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This study utilized a validated questionnaire that aimed to assess pharmacists' awareness and attitude towards drug repurposing for antimicrobial use. Despite the reasonable awareness, pharmacists reported unfavourable attitudes. Pharmacists with a B.Pharm. or Pharm.D. degree reported less awareness than pharmacists with a master's or PhD degree. In contrast, pharmacists who dispensed fewer than 10 prescriptions or 10-29 prescriptions had significantly higher awareness than those who dispensed 30 prescriptions daily or more. Pharmacists who had 1-5 years of experience and those who dispensed less than 10 prescriptions daily had significantly lower attitude scores than their counterpats. The most reported facilitator was the reduced risk of antimicrobial resistance, while the most reported barrier was patient safety. Pharmacists' perception of drug repurposing for antimicrobial needs to improve via implementing educational sessions that highlight the impact of drug repurposing on supporting the fight against antimicrobial resistance and promoting a more sustainable and resilient healthcare system.

Financial resources alone cannot guarantee effective public health policy. In Abu Dhabi, massive economic growth in the desert climate resulted in concentrated urbanization and led to challenges in the regulation of air pollution. The Environment Agency in Abu Dhabi commissioned us to scope the regulatory challenges for air pollution. Part of this project relied on the participation and involvement of key stakeholders. We found three barriers: (1) limited appreciation of uncertainties in risk estimates and discussion on the importance of considering control costs and the societal trade-offs between health and wealth inherent in such decisions, (2) compartmentalization of efforts, and (3) challenges to decide how to prioritize risks in policy agendas. We propose a consortium-like approach that brings stakeholders together and places risk, uncertainty, and tradeoffs between health and wealth at the forefront of decision-making. Expected outcomes include improved collaboration and information sharing, strategic prioritization of emission controls, and a better understanding and consideration of uncertainty to guide future public health research., (© 2024. The Author(s).)

Background: Antimicrobial stewardship (ASP) is considered a key prevention strategy in addressing the worldwide concern of accelerating antimicrobial resistance. Limited research is available regarding healthcare providers' knowledge and attitude toward antimicrobial stewardship and the barriers for its implementation., Methods: The present cross-sectional study was conducted on pharmacists and healthcare prescribers (HCPs) in different hospital sites across Jordan. A validated survey was used to evaluate HCPs and pharmacists' knowledge, and attitudes towards ASP and the barriers for its implementation. Logistic and linear regression were conducted to identify the factors associated with knowledge and attitude toward ASP, respectively., Results: A total of 603 participants, 69 (11.4%) pharmacists and 534 (88.6%) HCPs completed the study questionnaire, with a response rate of 80.4%. The overall mean knowledge about ASP was 7.16 out of 10, ranging from 0 to 10 (SD 2.22). Being a pharmacist and increased awareness/familiarity about ASP were associated with improved ASP knowledge. The overall average attitude score was = 3.8 ± 0.49 (range: 1.8-4.8). Results revealed that being a pharmacist and improved knowledge were associated with improved attitude toward ASP. Lack of specialized staff with expertise in ASP and lack of access to education and training programs were the major barriers hinder ASP implementation., Conclusion: Despite the reasonable knowledge and the positive attitude toward the ASP, several barriers were reported, particularly by the pharmacists. Therefore, promoting the presence of adequately skilled healthcare personnel, creating easily accessible online courses, and establishing a comprehensive database of ASP resources are all suggested approaches to improve the application of ASP in healthcare settings., (© 2024. The Author(s).)

Objective: To assess hospital pharmacists' understanding of pharmaceutical care and their attitudes regarding the adoption of the patient-centered model, as well as investigate Jordan's current state of pharmaceutical care implementation and the associated barriers., Methods: A validated survey was distributed to hospital pharmacists in different major tertiary hospitals in Jordan. The study questionnaire contained five sections to assess sociodemographic characteristics, pharmacists' understanding of pharmaceutical care, attitudes towards pharmaceutical care, potential barriers that may limit the delivery of pharmaceutical care, and the extent of pharmaceutical care implementation in the hospital setting., Results: The survey was completed by 152 hospital pharmacists. Participants in this study demonstrated adequate levels of knowledge about pharmaceutical care (Mean = 9.36 out of 11, SD = 1.23) and expressed favorable perceptions of pharmaceutical care (mean = 3.77 out of 5; SD = 0.7). Although more than one-third of the pharmacists practiced pharmaceutical care, the study revealed a number of impediments to the delivery of pharmacological care services. Regression analysis revealed that age (P < 0.05) and years of experience (P < 0.05) were significant predictors of knowledge, while age (P < 0.05), gender (P < 0.05), the graduation university (governmental vs. private) (P < 0.05), and years of experience (P < 0.05) were significant predictors of attitude. Furthermore, Doctor of Pharmacy degree holders had fewer barriers to pharmaceutical care implementation but were more actively involved in pharmaceutical care practice than those with a Bachelor of Pharmacy degree (P < 0.01 and P < 0.05 respectively). Pharmacists with a Master's degree or higher in pharmacy were more actively involved in pharmaceutical care practice than those with a Bachelor of Pharmacy degree (P < 0.05). Pharmacists working in the Ministry of Health and the Royal Medical Services experienced more barriers than those working in teaching hospitals (P < 0.05)., Conclusions: Although the current study indicated high knowledge and perceptions regarding pharmaceutical care among hospital pharmacists, the provision of pharmaceutical care is not widely practiced in Jordan. Moreover, several barriers to the practice of pharmaceutical care were identified, highlighting the need for effective strategies to be put in place to overcome these obstacles. These strategies should include increasing the number of pharmacy staff, resolving timing issues, providing adequate financial initiatives, improving communication skills, changing the layout of pharmacies to include a private counseling room, developing specific policies that support the role of the pharmacist in patient care, and providing effective training and continuing professional education programs., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 Published by Elsevier Ltd.)

Aims: Type 2 diabetes (T2D) and coronary artery disease (CAD) often coexist and share genetic factors.This study aimed to investigate the common genetic factors underlying T2D and CAD in patients with CAD., Methods: A three-step association approach was conducted: a) a discovery step involving 943 CAD patients with T2D and 1,149 CAD patients without T2D; b) an eliminating step to exclude CAD or T2D specific variants; and c) a replication step using the UK Biobank data., Results: Ten genetic loci were associated with T2D in CAD patients. Three variants were specific to either CAD or T2D. Five variants lost significance after adjusting for covariates, while two SNPs remained associated with T2D in CAD patients (rs7904519*G: TCF7L2 and rs17608766*C: GOSR2). The T2D susceptibility rs7904519*G was associated with increased T2D risk, while the CAD susceptibility rs17608766*C was negatively associated with T2D in CAD patients. These associations were replicated in a UK Biobank data, confirming the results., Conclusions: No significant common T2D and CAD susceptibility genetic association was demonstrated indicating distinct disease pathways. However, CAD patients carrying the T2D susceptibility gene TCF7L2 remain at higher risk for developing T2D emphasizing the need for frequent monitoring in this subgroup., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Patients with heart failure (HF) are generally at higher risk of developing type 2 diabetes and having uncontrolled blood glucose. Furthermore, the prevalence of uncontrolled blood glucose in patients with HF is largely unknown. Identifying the factors associated with poor blood glucose control is a preliminary step in the development of effective intervention programs. The current cross-sectional study was conducted at two major hospitals to explore the factors associated with blood glucose control among patients with heart failure and type 2 diabetes. In addition to sociodemographic, medical records were used to collect medical information and a validated questionnaire was used to evaluate medication adherence. Regression analysis showed that poor medication adherence (OR = 0.432; 95%CI 0.204-0.912; P<0.05) and increased white blood cells count (OR = 1.12; 95%CI 1.033-1.213; P<0.01) were associated with poor glycemic control. For enhancing blood glucose control among patients with HF and diabetes, future intervention programs should specifically target patients who have high WBC counts and poor medication., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 S. Jarab et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

