in this analysis, and the outcomes of interest were levels of asthma control and quality of life. Random-effects model meta-analyses were performed.

    RESULTS: A total of 22 studies (10,281 participants) were included. Each of 11 studies investigated the effects of single-telemedicine and combined-telemedicine (combinations of telemedicine approaches), and the meta-analyses showed that combined tele-case management could significantly improve asthma control compared with usual care (standardized mean difference [SMD] = 0.78; 95% confidence interval [CI]: 0.56, 1.01). Combined tele-case management and tele-consultation (SMD = 0.52 [95% CI: 0.13, 0.91]) and combined tele-consultation (SMD = 0.28 [95% CI: 0.13, 0.44]) also significantly improved asthma outcomes, but to a lesser degree. In addition, combined tele-case management (SMD = 0.59 [95% CI: 0.31, 0.88]) was the most effective telemedicine for improving quality of life, followed by combined tele-case management and tele-consultation (SMD = 0.31 [95% CI: 0.03, 0.59]), tele-case management (SMD = 0.30 [95% CI: 0.05, 0.55]), and combined tele-consultation (SMD = 0.27 [95% CI: 0.11, 0.43]), respectively.

    CONCLUSIONS: Combined-telemedicine involving tele-case management or tele-consultation appear to be effective telemedicine interventions to improve asthma control and quality of life in adults. Our findings are expected to provide health care professionals with current evidence of the effects of telemedicine on asthma control and patients' quality of life.

  12. Kongpakwattana K, Dilokthornsakul P, Dejthevaporn C, Pattanaprateep O, Chaiyakunapruk N
    J Med Econ, 2019 Jan;22(1):26-34.
    PMID: 30303420 DOI: 10.1080/13696998.2018.1534739
    Aims: Due to the lack of studies evaluating compliance or persistence with Alzheimer's Disease (AD) treatment outside High-Income Countries (HICs), this study aimed to assess compliance, persistence, and factors associated with non-compliance and non-persistence by utilizing existing "real-world" information from multiregional hospital databases in Thailand.Materials and methods: Study subjects were retrospectively identified from databases of five hospitals located in different regions across Thailand. AD patients aged ≥60 years who were newly-prescribed with donepezil, galantamine, rivastigmine, or memantine between 2013 and 2017 were eligible for analysis. The Medication Possession Ratio (MPR) was used as a proxy for compliance, while the Kaplan-Meier survival analysis was employed to estimate persistence. Logistic and Cox regressions were used to assess determinants of non-compliance and non-persistence, adjusted for age and gender.Results: Among 698 eligible patients, mean (SD) MPR was 0.83 (0.25), with 70.3% of the patients compliant to the treatment (having MPR ≥ 0.80). Half of the patients discontinued their treatment (having a treatment gap >30 days) within 177 days with a 1-year persistence probability of 21.1%. The patients treated in the university-affiliated hospital were more likely to be both non-compliant (OR = 1.71; 95% CI = 1.21-2.42) and non-persistent (HR = 1.33; 95% CI = 1.12-1.58). In addition, non-compliance was higher for those prescribed with single AD treatment (OR = 2.52; 95% CI = 1.35-4.69), while non-persistence was higher for those unable to reimburse for AD treatment (HR = 1.34; 95% CI = 1.11-1.62).Limitations: By using retrospective databases, a difficulty in validating whether the medications are actually taken after being refilled may over-estimate the levels of compliance and persistence. Meanwhile, possible random coding errors may under-estimate the strength of association findings.Conclusions: This study reveals the situation of compliance and persistence on AD treatment for the first time outside HICs. The determinants of non-compliance and non-persistence underline key areas for improvement.
  13. Chaiyasothi T, Nathisuwan S, Dilokthornsakul P, Vathesatogkit P, Thakkinstian A, Reid C, et al.
    Front Pharmacol, 2019;10:547.
    PMID: 31191304 DOI: 10.3389/fphar.2019.00547
    Background: Currently, there is a lack of information on the comparative efficacy and safety of non-statin lipid-lowering agents (NST) in cardiovascular (CV) disease risk reduction when added to background statin therapy (ST). This study determine the relative treatment effects of NST on fatal and non-fatal CV events among statin-treated patients. Methods: A network meta-analysis based on a systematic review of randomized controlled trials (RCTs) comparing non-statin lipid-modifying agents among statin-treated patients was performed. PubMed, EMBASE, CENTRAL, and Clinicaltrial.gov were searched up to April 10, 2018. The primary outcomes were CV and all-cause mortalities. Secondary CV outcomes were coronary heart disease (CHD) death, non-fatal myocardial infarction (MI), any stroke, and coronary revascularization. Risks of discontinuations were secondary safety outcomes. Results: Sixty-seven RCTs including 259,429 participants with eight interventions were analyzed. No intervention had significant effects on the primary outcomes (CV mortality and all-cause mortality). For secondary endpoints, proprotein convertase subtilisin/kexin type 9 inhibitor (PCSK) plus statin (PCSK/ST) significantly reduced the risk of non-fatal MI (RR 0.82, 95% CI 0.72-0.93, p = 0.003), stroke (RR 0.74, 95% CI 0.65-0.85, p < 0.001), coronary revascularization (RR 0.84, 95% CI 0.75-0.94, p = 0.003) compared to ST. Combinations of ST and all NST except PCSK and ezetimibe showed higher rate of discontinuation due to adverse events compared to ST. Conclusions: None of NST significantly reduced CV or all-cause death when added to ST. PCSKs and to a lesser extent, ezetimibe may help reduce cardiovascular events with acceptable tolerability profile among broad range of patients.
  14. Dokbua S, Dilokthornsakul P, Chaiyakunapruk N, Saini B, Krass I, Dhippayom T
    J Manag Care Spec Pharm, 2018 Nov;24(11):1184-1196.
    PMID: 30362920 DOI: 10.18553/jmcp.2018.24.11.1184
    BACKGROUND: Current evidence of the effects of pharmacy services on asthma outcomes are not conclusive, since most pharmacy services comprise a variety of interventions.

