From Shadows to Spotlight: Exploring the Escalating Burden of Alcohol-Associated Liver Disease and Alcohol Use Disorder in Young Women.

INTRODUCTION: The burden of alcohol-related complications is considerable, particularly alcohol-associated liver disease and alcohol use disorder (AUD). However, there are deficiencies in comprehensive epidemiological research focusing on these issues, especially among young women who display higher susceptibility to such complications compared with their male counterparts. We thus aimed to determine the global burden of these conditions in this vulnerable group. METHODS: Leveraging data from the Global Burden of Disease Study 2019, we analyzed the prevalence, mortality, and disability-adjusted life years of alcohol-associated cirrhosis (AC), liver cancer from alcohol, and AUD in young women. The findings were categorized by region, nation, and sociodemographic index. RESULTS: The highest age-standardized prevalence rates were observed in AUD (895.96 [95% uncertainty interval (UI) 722.6-1,103.58]), followed by AC (65.33 [95% UI 48.37-86.49]) and liver cancer from alcohol (0.13 [95% UI 0.09-0.19]) per 100,000 people. The highest age-standardized mortality rates were observed in AC (0.75 [95% UI 0.55-0.97]), followed by AUD (0.48 [95% UI 0.43-0.53]) and liver cancer from alcohol (0.06 [95% UI 0.04-0.09]). The highest burdens of AC and AUD were observed in Central Europe, whereas the high-income Asia Pacific had the highest burden of liver cancer from alcohol. DISCUSSION: Throughout the past decade, the trend of AUD varied among regions while the impact of alcohol-associated liver disease has increased, requiring urgent public health strategy to mitigate these complications, particularly in female patients in Europe and the Asia-Pacific region.

Development and validation of a bleeding risk prediction score for patients with mitral valve stenosis and atrial fibrillation or mechanical heart valves receiving long-term warfarin therapy.

AIMS: This study aimed to develop and validate a new bleeding risk score to predict warfarin-associated major bleeding for patients with mitral valve stenosis with atrial fibrillation (MSAF) or mechanical heart valves (MHV). METHODS: A multicentre, retrospective cohort study was conducted at 3 hospitals in Thailand. Adult patients with MSAF or MHV receiving warfarin for ≥3 months during 2011-2015 were identified. Data collection and case validation were performed electronically and manually. Potential variables were screened using the least absolute shrinkage and selection operator. Multivariate logistic regression analysis using stepwise backward selection was used to construct a risk score. Predictive discrimination of the score was evaluated using the C-statistic. Calibration was assessed using the Hosmer-Lemeshow goodness-of-fit test. RESULTS: There were 1287 patients (3903.41 patient-year of follow-up), with 192 experiencing bleeding (4.92 event/100 patient-year) in the derivation cohort. A new bleeding risk score termed, the HEARTS-60 + 3 score (hypertension/history of bleeding; external factors, e.g., alcohol/drugs [aspirin or nonsteroidal anti-inflammatory drugs]; anaemia/hypoalbuminaemia; renal/hepatic insufficiency; time in therapeutic range of <60%; stroke; age ≥60 y; target international normalized ratio of 3.0 [2.5-3.5]), was developed and showed good predictive performance (C-statistic [95% confidence interval] of 0.88 [0.85-0.91]). In the external validation cohort of 832 patients (2018.45 patient-year with a bleeding rate of 4.31 event/100 patient-year), the HEARTS-60 + 3 score showed a good predictive performance with a C-statistic (95% confidence interval) of 0.84 (0.81-0.89). CONCLUSION: The HEARTS-60 + 3 score shows a potential as a bleeding risk prediction score in MSAF or MHV patients.

Validation and comparison of the stroke prognosis instrument (SPI-II) and the essen stroke risk score (ESRS) in predicting stroke recurrence in Asian population.

