Effect Profile Research Articles

Tratamiento farmacológico de las neoplasias asociadas con la enfermedad de von Hippel-Lindau. Revisión Sistemática

Background: Von Hippel-Lindau disease is an autosomal dominant syndrome characterized by the development of benign and malignant tumors throughout life. For many years, neoplasms associated with this disease were treated by surgical resection or ablation with the aim of reducing the risk of metastatic disease and controlling local or systemic sequelae. An effective systemic alternative could reduce the surgical burden and represents a new approach to oncological treatment. Objective: To evaluate the efficacy and safety of different drugs used in the treatment of neoplasms associated with Von Hippel-Lindau disease. Search methods: An electronic search was carried out without language restriction, until July 31, 2024, in the Cochrane Central Register of Controlled Trials (CENTRAL), PUBMED, and SCIELO databases. Selection criteria: Clinical trials with patients with malignancies associated with Von Hippel-Lindau disease, and any targeted drug therapy as intervention were included. Data collection and analysis: Data from each clinical study were entered into a data table for qualitative analysis. Results: Five articles were selected, four of them are prospective studies and one is a retrospective study that evaluates the efficacy of treatment with Sunitinib, Dovitinib, Pazopanib, and Belzutifan. Conclusions: The inhibition of HIF-2? with Belzutifan presents a safer and more effective profile than the antiangiogenic agents Sunitinib and Pazopanib.

Effect-based analysis of endocrine effects in surface and ground water with focus on progestagenicity using Arxula yeast-based reporter gene assays.

The use of effect-based methods in water monitoring for identifying risks to aquatic organisms and human health is important for aiding regulatory decisions. In the past decades, the database on monitoring, especially in surface waters, has grown as this aquatic environment is openly exposed to various contamination sources. With regard to endocrine disruption, estrogenic and androgenic effects have been primarily investigated. Here, yeast-based bioassays emerged as potent tools, offering sensitivity to environmentally relevant concentrations and high robustness. The objectives of this study were to investigate further endocrine endpoints and extend the monitoring to ground waters. The inclusion of progestagenic effects is crucial due to their multifaceted roles in various functions of organisms. Hence, three different Arxula-yeast hormone screens (estrogen, androgen, and progesterone receptors) were applied, revealing simultaneous exposure to diverse endocrine effects in surface and ground water matrices. Although effect profiles in surface waters showed mainly activation of hormone receptors, in-ground water samples inhibitory effects clearly predominate. Although toxicological thresholds are not yet legally binding, they are essential for effective regulatory measures and risk management to ensure the good ecological status of aquatic ecosystems. The results were compared with effect-based trigger values for ecological as well as human risk assessment depending on the sample matrix, none of which were exceeded.

Depigmented, Polymerized Cat Epithelium Extract Is Safe and Improves Rhinitis and Asthma Symptoms in Cat-Allergic Patients: A Real-World Retrospective Study.

Exposure to cat allergens is often difficult to avoid. Here, we evaluated the safety and effectiveness of a depigmented, polymerized cat epithelium extract (Dpg-pol-cat) for the treatment of allergic rhinoconjunctivitis and asthma. Real-world, retrospective study of patients ≥12 years of age with cat allergy and moderate to severe allergic rhinitis/rhinoconjunctivitis, with or without asthma, who started allergen immunotherapy (AIT) with Dpg-pol-cat extract during routine visits to the Allergy Department. Safety and effectiveness (improvement in FEV1) of AIT were evaluated. The use of rescue medication and patient perceptions were also assessed. A total of 62 patients were included, of whom 34 (54.8%) received AIT for at least 12 months. There were 15 adverse events, 8 local and 7 systemic, of which 3 led to discontinuation of AIT. Patients with moderate to severe rhinitis decreased from 88.2% at baseline to 29.4% at 12 months (p < 0.0001) and patients with moderate asthma decreased from 76.5% to 38.2% (p = 0.0004). FEV1 improved from a mean (standard deviation) of 3,188.9 (771.4) mL to 3,419.6 (878.4) mL (p = 0.0023). The use of rescue medication for rhinitis decreased from 94.1% to 23.5% (p < 0.0001). All patients requiring rescue medication for conjunctivitis (20.6%) were off medication at 12 months, and 97.1% and 92.6% of patients reported improvement in rhinitis and asthma symptoms, respectively. AIT with Dpg-pol-cat extract shows a favorable safety and effectiveness profile in patients with allergic rhinitis/rhinoconjunctivitis due to cat allergy, with or without allergic asthma, representing a valuable treatment option for these patients.