SARS-CoV-2 appears to induce diverse innate and adaptive immune responses, resulting in different clinical manifestations of COVID-19. Due to their function in presenting viral peptides and initiating the adaptive immune response, certain Human Leucocyte Antigen (HLA) alleles may influence the susceptibility to severe SARS-CoV-2 infection. In this study, 92 COVID-19 patients from 15 different nationalities, with mild (n = 30), moderate (n = 35), and severe (n = 27) SARS-CoV-2 infection, living in the United Arab Emirates (UAE) were genotyped for the Class I HLA -A, -C, and -B alleles using next-generation sequencing (NGS) between the period of May 2020 to June 2020. Alleles and inferred haplotype frequencies in the hospitalized patient group (those with moderate to severe disease, n = 62) were compared to non-hospitalized patients (mild or asymptomatic, n = 30). An interesting trend was noted between the severity of COVID-19 and the HLA-C*04 (P = 0.0077) as well as HLA-B*35 (P = 0.0051) alleles. The class I haplotype HLA-C*04-B*35 was also significantly associated (P = 0.0049). The involvement of inflammation, HLA-C*04, and HLA-B*35 in COVID-19 severity highlights the potential roles of both the adaptive and innate immune responses against SARS-CoV-2. Both alleles have been linked to several respiratory diseases, including pulmonary arterial hypertension along with infections caused by the coronavirus and influenza. This study, therefore, supports the potential use of HLA testing in prioritizing public healthcare interventions for patients at risk of COVID-19 infection and disease progression, in addition to providing personalized immunotherapeutic targets., Competing Interests: The authors have no conflicts of interest to declare., (Copyright: © 2023 Tay et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Heart Failure (HF) is a chronic disease associated with life-limiting symptoms that could negatively impact patients' health-related quality of life (HRQOL). This study aimed to evaluate HRQOL and explore the factors associated with poor HRQOL among patients with HF in Jordan., Methods: This cross-sectional study used the validated Arabic version of the Minnesota Living with Heart Failure Questionnaire to assess HRQOL in outpatients with HF visiting cardiology clinics at two public hospitals in Jordan. Variables were collected from medical records and custom-designed questionnaires, including socio-demographics, biomedical variables, and disease and medication characteristics. Ordinal regression analysis was used to explore variables associated with poor HRQOL among HF patients., Results: Ordinal regression analysis showed that the number of HF medications (P < 0.05) and not taking a loop diuretic (P < 0.05) significantly increased HRQOL, while the number of other chronic diseases (P < 0.05), stage III/IV of HF (P < 0.01), low monthly income (P < 0.05), and being unsatisfied with the prescribed medications (P < 0.05) significantly decreased HRQOL of HF patients., Conclusions: Although the current study demonstrated low HRQOL among patients with HF in Jordan, HRQOL has a considerable opportunity for improvement in those patients. Variables identified in the present study, including low monthly income, higher New York Heart Association (NYHA) classes, a higher number of comorbidities, and/or taking a loop diuretic, should be considered in future intervention programs, aiming to improve HRQOL in patients with HF., (© 2023. The Author(s).)

Familial hypercholesterolemia (FH) is a globally underdiagnosed genetic condition associated with premature cardiovascular death. The genetic etiology data on Arab FH patients is scarce. Therefore, this study aimed to identify the genetic basis of FH in a Saudi family using whole exome sequencing (WES) and multidimensional bioinformatic analysis. Our WES findings revealed a rare heterozygous gain-of-function variant (R496W) in the exon 9 of the PCSK9 gene as a causal factor for FH in this family. This variant was absent in healthy relatives of the proband and 200 healthy normolipidemic controls from Saudi Arabia. Furthermore, this variant has not been previously reported in various regional and global population genomic variant databases. Interestingly, this variant is classified as "likely pathogenic" (PP5) based on the variant interpretation guidelines of the American College of Medical Genetics (ACMG). Computational functional characterization suggested that this variant could destabilize the native PCSK9 protein and alter its secondary and tertiary structural features. In addition, this variant was predicted to negatively influence its ligand-binding ability with LDLR and Alirocumab antibody molecules. This rare PCSK9 (R496W) variant is likely to expand our understanding of the genetic basis of FH in Saudi Arabia. This study also provides computational structural insights into the genotype-protein phenotype relationship of PCSK9 pathogenic variants and contributes to the development of personalized medicine for FH patients in the future., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Shaik, Al-Shehri, Athar, Awan, Khalili, Al Mahadi, Hejazy, Saadah, Al-Harthi, Elango, Banaganapalli, Alefishat and Awan.)

Background and Objectives: High homocysteine levels are associated with increased risk of hypertension and stroke. Homocysteine is metabolized by the methylenetetrahydrofolate reductase ( MTHFR ). We aimed to investigate the levels of homocysteine and their association with hypertension, stroke, and antihypertensive medication usage in patients with different MTHFR C677T genotypes., Methods and Results: Genotype frequency of MTHFR polymorphism was performed, and plasma homocysteine levels were measured in 2,640 adult Lebanese patients. Hypertension, history of stroke, and list of medications were documented, among other clinical and demographic parameters. The TT mutant genotype and the T mutant allele of MTHFR were more prevalent in hyperhomocysteinemia (HHcy) and H-hypertensive (H-HTN, defined as hypertension with hyperhomocysteinemia) patients when compared to non-HHcy subjects and non H-HTN patients respectively. Homocysteine levels were significantly higher in hypertensive patients specifically among those on diuretics. A higher level of homocysteine was found in hypertensive patients with the MTHFR T allele compared to patients carrying the C allele. Among the T allele carriers, the average plasma homocysteine level was 13.3 ± 0.193 μmol/L for hypertensive subjects compared to 11.9 ± 0.173 μmol/L (non-hypertensives). Furthermore, homocysteine levels significantly correlated with stroke risk in patients with the T alleles., Conclusions: We found an association of homocysteine with hypertension, hypertensive medication, and stroke risk among patients with the MTHFR T allele and the TT genotype. The association of diuretics therapy with higher homocysteine levels calls for routine measurements and therapeutic control of homocysteine in patients on diuretic, to improve health-related outcomes., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Background: Poor adherence to heart failure (HF) medications represents a major barrier to achieve the desired health outcomes in those patients., Objective: To assess medication adherence and to explore the factors associated with medication non-adherence among patient with HF in Jordan., Methods: The current cross-sectional study was conducted at the outpatient cardiology clinics at two main hospitals in Jordan from August 2021 through April 2022. Variables including socio-demographics, biomedical variables, in addition to disease and medication characteristics were collected using medical records and custom-designed questionnaire. Medication adherence was assessed using the 4-item Morisky Medication Adherence Scale. Multinomial logistic regression analysis was performed to identify the factors that are significantly and independently associated with medication non-adherence., Results: Of the 427 participating patients, 92.5% had low to moderate medication adherence. Results of the regression analysis revealed that that patients who had higher education level (OR=3.36; 95% CI 1.08-10.43; P=0.04) and were not suffering from medication-related side effects (OR=4.7; 95% CI 1.91-11.5; P=0.001) had significantly higher odds of being in the moderate adherence group. Patients who were taking statins (OR=16.59; 95% CI 1.79-153.98; P=0.01) or ACEIs/ ARBs (OR=3.95; 95% CI 1.01-15.41; P=0.04) had significantly higher odds of being in the high adherence group. Furthermore, Patients who were not taking anticoagulants had higher odds of being in the moderate (OR=2.77; 95% CI 1.2-6.46; P=0.02) and high (OR=4.11; 95% CI 1.27-13.36; P=0.02) adherence groups when compared to patients who were taking anticoagulants., Conclusion: The poor medication adherence in the present study sheds the light on the importance of implementing intervention programs which focus on improving patients' perception about the prescribed medications particularly for patients who have low educational levels, receive an anticoagulant, and do not receive a statin or an ACEI/ ARB., Competing Interests: The authors declare that they have no competing interests., (© 2023 Jarab et al.)

The Parkinson disease (PD) is the second most common neurodegenerative disorder affecting the central nervous system and motor functions. The biological complexity of PD is yet to reveal potential targets for intervention or to slow the disease severity. Therefore, this study aimed to compare the fidelity of blood to substantia nigra (SN) tissue gene expression from PD patients to provide a systematic approach to predict role of the key genes of PD pathobiology. Differentially expressed genes (DEGs) from multiple microarray data sets of PD blood and SN tissue from GEO database are identified. Using the theoretical network approach and variety of bioinformatic tools, we prioritized the key genes from DEGs. A total of 540 and 1024 DEGs were identified in blood and SN tissue samples, respectively. Functional pathways closely related to PD such as ERK1 and ERK2 cascades, mitogen-activated protein kinase (MAPK) signaling, Wnt, nuclear factor-κB (NF-κB), and PI3K-Akt signaling were observed by enrichment analysis. Expression patterns of 13 DEGs were similar in both blood and SN tissues. Comprehensive network topological analysis and gene regulatory networks identified additional 10 DEGs functionally connected with molecular mechanisms of PD through the mammalian target of rapamycin (mTOR), autophagy, and AMP-activated protein kinase (AMPK) signaling pathways. Potential drug molecules were identified by chemical-protein network and drug prediction analysis. These potential candidates can be further validated in vitro/in vivo to be used as biomarkers and/or novel drug targets for the PD pathology and/or to arrest or delay the neurodegeneration over the years, respectively., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2023.)