BACKGROUND: Currently, there are limited data on the accuracy of available risk scores to predict stroke recurrence in the Asian population. METHOD: A single-center, retrospective cohort study was conducted among patients with acute ischemic stroke during January 2014 - December 2018. Longitudinal data with three years of follow-up among these patients were collected and validated through both electronic and manual chart review. The area under the receiver-operating curve (AUROC) method or C-statistic and calibration plot were used to evaluate and compare the Stroke Prognosis Instrument II (SPI-II) and the Essen Stroke Risk Score (ESRS) in predicting the long-term risk of recurrent ischemic stroke. The predictive performances of the two scores were compared using DeLong's method. RESULTS: The study cohort consisted of 543 patients, including 181 and 362 patients with and without recurrent events. There were no significant differences in mean age and gender between the two groups. Recurrence cases tended to have significant more risk factors compared to those without events. Among cases with recurrent events, 134 (74.03%) and 65.74% (119) cases were classified as high-risk based on SPI-II and ESRS, respectively. The AUROC curve of the SPI-II and ESRS score was 0.646 (95% CI, 0.594-0.697) and 0.614 (95%CI, 0.563-0.665), respectively (p = 0.394). Based on the calibration plot, the SPI-II and ESRS scores showed similar moderate predictive performance on recurrence stroke with a C statistic (95% CI) of 0.655 (95% CI: 0.603-0.707) and 0.631 (95% CI 0.579-0.684), respectively. CONCLUSION: Both ESRS and SPI-II scores had moderate predictive performance in Thai population.

Drug-Related Problems and Pharmacists' Interventions in Hypertensive Outpatients: A Multicenter Prospective Study in 3 Vietnamese Hospitals.

Background: Clinical pharmacists' interventions (PIs) on drug-related problems (DRPs) in Vietnamese hypertensive outpatients are limited. Objectives: The objective was to investigate the prevalence and nature of DRPs, and factors which are likely to have DRPs, types of PIs, and their acceptance rate in 3 Vietnamese hospitals. Method: A prospective interventional study was conducted over a period of 3 months in 3 hospitals (from October 2021 to March 2022). Clinical pharmacists conducted medication reviews after collecting patient information from prescriptions and patient interviewing, and then identified the DRPs and suggested PIs according to the Vi-Med tool. These DRPs and PIs were reviewed by other superior clinical pharmacists and a consensus meeting with 3 cardiologists. Results: Of 381 patients included, 344 (90.23%) experienced 1 or more DRPs. A total of 820 DRPs were identified with an average of 2.15 DRPs per patient and 415 (50.61%) were hypertension-related issues. The most common DRPs identified were "administration mode" (46.34%), "missing indication" (18.05%), "non-conformity indication" (17.80%), and "dosage" (11.95%). Comorbidity (adjusted odds ratio [AOR] = 3.985, 95% CI: 1.597-9.942, P = 0.003) was the predictor of DRPs. Clinical pharmacists provided 739 PIs and 94.45% were accepted by physicians. Conclusion: The results of this study showed that DRPs were very common in hypertensive outpatients and highlighted the role of clinical pharmacists to identify and resolve DRPs through prompt interventions.

Effects of pharmacist interventions on cardiovascular risk factors and outcomes: An umbrella review of meta-analysis of randomized controlled trials.

AIMS: To grade the evidence from published meta-analyses of randomized controlled trials (RCTs) that assessed effects of pharmacist intervention on cardiovascular risk factors and cardiovascular outcomes. METHODS: MEDLINE, Embase, and the Cochrane Library were searched from database inception to July 2021. Meta-analyses of RCTs were eligible. Quality of evidence were assessed by GRADE approach. RESULTS: From 9308 publications, 149 full-text articles were evaluated for eligibility, and 24 studies with 85 unique meta-analyses that assessed effects of pharmacist intervention on cardiovascular risk factors and cardiovascular outcomes were selected. Overall, 71.7% (61/85) of unique meta-analyses showed significant impacts of pharmacist intervention. For the quality of evidence, 63.4% of meta-analyses had large heterogeneity (I2 > 50%) while 1.2, 16.5, 32.9 and 49.4% of meta-analyses were graded as high, moderate, low and very low quality based on GRADE approach, respectively. Among meta-analyses with moderate quality, pharmacist interventions significantly mitigated risk factors (including 6/3 mmHg reduction of blood pressure, increased the rate of lipid control, glucose control and smoking cessation (pooled odds ratio, [95% confidence interval] 1.91 [1.55, 2.35], 3.11 [2.3, 4.3] and 2.3 [1.33, 3.97], respectively) and improved medication adherence (1.67 [1.38, 2.02]). Furthermore, pharmacist interventions significantly reduced all-cause mortality (0.72 [0.58, 0.89]) and improved quality of life in patients suffering from chronic heart failure. CONCLUSION: This umbrella review found convincing evidence that pharmacist intervention can provide a wide range of benefits in cardiovascular disease management, ranging from risk factor control, improvement in medication adherence and, in some settings, reduction in morbidity and mortality.