Magnitude and associated factors of prescribing drugs by their brand names among prescribers working at selected hospitals in Addis Ababa, Ethiopia

Background One possible mechanism for lowering expenditure on drugs and increasing their accessibility is by prescribing generic drugs, which are less costly and have equivalent safety and effectiveness profile as brand drugs. However, in Addis Ababa brand-prescribing practice is so common to the extent of making the health department administration of the city to write letters to subcities and hospitals discouraging brand prescribing. This study tried to identify the magnitude and factors affecting brand prescribing in the city. Objective: General objective of this study was to assess magnitude and associated factors of prescribing drugs by brand names at Addis Ababa. Methods An institution based analytical cross-sectional study design was employed from May to August, 2022, using a sample of 485 prescribers. The hospitals were selected by using simple random sampling method and prescribers from different departments were selected by using systematic random sampling method. Data was collected using semistructured, self-administered questionnaire and entered into Statistical Package for Social Sciences version 25 for analysis. The data was described using percentages, graphs and tables. Mean and standard deviations were calculated to identify measures of central tendency and dispersion. Association between dependent and independent variables was checked using bivariate and multivariable logistic regression models. Statistical significance was declared at 95% confidence interval and p &lt; .05. Results The magnitude of prescribing drugs by their brand names was 54.0%. Being trained on good prescribing practice (AOR: 6.81; 95%CI: 2.08-22.28), confidence on Ethiopian Food and Drug Administration Authority (AOR: 18.18; 95%CI: 6.78-48.80), and knowledge about generic drugs (AOR: 11.86; 95%CI: 4.76-29.55) were found to be independent predictors of prescribing drugs by their brand names. Conclusion and recommendation Brand medicine prescribing is positively associated with training on good prescribing practice and knowledge about generic drugs. Hence, training prescribers on good prescribing practice and educating them about generic drugs can minimize brand prescribing.

Safety and Effectiveness of Oral Anticoagulants in Atrial Fibrillation: Real-World Insights Using Natural Language Processing and Machine Learning.

Background/Objectives: We assessed the effectiveness and safety of vitamin K antagonists (VKAs) versus direct oral anticoagulants (DOACs) in patients with atrial fibrillation (AF) using artificial intelligence techniques. Methods: This is a retrospective study in 15 Spanish hospitals (2014-2020), including adult AF patients with no history of anticoagulation, thrombosis events, rheumatic mitral valvular heart disease, mitral valve stenosis, or pregnancy. We employed EHRead® technology based on natural language processing (NLP) and machine learning (ML), along with SNOMED-CT terminology, to extract clinical data from electronic health records (EHRs). Using propensity score matching (PSM), the effectiveness, safety, and hospital mortality of VKAs versus DOACs were analyzed through Kaplan-Meier curves and Cox regression. Results: Out of 138,773,332 EHRs from 4.6 million individuals evaluated, 44,292 patients were included, 79.6% on VKAs and 20.4% on DOACs. Most patients were elderly [VKA 78 (70, 84) and DOAC 75 (66, 83) years], with numerous comorbidities (75.5% and 70.2% hypertension, 47.2% and 39.9% diabetes, and 40.3% and 34.8% heart failure, respectively). Additionally, 60.4% of VKA and 48.7% of DOAC users had a CHA2DS2-VASc Score ≥4. After PSM, 8929 patients per subgroup were selected. DOAC users showed a lower risk of thrombotic events [HR 0.81 (95% CI 0.70-0.94)], minor bleeding [HR 0.89 (95% CI 0.83-0.96)], and mortality [HR 0.80 (95% CI 0.69-0.92)]. Conclusions: Applying NLP and ML, we generated valuable real-world evidence on anticoagulated AF patients in Spain. Even in complex populations, DOACs have demonstrated a better safety and effectiveness profile than VKAs.

