How do we translate gaps and unmet needs of blood management for thalassemia into a collaborative implementation framework?

BACKGROUND AND OBJECTIVE: The mainstay of management for thalassemia is regular blood transfusions. However, gaps and unmet needs of blood services for thalassemia are still not clearly identified and addressed in Thailand, a country prevalent with thalassemia. What can be a collaborative implementation framework that helps advance practices and policies relating to blood management for thalassemia? METHODS: The first Blood & Beyond Roundtable Discussion was held in July 2022 to gather the current situation, gaps, and unmet needs of blood services for thalassemia from multidisciplinary experts and thalassemic patients. The Implementation Guide as suggested by the Centre for Effective Services was applied as a tool to consolidate information from the discussions and construct the collaborative implementation framework. RESULTS: The National Blood Center and hospitals in Thailand followed the missions specified in the National Blood Policy and the standard guidelines to ensure the best practice of blood management for thalassemia. However, there were six gaps and unmet needs identified from the discussions. After all discussion points were mapped onto the framework, an implementation plan comprised of five specific activities became clear and actionable. CONCLUSION: Without the complete information from both experts and patients, the implementation plan would not have been successfully constructed. The method that we employed to translate all information into the framework can be adapted by other countries to develop their own specific framework efficiently.

Clinical and economic burden of postsurgical complications of high-risk surgeries: a cohort study in Thailand.

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.

Application of Discrete-Event Simulation in Health Technology Assessment: A Cost-Effectiveness Analysis of Alzheimer's Disease Treatment Using Real-World Evidence in Thailand.

OBJECTIVES: Decision-analytic models for Alzheimer's disease (AD) have been advanced to a discrete-event simulation (DES), in which individual-level modeling of disease progression across continuous severity spectra become feasible. This study aimed to apply DES to perform cost-effectiveness analysis of AD treatment in Thailand. METHODS: A data set of Thai AD patients, representing unique demographic and clinical characteristics, was bootstrapped to generate a baseline cohort of 50 000 patients. Each patient was cloned and assigned to donepezil, galantamine, rivastigmine, memantine, or no treatment. Correlated changes in cognitive and behavioral status over time were developed using patient-level data. Treatment effects were obtained from the most recent network meta-analysis. Treatment persistence; mortality; and predictive equations for functional status, costs (Thai baht in 2017), and quality-adjusted life-year (QALY) were derived from country-specific real-world data. RESULTS: From a societal perspective, only the prescription of donepezil to AD patients with all disease-severity levels was found to be cost-effective (incremental cost-effectiveness ratio): 138 524 Thai baht/QALY ($4062/QALY)]. Regardless of whether the treatment-stopping rule when the mini-mental state examination score <10 was introduced, providing early treatment with donepezil to mild AD patients further reduced the incremental cost-effectiveness ratio. Extensive sensitivity analyses indicated robust simulation findings. CONCLUSIONS: Discrete-event simulation greatly enhances the real-world representativeness of decision-analytic models for AD. Donepezil is the most cost-effective treatment option for AD in Thailand and is worth being considered for universal financial coverage. Application of DES in heath technology assessment should be encouraged, especially when the validity of the model is questionable with classical modeling methods.

Estimating the Productivity Burden of Pediatric Pneumococcal Disease in Thailand.

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.

Comparative efficacy and safety of warfarin care bundles and novel oral anticoagulants in patients with atrial fibrillation: a systematic review and network meta-analysis.

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.

A Real-World Evidence Analysis of Associations Among Costs, Quality of Life, and Disease-Severity Indicators of Alzheimer's Disease in Thailand.

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 <.001). CONCLUSION: Our real-world findings suggest the distinct major cost driver that results from expensive AD treatment, emphasizing the demand of country-specific cost evidence. Increases in cognitive and functional status are significantly associated with decreases in total costs of AD care and improvement in patient's HRQOL.

Cost-Effectiveness Analysis of Non-Statin Lipid-Modifying Agents for Secondary Cardiovascular Disease Prevention Among Statin-Treated Patients in Thailand.

BACKGROUND: Using non-statin lipid-modifying agents in combination with statin therapy provides additional benefits for cardiovascular disease (CVD) risk reduction, but their value for money has only been evaluated in high-income countries (HICs). Furthermore, studies mainly derive effectiveness data from a single trial or older meta-analyses. OBJECTIVES: Our study used data from the most recent network meta-analysis (NMA) and local parameters to assess the cost effectiveness of non-statin agents in statin-treated patients with a history of CVD. METHODS: A published Markov model was adopted to investigate lifetime outcomes: (1) number of recurrent CVD events prevented, (2) quality-adjusted life-years (QALYs) gained, (3) costs and (4) incremental cost-effectiveness ratios (ICERs) of proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) and ezetimibe added to statin therapy. Event rates and effectiveness inputs were obtained from the NMA. Cost and utility data were gathered from published studies conducted in Thailand. A series of sensitivity analyses were performed. RESULTS: Patients receiving PCSK9i and ezetimibe experienced fewer recurrent CVD events (number needed to treat [NNT] 17 and 30) and more QALYs (0.168 and 0.096 QALYs gained per person). However, under the societal perspective and at current acquisition costs in 2018, ICERs of both agents were $US1,223,995 and 27,361 per QALY gained, respectively. Based on threshold analyses, the costs need to be reduced by 97 and 85%, respectively, for PCSK9i and ezetimibe to be cost-effective. CONCLUSIONS: Despite the proven effectiveness of PCSK9i and ezetimibe, the costs of these agents need to reduce to a much greater extent than in HICs to be cost-effective in Thailand.

