Trends in Anticoagulant Utilization and Clinical Outcomes for Cancer-Associated Thrombosis: A Multicenter Cohort Study in Thailand's Upper-Middle-Income Country Setting.

PURPOSE: To evaluate anticoagulant trends and clinical outcomes in the management of cancer-associated thrombosis (CAT) within Thailand, an upper-middle-income country (UMIC). METHODS: This multicenter retrospective cohort study included adult patients with cancer diagnosed with venous thromboembolism (VTE) hospitalized in Thailand from 2017 to 2021. Anticoagulants were classified as low-molecular-weight heparin (LMWH), direct oral anticoagulants (DOACs), and warfarin. Prescription trends were assessed, and patients were followed for 1 year, or until 2022 to evaluate outcomes. The primary effectiveness outcome was recurrent VTE, whereas the primary safety outcome was major bleeding. Secondary outcomes included net clinical benefit and all-cause mortality. Treatment effects were examined using inverse probability of treatment weighting (IPTW) Cox proportional hazards models. RESULTS: Among 1,611 patients (61.3% female; mean age, 58.8 years; standard deviation, 13.1 years), 86% received LMWH, 10% warfarin, and 4% DOACs. In the study cohort, LMWH prescriptions remained consistent, warfarin use declined, and DOAC prescriptions notably increased. In IPTW analysis, DOACs showed comparable rates of VTE recurrence (weighted hazard ratio [HR], 0.77 [95% CI, 0.22 to 2.70]; P = .679) and major bleeding (weighted HR, 0.62 [95% CI, 0.15 to 2.55]; P = .506) with LMWH. Warfarin had a higher risk of major bleeding (weighted HR, 2.74 [95% CI, 1.12 to 6.72]; P = .028) but a similar rate of VTE recurrence (weighted HR, 1.46 [95% CI, 0.75 to 2.84]; P = .271) compared with LMWH. Secondary outcomes were consistent across groups. CONCLUSION: LMWH remains the primary treatment for CAT, in line with current guidelines. The study highlights the challenges faced in these settings with the continuous use of warfarin. The comparable efficacy and safety of DOACs with LMWH suggest a potential shift in CAT management within UMICs.

Cost-utility and budget impact analyses of cervical cancer screening using self-collected samples for HPV DNA testing in Thailand.

INTRODUCTION: Cervical cancer ranks as the third most prevalent cancer among women in Thailand. However, the effectiveness of cervical cancer screening programs is limited by several factors that impede the screening rate. The utilization of self-collected samples for screening purposes has the potential to alleviate barriers to screening in Thai women. This study assessed the cost-utility and budget impact of implementing cervical cancer screening using self-collected samples for human papillomavirus (HPV) deoxyribonucleic acid (DNA) testing in Thailand. MATERIALS AND METHODS: We employed a decision tree integrated with a Markov model to estimate the lifetime costs and health benefits associated with the cervical cancer screening program for women aged 25-65. The analysis was conducted from a societal perspective. Four screening policy options were compared: (1) additional self-collected samples for HPV DNA testing, (2) clinician-collected samples for HPV DNA testing only, (3) clinician-collected samples for cytology test (i.e., status quo), and (4) no screening. The model inputs were based on unvaccinated women. The screening strategies and management in those with positive results were assumed followed to the Thai clinical practice guideline. Costs were reported in 2022 Thai baht. Sensitivity analyses were conducted. The ten-year budget impacts of the additional self-collected samples for HPV DNA testing were calculated from a payer perspective. RESULTS: All screening policies were cost-saving compared to no screening. When comparing the additional self-collected samples for HPV DNA testing with the clinician-collected samples policy, it emerged as the dominant strategy. The incremental benefit in cervical cancer prevention achieved by incorporating self-collected samples for screening was observed at any additional screening rate that could be achieved through their use. Sensitivity analyses yielded consistently favorable results for the screening policies. The average annual budget impact of the additional self-collected samples for screening policy amounted to 681 million Thai baht. This budget allocation could facilitate cervical cancer screening for over 10 million women. CONCLUSIONS: An addition of self-collected samples for HPV DNA testing into the cervical cancer screening program is cost-saving. The benefits of this screening policy outweigh the associated incremental costs. Policymakers should consider this evidence during the policy optimization process.