Discovery of Small Molecule Inhibitors Targeting CTNNB1 (β-catenin) for Endometrial cancer: Employing 3D QSAR, Drug-Likeness Assessment, ADMET Predictions, Molecular Docking and Simulation.

Endometrial carcinoma (EC) is a type of cancer that originates in the lining of the uterus, known as the endometrium. It is associated with various treatment options such as surgery, radiation therapy, chemotherapy, and hormone therapy, each presenting unique challenges and limitations. Beta-catenin, a protein involved in the development and progression of several cancers, including EC, plays a crucial role. Abnormal beta-catenin signaling is often linked to the emergence of specific EC subtypes, affecting tumor growth and invasion. The study's objective is to identify compounds targeting the beta-catenin protein for treating endometrial cancer (EC) using in silico drug design. Our approach includes molecular docking to evaluate binding affinities, ADME profiling for pharmacokinetic properties, toxicity assessments, and molecular dynamics simulations to assess compound stability and interactions. Approximately one thousand anti-cancer phytochemicals were sourced from PubChem and subjected to molecular docking simulations against the beta-catenin protein. The compounds were evaluated based on their binding affinities, with the top five selected for further analysis. These five molecules underwent toxicity and ADME profiling. The Prediction of Activity Spectra for Substances (PASS) tool was used to identify compounds targeting CTNNB1. Comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) were employed to establish quantitative structure-activity relationship (QSAR) models for the five CTNNB1 antagonist molecules. The selected five compounds, namely Pazopanib, Binimetinib, Telatinib, 4-(2,3-Dihydrobenzo[ b][1,4]dioxin-6-yl)-3-((5-nitrothiazol-2-yl)thio)-1H-1,2,4-triazol-5(4H)-one, and Ribavirin, demonstrated efficacy against CTNN1. MD simulations of the docked complexes confirmed the stability of these drugs in binding to the target protein. All five molecules showed promising safety and effectiveness profiles according to their ADME and toxicity evaluations. Through a comprehensive screening process employing in silico drug design methods, this study successfully identified five potential human anticancer drug candidates targeting the beta-catenin protein. These findings offer a foundation for further experimental validation and development towards the treatment of EC.

516. HELLER MYOTOMY FOR SYMPTOMATIC ACHALASIA: TRADITIONAL LAPAROSCOPY OR ROBOTICS? A SYSTEMATIC REVIEW WITH META-ANALYSIS

Abstract Background Laparoscopic Heller myotomy (LH) has been established as the gold standard for symptomatic achalasia; robotic-assisted laparoscopic myotomy (RH) has shown promising outcomes regarding safety and effectiveness. We aim to meta-analyse data comparing LH and RH surgical outcomes and complications. Methods A systematic search was conducted in February 2024 without restrictions according to PRISMA guidelines in PubMed, Web of Science, Scopus, and Cochrane Register. Studies comparing laparoscopic and robotic approach for Heller myotomy in adults with symptomatic achalasia were included for systematic review. Meta-analysis was performed trough generalized linear mixed model in R 4.3.2. Results 16 observational studies, out of 273, were included; reporting on 15076 patients. No statistically differences in preop characteristics were noted. RH had significantly fewer intraoperative esophageal perforations (OR=7.29, p&amp;lt; 0.0001, 95%), fewer subsequent myotomies and endoscopic treatments for recurrence (OR= 3.64, p=0.01 and OR= 3.38, p=0.03) and better symptom score improvement (OR=0.507, p=0.04). Although not clinically significant, RH had shorter hospital stays (MD=0.45 days, p= 0.005,) and reduced intraoperative blood loss (MD=10.46 ml, p=0.0002). Although not statistically significant, RH had fewer bleeding episodes, lower conversion, reintervention and mortality rates, comparable morbidity and postoperative GERD and higher operative time. Conclusion This updated meta-analysis suggests that RH is associated with lower regarding perforations, recurrence rates and symptom improvement compared to LH, with negligible lengthening of operative times. RH for symptomatic achalasia represents a feasible treatment for symptomatic achalasia, with a satisfying safety and effectiveness profile. RCTs on the topic and about cost-effectiveness evaluations are necessary to support the reported data.