Comparison of the HAS-BLED versus ORBIT scores in predicting major bleeding among Asians receiving direct-acting oral anticoagulants.

AIMS: This study aimed to evaluate the performance of HAS-BLED and ORBIT scores in predicting bleeding risk among Asian patients with nonvalvular atrial fibrillation (NVAF) using direct-acting oral anticoagulants (DOACs). METHODS: A retrospective chart review was conducted among adult patients receiving DOACs for ≥6 months during January 2013 to December 2017 in 10 tertiary care hospitals in Thailand. The area under the receiver operating curve (AUROC) method or C-statistic was used to test the diagnostic accuracy for bleeding risk classification of HAS-BLED and ORBIT scores. The predictive performances of the two scores were compared using DeLong's method. RESULTS: A total of 961 NVAF patients, 52.5% warfarin-naïve and 47.5% warfarin-experienced, with mean age of 74.25 ± 10.08 years, were included in the analysis. Mean HAS-BLED and ORBIT scores of the cohort were 1.98 ± 1.10 and 2.37 ± 1.71, respectively. During the mean follow-up time of 1.55 ± 1.13 years, 34 patients experienced major bleeding (2.28 events/100 patient-year). For the overall cohort, both the HAS-BLED and ORBIT scores showed similarly moderate predictive performance on bleeding with C-statistic (95% confidence interval) of 0.65 (0.57-0.74) and 0.64 (0.56-0.71), respectively. There was no statistical significance between the two scores (P = .62). Analysis based on the status of previous warfarin use was consistent with the overall cohort. Based on the calibration analysis, both HAS-BLED and ORBIT scores possessed moderate ability to identify those who experienced major bleeding from those who did not. CONCLUSION: Both HAS-BLED and ORBIT bleeding risk scores had moderate predictive performance in Asian NVAF patients receiving DOACs.

Prescriber compliance to direct oral anticoagulant labels and impact on outcomes in Thailand.

AIMS: This study aimed to evaluate the prescriber compliance to the approved labels of direct oral anticoagulants (DOACs) and impact of appropriateness of dosing on clinical outcomes. METHODS: A retrospective study was conducted using simple-stratified random sampling of adult patients receiving ≥6 months of DOACs for various indications during 2013-2017 in 10 tertiary care hospitals. Patients were classified into 3 dosing groups including approved dose, underdosing and overdosing based on the Thai Food and Drug Administration-approved labels. Cox proportional hazard models were used to evaluate the impact of different dosings on thromboembolic and bleeding events. RESULTS: From 1200 patients included in the data analysis, prescribing of DOACs was consistent with the approved indications in 1130 cases (94.2%) while 70 patients (5.8%) received DOACs despite having contraindications or with off-label usage. Among 1026 cases of dosing evaluation cohort, 688 patients (67.1%) received approved doses. There were 227 (21.9%) and 110 (10.7%) cases of underdosing and overdosing, respectively. Multivariate analysis showed that underdosing was associated with an increased risk of thromboembolism 3.023 (95% confidence interval [CI]: 1.291-7.080; P = .011) while overdosing was associated with an increased risk of bleeding requiring hospitalization (adjusted hazard ratio, 3.045; 95% CI, 1.501-6.178; P = .002) and Bleeding Academic Research Consortium type 2 or more (adjusted hazard ratio, 2.196; 95% CI, 1.083-4.452; P = .029). CONCLUSION: Prescribers' compliance to approved indications were high. However, 1/3 of DOAC prescriptions were inconsistent with approved dosing. Dosing deviation was associated with an increase in adverse clinical outcomes.

Real-world experience of angiotensin receptor/neprilysin inhibitor (ARNI) usage in Thailand: a single-center, retrospective analysis.

