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ObjectiveTo evaluate efficacy and safety of oral anticoagulant regimens and aspirin for extended venous thromboembolism (VTE) treatment.MethodsWe searched MEDLINE, Embase, CENTRAL and conference proceedings for randomised controlled trials studying vitamin K antagonists (VKAs), direct oral anticoagulants (DOACs) or aspirin for secondary prevention of VTE beyond 3 months. ORs (95% credible intervals) between treatments were estimated using random-effects Bayesian network meta-analysis.ResultsSixteen studies, totaling more than 22 000 patients, were included. Compared with placebo or observation and with aspirin, respectively, the risk of recurrent VTE was lower with standard-intensity VKAs (0.15 (0.08 to 0.24) and 0.23 (0.09 to 0.54)), low-dose factor Xa inhibitors (0.16 (0.06 to 0.38) and 0.25 (0.09 to 0.66)), standard-dose factor Xa inhibitors (0.17 (0.08 to 0.33) and 0.27 (0.11 to 0.65)) and the direct thrombin inhibitor (0.15 (0.04 to 0.37) and 0.23 (0.06 to 0.74)) although the risk of major bleeding was higher with standard-intensity VKAs (4.42 (1.99 to 12.24) and 4.14 (1.17 to 18.86)). Effect estimates were consistent in male patients and those with index pulmonary embolism or with unprovoked VTE and in sensitivity analyses. In addition, compared with placebo or observation, the risk of all-cause mortality was reduced with standard-intensity VKAs (0.44 (0.20 to 0.87)) and low-dose factor Xa inhibitors (0.38 (0.12 to 0.995)).ConclusionsStandard-intensity VKAs and DOACs are more efficacious than aspirin for extended VTE treatment. Despite a higher risk of major bleeding, standard-intensity VKAs was associated with a lower risk of all-cause mortality. Since overall efficacy and safety of standard-intensity VKAs and DOACs are in equipoise, patient factors, costs and patient preferences should be considered when recommending extending anticoagulation treatment.

Although the incidence of venous thromboembolism (VTE) in Asian populations is lower than in Western countries, the overall burden of VTE in Asia has been considerably underestimated. Factors that may explain the lower prevalence of VTE in Asian populations relative to Western populations include the limited availability of epidemiological data in Asia, ethnic differences in the genetic predisposition to VTE, underdiagnoses, low awareness toward thrombotic disease, and possibly less symptomatic VTE in Asian patients. The clinical assessment, diagnostic testing, and therapeutic considerations for VTE are, in general, the same in Asian populations as they are in Western populations. The management of VTE is based upon balancing the treatment benefits against the risk of bleeding. This is an especially important consideration for Asian populations because of increased risk of intracranial hemorrhage with vitamin K antagonists. Non-vitamin K antagonist oral anticoagulants have shown advantages over current treatment modalities with respect to bleeding outcomes in major phase 3 clinical trials, including in Asian populations. Although anticoagulant therapy has been shown to reduce the risk of postoperative VTE in Western populations, VTE prophylaxis is not administered routinely in Asian countries. Despite advances in the management of VTE, data in Asian populations on the incidence, prevalence, recurrence, risk factors, and management of bleeding complications are limited and there is need for increased awareness. To that end, this review summarizes the available data on the epidemiology, risk stratification, diagnosis, and treatment considerations in the management of VTE in Asia.