Methodical and Immunological Insights of Prime COVID-19 Vaccines

Abstract:: Vaccines' discovery, manufacturing, and distribution have been on a historic uptick in response to this worldwide COVID-19 pandemic. A handful of vaccines have been approved on an emergency basis after passing minimal clinical trials. There are voids in the existing body of research and the published body of work on phase II and III clinical trial outcomes, efficacy, and recently developed side effects of the approved COVID-19 vaccines. Furthermore, the immunological and methodological insights of successful vaccinations are still unpopular and are not publicly reported. We have attempted to review some major classes of COVID-19 vaccines, namely inactivated viral particle vaccine (BBV152 - Covaxin), mRNA vaccines (BNT162b2 - Pfizer and mRNA-1273- Moderna), viral vector vaccines (Gam-COVID-Vac-Sputnik and ChAdOx1-S-Astrazeneca) and protein subunit vaccine (NVX-CoV2373-Novavax) and discuss their methodological and immunological formulations. This review intends to address the existing literature's gaps and limitations and the vaccine’s safety, efficiency, and effectiveness profiles. This report, by accumulating and comparing the existing publicly available literature and datasheets of the vaccines, concludes that the efficacy of the vaccinations has been found to be 81% for BBV152 (COVAXIN), 94.5% for BNT162b2 (Pfizer), 94.5% for mRNA-1273 (Moderna), 91.6% for Gam-COVID-Vac (Sputnik V), 62–90% for ChAdOx1-S (AstraZeneca), and 96.4% for NVX-CoV2373 (Novavax), demonstrating their efficacy in lowering the severity and frequency of SARS-CoV-2 infection. We conclude that while the commercially approved vaccines have a few limitations regarding clinical trials and side effects, they provide immunity with efficacy ranging from 81% to 96.4% against COVID-19.

Damoctocog Alfa Pegol, a PEGylated B-domain Deleted Recombinant Extended Half-life Factor VIII for the Treatment of Hemophilia A: A Product Review.

Damoctocog alfa pegol (BAY 94-9027, Jivi®), is a site-specifically PEGylated, extended half-life recombinant factor VIII (FVIII) that is approved in several European and non-European countries for on-demand treatment and prophylaxis of bleeding in previously treated patients aged ≥ 12 years with hemophilia A. Reliable measurements can be obtained using most one-stage and chromogenic FVIII assays over a wide concentration range. The efficacy, safety and pharmacokinetics (PK) of damoctocog alfa pegol have been studied extensively in the PROTECT VIII clinical trials, and its long-term safety and effectiveness profile is continuing to build through observational and interventional real-world studies. The PK of damoctocog alfa pegol was shown to be improved as compared with that of sucrose-formulated rFVIII (rFVIII-FS, Kogenate®), and was also demonstrated to be non-inferior to and, for some variables, more favorable than rFVIII-Fc fusion protein, efmoroctocog alfa (Elocta®; NCT03364998), rurioctocog alfa pegol (BAX 855, Adynovate®/Adynovi®; NCT04015492), and antihemophilic factor (recombinant) plasma/albumin-free method (rAHF-PFM, Advate®; NCT02483208). Damoctocog alfa pegol was generally well tolerated and none of the patients in any of the clinical trials, including the PROTECT VIII clinical program, HEM-POWR, or ongoing single-center studies, developed FVIII inhibitors. Efficacy for perioperative hemostasis has been demonstrated. Low bleeding rates were achieved across the studies, with twice weekly, every 5-day and every 7-day prophylaxis offering patients ≥ 12 years and their clinicians the chance to tailor treatment to individual needs and lifestyles, while maintaining long-term protection from bleeds and their consequences.