BACKGROUND: Treatment of heart failure with reduced ejection fraction (HFrEF) has been revolutionized by angiotensin receptor/neprilysin inhibitor (ARNI). ARNI has been shown to significantly reduce morbidity and mortality in a large, randomized controlled trial. However, real-world evaluation of ARNI with a diverse population is still limited. METHODS: HFrEF patients receiving angiotensin receptor/neprilysin inhibitor (ARNI) or standard HF treatment at a university hospital in Thailand were prospectively followed-up from January 2015 to December 2019. The primary outcome was a composite of all-cause mortality and heart failure hospitalization. Survival analysis and the Cox proportional hazard model were used to compare clinical outcomes between the two groups. RESULTS: During a follow-up period of 12 months, the primary outcome occurred in 10 patients in the ARNI group (11.5%) and 28 in the standard treatment group (28.0%) (hazard ratio 0.34; 95% CI: 0.15-0.80; p = 0.013). After adjustment for confounding factors, ARNI was significantly associated with a significant reduction in the primary outcome (HR 0.32, 95% CI: 0.13-0.82, p = 0.017). In addition, ARNI was also significantly associated with a decrease in the clinical signs and symptoms of HF, including dyspnea, orthopnea, and fatigue. Orthostatic hypotension was more frequently reported among the ARNI group than among the standard treatment group. The rates of target dose achievement were comparable between the two groups. CONCLUSION: In real-world practice, ARNI use was associated with a significant reduction in both clinical outcomes and symptom improvement, while orthostatic hypotension was more common in patients in the ARNI group than in patients in the standard treatment group.

A systematic review and meta-analysis of randomized controlled trials of cardiovascular toxicity of medical cannabinoids.

BACKGROUND: Several systematic reviews (SRs) have summarized the potential effectiveness of medical cannabinoids, but it is unclear to what extent safety-related outcomes were incorporated. OBJECTIVE: The objective of this study was to evaluate the cardiovascular toxicity associated with medical use of cannabinoids. METHODS: A 2-stage systematic review (SR) approach was undertaken to assess the current evidence on cannabinoid-associated cardiovascular events reported among randomized controlled trials (RCTs). First, we searched for SRs in multiple sources until June 2019. Second, RCTs identified from the SRs were included if they assessed medical cannabis and reported cardiovascular events. The outcomes of interest were all types of cardiovascular events. Data were extracted by 2 independent reviewers. Study quality was assessed using the Cochrane risk of bias. A statistical test of heterogeneity was performed. The summary risk ratios (RRs) and 95% CIs were calculated using a random-effects model. RESULTS: A total of 47 studies involving 2800 patients were included. The median duration of cannabinoid use was 15.8 days (range 1 to 322), and 45% of the studies excluded patients with underlying cardiovascular diseases. Cannabinoid use was significantly associated with increased risks of orthostatic hypotension (RR 3.16 [95% CI 2.27-4.40], I2 = 2.3%) and hypotension (3.55 [1.45-8.71], I2 = 31.8%), with a trend of increased risk of tachycardia (1.94 [0.81-4.64], I2 = 48.6%). No study reported serious cardiovascular events. CONCLUSIONS: Cannabinoid use was associated with tachycardia, hypotension, and orthostatic hypotension. There is a paucity of data for other cardiovascular events among medical cannabis users. More data, especially regarding long-term effects among patients with existing cardiovascular diseases, are needed.

Cost-Effectiveness Analysis of Non-Vitamin K Antagonist Oral Anticoagulants Versus Warfarin in Thai Patients With Non-Valvular Atrial Fibrillation.

BACKGROUND: Non-vitamin K antagonist oral anticoagulants (NOACs) have been recommended as preferred options for stroke prevention in patients with atrial fibrillation (AF) versus warfarin by guidelines worldwide. AIM: This study aimed to evaluate the cost-effectiveness of each NOAC in a Thai health care environment, a country with upper middle-income economies based on the World Bank's classification. METHOD: A lifetime Markov model was created from a Thai societal perspective. The model consisted of 19 health states separated into two cycles: event cycle and consequence cycle. The consequences of AF included in the model were ischaemic stroke, intracranial haemorrhage, extracranial haemorrhage, and myocardial infarction. All NOACs available in Thailand (dabigatran 150 mg and 110 mg twice daily; rivaroxaban 20 mg once daily; apixaban 5 mg twice daily; edoxaban 60 mg and 30 mg once daily) were assessed using warfarin with an international normalised ratio of 2-3 as the reference. Inputs were a combination of published literature and local data when available. A willingness-to-pay of 160,000 Thai baht (THB)/quality-adjusted life year (QALY) was used as the threshold of being cost-effective. Incremental cost-effectiveness ratios and cost-effectiveness acceptability curves were estimated. RESULTS: All NOACs were not cost-effective strategies for the Thai AF population. The ranking of incremental cost-effectiveness ratios from lowest to highest were apixaban 5 mg twice daily (THB 692,136 or US$21,862) followed by edoxaban 60 mg once daily (THB 911,772 or US$28,799), edoxaban 30 mg once daily (THB 913,749 or US$28,861), dabigatran 150 mg twice daily (THB 1,102,106 or US$34,811), dabigatran 110 mg twice daily (THB 1,195,347 or US$37,756), and rivaroxaban 20 mg once daily (THB 1,347,650 or US$42,566). Cost-effectiveness acceptability curve indicated that apixaban had the highest potential to be a cost-effective strategy versus other NOACs. CONCLUSIONS: Our findings indicated that all NOACs were not cost-effective in the Thai AF population. Of the NOACs, apixaban may be the most likely to be cost-effective. These data may be useful for policymakers to perform a comprehensive evaluation of these agents for formulary decision and pricing negotiation.