Efficacy and safety of different dual antiplatelet strategies in patients undergoing percutaneous coronary intervention: A systematic review and network meta-analysis.

Background: Dual antiplatelet therapy (DAPT) is key for preventing ischaemic events post-percutaneous coronary intervention (PCI). Various DAPT modifications like the shortened duration or P2Y12 inhibitor (P2Y12i) de-escalation are implemented to reduce bleeding risk. However, these strategies lack direct comparative studies. This study aimed to assess the efficacy and safety of such DAPT strategies, including de-escalated and short DAPT, in patients undergoing PCI. Methods: We searched PubMed, Embase, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov databases for relevant randomized controlled trials (RCTs). We performed a network meta-analysis (NMA) to estimate risk ratios (RRs) and 95% confidence intervals (CIs). The primary efficacy endpoint was major adverse cardiac events (MACEs), and the primary safety endpoint was major bleeding. Secondary endpoints included individual components of MACEs and net adverse clinical events (NACEs). Results: A total of 17 RCTs comprising 53,156 patients (median age, 62.0 years, 24.8% female) were included. NMA suggested that de-escalation DAPT was associated with a significantly lower risk of MACEs (risk ratio [RR] = 0.79, 95% confidence interval [CI] = 0.64-0.98), bleeding (RR = 0.63, 95% CI = 0.49-0.82), and NACEs (RR = 0.69, 95% CI = 0.60-0.79) compared with standard DAPT. Short DAPT followed by P2Y12i monotherapy exhibited a significantly decreased risk of major bleeding (RR = 0.63, 95% CI = 0.46-0.86) compared with standard DAPT. Conclusions: De-escalation DAPT was the most effective strategy for preventing the risk of MACEs without increasing bleeding events, while short DAPT followed by P2Y12i monotherapy was the most effective strategy for reducing the risk of bleeding among patients undergoing PCI.

Economic burden of antimicrobial resistance and inappropriate empiric treatment in Thailand.

Objective: To quantify the economic burden of bacterial antimicrobial resistance in Thailand and estimate potential savings from improving the rate of appropriate empiric treatment, where effective coverage is provided within the first days of infection. Design: Cost-of-illness study. Methods: A cost-calculator, decision-tree model was developed using published data and records from 3 Thai hospitals for patients hospitalized with antimicrobial-resistant infections between 2015 and 2019. Direct and indirect costs of antimicrobial-resistant infections were assessed over a 5-year time horizon, with outcomes derived separately for cases having received appropriate empiric treatment versus inappropriate empiric treatment. In a real-world scenario, outcomes were estimated using actual rates of inappropriate empiric treatment, and in a hypothetical scenario, outcomes were estimated using decreased rates of inappropriate empiric treatment. Results: Over 5 years, in-hospital antimicrobial-resistant infections produced costs of approximately Thai baht (THB) 66.4 billion (USD 2.1 billion) in the real-world scenario and THB 65.8 billion (USD 2.1 billion) in the hypothetical scenario (0.9% cost savings relative to the real-world scenario). Most costs were attributable to income loss due to in-hospital mortality (real world: THB 53.7 billion [USD 1.7 billion]; 80.9% of costs; hypothetical: THB 53.2 billion [USD 1.7 billion]; 80.8% of costs) and hospitalization (real world: THB 10.3 billion [USD 330.8 million]; 15.5% of costs; hypothetical: THB 10.2 billion [USD 328.9 million]; 15.5% of costs). Conclusions: In-hospital antimicrobial-resistant infections produced a substantial economic toll in Thailand. This public health burden could be reduced with a strategy aimed at decreasing the rate of patients receiving inappropriate empiric treatment.

Pharmacotherapy treatment patterns at hospital discharge and clinical outcomes among patients with heart failure with reduced ejection fraction.

