Racial/Ethnic Disparities in Use of Angiotensin II Receptor Type 2/4 Stimulatory Vs. Inhibitory Antihypertensive Among Hypertensive Adults in the USA.

OBJECTIVES: Studies showed angiotensin II type 2 receptor/angiotensin II type 4 receptor (AT2R/AT4R) stimulatory antihypertensive was associated with a lower risk of dementia and cognitive impairment compared to the inhibitory one. This study aimed to identify the racial and ethnic differences in using these agents among the USA adults with hypertension. METHODS: A cross-sectional study was conducted using data from the Medical Expenditure Panel Survey (MEPS, 2016-2019). Individuals with a diagnosis of hypertension or self-reported hypertension and without dementia or Alzheimer's disease diagnosis were included in the analysis. We applied two multivariable logistic regressions to compare racial/ethnic differences in AT2R/AT4R stimulatory antihypertensive use and AT2R/AT4R inhibitory antihypertensive use, adjusting for covariates. RESULTS: Twenty-four thousand five hundred eighty-one individuals with hypertension and without dementia or Alzheimer's disease were identified. Among non-Hispanic Whites, 72.39% were using AT2R/AT4R inhibitory antihypertensive agents, vs. 66.97% using AT2R/AT4R stimulatory antihypertensive agents. In contrast, both non-Hispanic Black and Asian Americans were using more AT2R/AT4R stimulatory agents than inhibitory ones (16.40% vs. 12.16% and 4.79% vs. 3.43%, respectively). Compared to non-Hispanic White, non-Hispanic Black (OR 1.980, 95% CI 1.839-2.132) and non-Hispanic Asian Americans (OR 1.545, 95% CI 1.356-1.761) were significantly associated with higher odds of prescribing AT2R/AT4R stimulatory agents, while Hispanics (OR 0.744, 95% CI 0.685-0.808) were associated with lower odds of prescribing AT2R/AT4R inhibitory agents compared to non-Hispanic Whites. CONCLUSIONS: The results showed that the high-dementia risk populations like non-Hispanic Black and Asian American races are proportionally prescribed with higher use of low-dementia risk antihypertensive agents, compared to non-Hispanic Whites.

Treatment of Stage III Resectable Melanoma-Adjuvant and Neoadjuvant Approaches.

ABSTRACT: Patients with stage III resectable melanoma carry a high risk of melanoma recurrence that ranges from approximately 40% to 90% at 5 years following surgical management alone. Postoperative systemic adjuvant therapy targets residual micrometastatic disease that could be the source of future recurrence and death from melanoma. Randomized phase III adjuvant trials reported significant improvements in overall survival with high-dose interferon α in 2 of 3 studies (compared with observation and GMK ganglioside vaccine) and with anti-cytotoxic T-lymphocyte antigen 4 ipilimumab at 10 mg/kg compared with placebo and ipilimumab 3 mg/kg compared with high-dose interferon α. In the modern era, more recent phase III trials demonstrated significant recurrence-free survival improvements with anti-programmed cell death protein 1, pembrolizumab, and BRAF-MEK inhibitor combination dabrafenib-trametinib (for BRAF mutant melanoma) versus placebo. Furthermore, anti-programmed cell death protein 1, nivolumab and pembrolizumab have both been shown to significantly improve recurrence-free survival as compared with ipilimumab 10 mg/kg. For melanoma patients with clinically or radiologically detectable locoregionally advanced disease, emerging data support an important role for preoperative systemic neoadjuvant therapy. Importantly, a recent cooperative group trial (S1801) reported superior event-free survival rates with neoadjuvant versus adjuvant therapy. Collectively, current data from neoadjuvant immunotherapy and targeted therapy trials support a future change in clinical practice in favor of neoadjuvant therapy for eligible melanoma patients.

A Bioinformatics Tool for Identifying Intratumoral Microbes from the ORIEN Dataset.