Microparticles Made with Silk Proteins for Melanoma Adjuvant Therapy.

Melanoma is one of the most aggressive forms of skin cancer, which is characterized by metastasis and poor prognosis due to the limited effectiveness of current therapies and the toxicity of conventional drugs. For this reason and in recent years, one of the most promising strategies in the treatment of this form of cancer is the use of drug delivery systems as carriers capable of conveying the therapeutic agent into the tumor microenvironment, thus preventing its degradation and improving its safety and effectiveness profiles. In the present work, microparticles based on silk fibroin and epifibroin 0039, silk-derived proteins loaded with idebenone, were created, which act as therapeutic carriers for topical use in the treatment of melanoma. The resulting particles have a spherical shape, good loading efficiency, and release capacity of idebenone. Efficacy studies have demonstrated a reduction in the proliferation of COLO-38, melanoma tumor cells, while safety tests have demonstrated that the microparticles are not cytotoxic and do not possess prosensitizing activity. Notably, transdermal release studies revealed that all particles released idebenone over more days. The analysis of the stimulatory markers of the proinflammatory process, CD54 and CD86, did not show any increase in expression, thus confirming the absence of potential prosesensitization effects of the silk fibroin-based particles. The research, therefore, found that idebenone-loaded silk protein microparticles could effectively reduce the proliferation of melanoma cells without cytotoxicity. This indicates the promise of a safe and effective treatment of melanoma.

Implementasi Strategi Customer Relationship Management (CRM) Pada PT PLN (Persero) UP3 Surabaya Barat

Customer Relationship Management (CRM) is a crucial strategy in strengthening relationships with customers and improving service quality. This research examines the implementation of CRM at PT PLN (Persero) UP3 West Surabaya, which aims to improve the efficiency of collecting and analyzing customer data through the use of application technology and websites. By understanding customer characteristics, behavior, and needs through effective profiling, PT PLN (Persero) UP3 West Surabaya can develop a more personalized and responsive CRM strategy, and improve ongoing interaction with customers. This research uses observation method and qualitative approach with literature review method to examine CRM implementation at PT PLN (Persero) UP3 West Surabaya. The results showed that the use of a customer profiling database can help PT PLN in creating a better customer experience and increasing customer loyalty. Successful CRM implementation requires careful planning, adequate technology, and support from all parties in the organization.

Analgesic and Anti-Inflammatory Activity: A Comprehensive Review on Invitro and In Vivo Screening Methods

Modern pharmacotherapy includes analgesic and anti-inflammatory medicines as essential components to relieve pain and inflammation brought on by a variety of medical diseases. Robust screening techniques are essential for the identification of possible candidates with appropriate safety and effectiveness profiles in the search and development of new analgesic and anti-inflammatory medications. This study looks at the many screening methods used in preclinical studies to assess new drugs' analgesic and anti-inflammatory quality. Conventional techniques like the tail flick, hot plate, and writhing’s tests measure analgesic activity by having animals respond to unpleasant stimuli. Comparably, anti-inflammatory activity is frequently assessed using assays like the cotton pellet granuloma test, which gauges tissue granuloma formation, and the carrageenan-induced paw edema model, which measures inflammation. These traditional techniques offer insightful information about the pharmacological effects of test substances. Despite the wide range of screening techniques available, each strategy has advantages and disadvantages. Preclinical studies are more reliable and have higher predictive value when various assays and techniques are integrated into a tiered screening strategy. Furthermore, the successful translation of preclinical findings to human applications depends on taking into account translational variables including species differences and clinical relevancies. As a result, choosing the right screening techniques is critical to the effective identification and characterization of new analgesic and anti-inflammatory drugs.

Safety and effectiveness of clofarabine in Japanese patients with relapsed/refractory acute lymphoblastic leukaemia: a post-marketing surveillance study.