Background: This study aimed to assess the prescribing patterns of evidence-based pharmacotherapy and their association with clinical outcomes in patients with heart failure with reduced ejection fraction (HFrEF) in Thailand. Methods: A retrospective cohort study of patients with HFrEF was conducted. Treatment with a ß-blocker and renin-angiotensin system inhibitors (RASIs) with or without mineralocorticoid receptor antagonists (MRAs) at discharge was regarded as guideline-directed medical therapy (GDMT). All others were considered non-GDMT. The primary endpoint was the composite of all-cause mortality or heart failure (HF) rehospitalization. Inverse-probability-treatment-weighted adjusted Cox proportional hazard models were used to examine the treatment effects. Results: In total, 653 patients with HFrEF (mean age 64.1 ± 14.3 years; 55.9% male) were included. GDMT with ß-blockers and RASIs with or without MRAs was prescribed at a rate of 35.4%. During a median of 1-year follow-up, 167 patients (27.5%) had a composite event, 81 patients (13.3%) had all-cause mortality, and 109 patients (18.0%) had HF rehospitalization. Patients treated with GDMT at discharge showed significantly lower rates of the primary endpoint (adjusted hazard ratio [HR] 0.63; 95% CI 0.44-0.89; p = 0.009) compared with patients who did not receive GDMT. The use of GDMT was also associated with a significantly lower risk of all-cause mortality (adjusted HR 0.59; 95% CI 0.36-0.98; p = 0.045) and HF rehospitalization (adjusted HR 0.65; 95% CI 0.43-0.96; p = 0.031). Conclusions: For HFrEF treatment, GDMT initiation at hospital discharge was associated with a significantly reduced risk of all-cause mortality and HF rehospitalization. Nevertheless, prescribing GDMT remains underused, and it could be encouraged to improve HF outcomes in real-world settings.

Diagnostic accuracy of Doppler twinkling artifact for identifying urolithiasis: a systematic review and meta-analysis.

OBJECTIVE: The goal of this study was to perform a comprehensive meta-analysis to assess the overall diagnostic value of Doppler twinkling for the diagnosis of urolithiasis. METHODS: We systematically searched the PubMed, EMBASE, and Cochrane Library databases from inception through May 31, 2021. Studies including patients with urolithiasis who underwent color flow Doppler sampling to highlight the twinkling artifact and computed tomography were included. Diagnostic test meta-analysis was performed with a bivariate model. We used summary receiver operating characteristic curves to summarize the overall diagnostic performance. The weighted sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio were calculated. RESULTS: Sixteen studies involving 4572 patients were included in the systematic review and meta-analysis. The weighted sensitivity was 0.86 (95% confidence interval [CI] 0.72-0.94), specificity 0.92 (95% CI 0.75-0.98), positive likelihood ratio 11.3, negative likelihood ratio 0.2, and diagnostic odds ratio 75.5. CONCLUSION: The Doppler twinkling artifact has good diagnostic value for the diagnosis of urolithiasis and should be used as a complementary tool in the diagnosis of urolithiasis.

Effect of drug use calendar on adherence to iron chelation therapy in young thalassemia patients.

Background: Regular blood transfusions in thalassemia patients can lead to severe complications and iron chelation therapy is required as a treatment. Thalassemia is common in Thailand and the drugs used in iron chelation therapy are deferoxamine and deferiprone. Adherence to the therapy is a key factor for treatment success. Objective: To assess the impact of a drug use calendar on deferiprone and deferoxamine adherence in young thalassemia patients. Methods: A total of 86 young thalassemia outpatients at a Thai tertiary care hospital were recruited into the study. Patients were stratified into two groups based on self-assessment of adherence using a visual analogue scale. One group (n=41) was given a calendar with the schedule of drug use in addition to counselling as standard pharmaceutical care. The second group (n=45) only received the counselling. Adherence to iron chelation therapy was assessed by deferiprone pill or deferoxamine vial counts on six visits (V1 to V6) and results were compared between visits and groups using a multilevel linear regression model. Change in serum ferritin levels after 6 visits (n = 81) were compared using a linear regression model. Results: Adherence significantly increased in both the calendar and non-calendar groups for deferiprone mono- and combination-therapy and for deferoxamine monotherapy. In the calendar groups, average adherence increased by between 2.05 and 5.66% per visit compared to increases of 0.31 to3.92% per visit in the non-calendar groups. A significant difference in the increase in adherence per visit between the calendar and non-calendar groups was only observed for deferiprone monotherapy (3.03% SEM = 0.49vs 1.42% SEM =0.49, respectively, P-value = 0.0078). The serum ferritin level decreased in the calendar group by 20.25ng/mL (SEM = 23.80) and increased in the non-calendar group by 59.63 ng/mL (SEM = 23.01, P-value = 0.0147). Conclusion: Provision of a drug use calendar improved adherence to deferoxamine and deferiprone and decreased serum ferritin levels in young Thai thalassemia patients over the improvements obtained from standard counselling.