Evidence supports significant interactions among microbes, immune cells, and tumor cells in at least 10%-20% of human cancers, emphasizing the importance of further investigating these complex relationships. However, the implications and significance of tumor-related microbes remain largely unknown. Studies have demonstrated the critical roles of host microbes in cancer prevention and treatment responses. Understanding interactions between host microbes and cancer can drive cancer diagnosis and microbial therapeutics (bugs as drugs). Computational identification of cancer-specific microbes and their associations is still challenging due to the high dimensionality and high sparsity of intratumoral microbiome data, which requires large datasets containing sufficient event observations to identify relationships, and the interactions within microbial communities, the heterogeneity in microbial composition, and other confounding effects that can lead to spurious associations. To solve these issues, we present a bioinformatics tool, microbial graph attention (MEGA), to identify the microbes most strongly associated with 12 cancer types. We demonstrate its utility on a dataset from a consortium of nine cancer centers in the Oncology Research Information Exchange Network. This package has three unique features: species-sample relations are represented in a heterogeneous graph and learned by a graph attention network; it incorporates metabolic and phylogenetic information to reflect intricate relationships within microbial communities; and it provides multiple functionalities for association interpretations and visualizations. We analyzed 2,704 tumor RNA sequencing samples and MEGA interpreted the tissue-resident microbial signatures of each of 12 cancer types. MEGA can effectively identify cancer-associated microbial signatures and refine their interactions with tumors. SIGNIFICANCE: Studying the tumor microbiome in high-throughput sequencing data is challenging because of the extremely sparse data matrices, heterogeneity, and high likelihood of contamination. We present a new deep learning tool, MEGA, to refine the organisms that interact with tumors.

The T Cell Immunoscore as a Reference for Biomarker Development Utilizing Real-World Data from Patients with Advanced Malignancies Treated with Immune Checkpoint Inhibitors.

BACKGROUND: We aimed to determine the prognostic value of an immunoscore reflecting CD3+ and CD8+ T cell density estimated from real-world transcriptomic data of a patient cohort with advanced malignancies treated with immune checkpoint inhibitors (ICIs) in an effort to validate a reference for future machine learning-based biomarker development. METHODS: Transcriptomic data was collected under the Total Cancer Care Protocol (NCT03977402) Avatar® project. The real-world immunoscore for each patient was calculated based on the estimated densities of tumor CD3+ and CD8+ T cells utilizing CIBERSORTx and the LM22 gene signature matrix. Then, the immunoscore association with overall survival (OS) was estimated using Cox regression and analyzed using Kaplan-Meier curves. The OS predictions were assessed using Harrell's concordance index (C-index). The Youden index was used to identify the optimal cut-off point. Statistical significance was assessed using the log-rank test. RESULTS: Our study encompassed 522 patients with four cancer types. The median duration to death was 10.5 months for the 275 participants who encountered an event. For the entire cohort, the results demonstrated that transcriptomics-based immunoscore could significantly predict patients at risk of death (p-value < 0.001). Notably, patients with an intermediate-high immunoscore achieved better OS than those with a low immunoscore. In subgroup analysis, the prediction of OS was significant for melanoma and head and neck cancer patients but did not reach significance in the non-small cell lung cancer or renal cell carcinoma cohorts. CONCLUSIONS: Calculating CD3+ and CD8+ T cell immunoscore using real-world transcriptomic data represents a promising signature for estimating OS with ICIs and can be used as a reference for future machine learning-based biomarker development.

Adjuvant Therapy for High-Risk Melanoma: An In-Depth Examination of the State of the Field.

The consideration of systemic adjuvant therapy is recommended for patients with stage IIB-IV melanoma who have undergone surgical resection due to a heightened risk of experiencing melanoma relapse and mortality from melanoma. Adjuvant therapy options tested over the past three decades include high-dose interferon-α, immune checkpoint inhibitors (pembrolizumab, nivolumab), targeted therapy (dabrafenib-trametinib for BRAF mutant melanoma), radiotherapy and chemotherapy. Most of these therapies have been demonstrated to enhance relapse-free survival (RFS) but with limited to no impact on overall survival (OS), as reported in randomized trials. In contemporary clinical practice, the adjuvant treatment approach for surgically resected stage III-IV melanoma has undergone a notable shift towards the utilization of nivolumab, pembrolizumab, and BRAF-MEK inhibitors, such as dabrafenib plus trametinib (specifically for BRAF mutant melanoma) due to the significant enhancements in RFS observed with these treatments. Pembrolizumab has obtained regulatory approval in the United States to treat resected stage IIB-IIC melanoma, while nivolumab is currently under review for the same indication. This review comprehensively analyzes completed phase III adjuvant therapy trials in adjuvant therapy. Additionally, it provides a summary of ongoing trials and an overview of the main challenges and future directions with adjuvant therapy.