Clofarabine is used to treat acute lymphoblastic leukaemia, but evidence of its safety and effectiveness in Japanese patients is limited. We evaluated the safety and effectiveness of clofarabine in patients with relapsed/refractory acute lymphoblastic leukaemia in real-world clinical practice in Japan. An observational, multicenter, post-marketing, all-case surveillance was conducted for safety. Effectiveness analyses were conducted in patients aged ≤21years and those treated with clofarabine monotherapy and combination therapy (clofarabine plus etoposide and cyclophosphamide). In the all-case survey, 260 of 264 registered patients were eligible for safety analysis. Among the 225 patients eligible for effectiveness analysis, 139 were aged ≤21years. For monotherapy and combination therapy, 20/31 and 34/88 patients were eligible, respectively. In the all-case survey, the median age was 16.0years, and 47.7% of patients were<15years old. Adverse drug reaction incidence was 83.5% and the most common were hematologic toxicities. The best overall response rates in the population aged ≤21years were complete remission, 29.7%; complete remission without platelet recovery, 7.3% and partial remission, 10.9%. The rest (52.2%) were classified as ineffective. The sum of complete remission, complete remission without platelet recovery and partial remission rates (effectiveness rate) was 47.8% (66/138 patients). The effectiveness rates in the monotherapy and combination therapy surveys were 10.0% (2/20 patients) and 58.8% (20/34 patients), respectively. These post-marketing surveys provide real-world evidence of the safety and effectiveness of clofarabine regimens, including monotherapy and combination therapy in Japanese patients with relapsed/refractory acute lymphoblastic leukaemia. The safety and effectiveness profiles were comparable with those of previous prospective studies.

Embolization of a pseudoaneurysm of the innominate artery with a Woven EndoBridge (WEB) device.

The Woven EndoBridge (WEB) is an intra-aneurysmal flow disruptor designed for the treatment of broad-based arterial aneurysms with a high safety and effectiveness profile.1, 2 It does not require concomitant antiplatelet therapy compared to other devices such as flow diverters or intracranial stents. Innominate artery pseudoaneurysms are a rare consequence of blunt traumatic injury, infection, or atherosclerotic disease.3, 4 We describe the case of an innominate artery pseudoaneurysm successfully treated with a WEB SL device instead of stenting, therefore alleviating the need for dual antiplatelet therapy. The treatment was successful and uneventful and postprocedural computed tomography angiography confirmed the complete occlusion of the pseudoaneurysm.

Adjuvant Novel Nanocarrier-Based Targeted Therapy for Lung Cancer.

Lung cancer has the lowest survival rate due to its late-stage diagnosis, poor prognosis, and intra-tumoral heterogeneity. These factors decrease the effectiveness of treatment. They release chemokines and cytokines from the tumor microenvironment (TME). To improve the effectiveness of treatment, researchers emphasize personalized adjuvant therapies along with conventional ones. Targeted chemotherapeutic drug delivery systems and specific pathway-blocking agents using nanocarriers are a few of them. This study explored the nanocarrier roles and strategies to improve the treatment profile's effectiveness by striving for TME. A biofunctionalized nanocarrier stimulates biosystem interaction, cellular uptake, immune system escape, and vascular changes for penetration into the TME. Inorganic metal compounds scavenge reactive oxygen species (ROS) through their photothermal effect. Stroma, hypoxia, pH, and immunity-modulating agents conjugated or modified nanocarriers co-administered with pathway-blocking or condition-modulating agents can regulate extracellular matrix (ECM), Cancer-associated fibroblasts (CAF),Tyro3, Axl, and Mertk receptors (TAM) regulation, regulatory T-cell (Treg) inhibition, and myeloid-derived suppressor cells (MDSC) inhibition. Again, biomimetic conjugation or the surface modification of nanocarriers using ligands can enhance active targeting efficacy by bypassing the TME. A carrier system with biofunctionalized inorganic metal compounds and organic compound complex-loaded drugs is convenient for NSCLC-targeted therapy.

Real-world outcomes of nivolumab plus ipilimumab combination therapy for advanced renal cell carcinoma in Japanese patients: data with a minimum of 3years of follow-up.