    OBJECTIVE: To assess the effect of a service containing self-management support delivered by community pharmacists to patients with asthma.

    METHODS: A systematic search was performed in the following databases from inception to January 2017: PubMed, Embase, Cochrane Library's Central Register of Controlled Trials, CINAHL (Cumulative Index to Nursing and Allied Health Literature) Plus, International Pharmaceutical Abstracts, and PsycInfo. Original studies were selected if they met the following criteria: (a) provided by community pharmacists; (b) the intervention service included the essential components of asthma self-management; (c) included a usual care group; and (d) measured control/severity of asthma symptoms, health-related quality of life (HRQOL), or medication adherence.

    RESULTS: Of the 639 articles screened, 12 studies involving 2,121 asthma patients were included. Six studies were randomized trials, and the other 6 were nonrandomized trials. Patients with asthma who received a self-management support service by community pharmacists had better symptom control/lower severity compared with those receiving usual care (standardized mean difference [SMD] = 0.46; 95% CI = 0.09-0.82) with high heterogeneity (I2=82.6%; P = 0.000). The overall improvement in HRQOL and medication adherence among patients in the asthma self-management support group was greater than for those in the usual care group with SMD of 0.23 (95% CI = 0.12-0.34) and 0.44 (95% CI = 0.27-0.61), respectively. Evidence of heterogeneity was not observed in these 2 outcomes.

    CONCLUSIONS: Self-management support service provided by community pharmacists can help improve symptom control, quality of life, and medication adherence in patients with asthma.

    DISCLOSURES: This study received financial support from Naresuan University's Faculty of Pharmaceutical Sciences Research Fund. Two authors, Saini and Krass, have studies that were included in this review. However, they were not involved in the processes that could bias outcomes of the present study, that is, quality assessment and meta-analysis. The remaining authors have declared no conflicts of interest.