The tumor microbiome as a predictor of outcomes in patients with metastatic melanoma treated with immune checkpoint inhibitors.

Emerging evidence supports the important role of the tumor microbiome in oncogenesis, cancer immune phenotype, cancer progression, and treatment outcomes in many malignancies. In this study, we investigated the metastatic melanoma tumor microbiome and potential roles in association with clinical outcomes, such as survival, in patients with metastatic disease treated with immune checkpoint inhibitors (ICIs). Baseline tumor samples were collected from 71 patients with metastatic melanoma before treatment with ICIs. Bulk RNA-seq was conducted on the formalin-fixed paraffin-embedded (FFPE) tumor samples. Durable clinical benefit (primary clinical endpoint) following ICIs was defined as overall survival ≥24 months and no change to the primary drug regimen (responders). We processed RNA-seq reads to carefully identify exogenous sequences using the {exotic} tool. The 71 patients with metastatic melanoma ranged in age from 24 to 83 years, 59% were male, and 55% survived >24 months following the initiation of ICI treatment. Exogenous taxa were identified in the tumor RNA-seq, including bacteria, fungi, and viruses. We found differences in gene expression and microbe abundances in immunotherapy responsive versus non-responsive tumors. Responders showed significant enrichment of several microbes including Fusobacterium nucleatum, and non-responders showed enrichment of fungi, as well as several bacteria. These microbes correlated with immune-related gene expression signatures. Finally, we found that models for predicting prolonged survival with immunotherapy using both microbe abundances and gene expression outperformed models using either dataset alone. Our findings warrant further investigation and potentially support therapeutic strategies to modify the tumor microbiome in order to improve treatment outcomes with ICIs.

A bioinformatics tool for identifying intratumoral microbes from the ORIEN dataset.

Evidence supports significant interactions among microbes, immune cells, and tumor cells in at least 10-20% of human cancers, emphasizing the importance of further investigating these complex relationships. However, the implications and significance of tumor-related microbes remain largely unknown. Studies have demonstrated the critical roles of host microbes in cancer prevention and treatment responses. Understanding interactions between host microbes and cancer can drive cancer diagnosis and microbial therapeutics (bugs as drugs). Computational identification of cancer-specific microbes and their associations is still challenging due to the high dimensionality and high sparsity of intratumoral microbiome data, which requires large datasets containing sufficient event observations to identify relationships, and the interactions within microbial communities, the heterogeneity in microbial composition, and other confounding effects that can lead to spurious associations. To solve these issues, we present a bioinformatics tool, MEGA, to identify the microbes most strongly associated with 12 cancer types. We demonstrate its utility on a dataset from a consortium of 9 cancer centers in the Oncology Research Information Exchange Network (ORIEN). This package has 3 unique features: species-sample relations are represented in a heterogeneous graph and learned by a graph attention network; it incorporates metabolic and phylogenetic information to reflect intricate relationships within microbial communities; and it provides multiple functionalities for association interpretations and visualizations. We analyzed 2704 tumor RNA-seq samples and MEGA interpreted the tissue-resident microbial signatures of each of 12 cancer types. MEGA can effectively identify cancer-associated microbial signatures and refine their interactions with tumors.

Granulomatous and Sarcoid-like Immune-Related Adverse Events following CTLA4 and PD1 Blockade Adjuvant Therapy of Melanoma: A Combined Analysis of ECOG-ACRIN E1609 and SWOG S1404 Phase III Trials and a Literature Review.