Background: Dyslipidemia is common among patients with heart failure, and it negatively impacts clinical outcomes. Limited data regarding the factors associated with poor lipid control in patients with HF patients. Therefore, this study aimed to evaluate lipid control and to explore the factors associated with poor lipid control in patients with HF., Methods: The current cross-sectional study was conducted at outpatient cardiology clinics at two major hospitals in Jordan. Variables including socio-demographics, biomedical variables, in addition to disease and medication characteristics were collected using medical records and custom-designed questionnaire. Medication adherence was assessed using the validated 4-item Medication Adherence Scale. Binary logistic regression analysis was conducted to explore significant and independent predictors of poor lipid control among the study participants., Results: A total of 428 HF patients participated in the study. Results showed that 78% of the participants had poor lipid control. The predictors that were associated with poor lipid control included uncontrolled BP (OR = 0.552; 95% CI: 0.330-0.923; P  < 0.05), higher Hb levels (OR = 1.178; 95% CI: 1.013-1.369; P  < 0.05), and higher WBC (OR = 1.133; 95% CI: 1.031-1.246; P  < 0.05)., Conclusions: This study revealed poor lipid control among patients with HF. Future intervention programs should focus on blood pressure control in order to improve health outcomes among HF patients with dyslipidemia., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Jarab, Al-Qerem, Hamam, Abu Heshmeh, Mukattash and Alefishat.)

Previous studies on biocatalytic transformations of pinenes by cytochrome P450 (CYP) enzymes reveal the formation of different oxygenated products from a single substrate due to the multistate reactivity of CYP and the many reactive sites in the pinene scaffold. Up until now, the detailed mechanism of these biocatalytic transformations of pinenes have not been reported. Hereby, we report a systematic theoretical study of the plausible hydrogen abstraction and hydroxylation reactions of α- and β-pinenes by CYP using the density functional theory (DFT) method. All DFT calculations in this study were based on B3LYP/LAN computational methodology using the Gaussian09 software. We used the B3LYP functional with corrections for dispersive forces, BSSE, and anharmonicity to study the mechanism and thermodynamic properties of these reactions using a bare model (without CYP) and a pinene-CYP model. According to the potential energy surface and Boltzmann distribution for radical conformers, the major reaction products of CYP-catalyzed hydrogen abstraction from β-pinene are the doublet trans (53.4%) and doublet cis (46.1%) radical conformer at delta site. The formation of doublet cis/trans hydroxylated products released a total Gibbs free energy of about 48 kcal/mol. As for alpha pinene, the most stable radicals were trans-doublet (86.4%) and cis-doublet (13.6%) at epsilon sites, and their hydroxylation products released a total of ~50 kcal/mol Gibbs free energy. Our results highlight the likely C-H abstraction and oxygen rebounding sites accounting for the multi-state of CYP (doublet, quartet, and sextet spin states) and the formation of different conformers due to the presence of cis/trans allylic hydrogen in α-pinene and β-pinene molecules.

Backgrounds and Aims: The role of Lipoprotein(a) (Lp(a)) in increasing the risk of cardiovascular diseases is reported in several populations. The aim of this study is to investigate the correlation of high Lp(a) levels with the degree of coronary artery stenosis., Methods: Two hundred and sixty-eight patients were enrolled for this study. Patients who underwent coronary artery angiography and who had Lp(a) measurements available were included in this study. Binomial logistic regressions were applied to investigate the association between Lp(a) and stenosis in the four major coronary arteries. The effect of LDL and HDL Cholesterol on modulating the association of Lp(a) with coronary artery disease (CAD) was also evaluated. Multinomial regression analysis was applied to assess the association of Lp(a) with the different degrees of stenosis in the four major coronary arteries., Results: Our analyses showed that Lp(a) is a risk factor for CAD and this risk is significantly apparent in patients with HDL-cholesterol ≥35 mg/dL and in non-obese patients. A large proportion of the study patients with elevated Lp(a) levels had CAD even when exhibiting high HDL serum levels. Increased HDL with low Lp(a) serum levels were the least correlated with stenosis. A significantly higher levels of Lp(a) were found in patients with >50% stenosis in at least two major coronary vessels arguing for pronounced and multiple stenotic lesions. Finally, the derived variant (rs1084651) of the LPA gene was significantly associated with CAD., Conclusion: Our study highlights the importance of Lp(a) levels as an independent biological marker of severe and multiple coronary artery stenosis., Competing Interests: The authors report no conflicts of interest in this work., (© 2023 Al Hageh et al.)

Several psychosocial, sleep/circadian, and cardiometabolic disorders have intricately interconnected pathologies involving melatonin disruption. Therefore, we hypothesize that melatonin could be a therapeutic target for treating potential comorbid diseases associated with this triad of psychosocial-sleep/circadian-cardiometabolic disorders. We investigated melatonin's target prediction and tractability for this triad of disorders. The melatonin's target prediction for the proposed psychosocial-sleep/circadian-cardiometabolic disorder triad was investigated using databases from Europe PMC, ChEMBL, Open Targets Genetics, Phenodigm, and PheWAS. The association scores for melatonin receptors MT1 and MT2 with this disorder triad were explored for evidence of target-disease predictions. The potential of melatonin as a tractable target in managing the disorder triad was investigated using supervised machine learning to identify melatonin activities in cardiovascular, neuronal, and metabolic assays at the cell, tissue, and organism levels in a curated ChEMBL database. Target-disease visualization was done by graphs created using "igraph" library-based scripts and displayed using the Gephi ForceAtlas algorithm. The combined Europe PMC (data type: text mining), ChEMBL (data type: drugs), Open Targets Genetics Portal (data type: genetic associations), PhenoDigm (data type: animal models), and PheWAS (data type: genetic associations) databases yielded types and varying levels of evidence for melatonin-disease triad correlations. Of the investigated databases, 235 association scores of melatonin receptors with the targeted diseases were greater than 0.2; to classify the evidence per disease class: 37% listed psychosocial disorders, 9% sleep/circadian disorders, and 54% cardiometabolic disorders. Using supervised machine learning, 546 cardiovascular, neuronal, or metabolic experimental assays with predicted or measured melatonin activity scores were identified in the ChEMBL curated database. Of 248 registered trials, 144 phase I to IV trials for melatonin or agonists have been completed, of which 33.3% were for psychosocial disorders, 59.7% were for sleep/circadian disorders, and 6.9% were for cardiometabolic disorders. Melatonin's druggability was evidenced by evaluating target prediction and tractability for the triad of psychosocial-sleep/circadian-cardiometabolic disorders. While melatonin research and development in sleep/circadian and psychosocial disorders is more advanced, as evidenced by melatonin association scores, substantial evidence on melatonin discovery in cardiovascular and metabolic disorders supports continued R&D in cardiometabolic disorders, as evidenced by melatonin activity scores. A multiplatform analysis provided an integrative assessment of the target-disease investigations that may justify further translational research.