Computed tomography coronary angiography (CTCA) offers detailed assessment of the presence of coronary atherosclerosis and helps guide patient management. We investigated influences of early CTCA on the subsequent use of preventative treatment in patients with suspected acute coronary syndrome. In this secondary analysis of a multicenter randomized controlled trial of early CTCA in intermediate-risk patients with suspected acute coronary syndrome, prescription of aspirin, P2Y12 receptor antagonist, statin, renin–angiotensin system blocker, and beta-blocker therapies from randomization to discharge were compared within then between those randomized to early CTCA or to standard of care only. Effects of CTCA findings on adjustment of these therapies were further examined. In 1,743 patients (874 randomized to early CTCA and 869 to standard of care only), prescription of P2Y12 receptor antagonist, dual antiplatelet, and statin therapies increased more in the early CTCA group (between-group difference: 4.6% [95% confidence interval, 0.3-8.9], 4.5% [95% confidence interval, 0.2-8.7], and 4.3% [95% confidence interval, 0.2-8.5], respectively), whereas prescription of other preventative therapies increased by similar extent in both study groups. Among patients randomized to early CTCA, there were additional increments of preventative treatment in those with obstructive coronary artery disease and higher rates of reductions in antiplatelet and beta-blocker therapies in those with normal coronary arteries. Prescription patterns of preventative treatment varied during index hospitalization in patients with suspected acute coronary syndrome. Early CTCA facilitated targeted individualization of these therapies based on the extent of coronary artery disease. [Display omitted]

Atopic dermatitis (AD, eczema) is a condition that causes dry, itchy, and inflamed skin and occurs most frequently in children but also affects adults. However, common clinical treatments provide limited relief and have some side effects. Therefore, there is a need to develop new effective therapies to treat AD. Epi-oxyzoanthamine is a small molecule alkaloid isolated from Formosan zoanthid. Relevant studies have shown that zoanthamine alkaloids have many pharmacological and biological activities, including anti-lymphangiogenic functions. However, there are no studies on the use of epi-oxyzoanthamine on the skin. In this paper, epi-oxyzoanthamine has been shown to have potential in the treatment of atopic dermatitis. Through in vitro studies, it was found that epi-oxyzoanthamine inhibited the expression of cytokines in TNF-α/IFN-γ-stimulated human keratinocyte (HaCaT) cells, and it reduced the phosphorylation of MAPK and the NF-κB signaling pathway. Atopic dermatitis-like skin inflammation was induced in a mouse model using 2,4-dinitrochlorobenzene (DNCB) in vivo. The results showed that epi-oxyzoanthamine significantly decreased skin barrier damage, scratching responses, and epidermal hyperplasia induced by DNCB. It significantly reduced transepidermal water loss (TEWL), erythema, ear thickness, and spleen weight, while also increasing surface skin hydration. These results indicate that epi-oxyzoanthamine from zoanthid has good potential as an alternative medicine for treating atopic dermatitis or other skin-related inflammatory diseases.

We compared a standard antihypertensive losartan treatment with a pharmacogenomics-guided rostafuroxin treatment in never-treated Caucasian and Chinese patients with primary hypertension. Rostafuroxin is a digitoxigenin derivative that selectively disrupts the binding to the cSrc-SH2 domain of mutant α-adducin and of the ouabain-activated Na-K pump at 10–11 M. Of 902 patients screened, 172 were enrolled in Italy and 107 in Taiwan. After stratification for country and genetic background, patients were randomized to rostafuroxin or losartan, being the difference in the fall in office systolic blood pressure (OSBP) after 2-month treatment the primary endpoint. Three pharmacogenomic profiles (P) were examined, considering: P1, adding to the gene variants included in the subsequent P2, the variants detected by post-hoc analysis of a previous trial; P2, variants of genes encoding enzymes for endogenous ouabain (EO) synthesis (LSS and HSD3B1), EO transport (MDR1/ABCB1), adducin (ADD1 and ADD3); P3, variants of the LSS gene only. In Caucasians, the group differences (rostafuroxin 50 μg minus losartan 50 mg in OSBP mmHg) were significant both in P2 adjusted for genetic heterogeneity (P2a) and P3 LSS rs2254524 AA [9.8 (0.6–19.0), P = 0.038 and 13.4 (25.4–2.5), P = 0.031, respectively]. In human H295R cells transfected with LSS A and LSS C variants, the EO production was greater in the former (P = 0.038); this difference was abolished by rostafuroxin at 10–11 M. Chinese patients had a similar drop in OSBP to Caucasians with losartan but no change in OSBP with rostafuroxin. These results show that genetics may guide drug treatment for primary hypertension in Caucasians.