Incidence, risk factors, and outcomes of warfarin-associated major bleeding in Thai population.

PURPOSE: This study aimed to describe incidence, risk factors, and outcomes of warfarin-associated major bleeding (WAMB) in Thai patients. METHOD: A nested case-control study was conducted in a cohort of adult patients receiving ≥6 months of warfarin therapy who were prospectively followed up at a tertiary care hospital in Thailand during January 2011 to December 2014. Logistic regression was used to identify risk factors associated with WAMB. The area under the receiver operating characteristic (AUROC) curve was used to assess the performance of the HAS-BLED score to predict WAMB in patients with non-valvular atrial fibrillation (NVAF). RESULTS: Among 1604 patients (2972 patient-year of follow-up), there were 93 major bleeding that occurred in 76 patients. The incidence of WAMB was 3.13 events per 100 patient-year. Time in therapeutic range (TTR) of <60% (RR: 3.62, 95% CI: 1.94-6.73, P < 0.001), mechanical valve replacement at mitral position (RR 3.43, 95% CI: 1.92-6.16, P < 0.001) cancer (RR: 2.84, 95% CI: 1.11-7.29, P = 0.029), and age ≥ 65 years (RR: 2.37, 95% CI: 1.20-4.67, P = 0.012) were independent risk factors for WAMB. There were 17 fatalities and 12 cases of disabilities from WAMB. Mean cost of WAMB was 45 341.54 THB/event. An exploratory analysis suggested that HASBLED score demonstrated an excellent discriminatory capacity to predict WAMB among NVAF patients (AUROC of 0.91, 95% CI: 0.85-0.97, P < 0.001). CONCLUSION: WAMB in Thai population is common and associated with high rate of morbidity and mortality. Improvement in anticoagulation control is clearly needed.

Comparative efficacy and safety of reperfusion therapy with fibrinolytic agents in patients with ST-segment elevation myocardial infarction: a systematic review and network meta-analysis.

BACKGROUND: Fibrinolytic therapy offers an alternative to mechanical reperfusion for ST-segment elevation myocardial infarction (STEMI) in settings where health-care resources are scarce. Comprehensive evidence comparing different agents is still unavailable. In this study, we examined the effects of various fibrinolytic drugs on clinical outcomes. METHODS: We did a network meta-analysis based on a systematic review of randomised controlled trials comparing fibrinolytic drugs in patients with STEMI. Several databases were searched from inception up to Feb 28, 2017. We included only randomised controlled trials that compared fibrinolytic agents as a reperfusion therapy in adult patients with STEMI, whether given alone or in combination with adjunctive antithrombotic therapy, against other fibrinolytic agents, a placebo, or no treatment. Only trials investigating agents with an approved indication of reperfusion therapy in STEMI (streptokinase, tenecteplase, alteplase, and reteplase) were included. The primary efficacy outcome was all-cause mortality within 30-35 days and the primary safety outcome was major bleeding. This study is registered with PROSPERO (CRD42016042131). FINDINGS: A total of 40 eligible studies involving 128 071 patients treated with 12 different fibrinolytic regimens were assessed. Compared with accelerated infusion of alteplase with parenteral anticoagulants as background therapy, streptokinase and non-accelerated infusion of alteplase were significantly associated with an increased risk of all-cause mortality (risk ratio [RR] 1·14 [95% CI 1·05-1·24] for streptokinase plus parenteral anticoagulants; RR 1·26 [1·10-1·45] for non-accelerated alteplase plus parenteral anticoagulants). No significant difference in mortality risk was recorded between accelerated infusion of alteplase, tenecteplase, and reteplase with parenteral anticoagulants as background therapy. For major bleeding, a tenecteplase-based regimen tended to be associated with lower risk of bleeding compared with other regimens (RR 0·79 [95% CI 0·63-1·00]). The addition of glycoprotein IIb or IIIa inhibitors to fibrinolytic therapy increased the risk of major bleeding by 1·27-8·82-times compared with accelerated infusion alteplase plus parenteral anticoagulants (RR 1·47 [95% CI 1·10-1·98] for tenecteplase plus parenteral anticoagulants plus glycoprotein inhibitors; RR 1·88 [1·24-2·86] for reteplase plus parenteral anticoagulants plus glycoprotein inhibitors). INTERPRETATION: Significant differences exist among various fibrinolytic regimens as reperfusion therapy in STEMI and alteplase (accelerated infusion), tenecteplase, and reteplase should be considered over streptokinase and non-accelerated infusion of alteplase. The addition of glycoprotein IIb or IIIa inhibitors to fibrinolytic therapy should be discouraged. FUNDING: None.