Long-term follow-up data regarding treatment outcomes of nivolumab plus ipilimumab combination therapy for advanced renal cell carcinoma as a first-line therapy are limited in real-world Japanese populations. We retrospectively evaluated data of 56 advanced renal cell carcinoma patients treated with nivolumab plus ipilimumab, with a follow-up of at least 3years. Survival, tumour response and adverse event profiles were assessed. A total of 41 patients (73%) were histopathologically diagnosed with clear-cell renal cell carcinoma, and 34 (61%) were categorized into the International Metastatic renal cell carcinoma Database Consortium intermediate-risk group. The median follow-up period was 34.4months. Regarding an effectiveness profile, median progression-free survival, time to treatment failure and overall survival were 9.01, 12.5 and 49.0months, respectively. Objective response was observed in 27 patients (48%), including eight patients with complete response (14%), and the median duration of response was 30.8months. Multivariate analyses showed that clear-cell histology was an independent factor of longer overall survival (hazard ratio: 0.23, P=0.0013). Regarding safety profiles, adverse events of any grade and those with grade≥3 developed in 40 (71%) and 25 patients (45%), respectively. Median time to adverse event development was 1.68months. Treatment was interrupted in 28 patients (50%), and corticosteroid administration was needed in 25 (45%). The 3-year follow-up data showed that nivolumab plus ipilimumab combination therapy exhibited a feasible effectiveness in real-world Japanese patients with advanced renal cell carcinoma. Accordingly, the high risk of adverse event development, which often requires treatment withdrawal and corticosteroid administration, should be considered.

Study Design of a Brazilian Observational Study of Edoxaban in Patients with Atrial Fibrillation (EdoBRA).

Clinical trials showed the safety of Edoxaban, a non-vitamin K-dependent oral anticoagulant (NOAC), and its efficacy to prevent stroke and systemic embolism in non-valvular atrial fibrillation (NVAF) patients and also to prevent and treat venous thromboembolism. However, additional research is needed to evaluate the safety and effectiveness of Edoxaban in a real-world scenario in the Brazilian population. In order to understand the risks and benefits of Edoxaban use in routine clinical settings, the EdoBRA study is being conducted to gain insight into the safety and effectiveness of Edoxaban use in non-preselected patients with NVAF in Brazil. The EdoBRA study is a multicenter, prospective, observational study conducted in 36 sites in Brazil. NVAF patients ≥ 18 years treated with commercially available Edoxaban who initiated treatment for at least 14 days and no longer than 90 days prior to enrollment, and who are not simultaneously participating in any interventional study are eligible for this study. Seven hundred patients are planned to be enrolled and one-year of follow up, with data collections expected at baseline and 3, 6, and 12 months after the study enrollment. The primary safety objective is ISTH Clinically Relevant Bleeding, and the secondary effectiveness objective focuses on relevant cardiovascular outcomes related to NVAF. EdoBRA observational study will generate relevant additional information about NOAC Edoxaban on various aspects of patient management in routine care, such as its safety and effectiveness profile in patients with NVAF in Brazil.

Desenho de Estudo de um Estudo Observacional Brasileiro sobre o uso de Edoxabana em Pacientes com Fibrilação Atrial (EdoBRA)

Abstract Background: Clinical trials showed the safety of Edoxaban, a non-vitamin K-dependent oral anticoagulant (NOAC), and its efficacy to prevent stroke and systemic embolism in non-valvular atrial fibrillation (NVAF) patients and also to prevent and treat venous thromboembolism. However, additional research is needed to evaluate the safety and effectiveness of Edoxaban in a real-world scenario in the Brazilian population. Objective: In order to understand the risks and benefits of Edoxaban use in routine clinical settings, the EdoBRA study is being conducted to gain insight into the safety and effectiveness of Edoxaban use in non-preselected patients with NVAF in Brazil. Methods: The EdoBRA study is a multicenter, prospective, observational study conducted in 36 sites in Brazil. NVAF patients ≥ 18 years treated with commercially available Edoxaban who initiated treatment for at least 14 days and no longer than 90 days prior to enrollment, and who are not simultaneously participating in any interventional study are eligible for this study. Seven hundred patients are planned to be enrolled and one-year of follow up, with data collections expected at baseline and 3, 6, and 12 months after the study enrollment. The primary safety objective is ISTH Clinically Relevant Bleeding, and the secondary effectiveness objective focuses on relevant cardiovascular outcomes related to NVAF. Conclusion: EdoBRA observational study will generate relevant additional information about NOAC Edoxaban on various aspects of patient management in routine care, such as its safety and effectiveness profile in patients with NVAF in Brazil.