Abstract: Background: Patients with severe coronavirus disease 2019 (COVID-19) are at an increased risk of acute respiratory distress syndrome and mortality. This is due to the increased levels of pro-inflammatory cytokines that amplify downstream pathways that are controlled by immune regulators. Objective: This study aimed to investigate the association between cytokine genetic variants, cytokine serum levels/profiles, and disease severity in critically and noncritically ill COVID-19 patients. Methods: This cross-sectional study recruited 646 participants who tested positive for severe acute respiratory syndrome coronavirus 2 from six collection sites across the United Arab Emirates. Medical files were accessed to retrieve clinical data. Blood samples were collected from all participants. Patients were divided into two clinical groups, noncritical (n = 453) and critical (n = 193), according to World Health Organization classification guidelines for COVID-19 patients. Cytokine analyses were conducted on serum of a subset of the cohort, specifically on 426 participants (noncritical, 264; critical, 162). Candidate gene analyses of 33 cytokine-related genes (2,836 variants) were extracted from a genome-wide association study to identify genetic variants with pleiotropic effects on a specific cytokine and the severity of COVID-19 disease. Results: Age, body mass index (BMI), and pre-existing medical conditions were found to be significant risk factors that contribute to COVID-19 disease severity. After correcting for age, sex, and BMI, IP-10 ( P < 0.001), IFN ( P = 0.001), IL-6 ( P < 0.001), and CXCL-16 ( P < 0.001) serum levels were significantly higher among critical COVID-19 cases, when compared with noncritically ill patients. To investigate if the genetic variants involved in the serum cytokine levels are associated with COVID-19 severity, we studied several genes. Single nucleotide polymorphisms in IL6 (rs1554606; odd ratio (OR) G = 0.67 [0.66, 0.68]; P = 0.017), IFNG (rs2069718; OR G = 0.63 [0.62, 0.64]; P = 0.001), MIP (rs799187; OR A = 1.69 [1.66, 1.72]; P = 0.034), and CXCL16 (rs8071286; OR A = 1.42 [1.41, 1.44]; P = 0.018) were found to be associated with critically ill patients. Polymorphisms in the CXCL10 , CCL2 , IL1 , CCL7 , and TNF genes were not associated with the COVID-19 critical phenotype. The genotypes of IL-6 (gene, IL6 [7p15.3]) and CXCL-16 (gene, CXCL16 [17p13.2]) were significantly associated with the serum levels of the respective cytokine in critical cases of COVID-19. Conclusion: Data obtained from measuring cytokine levels and genetic variant analyses suggest that IL-6 and CXCL-16 could potentially be used as potential biomarkers for monitoring disease progression of COVID-19 patients. The findings in this study suggest that specific cytokine gene variants correlate with serum levels of the specific cytokine. These genetic variants could be of assistance in the early identification of high-risk patients on admission to the clinic to improve the management of COVID-19 patients and other infectious diseases., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 by the Shock Society.)

Objectives: This cross-sectional study was conducted at Jordan university hospital to evaluate the impact of microbial culture data and sensitivity results on optimizing UTI treatment. Methods: All positive urine cultures requested for adult patients (≥18 years) admitted to Jordan University Hospital (JUH) within the period from January 2019-July 2021 were evaluated. The antibiotics prescribed before and after culture data and sensitivity results were compared to evaluate the impact of these diagnostic measures on optimizing UTI treatment. Results: During the study period, 2400 urine cultures revealed positive results. Among those patients, 1,600 (66.7%) were discharged before the availability of culture results and excluded. Of the remaining 800 patients, 701 patients (87.6%) received empiric treatment. After culture and sensitivity results were available, overall, 84 (10.5%) patients had optimization (improvement) in their UTI management after culture results were known, while 6 (0.8%) patients had a worsening in their treatments. Based on the culture results, we found that only 12.4% of patients were appropriately treated before and after the culture results. Moreover, our results revealed that 31.9% were inappropriately treated for their UTIs before and after culture results. Conclusion: This study revealed an alarmingly high rate of inappropriate treatment of UTIs despite the availability of urine culture and sensitivity data, and that culture results were not used to optimize treatment strategies for UTI. This practice can potentially result in poor health-related outcomes and adversely affects efforts to battle AMR. Multifaceted strategies must be implemented to help clinicians follow the best current evidence and current guidelines in their selection of antibiotics for the management of UTIs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Alkhawaldeh, Abu Farha, Abu Hammour and Alefishat.)

Objectives: The main goal of the current study was to investigate pharmacists' perception of home delivery of medications service in Jordan and their willingness to use the service., Method: This cross-sectional observational study was conducted between March and April 2022. The study targeted community pharmacists working at different community pharmacies across Jordan. The study questionnaire was distributed through Facebook to target Jordanian community pharmacists' groups., Results: Three hundred and twenty-four community pharmacists participated in the study, 75% ( n = 244) of pharmacists reported being willing to use the home delivery and 274 (84.6%) thought it increases the efficiency of their community pharmacies' services. Only 129 (39.8%) pharmacists agreed or strongly agreed that unlike in-store service, home delivery of medications is suitable only for OTC but not for prescriptions medications Nearly half the number of participating pharmacists ( n = 153, 47.2%) believe that the service is suitable for refill prescriptions but not for new prescriptions. Pharmacists believe that the foremost pros of the service were to continue life-saving medical treatment ( n = 249, 76.9%), serve sick, elderly, and disabled patients ( n = 241, 74.4%), and decrease congestion at health facilities ( n = 228, 70.4%). On the other hand, the cons of this service, as perceived by pharmacists included failing to build a professional relationship with patients ( n = 203, 62.7%), and the contribution to communication errors ( n = 147, 45.4%). Logistic regression showed that pharmacists who serve 50 patients or more per day were more willing to use the service than those serving less than 50 patients per day (OR = 2.058, P = 0.032)., Conclusion: The majority of participating pharmacists in this study were willing to use the service at their community pharmacies, especially those serving a large number of patients per day which may indicate the potential of this service in relieving the pressure on community pharmacies and allowing them to serve more patients efficiently., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Abu-Farha, Alzoubi, Alkhawaldeh, Itani, Karout, Mukattash and Alefishat.)

Introduction: Home medication delivery service is a major service for the public. It reduces overcrowding and unnecessary visits to health centers. This study aims to investigate the public perception of home delivery of medication service in Jordan and evaluate factors affecting the use of this service., Methods: The study was conducted in March 2022 using an online survey. Participants were asked to fill out a validated questionnaire to evaluate their perception of home delivery of medication service., Results: Among the 1032 adult participated in this study, the majority reported that they had heard of home delivery of medication service (n = 832, 80.6%). However, only 30.9% of them have used this service before. Results showed that 71.4% of the participants (n = 737) believe that home delivery of medication service is more convenient and accessible than in-store drug refill. In addition, 65.6% of the participants (n = 677) believed that home delivery of medication service is suitable only for refill-prescription drugs (65.0%). The main pros of the service as perceived by the study participants were to serve sick patients, elderly, and disabled people (n = 822, 79.7%). In contrast, the inability of patients to build a professional relationship with pharmacists using home delivery of medications service was the most perceived con of this service (n = 627, 60.8%). Finally, regression analysis revealed that older participants, those with chronic diseases, and those who visit community pharmacies two times or more per month revealed higher use of the service (P = <0.05)., Conclusion: This study has shown that most participants showed positive perceptions toward the home delivery of medication services. However, participants believed that this service may decrease pharmacist's patient contact time, thus affecting the quality of medication counseling. More comprehensive future studies are necessary to examine the financial aspects of such a service and its associated drawbacks., Competing Interests: The authors declare that there is no conflicts of interest., (© 2022 Abu-Farha et al.)

The sinoatrial node (SAN) is composed of highly specialized cells that mandate the spontaneous beating of the heart through self-generation of an action potential (AP). Despite this automaticity, the SAN is under the modulation of the autonomic nervous system (ANS). In diabetes mellitus (DM), heart rate variability (HRV) manifests as a hallmark of diabetic cardiomyopathy. This is paralleled by an impaired regulation of the ANS, and by a pathological remodeling of the pacemaker structure and function. The direct effect of diabetes on the molecular signatures underscoring this pathology remains ill-defined. The recent focus on the electrical currents of the SAN in diabetes revealed a repressed firing rate of the AP and an elongation of its tracing, along with conduction abnormalities and contractile failure. These changes are blamed on the decreased expression of ion transporters and cell-cell communication ports at the SAN (i.e., HCN4, calcium and potassium channels, connexins 40, 45, and 46) which further promotes arrhythmias. Molecular analysis crystallized the RGS4 (regulator of potassium currents), mitochondrial thioredoxin-2 (reactive oxygen species; ROS scavenger), and the calcium-dependent calmodulin kinase II (CaMKII) as metabolic culprits of relaying the pathological remodeling of the SAN cells (SANCs) structure and function. A special attention is given to the oxidation of CaMKII and the generation of ROS that induce cell damage and apoptosis of diabetic SANCs. Consequently, the diabetic SAN contains a reduced number of cells with significant infiltration of fibrotic tissues that further delay the conduction of the AP between the SANCs. Failure of a genuine generation of AP and conduction of their derivative waves to the neighboring atrial myocardium may also occur as a result of the anti-diabetic regiment (both acute and/or chronic treatments). All together, these changes pose a challenge in the field of cardiology and call for further investigations to understand the etiology of the structural/functional remodeling of the SANCs in diabetes. Such an understanding may lead to more adequate therapies that can optimize glycemic control and improve health-related outcomes in patients with diabetes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Al Kury, Chacar, Alefishat, Khraibi and Nader.)