Effect of drug use calendar on adherence to iron chelation therapy in young thalassemia patients

Background: Regular blood transfusions in thalassemia patients can lead to severe complications and iron chelation therapy is required as a treatment. Thalassemia is common in Thailand and the drugs used in iron chelation therapy are deferoxamine and deferiprone. Adherence to the therapy is a key factor for treatment success. Objective: To assess the impact of a drug use calendar on deferiprone and deferoxamine adherence in young thalassemia patients. Methods: A total of 86 young thalassemia outpatients at a Thai tertiary care hospital were recruited into the study. Patients were stratified into two groups based on self-assessment of adherence using a visual analogue scale. One group (n=41) was given a calendar with the schedule of drug use in addition to counselling as standard pharmaceutical care. The second group (n=45) only received the counselling. Adherence to iron chelation therapy was assessed by deferiprone pill or deferoxamine vial counts on six visits (V1 to V6) and results were compared between visits and groups using a multilevel linear regression model. Change in serum ferritin levels after 6 visits (n = 81) were compared using a linear regression model. Results: Adherence significantly increased in both the calendar and non-calendar groups for deferiprone mono- and combination-therapy and for deferoxamine monotherapy. In the calendar groups, average adherence increased by between 2.05 and 5.66% per visit compared to increases of 0.31 to3.92% per visit in the non-calendar groups. A significant difference in the increase in adherence per visit between the calendar and non-calendar groups was only observed for deferiprone monotherapy (3.03% SEM = 0.49vs 1.42% SEM =0.49, respectively, P-value = 0.0078). The serum ferritin level decreased in the calendar group by 20.25ng/mL (SEM = 23.80) and increased in the non-calendar group by 59.63 ng/mL (SEM = 23.01, P-value = 0.0147). (AU)

Clinical and economic outcomes attributable to carbapenem-resistant Enterobacterales and delayed appropriate antibiotic therapy in hospitalized patients.

OBJECTIVE: To assess the impact of carbapenem resistance and delayed appropriate antibiotic therapy (DAAT) on clinical and economic outcomes among patients with Enterobacterales infection. METHODS: This retrospective cohort study was conducted in a tertiary-care medical center in Thailand. Hospitalized patients with Enterobacterales infection were included. Infections were classified as carbapenem-resistant Enterobacterales (CRE) or carbapenem-susceptible Enterobacterales (CSE). Multivariate Cox proportional hazard modeling was used to examine the association between CRE with DAAT and 30-day mortality. Generalized linear models were used to examine length of stay (LOS) and in-hospital costs. RESULTS: In total, 4,509 patients with Enterobacterales infection (age, mean 65.2 ±18.7 years; 43.3% male) were included; 627 patients (13.9%) had CRE infection. Among these CRE patients, 88.2% received DAAT. CRE was associated with additional medication costs of $177 (95% confidence interval [CI], 114­239; P < .001) and additional in-hospital costs of $725 (95% CI, 448­1,002; P < .001). Patients with CRE infections had significantly longer LOS and higher mortality rates than patients with CSE infections: attributable LOS, 7.3 days (95% CI, 5.4­9.1; P < .001) and adjusted hazard ratios (aHR), 1.55 (95% CI, 1.26­1.89; P < .001). CRE with DAAT were associated with significantly longer LOS, higher mortality rates, and in-hospital costs. CONCLUSION: CRE and DAAT are associated with worse clinical outcomes and higher in-hospital costs among hospitalized patients in a tertiary-care hospital in Thailand.