Cost-Effectiveness Analysis of Fondaparinux vs Enoxaparin in Non-ST Elevation Acute Coronary Syndrome in Thailand.

BACKGROUND: Non-ST elevation acute coronary syndrome (NSTE-ACS) imposes a significant health and economic burden on a society. Anticoagulants are recommended as standard therapy by various clinical practice guidelines. Fondaparinux was introduced and evaluated in a number of large randomised, controlled trials. This study therefore aimed to determine the cost-effectiveness of fondaparinux versus enoxaparin in the treatment of NSTE-ACS in Thailand. METHODS: A two-part construct model comprising a one-year decision tree and a Markov model was developed to capture short and long-term costs and outcomes from the perspective of provider and society. Effectiveness data were derived from OASIS-5 trial while bleeding rates were derived from the Thai Acute Coronary Syndrome Registry (TACSR). Costs data were based on a Thai database and presented in the year of 2013. Both costs and outcomes were discounted by 3% annually. A series of sensitivity analyses were performed. RESULTS: The results showed that compared with enoxaparin, fondaparinux was a cost-saving strategy (lower cost with slightly higher effectiveness). Cost of revascularisation with major bleeding had a greater impact on the amount of cost saved both from societal and provider perspectives. With a threshold of 160,000 THB ((4,857.3 USD) per QALY in Thailand, fondaparinux was about 99% more cost-effective compared with enoxaparin. CONCLUSION: Fondaparinux should be considered as a cost-effective alternative when compared to enoxaparin for NSTE-ACS based on Thailand's context, especially in the era of limited healthcare resources.

Renin angiotensin system blockers-associated angioedema in the Thai population: analysis from Thai National Pharmacovigilance Database.

BACKGROUND: Renin-angiotensin-aldosterone system (RAS) blockers are commonly used for cardiovascular diseases. Currently, little information exists for the Asian population on angioedema, a rare yet serious adverse event. OBJECTIVE: This study aimed to describe characteristics of RAS blockers-associated angioedema (RASBA) in Thai patients. METHODS: A retrospective study using the national pharmacovigilance database of Thailand was undertaken. Cases indicating the presence of angioedema with RAS blockers uses from 1984-2011 were identified. Patient demographics, co-morbidities, concomitant drugs, information for the RAS blockers and angioedema were obtained as well as causality assessment and quality of reports. RESULTS: A total of 895 cases were identified. Mean age was 59.9+12.8 years and 66.5% being female. Most angioedema events (48.6%) occurred during the first week of treatment. Angiotensin converting enzyme inhibitors (87.7%) were the most commonly implicated agents followed by angiotensin receptor blockers (10.5%), aldosterone antagonist (2.1%) and direct renin inhibitor (0.2%). Out of the 895 cases incorporated in this study, 165 (18.4%) were classified as serious events and resulted in hospitalization. The overall case fatality rate was 0.4%. Respiratory disturbance occurred in 46 cases (5.1%). Patients with respiratory complications tended to be younger (53.4+13.9 vs 60.3+12.7 years old; p=0.002) and with higher frequency of allergy history (26.1% vs 14.7%; p=0.032) compared to those without respiratory complications. Based on multivariate logistic regression, the adjusted OR for history of allergy was 2.23 (95%CI: 1.04 - 4.78, p = 0.041). CONCLUSIONS: RASBA in Thai population occurred mostly in elderly female patients and often led to hospitalization. Since large number of patients is regularly exposed to RAS-blockers, a nationwide attempt to raise awareness of clinicians when prescribing RAS-blockers is prudent.