Purpose: The main aim of the study is to assess physicians' prescribing patterns using the World Health Organization (WHO) prescribing indicators among pediatric outpatient clinics, and to identify areas in need of intervention regarding the rational use of medicines among pediatric outpatients in Jordan., Methods: This is a descriptive observational cross-sectional study that was conducted at the outpatient pediatric clinics at Jordan University Hospital (JUH). During the study period, prescriptions were collected over a period of two months. Prescribing patterns were assessed using the five WHO drug prescribing indicators., Results: A total of 1011 prescriptions/encounters were assessed. More than half of the encounters were for male patients (n= 595, 58.9%), and the median age of patients was eight years (IQR = 7.9). The average number of drugs prescribed per encounter was 1.8 ± 1.3; however, a specific individual clinic, the respiratory clinic, witnessed an average of 2.1 drugs prescribed per encounter. All of the prescribed drugs were prescribed by generic name (100%). Only 47.7% of the drugs were from the essential drug list of the JUH. Overall, antibiotics were prescribed in 19.5% of the encounters, but at higher rates in some clinics such as respiratory clinics (50.8%). Injectables were prescribed in 9.5% of the 1011 encounters; however, they were prescribed at higher rates in endocrinology and neurology clinics, in 44.8% and 31.3% of encounters, respectively., Conclusion: This study revealed some adequate prescribing habits with an optimal prescribing pattern of generics and number of drugs per encounter among pediatric patients. However, the prescribing patterns of the essential drug list, antibiotics, and injectables, in specific clinics, failed to meet WHO standards. The findings of this study shed light on the need to establish national strategies to improve prescribing practices among the pediatric population., Competing Interests: The authors declare that they have no competing interests in this work., (© 2022 Aldabagh et al.)

This is a cross-sectional study that was conducted at Jordan University Hospital (JUH) to evaluate the appropriateness of Urinary Tract Infection (UTI) empiric treatment based on microbial culture data and susceptibility testing. All urine cultures requested for adult patients (≥18 years) admitted to JUH within the period from January 2019-July 2021 were reviewed and only those cultures with positive episodes of infection were considered. In this study, 6950 urine culture episodes were screened; among them, 34.5% ( n = 2400) revealed positive results. Among those patients with positive culture episodes, 1600 patients (66.7%) were discharged before the availability of culture results and were excluded. Of the remaining eligible 800 patients, 701 (87.6%) received empiric treatment. In 26.8% of the eligible cases ( n = 214), the prescribed empiric agents failed to have appropriate coverage of the identified pathogens, and in 14.6% of the cases ( n = 117) the identified microorganisms were reported as resistant to the prescribed empiric agents. Furthermore, only 13.4% of the patients ( n = 107) were appropriately treated for their UTI with empiric antibacterial agents. We were not able to judge the appropriateness of UTI treatment for one third ( n = 263, 32.9%) of the patients, because they did not have susceptibility reports performed. This study revealed an alarmingly high rate of inappropriate treatment of UTIs, which encourages the emergence of bacterial resistance and affects health-related outcomes negatively. Therefore, antimicrobial stewardship programs must be applied to optimize antibiotic consumption in hospital settings.

Introduction: The objective of this study was to investigate the psychosocial and cardiovascular markers in healthcare professionals during the COVID-19 pandemic., Methods: This was a STROBE compliant, blended exploratory study. Residents, staff physicians, nurses, and auxiliary healthcare professionals from both inpatient and outpatient medicine services were recruited using a planned random probability sample. The Maslach Burnout Inventory (MBI), Fuster-BEWAT score (FBS), and socio-demographic factors, as well as sleep quality, were studied. The correlations between burnout severity and cardiovascular risk were examined using multivariable linear regression models adjusted for confounding variables, such as sociodemographic and anthropometric characteristics., Results: The regression analysis with FBS as the outcome showed a negative association between cardiovascular health and emotional exhaustion [Coef.(95%CI): -0.029 (-0.048, -0.01), p = 0.002]. The higher the emotional exhaustion the lower the cardiovascular health. Further, the model showed a positive association between personal accomplishment and cardiovascular health [Coef.(95%CI): 0.045 (0.007, 0.082), p = 0.02]. Emotional exhaustion was significantly positive correlated with REM sleep and light average (Spearman's rank correlation: 0.37 and 0.35, respectively, with P < 0.05)., Conclusion: The data from this study show that healthcare practitioners who are with burnout and emotional exhaustion have an elevated cardiovascular risk, however, causality cannot be determined. As an adaptive response to stressful situations, REM sleep increases. The findings of this study may be relevant in creating preventive strategies for burnout and cardiovascular risk reduction or prevention., Clinical Trial Registration: [www.ClinicalTrials.gov], identifier [NCT04422418]., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Alameri, Aldaheri, Almesmari, Basaloum, Albeshr, Simsekler, Ugwuoke, Dalkilinc, Al Qubaisi, Campos, Almahmeed, Alefishat, Al Tunaiji and Baltatu.)

Background: Enhancing the contribution of practicing pharmacists into scientific evidence via practice-based research (PBR) is crucial in maintaining high-quality clinical practice and healthcare delivery. Involving community pharmacists in PBR can potentially can also help break barriers to the utilization of the current best evidence in everyday pharmacy practice. The impact of pharmacists' attitude towards PBR on their utilization of current best evidence in pharmacy practice is understudied., Objectives: The aim of the study was to investigate the impact of community pharmacists' attitudes toward PBR on their utilization of current best evidence, barriers for conducting PBR in clinical practice were also investigated., Methods: In this cross-sectional study, 169 community pharmacists working across Jordan filled a questionnaire to assess their attitudes towards PBR, barriers to PBR, and their utilization of the current best evidence in clinical practice., Results: Pharmacists in this study showed a positive attitude toward PBR (attitude mean score >3.5). A positive attitude towards PBR was associated with high utilization of the best current scientific evidence. We also investigated several barriers to PBR and their association with utilization those included; the lack of perceived benefits, lack of institutional support, and lack of self-engagements of community pharmacists to PBR. The lack of perceived benefit was found to be negatively associated with pharmacists' utilization of the current best scientific evidence., Conclusion: In this study, pharmacists' utilization of current best evidence was found to be significantly impacted by their attitude toward PBR. The current study findings highlight the importance of supporting, promoting, and facilitating PBR among community pharmacists which can potentially enhance their utilization of the current best evidence in their everyday pharmacy practice., Competing Interests: The authors have declared that no competing interests exist.

Global and local whole genome sequencing of SARS-CoV-2 enables the tracing of domestic and international transmissions. We sequenced Viral RNA from 37 sampled Covid-19 patients with RT-PCR-confirmed infections across the UAE and developed time-resolved phylogenies with 69 local and 3,894 global genome sequences. Furthermore, we investigated specific clades associated with the UAE cohort and, their global diversity, introduction events and inferred domestic and international virus transmissions between January and June 2020. The study comprehensively characterized the genomic aspects of the virus and its spread within the UAE and identified that the prevalence shift of the D614G mutation was due to the later introductions of the G-variant associated with international travel, rather than higher local transmissibility. For clades spanning different emirates, the most recent common ancestors pre-date domestic travel bans. In conclusion, we observe a steep and sustained decline of international transmissions immediately following the introduction of international travel restrictions., Competing Interests: All authors declare that they have no conflict of interest.

Elevated concentrations of interleukin-6 have been demonstrated to be an important key factor in COVID-19 host immune impairment. It represents an important prognostic factor of harm associated with COVID-19 infection by stimulating a vigorous proinflammatory response, leading to the so-called "cytokine storm". Therefore, immunomodulatory interventions targeting interleukin-6 receptor antagonism have been investigated as potential treatments to counterbalance the host immune dysregulation and to support the advantageous effects of corticosteroids. Tocilizumab is a recombinant humanized monoclonal antibody that has gained much interest during the COVID-19 pandemic as an interleukin-6 receptor antagonist. Various early observational studies have reported beneficial effects of tocilizumab. Moreover, consequent randomized controlled trials have subsequently shown significant positive results about tocilizumab efficacy and safety, focusing on outcomes like mortality, risk of intensive care unit admission, and the need for mechanical ventilation, while others presented conflicting findings. In this review, we first described the pathophysiology of COVID-19 infection while highlighting the role of interleukin-6. Furthermore, we also discussed the non-conclusive evidence about tocilizumab to be used as the standard of care therapy for all patients with COVID-19 pneumonia, as well as its beneficial effects in selected patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Abidi, El Nekidy, Alefishat, Rahman, Petroianu, El-Lababidi and Mallat.)