BACKGROUND: Treatment with immune checkpoint inhibitors (ICIs) has been linked to granulomatous and sarcoid-like lesions (GSLs) affecting different organs. This study sought to evaluate GSL incidence in patients with high-risk melanoma treated with cytotoxic T-lymphocyte antigen 4 (CTLA4) or programmed cell death 1 (PD1) blockade adjuvant therapy in two clinical trials: ECOG-ACRIN E1609 and SWOG S1404. Descriptions and GSL severity ratings were recorded. METHODS: Data were collected from ECOG-ACRIN E1609 and SWOG S1404. Descriptive statistics along with GSL severity grades were reported. Additionally, a literature review for such cases was summarized. RESULTS: A total of 11 GSL cases were reported among 2878 patients treated with either ICI or with High-Dose Interferon Alfa-2b (HDI) in ECOG-ACRIN E1609 and SWOG S1404 trials. Cases were numerically more commonly reported with ipi10, followed by pembrolizumab, ipi3, and HDI, respectively. Most of the cases were grade III. Further, organs involved included lung, mediastinal lymph nodes, skin and subcutaneous tissue, and eye. Furthermore, a summary of 62 reports in the literature was described. CONCLUSIONS: GSLs following anti-CTLA4 and anti-PD1 antibody therapy in patients with melanoma were reported unusually. Reported cases ranged in grade from I to III and appeared manageable. Careful attention to these events and their reporting will be essential to better guide practice and management guidelines.

A Tumor and Immune-Related Micro-RNA Signature Predicts Relapse-Free Survival of Melanoma Patients Treated with Ipilimumab.

Despite the unprecedented advances in the treatment of melanoma with immunotherapy, there continues to be a major need for biomarkers of clinical benefits and immune resistance associated with immune checkpoint inhibitors; microRNA could play a vital role in these efforts. This study planned to identify differentially expressed miRNA molecules that may have prognostic value for clinical benefits. Patients with surgically operable regionally advanced melanoma were treated with neoadjuvant ipilimumab (10 mg/kg intravenously every 3 weeks × two doses) bracketing surgery. Tumor biospecimens were obtained at baseline and surgery, and microRNA (miRNA) expression profiling was performed on the tumor biopsies. We found that an expression profile consisting of a 4-miRNA signature was significantly associated with improved relapse-free survival (RFS). The signature consisted of biologically relevant molecules previously reported to have prognostic value in melanoma and other malignancies, including miR-34c, miR-711, miR-641, and miR-22. Functional annotation analysis of target genes for the 4-miRNA signature was significantly enriched for various cancer-related pathways, including cell proliferation regulation, apoptosis, the MAPK signaling pathway, and the positive regulation of T cell activation. Our results presented miRNAs as potential biomarkers that can guide the treatment of melanoma with immune checkpoint inhibitors. These findings warrant further investigation in relation to CTLA4 blockade and other immune checkpoint inhibitors. ClinicalTrials.gov NCT00972933.

Cost-Benefit Analysis of Genotype-Guided Interruption Days in Warfarin Pre-Procedural Management.

Warfarin is commonly used in thromboembolic conditions. Warfarin interruption represents a significant challenge in pre-operative warfarin management as it is associated with major consequences. Genetics polymorphism demonstrated to be a significant predictor of the required days of warfarin interruption. This study sought to assess the economic benefit of implementing a pharmacogenetic-guided approach in the preprocedural warfarin management. From the hospital's perspective, a cost-benefit analysis was conducted based on a 1-year decision-analytic follow-up model of the economic implications of using a pharmacogenetic algorithm vs standard of care in pre-operative warfarin management in the Hamad Medical Corporation, Qatar. The benefit of the interventional algorithm was based on estimated reduction in the probabilities of clinical events and their cost, added to the avoided cost because of canceled procedures. The cost of the algorithm was the cost of the genotyping assay. The model event probability inputs were extracted from major literature clinical trials, and the setting-specifc and cost inputs were locally obtained. The model was based on a multivariate analysis at its base case. As per 10.3% prevalence of genetic variants, 82% bridging, and a calculated 20% optimization in the preparative period of warfarin management, the benefit to cost ratio was 4.0 in favor genotype-guided approach. This positive benefit to cost ratio was maintained in 100% of the simulated study cases. Sensitivity analyses confirmed the robustness and generalizability of the study conclusion. A pharmacogenetic- guided pre-operative warfarin interruption management is a cost-beneficial approach in the Qatari practice.

The Dilemma of Peri-Procedural Warfarin Management: A Narrative Review.

