Adopting global tools for the advancement of pharmacy practice and workforce in Saudi Arabia

BackgroundThe continuing expansion of the pharmacist’s role necessitates continuous evaluation of current practice to identify strategies for improvements. The International Pharmaceutical Federation (FIP) has developed tools to support stakeholders in identifying development needs and planning advancement strategies. The aim of this research was to utilise the FIP Global Competency Framework, version 2 (GbCF v2), and FIP Development Goals (DGs) to evaluate competencies related to pharmacy practice in Saudi Arabia, and to understand the strategies needed to develop and improve the current practice.MethodsThe study involved four phases. Phase 1 involved translation of the FIP GbCF v2 into the Arabic language. Phase 2 was a consensus panel validation to establish the initial relevance of the competencies to current practice. Phase 3 included a national survey distributed to all registered pharmacists in Saudi Arabia. The final phase was conducted through mapping ‘not relevant’ competencies to FIP DGs to identify priorities.ResultsThe translation phase yielded a bilingual framework that could be utilized by pharmacists in Saudi Arabia. The initial validation phase identified 61 behavioral statements (from 124 in the GbCF v2) as ‘highly relevant’ or ‘relevant’ to pharmacy practice. Findings from the national survey identified a list of ‘not relevant’ competencies that could highlight gaps in current practice. The final mapping phase generated a list of three FIP DG priorities: DG5 (competency development), DG8 (working with others) and DG11 (impact and outcomes).ConclusionThe study indicated that competencies in the GbCF v2 were relevant to pharmacists practicing in the country. However, some competencies were perceived as ‘not relevant’ to current practice and these highlighted gaps in the current practice that need attention. Mapping ‘not relevant’ competencies to FIP DGs should be used as a starting point towards developing strategies, systems, and protocols to advance pharmacy practice in Saudi Arabia.     

Communicating regulatory high-throughput sequencing data using BioCompute Objects

This project demonstrates the use of the IEEE 2791–2020 Standard (BioCompute Objects [BCO]) to enable the complete and concise communication of results from next generation sequencing (NGS) analysis. One arm of a clinical trial was replicated using synthetically generated data made to resemble real biological data and then two independent analyses were performed. The first simulated a pharmaceutical regulatory submission to the US Food and Drug Administration (FDA) including analysis of results and a BCO. The second simulated an FDA review that included an independent analysis of the submitted data. Of the 118 simulated patient samples generated, 117 (99.15%) were in agreement in the two analyses. This process exemplifies how a template BCO (tBCO), including a verification kit, facilitates transparency and reproducibility, thereby reinforcing confidence in the regulatory submission process.     

High Order Finite Difference Hermite WENO Fixed-Point Fast Sweeping Method for Static Hamilton-Jacobi Equations

In this paper, we combine the nonlinear HWENO reconstruction in [43] and the fixed-point iteration with Gauss-Seidel fast sweeping strategy, to solve the static Hamilton-Jacobi equations in a novel HWENO framework recently developed in [22]. The proposed HWENO frameworks enjoys several advantages. First, compared with the traditional HWENO framework, the proposed methods do not need to introduce additional auxiliary equations to update the derivatives of the unknown function $\phi$. They are now computed from the current value of $\phi$ and the previous spatial derivatives of $\phi$. This approach saves the computational storage and CPU time, which greatly improves the computational efficiency of the traditional HWENO scheme. In addition, compared with the traditional WENO method, reconstruction stencil of the HWENO methods becomes more compact, their boundary treatment is simpler, and the numerical errors are smaller on the same mesh. Second, the fixed-point fast sweeping method is used to update the numerical approximation. It is an explicit method and does not involve the inverse operation of nonlinear Hamiltonian, therefore any Hamilton-Jacobi equations with complex Hamiltonian can be solved easily. It also resolves some known issues, including that the iterative number is very sensitive to the parameter $ε$ used in the nonlinear weights, as observed in previous studies. Finally, to further reduce the computational cost, a hybrid strategy is also presented. Extensive numerical experiments are performed on two-dimensional problems, which demonstrate the good performance of the proposed fixed-point fast sweeping HWENO methods.     

Targeting tissue-resident memory CD8+ T cells in the kidney is a potential therapeutic strategy to ameliorate podocyte injury and glomerulosclerosis

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Optical coherence tomography angiography in the evaluation of vascular patterns of ocular surface squamous neoplasia during topical medical treatment