The heterogeneous phenotypes among patients with coronavirus disease 2019 (COVID-19) has drawn worldwide attention, especially those with severe symptoms without comorbid conditions. Immune responses to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the causative virus of COVID-19, occur mainly by the innate immune response via the interferon (IFN)-mediated pathways, and the adaptive immunity via the T lymphocyte and the antibody mediated pathways. The ability of the original Wuhan SARS-CoV-2 strain, and possibly more so with new emerging variants, to antagonize IFN-mediated antiviral responses can be behind the higher early viral load, higher transmissibility, and milder symptoms compared to SARS-CoV and are part of the continued clinical evolution of COVID-19. Since it first emerged, several variants of SARS-CoV-2 have been circulating worldwide. Variants that have the potential to elude natural or vaccine-mediated immunity are variants of concern. This review focuses on the main host factors that may explain the immune responses to SARS-CoV-2 and its variants in the context of susceptibility, severity, and preexisting immunity., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

This study aimed to evaluate health professionals' perceptions regarding the level of implementation of the Antimicrobials Stewardship (AMS) programs in Jordanian tertiary hospitals and to assess the perceived barriers to its implementation. During this cross-sectional study, a total of 157 healthcare providers agreed to participate (response rate 96.3%). Participants were asked to complete an electronic survey after meeting them at their working sites. Only 43.9% of the healthcare providers ( n = 69) reported having an AMS committee in their hospital settings. The results suggested that private hospitals have significantly better AMS implementation compared to public hospitals among four areas ( p ≤ 0.05). Moreover, the results showed that the most widely available strategies to implement AMS were infectious disease/microbiology advice ( n = 112, 71.3%), and treatment guidelines ( n = 111, 70.7%). Additionally, the study revealed that the main barrier to AMS implementation was the lack of information technology support ( n = 125, 79.6%). These findings could draw managers' attention to the importance of AMS and support the health care provider's practice of AMS in Jordanian tertiary hospitals by making the right decisions and the required modifications regarding the strategies needed for the implementation of AMS programs.

Introduction: Coronavirus disease 2019 (COVID-19) disease severity differs widely due to numerous factors including ABO gene-derived susceptibility or resistance. The objective of this study was to investigate the association of the ABO blood group and genetic variations of the ABO gene with COVID-19 severity in a heterogeneous hospital population sample from the United Arab Emirates, with the use of an epidemiological and candidate gene approach from a genome-wide association study (GWAS). Methods: In this cross-sectional study, a total of 646 participants who tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were recruited from multiple hospitals and population-based (quarantine camps) recruitment sites from March 2020 to February 2021. The participants were divided into two groups based on the severity of COVID-19: noncritical ( n = 453) and critical [intensive care unit (ICU) patients] ( n = 193), as per the COVID-19 Reporting and Data System (CO-RADS) classification. The multivariate logistic regression analysis demonstrated the association of ABO blood type as well as circulating anti-A antibodies and anti-B antibodies as well as A and B antigens, in association with critical COVID-19 hospital presentation. A candidate gene analysis approach was conducted from a GWAS where we examined 240 single nucleotide polymorphisms (SNPs) (position in chr9 : 136125788-136150617) in the ABO gene, in association with critical COVID-19 hospital presentation. Results: Patients with blood group O [odds ratio (OR): 0.51 (0.33, 0.79); p = 0.003] were less likely to develop critical COVID-19 symptoms. Eight alleles have been identified to be associated with a protective effect of blood group O in ABO 3'untranslated region (UTR): rs199969472 ( p = 0.0052), rs34266669 ( p = 0.0052), rs76700116 ( p = 0.0052), rs7849280 ( p = 0.0052), rs34039247 ( p = 0.0104), rs10901251 ( p = 0.0165), rs9411475 ( p = 0.0377), and rs13291798 ( p = 0.0377). Conclusion: Our findings suggest that there are novel allelic variants that link genetic variants of the ABO gene and ABO blood groups contributing to the reduced risk of critical COVID-19 disease. This study is the first study to combine genetic and serological evidence of the involvement of the ABO blood groups and the ABO gene allelic associations with COVID-19 severity within the Middle Eastern population., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Jelinek, Mousa, Alkaabi, Alefishat, Daw Elbait, Kannout, AlHumaidan, Selvaraj, Imambaccus, Weber, Uddin, Abdulkarim, Mahboub, Tay and Alsafar.)

The class I and class II Human Leucocyte Antigens (HLA) are an integral part of the host adaptive immune system against viral infections. The characterization of HLA allele frequency in the population can play an important role in determining whether HLA antigens contribute to viral susceptibility. In this regard, global efforts are currently underway to study possible correlations between HLA alleles with the occurrence and severity of SARS-CoV-2 infection. Specifically, this study examined the possible association between specific HLA alleles and susceptibility to SARS-CoV-2 in a population from the United Arab Emirates (UAE). The frequencies of HLA class I (HLA-A, -B, and -C) and HLA class II alleles (HLA-DRB1 and -DQB1); defined using Next Generation Sequencing (NGS); from 115 UAE nationals with mild, moderate, and severe SARS-CoV-2 infection are presented here. HLA alleles and supertypes were compared between hospitalized and non-hospitalized subjects. Statistical significance was observed between certain HLA alleles and supertypes and the severity of the infection. Specifically, alleles HLA-B*51:01 and HLA-A*26:01 showed a negative association (suggestive of protection), whilst genotypes HLA-A*03:01, HLA-DRB1*15:01, and supertype B44 showed a positive association (suggestive of predisposition) to COVID-19 severity. The results support the potential use of HLA testing to differentiate between patients who require specific clinical management strategies., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.)

The COVID-19 pandemic created a worldwide debilitating health crisis with the entire humanity suffering from the deleterious effects associated with the high infectivity and mortality rates. While significant evidence is currently available online and targets various aspects of the disease, both inflammatory and noninflammatory kidney manifestations secondary to COVID-19 infection are still largely underrepresented. In this review, we summarized current knowledge about COVID-19-related kidney manifestations, their pathologic mechanisms as well as various pharmacotherapies used to treat patients with COVID-19. We also shed light on the effect of these medications on kidney functions that can further enhance renal damage secondary to the illness., (© 2021. The Author(s).)

Background: Medication errors remained among the top 10 leading causes of death worldwide. Furthermore, a high percentage of medication errors are classified as medication discrepancies. This study aimed to identify and quantify the different types of unintentional medication discrepancies among hospitalized hypertensive patients; it also explored the predictors of unintentional medication discrepancies among this cohort of patients., Methods: This was a prospective observational study undertaken in a large teaching hospital. A convenience sample of adult patients, taking ≥4 regular medications, with a prior history of treated hypertension admitted to a medical or surgical ward were recruited. The best possible medication histories were obtained by hospital pharmacists using at least two information sources. These histories were compared to the admission medication orders to identify any possible unintentional discrepancies. These discrepancies were classified based on their severity. Finally, the different predictors affecting unintentional discrepancies occurrence were recognized., Results: A high rate of unintentional medication discrepancies has been found, with approximately 46.7% of the patients had at least one unintentional discrepancy. Regression analysis showed that for every one year of increased age, the number of unintentional discrepancies per patient increased by 0.172 (P = 0.007), and for every additional medication taken prior to hospital admission, the number of discrepancies increased by 0.258 (P= 0.003). While for every additional medication at hospital admission, the number of discrepancies decreased by 0.288 (P < 0.001). Cardiovascular medications, such as diuretics and beta-blockers, were associated with the highest rates of unintentional discrepancies in our study. Medication omission was the most common type of the identified discrepancies, with approximately 46.1% of the identified discrepancies were related to omission. Regarding the clinical significance of the identified discrepancies, around two-third of them were of moderate to high significance (n= 124, 64.2%), which had the potential to cause moderate or severe worsening of the patient´s medical condition., Conclusions: Unintentional medication discrepancies are highly prevalent among hypertensive patients. Medication omission was the most commonly encountered discrepancy type. Health institutions should implement appropriate and effective tools and strategies to reduce these medication discrepancies and enhance patient safety at different care transitions. Further studies are needed to assess whether such discrepancies might affect blood pressure control in hypertensive patients., (© 2021. The Author(s).)

Exposure to or ingestion of turpentine can alter the scent of urine, conferring it a flowery, violet-like scent. Turpentine's effect on urine was initially noticed after its use either as medicine or as a preservative in winemaking. Regardless of the source of exposure, the phenomenon requires metabolic conversion of turpentine component(s) to ionone, the molecule mainly responsible for the scent of violets.The purpose of this study was to identify the presence of ionone in the urine of rats that received β-pinene, and thus to demonstrate that the postulated conversion occurs.We treated rats intraperitoneally with normal saline (negative control), β-ionone (positive control), low-dose β-pinene (1/3 of LD50), and high-dose β-pinene (1/2 of LD50). Urine samples were collected up to 72 h after administration of the compounds, followed by gas chromatography/mass spectrometry identification of the presence of ionone.β-Ionone was found in the urine of rats exposed to both low and high doses of β-pinene. In contrast, α-ionone appears unlikely to have been formed in rats exposed to either low or high doses of β-pinene. β-pinene was converted to β-ionone, followed by partial excretion in the urine of rats. β-Ionone is a minor metabolite of β-pinene.