Periprocedural vitamin K antagonist management is a complex process and inherently entails multiple clinical issues. Marked variations have been reported in different aspects of this process. These differences were noted at the clinician and institutional levels owing to the lack of evidence-based data leading to many discrepancies in decision-making. This review aims to address the gap of vitamin K antagonist periprocedural management acknowledged by previously published prescribers' questionnaires. One of the components of this process is "bridging," which aims to provide minimal interruption of the anticoagulation period through the use of heparin products. Recent studies showed that bridging is increasing bleeding risk. Secondly, interruption decision relies on the classification of thromboembolism risk which depends on trials that did not include patients with atrial fibrillation. Thirdly, the interruption duration is different among different International normalization ratio levels, which strengthens the difference in the clinical practice of preoperative vitamin K antagonist management. Lastly, the resumption of a vitamin-K antagonist after surgery has many scenarios according to the procedure and patient risk of bleeding. Vitamin-K antagonist periprocedural management is complicated due to individual practice and the lack of strictly implemented institutional standardized protocols to guide, manage and evaluate the process.

Genetic and Non-Genetic Factors Impact on INR Normalization in Preprocedural Warfarin Management.

BACKGROUND: Annually, 10% of warfarin patients will likely need to stop warfarin prior to elective surgery to achieve a baseline international normalization ratio (INR) level (INR ≤ 1.2) at the time of the procedure. This study explores the influence of genetic and non-genetic factors on INR normalization in the Arab (major part of Near Eastern) population in preprocedural warfarin management. METHODS: An observational prospective cohort study was designed to recruit Arab patients taking warfarin and scheduled for an elective procedure. Two INR readings were recorded. DNA extraction and genotyping of variants in CYP2C9*2, CYP2C9*3, CYP4F2*3, VKORC1*2, and FII (rs5896) and FVII (rs3093229) genes using real-time polymerase chain reaction were performed. RESULTS: Data from 116 patients were included in the analysis. CYP2C9 and VKORC1 genetic variants carriers required lower maintenance dose compared to non-carriers. The analysis showed that ciprofloxacin, antiplatelet medications, and INR index (INR at visit 1) are the only factors associated with the INR decline rate. Also, the proportion of CYP2C9*3 carriers with normal INR (≤1.2) on the day of surgery was significantly lower than those with wild-type genotype (28% vs 60%, p=0.013). In addition, heparin bridging, INR target, and Sudanese nationality are significant predictors of INR normalization (≤1.2) on the day of the procedure. CONCLUSION: Despite the confirmed effect of genetic factors on warfarin maintenance dose, the study was not able to find a significant effect of any genetic factor on the rate of INR normalization possibly due to the small sample size. Index INR and interacting medications showed to be significant predictors of INR decline rate.

Bridging vs Non-Bridging with Warfarin Peri-Procedural Management: Cost and Cost-Effectiveness Analyses.

The warfarin peri-procedural management in Qatar is predominantly based on bridging (63%), compared to non-bridging. This study sought to perform a first-time cost analysis of current warfarin peri-procedural management practices, including a cost-effectiveness analysis (CEA) of predominant bridging vs predominant non-bridging practices. From the hospital perspective, a one-year decision-analytic model followed the cost and success consequences of the peri-procedural warfarin in a hypothetical cohort of 10,000 atrial fibrillation patients. Success was defined as survival with no adverse events. Outcome measures were the cost and success consequences of the 63% bridging (vs not-bridging) practice in the study setting, ie, Hamad Medical Corporation, Qatar, and the incremental cost-effectiveness ratio (ICER, cost/success) of the warfarin therapy when predominantly bridging based vs when predominantly non-bridging based. The model was based on Monte Carlo simulation, and sensitivity analyses were performed to confirm the robustness of the study conclusions. As per 63% bridging practices, the mean overall cost of peri-procedural warfarin management per patient was USD 3,260 (QAR 11,900), associated with an overall success rate of 0.752. Based on the CEA, predominant bridging was dominant (lower cost, higher effect) over the predominant non-bridging practice in 62.2% of simulated cases, with a cost-saving of up to USD 2,001 (QAR 7,303) at an average of USD 272 (QAR 993) and was cost-effective in 36.9% of cases. Being between cost-saving and cost-effective, compared to predominant non-bridging practices, the predominant use of bridging with warfarin seems to be a favorable strategy in atrial fibrillation patients.