PurposeOptical coherence tomography angiography (OCTA) was utilized to examine changes in ocular surface squamous neoplasia (OSSN) vascular patterns over time in individuals treated with topical medical therapy.MethodsTen individuals with OSSN diagnosed by clinical examination and high resolution (HR)-optical coherence tomography (OCT) were recruited. All individuals received topical immuno- or chemotherapy. OCTA images were obtained and analyzed at three points: presentation, mid-treatment and tumor resolution. Tumor metrics including tumor area (TA), tumor volume (TV), tumor depth (TD), and total tumor density (TTD) were calculated. Vessel area density (VAD) was also quantified within the OSSN, the subepithelium under and adjacent to the OSSN and the subepithelium of the uninvolved, contralateral eye. Vascular network changes were also subjectively evaluated.ResultsTA, TV, TD and TTD all significantly decreased with time (p < 0.001). The mean VAD within the OSSN significantly decreased (p < 0.001) between visits (presentation: 26.52 ± 6.8%, mid-treatment: 7.19 ± 5.88%, tumor resolution: 0.11 ± 0.34%). The mean subepithelial VAD under the OSSN also decreased with time (23.22 ± 11.03%, 20.99 ± 5.99% and 19.58 ± 7.08%), and after resolution the sub-tumor VAD (19.58 ± 7.08%) was comparable to the subepithelial VAD in the contralateral eye (15.47 ± 4.37%, p > 0.05). The mean VAD in the subepithelium adjacent to the OSSN increased with treatment, then decreased significantly between mid-treatment and resolution (23.26 ± 4.54, 28.30 ± 7.43% and 21.68 ± 6.10%, p = 0.009). Qualitatively, the tumor subepithelial vascular network was complex and dense but with tumor resolution appeared less tortuous and similar to the uninvolved eye.ConclusionOCTA provided insight into the pathophysiology of tumor angiogenesis, showing decreased vascular density and normalization of vascular networks associated with tumor resolution.     

Survival effects of time to surgery for Stage I lung cancer: A population-based study

ObjectivesTo examine the impact of time to surgery (TTS) on survival among patients with stage I non-small cell lung cancer (NSCLC).MethodsAll patients in the Canadian province of Ontario with stage I NSCLC from 2007 to 2017 were included. A logistic regression identified the predictors of TTS and a flexible parametric model estimated survival rates based on TTS.ResultsOver the study period, 6428 patients with stage I NSCLC undergoing surgical resection were identified, of which 62.5% had TTS >28 days. Less than half these patients (40.8%) underwent open resection, with 19.3% undergoing open sublobar and 21.5% undergoing open lobectomy. Adenocarcinoma and squamous cell carcinoma tumors accounted for 33.3% and 22.0% of cases, respectively. The majority (85.6%) of patients lived in urban areas within 50 km of a regional cancer center (76.9%). Variables that predicted TTS >28 days include age and extent of resection. After adjustment for VATS vs. open resection, age, sex, frailty, year of diagnosis, histology of tumor, and extent of resection, the hazard ratio for TTS >28 days was 1.26 (95%CI:1.13–1.40), indicating a 26% increased risk of all-cause mortality (p < 0.0001). The highest 5-year survival was observed for patients with stage I disease undergoing resection within 28 days.ConclusionsThe present study found age and extent of resection to be associated with increased TTS. Importantly, patients with TTS >28 days had reduced long-term survival.     

Molecular imaging in oncology: Current impact and future directions

The authors define molecular imaging, according to the Society of Nuclear Medicine and Molecular Imaging, as the visualization, characterization, and measurement of biological processes at the molecular and cellular levels in humans and other living systems. Although practiced for many years clinically in nuclear medicine, expansion to other imaging modalities began roughly 25 years ago and has accelerated since. That acceleration derives from the continual appearance of new and highly relevant animal models of human disease, increasingly sensitive imaging devices, high-throughput methods to discover and optimize affinity agents to key cellular targets, new ways to manipulate genetic material, and expanded use of cloud computing. Greater interest by scientists in allied fields, such as chemistry, biomedical engineering, and immunology, as well as increased attention by the pharmaceutical industry, have likewise contributed to the boom in activity in recent years. Whereas researchers and clinicians have applied molecular imaging to a variety of physiologic processes and disease states, here, the authors focus on oncology, arguably where it has made its greatest impact. The main purpose of imaging in oncology is early detection to enable interception if not prevention of full-blown disease, such as the appearance of metastases. Because biochemical changes occur before changes in anatomy, molecular imaging—particularly when combined with liquid biopsy for screening purposes—promises especially early localization of disease for optimum management. Here, the authors introduce the ways and indications in which molecular imaging can be undertaken, the tools used and under development, and near-term challenges and opportunities in oncology.     

基于生物信息学的肥厚型心肌病易感基因TNNC1单核苷酸多态性致病表型分析

肥厚型心肌病(HCM)是一种常见的遗传性心脏病,是青少年及年轻运动员心源性猝死的最主要原因之一,其分子遗传学基础为基因突变。TNNC1是HCM的重要致病基因之一,目前仅发现其少量非同义单核苷酸多态性(nsSNPs)位点与HCM发病相关,但该基因其他nsSNPs数量较多,结合临床进行实验遗传检测其基因型与表型的关系,工作量巨大,尚不可行。因此,采用生物信息学方法,从dbSNP数据库中筛选出TNNC1基因全部的nsSNPs,联合4款(Mutation Taster、PolyPhen-2、PhD-SNP和MutPred)专业软件,进行有害性分级筛选和致病关联预测,最后进行突变蛋白三维结构建模及可视化分析。结果显示,首次从TNNC1基因102个nsSNPs位点中预测出疾病相关的18个(G159D、S69R、P52R、D149G、D3V、G140E、N51K、D151V、M47R、G110C、A23D、G140R、K158N、C35Y、R147C、L48P、F74C和V44G)高风险nsSNPs。基于生物信息学方法,以TNNC1基因的nsSNPs为示范,分析其nsSNPs与疾病表型的关系,这为其他遗传疾病致病基因nsSNPs的关联分析打下理论研究基础,具有重要的参考价值。