Purpose: The credibility and the reliability of Internet webpages to seek medication-related information is questionable. The main objective of the current study was to evaluate perception and experience of pharmacists with the use of Internet-based medication information by their patients., Methods: This is a cross-sectional descriptive study that was conducted to evaluate perception and experience of pharmacists with the use of Internet-based medication information by their patients. During the study period, 200 pharmacists were approached to participate in the study using a paper-based survey to assess their perceptions and current experience with the use of Internet-based medication information by their patients. Data were analyzed using descriptive statistics (mean/standard deviation for continuous variables, and frequency/percentages for qualitative variables). Also, simple linear regression was utilized to screen factors affecting pharmacists' perception scores of the use of Internet-based medication information., Results: Among 161 recruited pharmacists, the majority (n = 129, 80.1%) reported receiving inquiries from patients about Internet-based medication information within the last year. Among them, only 22.6% (n = 29) of pharmacists believed that Internet-based medication information is somewhat or very accurate. Unfortunately, only 24.2% (n = 31) of them stated that they always had enough time for their patient to discuss their Internet-based medication information. Regarding pharmacists' perception of the use of Internet-based medication information by their patients, more than half of the pharmacists (>50%) believe that Internet-based medication information could increase the patient's role in taking responsibility. On the other hand, 54.7% (n = 88) of the pharmacists believed that Internet-based medication information would contribute to rising the healthcare cost by obtaining unnecessary medications by patients. Finally, pharmacists' educational level was found to significantly affect their perception scores toward patient use of Internet-based medication information where those with higher educational level showed lower perception score (r = -0.200, P-value = 0.011)., Conclusion: Although pharmacists felt that usage of Internet-based data by patients is beneficial, they also have believed that it has a negative impact in terms of rising the healthcare cost, and it promotes unnecessary fear or concern about medications. We suggest that pharmacists be trained on principles of critical appraisal to become professional in retrieval information on the Internet that might improve their delivery of healthcare information and their recommendations to patients., Competing Interests: The authors have declared that no competing interests exist.

Objective: The aim of this study was to assess the impact of an online educational workshop on improving the knowledge, and perception of community pharmacists in Jordan towards the antimicrobial stewardship (AMS) and enhancing their ability to appropriately select correct antibiotic therapy., Methods: This is a pre-post study that was conducted in Jordan in December 2020. An electronic questionnaire was used to assess the awareness, perception of community pharmacists towards AMS, and their ability to appropriately select correct antibiotic before and after the educational workshop. The two-days' workshop was conducted on Zoom application. Analysis was conducted using Wilcoxon signed-rank test, McNemar's test using SPSS version 22., Results: During the study period, 100 community pharmacists attended the educational workshop. Pharmacists' knowledge was assessed prior to their participation which revealed a relatively good knowledge score with a median score of 6/10 (IQR = 4); their scores have improved significantly following the educational workshop with a median score of 7/10 (IOR = 2), p-value<0.001. Although one-third of the participants knew the definition of AMS prior to the workshop, almost half of the respondents (n = 56, 56%) knew the definition after the educational workshop. Regarding community pharmacist's ability to appropriately select correct antibiotic therapy, they showed a significant improvement in selecting the optimal antimicrobial for the virtual cases following the workshop (p-value < 0.05). Perceptions towards AMS were consistently positive before and after the workshop., Conclusion: This study revealed the benefit of AMS-focused workshops for improving community pharmacists' knowledge and appropriate antibiotic prescribing. Thus, efforts are required to implement more AMS educational workshops for community pharmacists., Competing Interests: The authors declare that there are no conflicts of interest in this work., (© 2021 Saleh et al.)

Lack of medication adherence among patients with dyslipidemia negatively affects health-related outcomes. This study aims to evaluate medication adherence; we also aim to investigate the predictors of non-adherence among patients with dyslipidemia in Jordan. Medication adherence was evaluated in a total of 228 dyslipidemia patients. The Beliefs about Medicines Questionnaire was also used to assess patients' beliefs about medications. The majority of the current study participants (73.2%) reported non-adherence to the prescribed medications. There were significant negative associations between medication adherence and concerns of prescription drug use (B = -0.41, p -value < 0.01), duration of dyslipidemia (B = -0.22, p -value < 0.01), and the number of medications (B = -0.64, p -value < 0.01). Positive associations were found between medication adherence and the necessity of prescription drug use (B = 0.43, p -value < 0.01), taking statin and fibrate (B = 2.04, p -value < 0.01), and moderate-intensity statin (B = 2.34, p -value < 0.01). As for patients' beliefs about medications, the item "My medicine to lower my cholesterol disrupted my life" had the highest mean (3.50 ± 0.99). This study revealed a low adherence rate to medication among patients with dyslipidemia. It also demonstrates modifiable factors such as beliefs regarding perceived risk, medication harms, treatment duration, and the number of medications associated with poor adherence in patients with dyslipidemia.

Coronavirus infections have been a part of the animal kingdom for millennia. The difference emerging in the twenty-first century is that a greater number of novel coronaviruses are being discovered primarily due to more advanced technology and that a greater number can be transmitted to humans, either directly or via an intermediate host. This has a range of effects from annual infections that are mild to full-blown pandemics. This review compares the zoonotic potential and relationship between MERS, SARS-CoV, and SARS-CoV-2. The role of bats as possible host species and possible intermediate hosts including pangolins, civets, mink, birds, and other mammals are discussed with reference to mutations of the viral genome affecting zoonosis. Ecological, social, cultural, and environmental factors that may play a role in zoonotic transmission are considered with reference to SARS-CoV, MERS, and SARS-CoV-2 and possible future zoonotic events., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer AV declared a shared affiliation with one of the authors JB, to the handling Editor at time of review., (Copyright © 2021 Jelinek, Mousa, Alefishat, Osman, Spence, Bu, Feng, Byrd, Magni, Sahibzada, Tay and Alsafar.)

Purpose: The study aim was to evaluate HRQOL and to explore the variables associated with poor HRQOL among patients with dyslipidemia in Jordan., Methods: The present study utilized the EQ-5D questionnaire which evaluates HRQOL in terms of mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Responses to the five dimensions were presented using the value set, which ranges from 1 for full health to - 0.594 for severe problems in all five dimensions. Multiple linear regression analysis was implemented to identify the variables that best predicted the total EQ-5D score and hence HRQOL in the study population., Results: The mean age of the 228 participants was 60.23 (SD = 10.64). The mean of the total EQ-5D score was 0.675 (SD = 0.14). Regression analysis identified necessity for dyslipidemia medication (B = 0.18, P < 0.01) and patients with controlled lipid profile (B = 0.28, P < 0.01) were positively associated with HRQOL, while having concerns about dyslipidemia medications (B = - 0.16, P < 0.01), number of medication (B = - 0.13, P = 0.02), duration of dyslipidemia (B = - 0.22, P < 0.01), receiving high-intensity statin (B = - 0.18, P < 0.01) or statin in combination with fibrate (B = - 0.15, P < 0.01) were associated with lower HRQOL., Conclusion: HRQOL has considerable scope for improvement in patients with dyslipidemia in Jordan. Improving dyslipidemia medications' beliefs and simplifying medication regimen by prescribing less medications, particularly for patients with longer disease duration and those on statin therapy, should be considered in future management programs aim at improving HRQOL in patients with dyslipidemia.