Compliance and persistence with Alzheimer's disease treatment: a retrospective analysis of multiregional hospital databases in Thailand.

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.

Pharmacological treatments for alleviating agitation in dementia: a systematic review and network meta-analysis.

AIMS: To determine the most efficacious and acceptable treatments of agitation in dementia. METHODS: MEDLINE, EMBASE, PsycINFO, CENTRAL and clinicaltrials.gov were searched up to 7 February 2017. Two independent reviewers selected randomized controlled trials (RCTs) of treatments to alleviate agitation in people with all-types dementia. Data were extracted using standardized forms and study quality was assessed using the revised Cochrane Risk of Bias Tool for RCTs. Data were pooled using meta-analysis. The primary outcome, efficacy, was 8-week response rates defined as a 50% reduction in baseline agitation score. The secondary outcome was treatment acceptability defined as treatment continuation for 8 weeks. RESULTS: Thirty-six RCTs comprising 5585 participants (30.9% male; mean ± standard deviation age, 81.8 ± 4.9 years) were included. Dextromethorphan/quinidine [odds ratio (OR) 3.04; 95% confidence interval (CI), 1.63-5.66], risperidone (OR 1.96; 95% CI, 1.49-2.59) and selective serotonin reuptake inhibitors as a class (OR 1.61; 95% CI, 1.02-2.53) were found to be significantly more efficacious than placebo. Haloperidol appeared less efficacious than nearly all comparators. Most treatments had noninferior treatment continuation compared to placebo, except oxcarbazepine, which was inferior. Findings were supported by subgroup and sensitivity analyses. CONCLUSIONS: Risperidone, serotonin reuptake inhibitors as a class and dextromethorphan/quinidine demonstrated evidence of efficacy for agitation in dementia, although findings for dextromethorphan/quinidine were based on a single RCT. Our findings do not support prescribing haloperidol due to lack of efficacy, or oxcarbazepine due to lack of acceptability. The decision to prescribe should be based on comprehensive consideration of the benefits and risks, including those not evaluated in this meta-analysis.

A Systematic Review of the Burden of Multidrug-Resistant Healthcare-Associated Infections Among Intensive Care Unit Patients in Southeast Asia: The Rise of Multidrug-Resistant Acinetobacter baumannii.

OBJECTIVETo summarize the clinical burden (cumulative incidence, prevalence, case fatality rate and length of stay) and economic burden (healthcare cost) of healthcare-associated infections (HAIs) due to multidrug-resistant organisms (MDROs) among patients in intensive care units (ICUs) in Southeast Asia.DESIGNSystematic review.METHODSWe conducted a comprehensive literature search in PubMed, EMBASE, CINAHL, EconLit, and the Cochrane Library databases from their inception through September 30, 2016. Clinical and economic burdens and study quality were assessed for each included study.RESULTSIn total, 41 studies met our inclusion criteria; together, 22,876 ICU patients from 7 Southeast Asian countries were included. The cumulative incidence of HAI caused by A. baumannii (AB) in Southeast Asia is substantially higher than has been reported in other regions, especially carbapenem-resistant AB (CRAB; 64.91%) and multidrug-resistant AB (MDR-AB) (58.51%). Evidence of a dose-response relationship between different degrees of drug resistance and excess mortality due to AB infections was observed. Adjusted odds ratios were 1.23 (95% confidence interval [CI], 0.51-3.00) for MDR-AB, 1.72 (95% CI, 0.77-3.80) for extensively drug-resistant AB (XDR-AB), and 1.82 (95% CI, 0.55-6.00) for pandrug-resistant AB (PDR-AB). There is, however, a paucity of published data on additional length of stay and costs attributable to MDROs.CONCLUSIONSThis review highlights the challenges in addressing MDROs in Southeast Asia, where HAIs caused by MDR gram-negative bacteria are abundant and have a strong impact on society. With our findings, we hope to draw the attention of clinicians and policy makers to the problem of antibiotic resistance and to issue a call for action in the management of MDROs.Infect Control Hosp Epidemiol 2018;39:525-533.