Periprocedural Anticoagulation Management of Patients receiving Warfarin in Qatar: A Prospective Cohort Study.

BACKGROUND: The use of anticoagulant bridging remains controversial. This study was conducted to evaluate our warfarin periprocedural management in Qatar and investigate the associated clinical outcomes with such management. METHODS: A prospective cohort study was designed to describe the periprocedural clinical practice in warfarin patients in Qatar and to compare clinical safety and efficacy outcomes between anticoagulant bridging and nonbridging. RESULTS: 103 patients were recruited. Bridging occurred in 82% of the participants. No thromboembolic events were observed, while 39.1% of patients experienced bleeding events during the study period. The incidence of overall bleeding and major bleeding were numerically higher for bridging group compared to nonbridging but did not reach statistical significance ([30.6% vs 22.2%, P = 0.478] and [12.9% vs 5.6%, P = 0.375], respectively). CONCLUSION: Warfarin interruption and bridging are overwhelmingly used in warfarin-treated patients in Qatar. While bridging was numerically associated with increased bleeding events, there is no statistical difference in reported clinical events between bridging and nonbridging strategies.

Genetic Polymorphism Effect on Warfarin-Rifampin Interaction: A Case Report and Review of Literature.

Warfarin-rifampin interaction has been reported since the 1970s. Due to rifampin's strong induction of CYP2C9, most cases could not attain the target international normalized ratio (INR) despite warfarin dose escalation. Genetic polymorphisms determine up to 50% of warfarin dose variability. A 38-year-old woman was started on warfarin and rifampin for cerebral venous sinus thrombosis and pulmonary tuberculosis. Over six weeks, the daily warfarin dose was increased from 3 to 10 mg to attain three consecutive in-clinic therapeutic INRs. She completed three complications-free months of warfarin treatment with time in therapeutic range (TTR) of 46%. We performed retrospective genetic testing to determine the patient's CYP2C9, CYP4F2, and VKORC1 genotypes and whether they had affected the interaction outcome. The analysis revealed that the subject carries CYP2C9*3*3 and VKORC1-1639 (GA) mutations, classifying her as a slow metabolizer and, hence, highly warfarin-sensitive. This was reflected on how the case responded to a relatively lower dose than previously reported cases that did not achieve the target on warfarin daily doses up to 35 mg. This is the first report addressing the genotype effect on this interaction. Patients with genetic variants requiring low warfarin doses are more likely to respond at a feasible dose while on rifampin. Future studies to evaluate warfarin-rifampin-gene interaction are warranted.

D-Dimer, Fibrinogen, and IL-6 in COVID-19 Patients with Suspected Venous Thromboembolism: A Narrative Review.

Coronavirus disease 2019 (COVID-19) emerged from the West District of Southern China Seafood Wholesale Market in late December 2019 and has been declared a global pandemic by the World Health Organization (WHO). Infection with severe acute respiratory syndrome coronavirus (SARS-CoV-2) presents with upper respiratory symptoms like cough, fever, and lethargy. At the same time, in later stages, critical COVID-19 patients develop acute respiratory distress syndrome (ARDS), venous thromboembolism (VTE), and multiple organ failure from cytokine storm and coagulation hyperactivity. Primary manifestations of thrombotic events include deep vein thrombosis (DVT), disseminated intravascular coagulation (DIC) and pulmonary embolism (PE). Initial coagulopathy in COVID-19 patients presents with elevated fibrin degradation products, especially D-dimers. In contrast, late presentations show evidence of prolonged prothrombin time (PT) and activated partial thromboplastin (aPTT), increased platelets, and fibrinogen levels. Diagnosis and monitoring of disease progression are done by regular screening of laboratory parameters, including D-dimer and fibrinogen. Management of coagulopathy in COVID-19 patients is like that of critically ill patients, including thromboprophylaxis. Coagulopathy is a poor prognostic factor, and optimum strategies should be developed for early diagnosis, prevention, and prompt treatment of VTE in COVID-19 patients. Thrombosis prophylaxis with low molecular weight heparin (LMWH) has shown beneficial results in preventing coagulopathy a reducing risk of mortality due to thrombotic events. We will discuss VTE in COVID-19 patients highlighting the role of D-dimer, fibrinogen, and interleukin-6 (IL-6).