Loop-mediated isothermal amplification assay targeting the blaCTX-M9 gene for detection of extended spectrum ß-lactamase-producing Escherichia coli and Klebsiella pneumoniae.

Extended-spectrum ß-lactamases (ESBLs) produced by Enterobacteriaceae are one of the resistance mechanisms to most ß-lactam antibiotics. ESBLs are currently a major problem in both hospitals and community settings worldwide. Rapid and reliable means of detecting ESBL-producing bacteria is necessary for identification, prevention and treatment. Loop-mediated isothermal amplification (LAMP) is a technique that rapidly amplifies DNA with high specificity and sensitivity under isothermal conditions. This study was aimed to develop a convenient, accurate and inexpensive method for detecting ESBL-producing bacteria by a LAMP technique. ESBLs-producing Escherichia coli and Klebsiella pneumoniae were isolated from a tertiary hospital in Bangkok, Thailand and reconfirmed by double-disk synergy test. A set of four specific oligonucleotide primers of LAMP for detection of bla(CTX-M9) gene was designed based on bla(CTX-M9) from E. coli (GenBank Accession No. AJ416345). The LAMP reaction was amplified under isothermal temperature at 63°C for 60 min. Ladder-like patterns of band sizes from 226 bp of the bla(CTX-M9) DNA target was observed. The LAMP product was further analyzed by restriction digestion with MboI and TaqI endonucleases. The fragments generated were approximately 168, 177 and 250 bp in size for MboI digestion and 165, 193, 229, 281 and 314 bp for TaqI digestion, which is in agreement with the predicted sizes. The sensitivity of the LAMP technique to bla(CTX-M9) was greater than that of the PCR method by at least 10,000-fold. These results showed that the LAMP primers specifically amplified only the bla(CTX-M9) gene. Moreover, the presence of LAMP amplicon was simply determined by adding SYBR Green I in the reaction. In conclusion, this technique for detection of ESBLs is convenient, reliable and easy to perform routinely in hospitals or laboratory units in developing countries.

Use of the CRUSADE bleeding risk score in the prediction of major bleeding for patients with acute coronary syndrome receiving enoxaparin in Thailand.

BACKGROUND: CRUSADE risk score stands out as a simple-to-use bleeding risk model. However, its use is still doubtful for Thai population. The aim of this study was to assess the prognostic value of CRUSADE in predicting risk of major bleeding among Thai patients with acute coronary syndrome (ACS) receiving enoxaparin. METHODS: A retrospective cohort study was performed using patients with ACS who were hospitalised at a university hospital in Bangkok between 2006 and 2009 and had received enoxaparin. The CRUSADE risk score was calculated. The model validation was tested by using C statistic and Hosmer-Lemeshow goodness-of-fit. RESULTS: The overall incidence of major bleeding was 18.3%. Median CRUSADE score for entire study population, unstable angina (UA), non-ST elevation myocardial infarction (NSTEMI), and ST elevation myocardial infarction (STEMI) were 49, 47, 53, and 39, respectively. Hosmer-Lemeshow goodness of fit revealed no statistical significance in all groups. The CRUSADE model demonstrated a satisfactory discriminatory capacity for the entire study population (C = 0.688), UA (C = 0.591), NSTEMI (C = 0.693), and STEMI groups (C = 0.736). CONCLUSIONS: Across the ACS spectrum, CRUSADE risk score was able to estimate in-hospital major bleeding of Thai patients with ACS who received treatment with enoxaparin. The application of these results in Thailand may be helpful in the identification of patients at high bleeding risk and also may lead to implementation of appropriate prevention.

Treatment seeking experiences of ACS patients in Yogyakarta, Indonesia during COVID-19 pandemic: A qualitative study.