Atopic dermatitis (AD) is a common chronic skin disease affecting both children and adults. Currently lacking a clinical cure, AD presents significant physical and emotional challenges for patients and their families, substantially impacting their quality of life. This underscores significant unmet needs in AD management and highlights the necessity for developing effective therapeutic applications. Recently, several chlorine-containing active substances with promising pharmacological activity have been discovered in soft corals cultivated through coral farming. Among these, brianolide, isolated from the soft coral Briareum stechei, has shown promising potential. This study investigated brianolide’s regulatory effects on the inflammatory response in atopic dermatitis and its underlying mechanisms. Using an in vitro human keratinocyte cell line (HaCaT) stimulated with tumor necrosis factor-α (TNF-α)/interferon-γ (IFN-γ) to mimic AD inflammation, brianolide was found to inhibit cytokine and chemokine expression via the mitogen-activated protein kinase (MAPK) and nuclear factor kappa-light-chain-enhancer of activated B cell (NFκB)-signaling pathways. In an in vivo animal model of 2,4-Dinitrochlorobenzene (DNCB)-induced AD, brianolide demonstrated anti-inflammatory effects, reducing transepidermal water loss (TEWL), ear thickness, erythema, and epidermal blood flow. These findings provide new insights into brianolide’s activity against AD-related inflammation, elucidate potential mechanisms, and contribute to understanding the pharmacological potential of natural coral products for AD treatment.

Nephropathy caused by diabetes mellitus (DM) is the main cause of end-stage renal disease (ESRD). To understand the association of dietary intake with renal function indicators among patients with diabetic nephropathy (DN), this cross-sectional study was conducted at the dietetic consultation clinic of the Taoyuan Armed Forces General Hospital in Taiwan. In total, 317 participants were recruited for this study. Patients with diabetes who had a urinary albumin–creatinine ratio (UACR) of ≥30 mg/g were defined as having DN. The anthropometric characteristics, blood biochemistry, and renal function of the participants were assessed. Furthermore, a semiquantitative food frequency questionnaire (SQFFQ) was administered to investigate the dietary intake of the participants in the DM and DN groups. The result showed that participants in the DN group were older, had longer diabetes duration and poorer glycemic control and renal function than those in the DM group. Logistic regression models revealed that intake of high-fat marine fishes had the lowest odds ratio (OR) for DN risk compared with other fishes (OR: 0.868; 95% CI: 0.781–0.965, p = 0.009). Shellfish, soybean products, and skim milk also provided better protective effects to decrease the risk of DN. A further analysis of polyunsaturated fatty acids revealed that Σn-3 PUFAs significantly reduced DN risk, while Σn-6 PUFAs did not, especially EPA (OR: 0.821; 95% CI: 0.688–0.979, p = 0.029) and DHA (OR: 0.903; 95% CI: 0.823–0.992, p = 0.033) regardless of whether the variables were adjusted, including diabetes duration, age, and HbA1c. Our findings suggest that a diet that incorporates high-fat fish, shellfish, soybean products, and a lower Σn-6/Σn-3 ratio can mitigate DN risk.