Assessment of the attitude, awareness and practice of periprocedural warfarin management among health care professional in Qatar. A cross sectional survey.

It is estimated that 10-15% of oral anticoagulant (OAC) patients, would need to hold their OAC for scheduled surgery. Especially for warfarin, this process is complex and requires multi-layer risk assessment and decisions across different specialties. Clinical guidelines deliver broad recommendations in the area of warfarin management before surgery which can lead to different trends and practices among practitioners. To evaluate the current attitude, awareness, and practice among health care providers (HCPs) on warfarin periprocedural management. A multiple-choice questionnaire was developed, containing questions on demographics and professional information and was completed by187 HCPs involved in warfarin periprocedural management. The awareness median (IQR) score was moderate [64.28% (21.43)]. The level of awareness was associated with the practitioner's specialty and degree of education (P = 0.009, 0.011 respectively). Practice leans to overestimate the need for warfarin discontinuation as well as the need for bridging. Participants expressed interest in using genetic tests to guide periprocedural warfarin management [median (IQR) score (out of 10) = 7 (5)]. In conclusion, the survey presented a wide variation in the clinical practice of warfarin periprocedural management. This study highlights that HCPs in Qatar have moderate awareness. We suggest tailoring an educational campaign or courses towards the identified gaps.

Cost-Minimization Analysis of Ranibizumab Versus Aflibercept for Treating Saudi Patients With Visual Impairment Owing to Age-Related Macular Degeneration or Diabetic Macular Edema.

OBJECTIVE: The standard-of-care treatment for age-related macular degeneration (AMD) and diabetic macular edema (DME) includes inhibiting blood vessel proliferation and reducing macular edema or swelling using anti-vascular endothelial growth factor therapies, such as ranibizumab and aflibercept. To conduct a cost-minimization analysis of ranibizumab and aflibercept for treating Saudi patients with visual impairment owing to AMD or DME. METHODS: Cost minimization was analyzed assuming that ranibizumab and aflibercept have equivalent clinical effectiveness. The third-party payer's perspective was used in several clinical scenarios. The base-case scenario was DME cases followed monthly using a protocol-specific follow-up. In scenario 1, AMD cases followed a treat-and-extend protocol over 2 years. In scenario 2, AMD cases followed the PRN (pro re nata) regimen over 2 years. In scenario 3, DME cases followed the PRN regimen for 1 year only. RESULTS: Aflibercept yielded cost savings of 25.75%, 31.54%, 51.30%, and 9.28% compared with ranibizumab for the base case, scenario 1, scenario 2, and scenario 3, respectively, which supports the premise that aflibercept is more cost saving than ranibizumab. CONCLUSIONS: From the third-party payer perspective, aflibercept is a cost-containment option that provides substantial savings over ranibizumab for treating Saudi patients with AMD or DME.

Evaluating quantity and quality of literature focusing on health economics and pharmacoeconomics in Gulf Cooperation Council countries.

BACKGROUND: The importance of pharmacoeconomics and health economics has been augmented. It has the potential to provide evidence to aid in optimal decision-making in the funding of cost-effective medicines and services in Gulf Cooperation Council countries (G.C.C). OBJECTIVE: To evaluate the quality and quantity of health economic researches published until the end of 2017 in G.C.C. and to identify the factors that affect the quality of studies. METHOD: Studies were included according to predefined inclusion and exclusion criteria. The quantity was recorded, and the quality was assessed using the Quality of Health Economic Studies (QHES) instrument. RESULTS: Forty-nine studies were included. The mean (SD) quality score of all studies was 57.83 (25.05), and a high number of reviewed studies (47%) were evaluated as either poor or extremely poor quality. The factors that affect the quality of studies with statistical significance were, the type and method of economic evaluation, the economic outcome was the objective of the research, author`s background, the perspective of the study, health intervention and source of funding. CONCLUSION: The use of economic evaluation studies in G.C.C was limited. Different factors that affect the quality of articles such as performing a full economic evaluation and choosing societal perspective were identified. Strategies to improve the quality of future studies were recommended.