Delay in treatment seeking is recognized as a major contributor for Acute Coronary Syndrome (ACS) mortality in Indonesia. Despite the significance of timely treatment, decline in admission and delay in presentation of patients with ACS were consistently reported during the COVID-19 pandemic. These suggested that treatment seeking performance of patients during the pandemic might be different from the previous period. This qualitative study aimed to explore treatment seeking behaviour, barriers in seeking medical treatment, and experiences of patients with ACS in Yogyakarta, Indonesia during COVID-19 pandemic. In depth-interviews were carried out with 30 patients, who were hospitalized with ACS at one of the three selected hospitals in Yogyakarta during the pandemic period. Thematic analysis was performed to create vital explanations for treatment seeking practices of patients with ACS during pandemic. Three significant themes were identified: treatment seeking decisions, barriers in seeking medical treatment during COVID-19, and experiencing both good and bad impression from entering and staying in the hospital. The intensity of ACS symptoms and fear of COVID-19 infection dominated the delay in seeking medical treatment. Strict safety measures, religious belief, and fear of ACS helped patients overcome barriers and seek medical treatment during pandemic. ACS patients also had convenient medical care during the pandemic and believed medical staff would provide excellent care to them. However, visit restriction policy could cause psychological discomfort. Increase awareness of ACS symptoms and the risk of delays ACS treatment are essential to support patients' decisions to seek medical helps in a timely manner at any situations including pandemic. Interventions aim at alleviating psychological distress should also be designed and implemented to improve treatment experiences of ACS patients, who sought medical treatment during the pandemic crisis.

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.

The burden of alcohol-related cardiovascular complications in young and middle-aged adults: rising burden of atrial fibrillation and hypertensive heart disease.

BACKGROUND AND AIMS: The burden of alcohol-related complications is high and rising. However, there are notable deficiencies in comprehensive epidemiological study focusing on cardiovascular complications from alcohol, especially among young and middle-aged adults. We thus aimed to determine the burden of these conditions in young and middle-aged adults globally. METHODS AND RESULTS: We used data from the Global Burden of Disease Study 2019 and analysed the mortality and disability-adjusted life years of alcohol-associated cardiovascular complications in young and middle-aged adults. The findings were classified by sex, region, country, and Sociodemographic Index (SDI). The highest age-standardized death rates (ASDR) were observed in stroke 0.84 (95% UI 0.60-1.09), followed by alcoholic cardiomyopathy 0.57 (95% UI 0.47-0.66) per 100,000 population. The overall burden of alcohol-associated cardiovascular complications decreased globally but increased in atrial fibrillation and hypertensive heart disease. Regionally, most regions underwent a decrease in ASDR, but an increase was observed in Southeast Asia (+2.82%), Western Pacific (+1.48%), low-middle (+1.81%), and middle SDI (+0.75%) countries. Nevertheless, the ASDR and ASDALYs were highest in Europe. CONCLUSIONS: The impact of alcohol-associated atrial fibrillation and hypertensive heart disease has increased over the last decades. Regarding region, the burden in Europe and the rising burden in Asia, require immediate public health policy to lessen these cardiovascular complications from alcohol in young and middle-aged adults.

Metabolic Syndrome and Metabolic Dysfunction-Associated Steatotic Liver Disease in Premenopausal Women: Global Trends and Projections to 2040.

OBJECTIVE: To quantify the burden of metabolic dysfunction-associated steatotic liver disease (MASLD) and related metabolic disorders in premenopausal women. PATIENTS AND METHODS: Between 2010 and 2019, global evaluations of prevalence, mortality, disability-adjusted life years (DALYs), and their age-standardized rate (ASR) were conducted for metabolic conditions such as MASLD, type 2 diabetes mellitus, dyslipidemia, hypertension (HTN), obesity, and polycystic ovarian syndrome. Subgroup assessments were conducted according to geographical regions and the sociodemographic index. The predictive models were established to estimate mortality and DALYs through 2040. RESULTS: In 2019, the most significant ASR of deaths was found in HTN (11.37; 9.52 to 13.45), followed by obesity (10.49; 7.57 to 13.64). In contrast, the greatest ASR of DALYs was attributed to obesity (816.13; 581.41 to 1073.32), followed by HTN (634.73; 536.75 to 744.77). The mortality rates for dyslipidemia (-0.55%) and HTN (-0.72%) have been decreasing over time, but there has been an increase in obesity (+0.58%), type 2 diabetes mellitus (+0.85%), and MASLD (+0.51%). Lower sociodemographic index countries exhibit a higher disability-to-prevalence ratio. In 2040, obesity is predicted to cause the most deaths (+41.59% from 2019). CONCLUSION: The escalating impact of metabolic syndrome, the rising trends in death rates linked to obesity, and the disparities based on region and socioeconomic status in premenopausal women underscore the alarming increase in the global burden of metabolic syndrome.