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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.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.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 trend0.001). 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).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.

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.

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], 114–239; P < .001) and additional in-hospital costs of $725 (95% CI, 448–1,002; 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, 5.4–9.1; P < .001) and adjusted hazard ratios (aHR), 1.55 (95% CI, 1.26–1.89; 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.

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 5048 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 2223 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.

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). 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. 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). 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.

Purpose To assess the efficacy and safety of prasugrel at low doses compared to clopidogrel by looking at the occurrence of major adverse cardiac events (MACE) and major bleeding in patients with acute coronary syndrome (ACS) or undergoing percutaneous coronary intervention (PCI). Methods We searched PubMed, EMBASE, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov for eligible randomized controlled trials (RCTs) and observational studies assessing efficacy and safety of low-dose prasugrel versus clopidogrel in patients with ACS or undergoing PCI up to May 22, 2020. We did a meta-analysis using a random-effects model to estimate relative risks (RRs). The primary efficacy and safety endpoints were MACE and major bleeding, respectively. Results Six RCTs (n = 6,131) and six observational studies (n = 31,426) were included. There was no MACE reduction in patients receiving low-dose prasugrel compared with those receiving clopidogrel (RR 1.02, 95%CI 0.91 to 1.14), but there was an increased risk of major bleeding (RR 1.35, 95%CI 1.10 to 1.67). Conclusions Low-dose prasugrel yields no increase in efficacy when compared with clopidogrel, but it does expose patients to an increased risk of bleeding. Most studies considered here were conducted in Japan. Studies conducted with non-Asian patients may find that low-dose prasugrel offers a more favorable efficacy and risk profile. Considering the results of this analysis we believe low-dose prasugrel should be prescribed with extreme caution as it may result in bleeding events without any additional benefit over clopidogrel.

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.To assess the impact of a drug use calendar on deferiprone and deferoxamine adherence in young thalassemia patients.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.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).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.

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.

Introduction Heart failure (HF) is a complex clinical syndrome with a significant economic and health burden. While practice guidelines recommend a multidisciplinary approach in HFrEF care, the impact of pharmacist participation on HF outcomes remains inconclusive. Methods A systematic review and meta-analysis was performed and reported according to PRISMA guideline from five databases including PubMed, Embase, Cochrane, Scopus and CINAHL. Randomized controlled trials (RCTs) that evaluated pharmacist interventions compared were compared with usual care in HFrEF patients. Data were pooled using a random-effects model. The primary outcome was all-cause mortality. Secondary outcomes were all-cause hospitalization and health-related quality of life (HRQoL) at 6 months. Results Twenty-nine trials identified 6,965 predominantly HFrEF patients. The average age was 72.0 years (IQR 66.0-76.0) and 48% were men (IQR 40.0%-68.0%). The majority of trials included NYHA FC II-III with median left ventricular ejection fraction (LVEF) of 38.5% (IQR 34.5-49.5%). Pharmacist interventions were associated with a significant reduction in all-cause mortality (RR 0.74; 95% CI 0.60-0.91; p= 0.004) and all-cause hospitalizations (RR 0.86; 95% CI 0.75-0.99; p =0.034). There was a significant improvement in 4 domains of SF-36 including role physical (SMD 0.20, 95% CI 0.04 to 0.37, p=0.015), role emotional (SMD 0.17, 95% CI 0.00 to 0.33, p=0.047), mental health (SMD 0.33, 95% CI 0.17 to 0.50, p Conclusions Pharmacist interventions in HFrEF population significantly reduced all-cause mortality and all-cause hospitalizations. Several dimensions of quality of life were also improved. Integration of pharmacist into a HFrEF care team or care pathway should be strongly considered as an important element of a multidisciplinary team.

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.

Supplementary_appendix for Clinical outcomes of theophylline use as add-on therapy in patients with chronic obstructive pulmonary disease: A propensity score matching analysis by Preyanate Wilairat, Kirati Kengkla, Chaiyawat Thayawiwat, Phongsathorn Phlaisaithong, Supakorn Somboonmee, and Surasak Saokaew in Chronic Respiratory Disease

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.