To investigate the impact on outcomes of changing treatment guideline recommendations by comparing the proportion of patients with atrial fibrillation (AF) recommended oral anticoagulants (OACs) under the 2011 and 2014 American College of Cardiology/American Heart Association (ACC/AHA) guidelines. We used the “National Health Insurance Research Database” in Taiwan, which included 354,649 patients with AF from January 1, 1996 through December 31, 2011. Patients with a CHADS2 (congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, and prior stroke or transient ischemic attack) score of 2 or more and a CHA2DS2-VASc (congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, prior stroke or transient ischemic attack, vascular disease, age 65-74 years, female sex category) score of 2 or more were considered to have a definitive indication for receiving OACs according to the 2011 and 2014 ACC/AHA guidelines, respectively. The percentages of patients with AF recommended OACs increased from 69.3% (n=245,598) under the 2011 guideline to 86.7% (n=307,640) under the new 2014 guidelines, an increment of 17.5% (95% CI, 17.4-17.6). Most women with AF (94.1%) and patients older than 65 years (97.2%) would receive OACs on the basis of the 2014 guidelines. Among patients previously not being recommended OACs in older guidelines, OAC use under the new guidelines was associated with a lower risk of adverse outcomes (ischemic stroke or intracranial hemorrhage or bleeding requiring blood transfusion or mortality) with an adjusted hazard ratio of 0.89 (95% CI, 0.85-0.94). In this nationwide cohort study, use of the 2014 guidelines led more patients with AF to receive OACs for stroke prevention, and this increased OAC use was associated with better outcomes. Better efforts to implement guidelines would lead to improved outcomes for patients with AF.

The Food and Drug Administration recently updated the safety warning concerning the association between statin therapy and new-onset diabetes mellitus (NODM). For prediabetes, little information is available for statins on cardiovascular outcome reduction and diabetogenic consequences. This study aimed to examine the risk of NODM and the reduction of cardiovascular events and death (MACE) after statin therapy in the prediabetic subjects. The medical and pharmacy claims of the prediabetic beneficiaries were retrieved from Taiwan National Health Insurance research database. The occurrence of NODM, MACE, and morbidity indexed by hospitalizations and emergency visits was ascertained by ambulatory and inpatient database. A propensity score–matched model was constructed for statin users and nonusers. During follow-up (4.1 ± 2.5 years), NODM and MACE occurred in 23.5% and 16.7%, respectively, of nonusers and 28.5% and 12.0%, respectively, of users. Statin therapy was associated with a greater risk of NODM (hazard ratio 1.20, 95% confidence interval 1.08 to 1.32) and less risk of MACE (hazard ratio 0.70, 95% confidence interval 0.61 to 0.80), both in dose-dependent fashions. The earlier and more persistent use correlated with the greater increase in risk of NODM offset by the proportionally larger reduction in MACE. Furthermore, the early persistent users had the lowest rate of hospitalizations and emergency visits. In conclusion, our findings suggested that the relation between NODM and therapeutic advantages of statins was parallel in the prediabetic population. Treatment benefits outweighed diabetic consequences in subjects receiving the earlier and more persistent treatment.

Pericardial fat (PCF) may induce local inflammation and subsequent structural remodeling of the left atrium (LA). However, the adverse effects of PCF on LA are difficult to be evaluated and quantified. The atrial electromechanical interval determined by transthoracic echocardiogram was shown to be a convenient parameter which can reflect the process of LA remodeling. The goal of the present study was to investigate the association between the electromechanical interval and PCF. A total of 337 patients with mean age of 51.9 ± 9.0 years were enrolled. The electromechanical interval (PA-PDI) defined as the time interval from the initiation of the P wave deflection to the peak of the mitral inflow A wave on the pulse wave Doppler imaging was measured for every patient. The amount of PCF was determined by multi-detector computed tomography. The PA-PDI interval was significantly correlated with the amount of PCF (r = 0.641, p value <0.001). Graded prolongation of PA-PDI interval was observed across 3 groups of patients divided according to the tertile values of PCF. The AUC for the PA-PDI interval in predicting an increased amount of PCF (third tertile) was 0.796. At a cutoff value of 130 ms identified by the ROC curve, the sensitivity and specificity of PA-PDI interval in identifying patients with a highest tertile of PCF were 63.4% and 85.3%, respectively. The PA-PDI intervals were longer in patients with an increased amount of PCF. It may be a useful parameter to represent the degree of PCF-related atrial remodeling.