  15. Kongkaew C, Scholfield NC, Dhippayom T, Dilokthornsakul P, Saokaew S, Chaiyakunapruk N
    J Ethnopharmacol, 2018 Apr 24;216:162-174.
    PMID: 29409850 DOI: 10.1016/j.jep.2018.01.028
    ETHNOPHARMACOLOGICAL RELEVANCE: Pueraria candollei var. mirifica (Airy Shaw & Suvat.) Niyomdham (commonly termed P. mirifica, PM) growing in upland Thailand has a long history as a postmenopausal rejuvenant therapy for indigenants. Its amelioration of menopause symptoms in clinical trials was assessed.

    MATERIALS AND METHODS: International and Thai databases were searched from inception to February 2017. Clinical trials investigating effects of PM menopausal or postmenopausal women were included. Outcomes were self-reported menopausal symptoms, serum reproductive hormones, urino-genital tract function, and bone surrogates. Methodological quality was assessed by Cochrane risk-of-bias v2.0, and a 22-parameter quality score based on the CONSORT checklist for herbal medicines.

    RESULTS: Eight studies (9 articles) used data from 309 menopausal patients. Five-studies demonstrated that PM was associated with climacteric scores reduced by ~50% compared to baseline. Other PM studies using limited numbers of placebo participants suggested improved vaginal and other urogenital tract symptoms. Bone alkaline phosphatase halved (suggesting lowered bone turnover). Variable serum reproductive hormone levels suggested menopausal status differed between studies. PM active ingredients and sources were not defined. Adverse event rates (mastodynia, vaginal spotting, dizziness) were similar in all groups (PM, conjugated equine estrogen, and placebos) but serum C-reactive protein doubled. These studies had design and reporting deficiencies, high risks of biases, and low quality scores.

    CONCLUSIONS: The efficacy of PM on menopausal symptoms remains inconclusive because of methodological short-comings especially placebo effects inherent in self-assessment/recall questionnaires and no PM standardization. PM efficacy and safety need a fundamental re-appraisal by: (i) cohort (retro- and prospective) studies on current users to define its traditional use for rejuvenation; (ii) tightly coupling long-term efficacy to safety of well-defined PM and multiple end-points; (iii) using study design related to current understanding of menopause progression and estrogen pharmacology (iv) robust pharmacovigilance.

  16. Mahlich J, Dilokthornsakul P, Sruamsiri R, Chaiyakunapruk N
    PMID: 29881328 DOI: 10.1186/s12962-018-0103-1
    Background: Health-care utilities differ considerably from country to country. Our objective was to examine the association of cultural values based on Hofstede's cultural dimensions' theory with utility values that were identified using the time trade off method.

    Methods: We performed a literature search to determine preference-based value algorithms in the general population of a given country. We then fitted a second-order quadratic function to assess the utility function curve that links health status with health-care utilities. We ranked the countries according to the concavity and convexity properties of their utility functions and compared this ranking with that of the Hofstede index to check if there were any similarities.

    Results: We identified 10 countries with an EQ-5D-5L-based value set and 7 countries with an EQ-5D-3L-based value set. Japan's degree of concavity was highest, while Germany's was lowest, based on the EQ-5D-3L and EQ-5D-5L value sets. Japan also ranked first in the Hofstede long-term orientation index, and rankings related to the degree of concavity, indicating a low time preference rate.

    Conclusions: This is the first evaluation to identify and report an association between different cultural beliefs and utility values. These findings underline the necessity to take local values into consideration when designing health technology assessment systems.