Efficacy and Safety of Low-Dose Prasugrel Versus Clopidogrel in Patients with Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention: a Systematic Review and Meta-analysis.

PURPOSE: To assess the efficacy and safety of low-dose prasugrel compared to clopidogrel based on the occurrence of major adverse cardiac events (MACEs) and major bleeding in patients with acute coronary syndromes (ACS) undergoing percutaneous coronary intervention (PCI). METHODS: The PubMed, Embase, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov databases were systematically searched up to May 2020 to identify relevant randomized controlled trials (RCTs) and observational studies. A meta-analysis was conducted using a random effects model to estimate relative risks (RRs) with 95% confidence intervals (CIs). The primary efficacy and safety endpoints were MACE and major bleeding, respectively. RESULTS: Three RCTs (n = 2884) and five observational studies (n = 30,117) were included. A meta-analysis of RCTs revealed no significant differences in terms of MACE (RR 0.92, 95% CI 0.74 to 1.16) or major bleeding (RR 0.97, 95% CI 0.57 to 1.65) between low-dose prasugrel and clopidogrel. A meta-analysis of observational studies revealed no significant difference in terms of MACE (RR 1.13, 95% CI 0.82 to 1.55) between the two groups, but low-dose prasugrel was associated with a significantly increased risk of major bleeding (RR 1.33, 95% CI 1.02 to 1.72). CONCLUSIONS: We found that low-dose prasugrel was not associated with changes in MACE or major bleeding compared with clopidogrel in RCTs. However, analysis of data from observational studies revealed that low-dose prasugrel was associated with an increased risk of major bleeding compared with clopidogrel.

Anti-Influenza with Green Tea Catechins: A Systematic Review and Meta-Analysis.

Influenza is one of the most serious respiratory viral infections worldwide. Although several studies have reported that green tea catechins (GTCs) might prevent influenza virus infection, this remains controversial. We performed a systematic review and meta-analysis of eight studies with 5,048 participants that examined the effect of GTC administration on influenza prevention. In a random-effects meta-analysis of five RCTs, 884 participants treated with GTCs showed statistically significant effects on the prevention of influenza infection compared to the control group (risk ratio (RR) 0.67, 95%CIs 0.51-0.89, P = 0.005) without evidence of heterogeneity (I2= 0%, P = 0.629). Similarly, in three cohort studies with 2,223 participants treated with GTCs, there were also statistically significant effects (RR 0.52, 95%CIs 0.35-0.77, P = 0.001) with very low evidence of heterogeneity (I2 = 3%, P = 0.358). Additionally, the overall effect in the subgroup analysis of gargling and orally ingested items (taking capsules and drinking) showed a pooled RR of 0.62 (95% CIs 0.49-0.77, P = 0.003) without heterogeneity (I2= 0%, P = 0.554). There were no obvious publication biases (Egger's test (P = 0.138) and Begg's test (P = 0.103)). Our analysis suggests that green tea consumption is effective in the prophylaxis of influenza infections. To confirm the findings before implementation, longitudinal clinical trials with specific doses of green tea consumption are warranted.

Trends in optimal medical therapy at discharge and clinical outcomes in patients with acute coronary syndrome in Thailand.