Direct Oral Anticoagulants in Chronic Thromboembolic Pulmonary Hypertension: First Meta-Analysis of Prospective Studies.

Direct oral anticoagulants (DOACs) are becoming increasingly popular clinically, but their safety and effectiveness profile in patients with chronic thromboembolic pulmonary hypertension (CTEPH) is not well-established. Literature from the PubMed and EMBASE databases was systematically screened up to February 2024 to identify relevant studies on the use of DOACs in CTEPH patients. The bias risk of RCTs was assessed using the Cochrane Risk of Bias Tool 2.0. The quality of observational prospective cohorts was assessed using the Newcastle-Ottawa Scale tool. Data pooled from different studies were analyzed. Results from 4 studies were gathered, including 2 randomized controlled trials and 2 prospective cohorts, with a total of 2038 patients, of which 751 were on DOACs and 1287 were on vitamin K antagonists (VKAs). Similar rates of all-cause mortality (3.33% vs 3.33%, RD = -0.01%, 95% CI [-0.02%, 0.00%], P = .17), VTE recurrence (1.46% vs 2.12%, RD = -0.00%, 95% CI [-0.01%, 0.01%], P = .92) were observed. DOACs were associated with a nonsignificant reduction in bleeding events including major bleeding (2.22% vs 3.71%, RD = -0.01%, 95% CI [-0.04%, 0.01%], P = .30), any bleeding (5.33% vs 9.94%, RD = -0.03%, 95% CI [-0.07%, 0.01%], P = .10), and minor bleeding (4.17% vs 13.3%, RD = -0.06%, 95% CI [-0.23%, 0.10%], P = .45). Data pooled from existing perspective trials suggests the use of DOACs in CTEPH patients as an effective and safe alternative to VKAs.

Cutaneous Toll-like Receptor 9 Pre-Defines Hydroxychloroquine Dosage in Patients with Both Discoid and Subacute Lupus Erythematosus.

Background and Objectives: Cutaneous lupus erythematosus (CLE) presents clinically heterogeneous manifestations, partially explained by the different expression of Toll-like receptors (TLRs) type 8 and 9, located to endosomal compartments where they are poised to recognize microbial nucleic acids. This disease is empirically treated with hydroxychloroquine (HCQ), which is hallmarked with a safe and effective profile, but induces a slow and sometimes clinically insufficient therapeutic response. Currently, no biomarkers predictive of response are validated or even proposed in the scientific literature. We aimed to evaluate endosomal TLR type 7, 8 and 9 as predictive biomarkers of HCQ efficacy. Materials and Methods: We conducted a case-control study comparing CLE patients retrospectively assigned to three subgroups based on 3-6-month Cutaneous LE Disease Area and Severity Index (CLASI) reduction upon treatment with HCQ (I = <40% vs. II = 40-80% vs. III = >80%). Before HCQ, lesional skin specimens were collected in untreated CLE and through immunohistochemistry; TLR-7, -8 and -9 expression was evaluated in the epidermis and the lymphocytic infiltrate was evaluated in the dermis. Results: Sixty-six lesional skin biopsies were compared with healthy controls. CLE patients displayed lower epidermal expression of total TLR 8 and 9 as well as infiltrating TLR-8, TLR9 + lymphocytes compared to controls. High HCQ responders differed from low responders for TLR-9 positivity (high vs. low) and for the lymphocytic dermal infiltrate (high vs. low). Conclusions: TLR9 could be envisaged as a possible biomarker to predict HCQ response level and dosage in CLE patients.