  17. Chongmelaxme B, Sruamsiri R, Dilokthornsakul P, Dhippayom T, Kongkaew C, Saokaew S, et al.
    Complement Ther Med, 2017 Dec;35:70-77.
    PMID: 29154071 DOI: 10.1016/j.ctim.2017.09.009
    Zingiber cassumunar Roxb. known locally as "Plai" in Thai, has been used for treating bruise, sprain and musculoskeletal pain. Several pre-clinical studies demonstrated the anti-inflammatory effect of Plai. However, current evidence of clinical effects of Plai is still unclear. This study aimed to determine the clinical efficacy and safety of Plai among all identified indications. Of the 808 articles identified by a systematic review, six studies were included. Four studies were randomized controlled trials, while two studies were quasi-experimental studies involving 178 patients in intervention group and 177 patients in control group. Duration of treatment ranged from 7days to 2 months. Our findings showed that 14% Plai cream had a strong trend of benefits in pain reduction for muscle pain and ankle sprain. However, evidence supporting the effects of Plai on acne vulgaris treatment and anti-histamine effect are still unclear.
  18. Puttarak P, Dilokthornsakul P, Saokaew S, Dhippayom T, Kongkaew C, Sruamsiri R, et al.
    Sci Rep, 2017 09 06;7(1):10646.
    PMID: 28878245 DOI: 10.1038/s41598-017-09823-9
    Centella asiatica (L.) Urb. has been used as an herbal brain tonic for mental disorders and enhancing memory, but no review of the overall evidence of C. asiatica and cognitive function has been conducted. This study aims to determine the effects of C. asiatica on cognitive function and its related properties. The current systematic review includes five randomized controlled trials (RCTs) conducted to determine the effect of C. asiatica alone and six RCTs conducted to determine the effect of C. asiatica-containing products. Meta-analysis indicated that there are no significant differences in all cognitive function domains of C. asiatica when compared to placebo. However, it could improve mood by increasing alert scores [SMD: 0.71 (95% CI; 0.01 to 1.41); I2 = 30.5%] and decreasing anger scores at 1 hour after treatment [SMD: -0.81 (95%CI; -1.51 to -0.09); I2 = 36.6%]. None of the studies reported adverse effects of C. asiatica. In conclusion, there is not strong evidence to support the use of C. asiatica for cognitive function improvement in each cognitive domain. C. asiatica could improve alertness and relieve anger. However, some limitations should be aware including dose regimen, plant preparation, standardization, and product variation. Future well-designed clinical trials using suitable doses of standardized C. asiatica are still needed.
  19. Permsuwan U, Thavorn K, Dilokthornsakul P, Saokaew S, Chaiyakunapruk N
    J Med Econ, 2017 Sep;20(9):991-999.
    PMID: 28649943 DOI: 10.1080/13696998.2017.1347792
    AIMS: An economic evidence is a vital tool that can inform the decision to use costly insulin analogs. This study aimed to evaluate long-term cost-effectiveness of insulin detemir (IDet) compared with insulin glargine (IGlar) in type 2 diabetes (T2DM) from the Thai payer's perspective.

    METHODS: Long-term costs and outcomes were projected using a validated IMS CORE Diabetes Model, version 8.5. Cohort characteristics, baseline risk factors, and costs of diabetes complications were derived from Thai data sources. Relative risk was derived from a systematic review and meta-analysis study. Costs and outcomes were discounted at 3% per annum. Incremental cost-effectiveness ratio (ICER) was presented in 2015 US Dollars (USD). A series of one-way and probabilistic sensitivity analyses were performed.

    RESULTS: IDet yielded slightly greater quality-adjusted life years (QALYs) (8.921 vs 8.908), but incurred higher costs than IGlar (90,417.63 USD vs 66,674.03 USD), resulting in an ICER of ∼1.7 million USD per QALY. The findings were very sensitive to the cost of IDet. With a 34% reduction in the IDet cost, treatment with IDet would become cost-effective according to the Thai threshold of 4,434.59 USD per QALY.

    CONCLUSIONS: Treatment with IDet in patients with T2DM who had uncontrolled blood glucose with oral anti-diabetic agents was not a cost-effective strategy compared with IGlar treatment in the Thai context. These findings could be generalized to other countries with a similar socioeconomics level and healthcare systems.

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