BACKGROUND: Optimal medical therapy (OMT) is recommended for patients with acute coronary syndrome (ACS) at discharge. This study aimed to assess temporal trends of OMT prescription as a five-drug regimen at discharge and its association with clinical outcomes in patients with ACS in Thailand. METHODS: A retrospective cohort study was conducted in a tertiary-care medical center in Thailand. Data were collected from an electronic medical database. Patients were categorized into OMT or non-OMT groups based on their discharge medications. OMT was defined as a combination of aspirin and P2Y12 inhibitors, statins, beta-blockers, and angiotensin-converting enzyme inhibitors, or angiotensin receptor blockers. The primary outcome was 1-year all-cause mortality. The secondary outcome was major adverse cardiac events (MACE) which was defined as a composite of non-fatal myocardial infarction, non-fatal stroke, and all-cause mortality. The prescription trends were also estimated. A multivariate Cox's proportional hazard model was used to assess the association of OMT prescriptions at discharge with all-cause mortality and MACE. RESULTS: A total of 3531 patients discharged with ACS [mean age, 69.5 (SD 12.4) years; 58.3% male] were identified. Only 42.6% were discharged with OMT. The rates of OMT prescriptions did not change over time. However, the prescription of OMT with high-intensity statin was significantly increased from 5.0% in 2013 to 38.3% in 2018 (p for trend <0.001). Multivariable analyses indicated that OMT significantly reduced all-cause mortality (adjusted HR: 0.77; 95%CI: 0.63-0.95; p=0.012) and MACE (adjusted HR 0.84; 95%CI: 0.71-0.99; p = 0.044). Subgroup analysis indicated that patients receiving OMT with high-intensity statins exhibited survival benefits (adjusted HR: 0.72; 95%CI: 0.56-0.92; p=0.008). CONCLUSIONS: The five-drugs comprising OMT were associated with a reduction in all-cause mortality and MACE in patients with ACS. Nevertheless, OMT prescribing remains underused and could be enhanced in the real-world setting.

Systematic review and network meta-analysis: efficacy of drugs for functional dyspepsia.

BACKGROUND: Functional dyspepsia (FD) is a relapsing and remitting condition affecting between 5% and 10% of people. Efficacious therapies are available, but their relative efficacy is unknown. AIM: To perform a systematic review with network meta-analysis to resolve this uncertainty. METHODS: We searched the medical literature through July 2020 for randomised controlled trials (RCTs) assessing efficacy of drugs for adults with FD, compared with each other, or placebo. Trials reported a dichotomous assessment of symptom status after completion of therapy. We pooled data using a random effects model. Efficacy was reported as a pooled relative risk (RR) of remaining symptomatic with a 95% confidence interval (CI) to summarise efficacy of each comparison tested. Relative ranking was assessed with surface under the cumulative ranking curve (SUCRA) probabilities. RESULTS: We identified 71 eligible RCTs (19 243 participants). Tricyclic antidepressants (TCAs) were ranked second for efficacy (RR of remaining symptomatic = 0.71; 95% CI 0.58-0.87, SUCRA 0.87), and first when only low risk of bias trials were included. Most RCTs that used TCAs recruited patients who were refractory to other drugs included in the network. Although sulpiride or levosulpiride were ranked first for efficacy (RR = 0.49; 95% CI 0.36-0.69, SUCRA 0.99), trial quality was low and only 86 patients received active therapy. TCAs were more likely to cause adverse events than placebo. CONCLUSIONS: TCAs, histamine-2 receptor antagonists, standard- and low-dose proton pump inhibitors, sulpiride or levosulpiride, itopride and acotiamide were all more efficacious than placebo for FD.

Effects of Inspiratory Muscle Training and Early Mobilization on Weaning of Mechanical Ventilation: A Systematic Review and Network Meta-analysis.