Background. This study evaluated the relative efficacy of strategies for the prevention of multidrug-resistant gram-negative bacteria (MDR-GNB) in adult intensive care units (ICUs). Methods. A systematic review and network meta-analysis was performed; searches of the Cochrane Library, PubMed, Embase, and CINAHL (Cumulative Index to Nursing and Allied Health Literature) included all randomized controlled trials and observational studies conducted in adult patients hospitalized in ICUs and evaluating standard care (STD), antimicrobial stewardship program (ASP), environmental cleaning (ENV), decolonization methods (DCL), or source control (SCT), simultaneously. The primary outcomes were MDR-GNB acquisition, colonization, and infection; secondary outcome was ICU mortality. Results. Of 3805 publications retrieved, 42 met inclusion criteria (5 randomized controlled trials and 37 observational studies), involving 62 068 patients (median age, 58.8 years; median APACHE [Acute Physiology and Chronic Health Evaluation] II score, 18.9). The majority of studies reported extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae and MDR Acinetobacter baumannii. Compared with STD, a 4-component strategy composed of STD, ASP, ENV, and SCT was the most effective intervention (rate ratio [RR], 0.05 [95% confidence interval {CI}, .01-.38]). When ENV was added to STD+ASP or SCT was added to STD+ENV, there was a significant reduction in the acquisition of MDR A. baumannii (RR, 0.28 [95% CI, .18-.43] and 0.48 [95% CI, .35-.66], respectively). Strategies with ASP as a core component showed a statistically significant reduction the acquisition of ESBLproducing Enterobacteriaceae (RR, 0.28 [95% CI, .11-.69] for STD+ASP+ENV and 0.23 [95% CI, .07-.80] for STD+ASP+DCL). Conclusions. A 4-component strategy was the most effective intervention to prevent MDR-GNB acquisition. As some strategies were differential for certain bacteria, our study highlighted the need for further evaluation of the most effective prevention strategies.

Background Microbiome-directed therapies are increasingly used preoperatively and postoperatively to improve postoperative outcomes. Recently, the effectiveness of probiotics, prebiotics, and synbiotics in reducing postoperative complications (POCs) has been questioned. This systematic review aimed to examine and rank the effectiveness of these therapies on POCs in adult surgical patients. Methods We searched for articles from PubMed, Embase, Cochrane, Web of Science, Scopus, and CINAHL plus. From 2002 to 2015, 31 articles meeting the inclusion criteria were identified in the literature. Risk of bias and heterogeneity were assessed. Network meta-analyses (NMA) were performed using random-effects modeling to obtain estimates for study outcomes. Risk ratios (RRs) and 95% confidence intervals (CIs) were estimated. We then ranked the comparative effects of all regimens with the surface under the cumulative ranking (SUCRA) probabilities. Results A total of 2,952 patients were included. We found that synbiotic therapy was the best regimen in reducing surgical site infection (SSI) (RR = 0.28; 95% CI, 0.12-0.64) in adult surgical patients. Synbiotic therapy was also the best intervention to reduce pneumonia (RR = 0.28; 95% CI, 0.09-0.90), sepsis (RR = 0.09; 95% CI, 0.01-0.94), hospital stay (mean = 9.66 days, 95% CI, 7.60-11.72), and duration of antibiotic administration (mean = 5.61 days, 95% CI, 3.19-8.02). No regimen significantly reduced mortality. Conclusions This network meta-analysis suggests that synbiotic therapy is the first rank to reduce SSI, pneumonia, sepsis, hospital stay, and antibiotic use. Surgeons should consider the use of synbiotics as an adjunctive therapy to prevent POCs among adult surgical patients. Increasing use of synbiotics may help to reduce the use of antibiotics and multidrug resistance.

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.

Background Extended spectrum β-lactamase-producing Escherichia coli (ESBL-EC) has important implications for infection control and empiric antibiotic prescribing. This study aims to develop a risk scoring system for predicting ESBL-EC infection based on local epidemiology. Methods The study retrospectively collected eligible patients with a positive culture for E. coli during 2011 to 2014. The risk scoring system was developed using variables independently associated with ESBL-EC infection through logistic regression-based prediction. Area under the receiver-operator characteristic curve (AuROC) was determined to confirm the prediction power of the model. Findings Predictors for ESBL-EC infection were male gender [odds ratio (OR): 1.53], age ≥55 years (OR: 1.50), healthcare-associated infection (OR: 3.21), hospital-acquired infection (OR: 2.28), sepsis (OR: 1.79), prolonged hospitalization (OR: 1.88), history of ESBL infection within one year (OR: 7.88), prior use of broad-spectrum cephalosporins within three months (OR: 12.92), and prior use of other antibiotics within three months (OR: 2.14). Points scored ranged from 0 to 47, and were divided into three groups based on diagnostic performance parameters: low risk (score: 0-8; 44.57%), moderate risk (score: 9-11; 21.85%) and high risk (score: ≥12; 33.58%). The model displayed moderate power of prediction (AuROC: 0.773; 95% confidence interval: 0.742-0.805) and good calibration (Hosmer-Lemeshow χ(2) = 13.29; P = 0.065). Conclusion This tool may optimize the prescribing of empirical antibiotic therapy, minimize time to identify patients, and prevent spreading of ESBL-EC. Prior to adoption into routine clinical practice, further validation study of the tool is needed.