Comparative efficacy and safety of treatment options for MDR and XDR Acinetobacter baumannii infections: a systematic review and network meta-analysis.

OBJECTIVES: To comprehensively compare and rank the efficacy and safety of available treatment options for patients with MDR and XDR Acinetobacter baumannii (AB) infection. METHODS: We searched PubMed, Embase and the Cochrane register of trials systematically for studies that examined treatment options for patients with MDR- and XDR-AB infections until April 2016. Network meta-analysis (NMA) was performed to estimate the risk ratio (RR) and 95% CI from both direct and indirect evidence. Primary outcomes were clinical cure and microbiological cure. Secondary outcomes were all-cause mortality and nephrotoxic and non-nephrotoxic adverse events. RESULTS: A total of 29 studies with 2529 patients (median age 60 years; 65% male; median APACHE II score 19.0) were included. Although there were no statistically significant differences between treatment options, triple therapy with colistin, sulbactam and tigecycline had the highest clinical cure rate. Colistin in combination with sulbactam was associated with a significantly higher microbiological cure rate compared with colistin in combination with tigecycline (RR 1.23; 95% CI 1.03-1.47) and colistin monotherapy (RR 1.21; 95% CI 1.06-1.38). No significant differences in all-cause mortality were noted between treatment options. Tigecycline-based therapy also appeared less effective for achieving a microbiological cure and is not appropriate for treating bloodstream MDR- and XDR-AB infections. CONCLUSIONS: Combination therapy of colistin with sulbactam demonstrates superiority in terms of microbiological cure with a safety profile similar to that of colistin monotherapy. Thus, our findings support the use of this combination as a treatment for MDR- and XDR-AB infections.

Global economic evaluations of rotavirus vaccines: A systematic review.

INTRODUCTION: World Health Organization (WHO) recommends Rotavirus vaccines to prevent and control rotavirus infections. Economic evaluations (EE) have been considered to support decision making of national policy. Summarizing global experience of the economic value of rotavirus vaccines is crucial in order to encourage global WHO recommendations for vaccine uptake. Therefore, a systematic review of economic evaluations of rotavirus vaccine was conducted. METHODS: We searched Medline, Embase, NHS EED, EconLit, CEA Registry, SciELO, LILACS, CABI-Global Health Database, Popline, World Bank - e-Library, and WHOLIS. Full economic evaluations studies, published from inception to November 2015, evaluating Rotavirus vaccines preventing Rotavirus infections were included. The methods, assumptions, results and conclusions of the included studies were extracted and appraised using WHO guide for standardization of EE of immunization programs. RESULTS: 104 relevant studies were included. The majority of studies were conducted in high-income countries. Cost-utility analysis was mostly reported in many studies using incremental cost-effectiveness ratio per DALY averted or QALY gained. Incremental cost per QALY gained was used in many studies from high-income countries. Mass routine vaccination against rotavirus provided the ICERs ranging from cost-saving to highly cost-effective in comparison to no vaccination among low-income countries. Among middle-income countries, vaccination offered the ICERs ranging from cost-saving to cost-effective. Due to low- or no subsidized price of rotavirus vaccines from external funders, being not cost-effective was reported in some high-income settings. CONCLUSION: Mass vaccination against rotavirus was generally found to be cost-effective, particularly in low- and middle-income settings according to the external subsidization of vaccine price. On the other hand, it may not be a cost-effective intervention at market price in some high-income settings. This systematic review provides supporting information to health policy-makers and health professionals when considering rotavirus vaccination as a national program.

"From safe source to safe sink" development of colorimetric assay for gabapentin in bulk drug and capsules using naturally derived genipin.

A novel colorimetric assay for gabapentin in bulk drug and capsules has been developed via a safety-and-sustainability concerning concept. The method relied on the reaction of primary amino group of drug with non-toxic and eco-friendly genipin in totally aqueous medium to form the blue product which was subsequently measured by visible spectrophotometry at 590 nm. Under the optimized conditions, Beer's law was obeyed in the concentration range of 0.15-0.50 mM (r(2)=0.9998). It was accurate, precise and insensitive to the interferences from all related compounds specified in the United States Pharmacopeia as well as commonly used excipients. Furthermore, it gave the assay results in agreement with the pharmacopeial chromatographic method. Owing to the environmental concern and responsibility, a fast and facile method was also proposed for the treatment of waste generated from the assay based on the decoloration by using gypsum as a cheap and commonly available adsorbent. After the treatment, more than 95% of the initial blue product was removed from the waste solution and the treated waste was proven to be safe for aquatic organisms, as studied in brine shrimp and guppy fishes. Therefore, this work not only reports for the first time the application of naturally derived genipin to drug analysis, but also presents a new and contemporary paradigm that illustrates the fully benign-by-design development of the analytical methodologies in the era of Green Chemistry, starting from the safe source of reagents toward the safe sink when waste is released into the environment.