OBJECTIVE: To compare the effectiveness and rank order of physical therapy interventions, including conventional physical therapy (CPT), inspiratory muscle training (IMT), and early mobilization (EM) on mechanical ventilation (MV) duration and weaning duration. DATA SOURCES: PubMed, The Cochrane Library, Scopus, and CINAHL complete electronic databases were searched through August 2019. STUDY SELECTION: Randomized controlled trials (RCTs) investigating the effect of IMT, EM, or CPT on MV duration and the weaning duration in patients with MV were included. Studies that were determined to meet the eligibility criteria by 2 independent authors were included. A total of 6498 relevant studies were identified in the search, and 18 RCTs (934 participants) were included in the final analysis. DATA EXTRACTION: Data were extracted independently by 2 authors and assessed the study quality by the Cochrane risk-of-bias tool. The primary outcomes were MV duration and weaning duration. DATA SYNTHESIS: Various interventions of physical therapy were identified in the eligible studies, including IMT, IMT+CPT, EM, EM+CPT, and CPT. The data analysis demonstrated that compared with CPT, IMT+CPT significantly reduced the weaning duration (mean difference; 95% confidence interval) (-2.60; -4.76 to -0.45) and EM significantly reduced the MV duration (-2.01; -3.81 to -0.22). IMT+CPT and EM had the highest effectiveness in reducing the weaning duration and MV duration, respectively. CONCLUSION: IMT or EM should be recommended for improving the weaning outcomes in mechanically ventilated patients. However, an interpretation with caution is required due to the heterogeneity.

Comparative efficacy and safety of interventions for preventing chemotherapy-induced oral mucositis in adult cancer patients: a systematic review and network meta-analysis.

Objective: To examine the comparative efficacy and safety of interventions for preventing chemotherapy-induced oral mucositis (OM) in adult cancer patients. Methods: We searched PubMed, Embase and the Cochrane Central systematically for the randomised control trials (RCTs) of interventions for preventing OM. Network meta-analysis (NMA) was performed to estimate risk ratios (RR) and 95% confidence intervals (CI) from both direct and indirect evidence. The primary outcome was any grade of OM. Secondary outcomes were mild-moderate OM, severe OM and adverse events, such as taste disturbance and gastrointestinal adverse events. This study was registered with PROSPERO, number CRD42016052489. Results: A total of 29 RCTs with 2348 patients (median age, 56.1 years; 57.5% male) were included. Cryotherapy was associated with a significantly lower risk of OM than control (RR 0.51, 95% CI 0.38 to 0.68), and zinc sulphate (RR 0.47, 95% CI 0.23 to 0.97), but not significantly lower than sucralfate and palifermin. No significant differences were observed between cryotherapy and control for taste disturbance and gastrointestinal adverse events. Palifermin was associated with the highest risk of taste disturbance. Conclusions: This NMA suggests that cryotherapy was the most effective intervention for preventing chemotherapy-induced OM with a safety profile similar to control, but not significantly lower than sucralfate and palifermin. Large RCTs are needed to confirm these findings.

An updated cost-effectiveness analysis of pneumococcal conjugate vaccine among children in Thailand.

BACKGROUND: A previous cost-effectiveness analysis (CEA) showed that Pneumococcal Conjugate Vaccine (PCV) 10 and PCV13 were not cost-effective for universal immunization among children in Thailand. Given recent changes in the evidence of efficacy, herd effects and price, a CEA of PCVs should be revisited. This study aimed to determine the cost-effectiveness of PCV10 and PCV13 compared to no PCV vaccination in Thai children. MATERIAL AND METHODS: A Markov model was developed under a societal perspective with a lifetime horizon. Inputs were derived from a comprehensive literature review. Costs were calculated using the Thai National Electronic Database and converted to the year 2017 value. All costs and outcomes were discounted at a rate of 3%. The findings were reported as incremental cost-effectiveness ratios (ICERs) in Thai Baht (THB) per quality-adjusted life year (QALY) gained. Sensitivity analyses were performed. A cost-effectiveness acceptability curve was generated with the cost-effectiveness threshold of 160,000 THB/QALY. RESULTS: Base-case analysis of 2 + 1 dose schedule and five-year protection, with no consideration of herd effect showed that ICER for PCV10 was 170,437 THB/QALY, while ICER for PCV13 was 73,674 THB/QALY. With consideration of herd effect, both PCV10 and PCV13 had lower costs and higher QALYs compared to no PCV vaccination. Based on our probabilistic sensitivity analysis at willingness-to-pay of 160,000 THB/QALY, PCV13 had 93% of being cost-effective, while 4.7% and 2.3%, for PCV10 and no PCV vaccination, respectively. CONCLUSION: At current prices, PCV13 is cost-effective, while PCV10 is not cost-effective in Thailand. When considering herd-effect, both PCV10 and PCV13 are cost-effective.

Economic Evaluation of Human Rotavirus Vaccine in Thailand.

INTRODUCTION: Rotavirus gastroenteritis is the leading cause of severe diarrhoea among young children < 5 years old. Previous cost-effectiveness analyses on rotavirus (RV) vaccination in Thailand have generated conflicting results. The aim of this current study is to evaluate the economic impact of introducing RV vaccination in Thailand, using updated Thai epidemiological and cost data. METHODS: Both cost-utility analysis (CUA) and budget impact analysis (BIA) of human rotavirus vaccine (HRV) under a universal mass vaccination (UMV) programme were conducted. A published static, deterministic, cross-sectional population model was adapted to assess costs and health outcomes associated with RV vaccination among Thai children < 5 years old during 1 year for CUA and over a 5-year period (2019-2023) for BIA. Data identified through literature review were incorporated into the model after consultation with local experts. Base case CUA was conducted from a societal perspective with quality-adjusted life year (QALY) discounted at 3% annually. Scenario analyses as well as one-way and probabilistic sensitivity analyses were conducted to assess the robustness of the base case CUA results. Costs were updated to 2017. RESULTS: At 99% coverage, HRV vaccination would substantially reduce RV-related disease burden. With an incremental cost-effectiveness ratio (ICER) of Thai baht (THB) 49,923/QALY gained, HRV vaccination versus no vaccination was cost-effective when assessed against a local threshold of THB 160,000/QALY gained. Scenario and sensitivity analyses confirmed the cost-effectiveness with all resultant ICERs falling below the willingness-to-pay threshold. HRV use in the UMV programme was estimated to result in a net expenditure of about THB 255-281 million to the Thai government in the 5th year of the programme, depending on vaccine uptake. CONCLUSION: HRV vaccination is estimated to be cost-effective in Thailand. The budget impact following inclusion of HRV into the UMV programme is expected to be partially offset by substantial reductions in RV-related disease costs. FUNDING: GlaxoSmithKline Biologicals SA GSK STUDY IDENTIFIER: HO-17-18213.

Clinical outcomes of theophylline use as add-on therapy in patients with chronic obstructive pulmonary disease: A propensity score matching analysis.

To examine clinical outcomes of theophylline use in patients with chronic obstructive pulmonary disease (COPD) receiving inhaled corticosteroids (ICS) and long-acting beta-2 agonists (LABA). Electronic data from five hospitals located in Northern Thailand between January 2011 and December 2015 were retrospectively collected. Propensity score (PS) matching (2:1 ratio) technique was used to minimize confounding factors. The primary outcome was overall exacerbations. Secondary outcomes were exacerbation not leading to hospital admission, hospitalization for exacerbation, hospitalization for pneumonia, and all-cause hospitalizations. Cox's proportional hazards models were used to estimate adjusted hazard ratio (aHR) and 95% confidence interval (CI). After PS matching, of 711 patients with COPD (mean age: 70.1 years; 74.4% male; 60.8% severe airflow obstruction), 474 theophylline users and 237 non-theophylline users were included. Mean follow-up time was 2.26 years. Theophylline significantly increased the risk of overall exacerbation (aHR: 1.48, 95% CI: 1.11-1.96; p = 0.008) and exacerbation not leading to hospital admission (aHR: 1.47, 95% CI: 1.06-2.03; p = 0.020). Theophylline use did not significantly increase the risk of hospitalization for exacerbation (aHR: 1.11, 95% CI: 0.79-1.58; p = 0.548), hospitalization for pneumonia (aHR: 1.28, 95% CI: 0.89-1.84; p = 0.185), and all-cause hospitalizations (aHR: 1.03, 95% CI: 0.80-1.33; p = 0.795). Theophylline use as add-on therapy to ICS and LABA might be associated with an increased risk for overall exacerbation in patients with COPD. A large-scale prospective study of theophylline use investigating both safety and efficacy is warranted.

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.