Background: Lipid control represents a cornerstone in the management of atherosclerotic cardiovascular disease (ASCVD). Nevertheless, little research has explored the factors associated with poor lipid control in patients with dyslipidaemia., Objective: The study aim was to investigate the variables associated with poor lipid control among patients with dyslipidaemia in Jordan., Method: In addition to socio-demographics, disease and medication-related variables, lipid profile including total cholesterol, LDL-C, HDL-C and triglyceride and other biomedical variables were collected for patients diagnosed with dyslipidaemia using hospital medical charts at three major outpatient clinics in Jordan. The validated 4-item medication adherence scale and the beliefs about medications questionnaire were used to evaluate medication adherence and medication beliefs among the study participants. The participants were classified to have controlled and uncontrolled dyslipidaemia using recent AHA guidelines. A stepwise forward conditional binary regression was conducted to explore the variables significantly and independently associated with dyslipidaemia control. A P-value of < .05 was considered statistically significant., Results: A total of 228 patients participated in the study. Most of the study participants (61%) were classified to have uncontrolled lipid profile and 60.1% of them were found to have ASCVD. Regression analysis revealed that increased necessity for dyslipidaemia medications increased the odds of dyslipidaemia control (OR = 1.14), whereas active smoking (OR = 0.42), low medication adherence (OR = 0.0.8) and the presence of ASCVD (odd ratio = 0.24) were significantly associated with poor dyslipidaemia control., Conclusion: Lipid profile has considerable scope for improvement in patients with dyslipidaemia in Jordan. Improving medication adherence by emphasising on medication necessity and simplifying the prescribed dosage regimen, particularly in smoking patients and those who have ASCVD, should be particularly considered in future clinical pharmacy service programmes aim at improving lipid control and health outcomes in patients with dyslipidaemia., (© 2021 John Wiley & Sons Ltd.)

The Center for Disease Control and Prevention and the World Health Organization issued a practical approach and Global Action Plan to control the threatening emerging antibacterial resistance. One of the main bases of this plan is the Antimicrobial Stewardship Program (ASPs). This study aimed to evaluate community pharmacists' awareness and perception towards antimicrobial resistance and ASPs in Jordan. Thus, a qualitative study was conducted through in-depth interviews with twenty community pharmacists. Convenience sampling was used in the study. Qualitative analysis of the data yielded four themes and eleven sub-themes. All the respondents showed a good understanding of the causes of antimicrobial resistance. The most important cause reported by them was the non-restricted prescription of antimicrobials. Most of the pharmacists believed that they are competent to provide ASPs, however, they believed that there are several barriers against the implementation of ASPs in community pharmacies in Jordan. Barriers demonstrated by the pharmacists, included organizational obstacles, resources obstacles, and personal obstacles. In conclusion, this study revealed several barriers against the implementation of ASPs in community pharmacies in Jordan. Incorporating ASPs in the community pharmacy settings requires proper pharmacist training, several academic disciplines team efforts, and good pharmacy practice of antimicrobial guidelines.

The hiccup (Latin singultus ) is an involuntary periodic contraction of the diaphragm followed by glottic closure, which can be a rare side effect of aripiprazole. In contrast to the structurally closely related aripiprazole, brexpiprazole was not associated with this particular adverse drug reaction. Having two very similar drugs that differ in their ability to induce hiccups represents a unique opportunity to gain insight into the receptors involved in the pathophysiology of the symptom and differences in clinical effects between aripiprazole and brexpiprazole. The overlap between maneuvers used to terminate paroxysmal supraventricular tachycardia and those employed to terminate bouts of hiccups suggests that activation of efferent vagal fibers can be therapeutic in both instances. Recent work seems to support a pivotal role for serotonin receptors in such vagal activation. It is unlikely that a unique receptor-drug interaction could explain the different effects of the examined drugs on hiccup. The different effect is most likely the consequence of several smaller effects at more than one receptor. Brexpiprazole is a highly affine (potent) α 2C antagonist and, therefore, also an indirect 5-HT 1A agonist. In contrast, aripiprazole is a partial 5-HT 1A agonist (weak antagonist) and an HT 3 antagonist. Activation of 5-HT 1A receptors enhances vagal activity while HT 3 blockade reduces it. Vagus nerve activation is therapeutic for hiccups. A definitive answer continues to be elusive., Competing Interests: The authors declare no conflict of interest., (© 2021 The Authors. Published by IMR Press.)

Background: The fact that pharmacists are in the front line of patients' care gives a great responsibility to focus on education and training of pharmacy students to build a 'patient-centered' clinicians. Unfortunately, pharmacy education in the developing countries, have been lagging behind actual practice delivered by pharmacists. This highlighted the need to evaluate the perceptions of undergraduate pharmacy students regarding their current pharmacy training practices and experiences., Methods: This is a cross-sectional study that was conducted in Jordan during the period from August 2018 to October 2018. During the study period, a questionnaire was distributed to pharmacy students to collect information regarding 1) pharmaceutical care services provided by them during their experiential training, 2) their perceptions towards training sites, 3) their perceptions of the outcomes of their training experience, 4) information about their training site and 5) their demographics characteristics., Results: A total of 202 pharmacy students responded to the questionnaire. The majority of them reported having the opportunity to dispense refill or new prescriptions (73.8%, n = 149), and conduct patient interviews (69.8%, n = 141, but they were not provided good opportunities to create electronic patient profiles using the information obtained (53.0%, n = 107), perform required dose calculations based on patient information (37.6%, n = 76), and interact with other healthcare professionals (34.6%, n = 70). In addition, students showed positive attitudes toward training sites, positive feedback about the outcomes of their training experience (median scores range between 4 and 5 for all statements (IQR = 1 for all))., Conclusion: Students showed positive feedback about the outcomes of their training experience, but they felt that the selected training sites do not have adequate resources to meet their training competencies. Memorandums of understanding development is needed to specify the purpose of training and define the responsibility for both parties of the training process.

Sneezing (sternutatio) is a poorly understood polysynaptic physiologic reflex phenomenon. Sneezing has exerted a strange fascination on humans throughout history, and induced sneezing was widely used by physicians for therapeutic purposes, on the assumption that sneezing eliminates noxious factors from the body, mainly from the head. The present contribution examines the various mixtures used for inducing sneezes (remedia sternutatoria) over the centuries. The majority of the constituents of the sneeze-inducing remedies are modulators of transient receptor potential (TRP) channels. The TRP channel superfamily consists of large heterogeneous groups of channels that play numerous physiological roles such as thermosensation, chemosensation, osmosensation and mechanosensation. Sneezing is associated with the activation of the wasabi receptor, (TRPA1), typical ligand is allyl isothiocyanate and the hot chili pepper receptor, (TRPV1), typical agonist is capsaicin, in the vagal sensory nerve terminals, activated by noxious stimulants.

Introduction: The coronavirus disease 2019 (COVID-19) pandemic has created new and unpredictable challenges for healthcare systems. Healthcare professionals are heavily affected by this rapidly changing situation, especially frontline healthcare professionals who are directly engaged in the diagnosis, treatment, and care of patients with COVID-19 and may experience psychological burdens. The objective of this study is to explore the evolution of psychosocial, cardiovascular, and immune markers in healthcare professionals with different levels of exposure to the COVID-19 pandemic. Methods and Analysis: This is a STROBE compliant, blended, exploratory study involving online and onsite approaches that use wearable monitoring. A planned random probability sample of residents, staff physicians, nurses, and auxiliary healthcare professionals will be recruited. The study sample will be stratified by exposure to the COVID-19 pandemic. As a first step, recruitment will be conducted online, with e-consent and using e-surveys with Maslach Burnout Inventory, Fuster-BEWAT score, and sociodemographic characteristics. Onsite visits will be planned for the second step where participants will receive a wearable setup that will measure heart rate, actimetry, and sleep quality monitoring, which will be used together with blood sampling for immune biomarkers. Steps 1 and 2 will then be repeated at 2-3 months, and 6 months. Power BI and Tableau will be used for data visualization, while front-end data capture will be used for data collection using specific survey/questionnaires, which will enable data linkage between e-surveys, internet of things wearable devices, and clinical laboratory data. Clinical Trial Registration: ClinicalTrials.gov; Identifier: NCT04422418., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2020 Al Tunaiji, Al Qubaisi, Dalkilinc, Campos, Ugwuoke, Alefishat, Aloum, Ross, Almahmeed and Baltatu.)

The term ionone is derived from "iona" (Greek for violet) which refers to the violet scent and "ketone" due to its structure. Ionones can either be chemically synthesized or endogenously produced via asymmetric cleavage of β-carotene by β-carotene oxygenase 2 (BCO2). We recently proposed a possible metabolic pathway for the conversion of α-and β-pinene into α-and β-ionone. The differences between BCO1 and BCO2 suggest a unique physiological role of BCO2; implying that β-ionone (one of BCO2 products) is involved in a prospective biological function. This review focuses on the effects of ionones and the postulated mechanisms or signaling cascades involved mediating these effects. β-Ionone, whether of an endogenous or exogenous origin possesses a range of pharmacological effects including anticancer, chemopreventive, cancer promoting, melanogenesis, anti-inflammatory and antimicrobial actions. β-Ionone mediates these effects via activation of olfactory receptor (OR51E2) and regulation of the activity or expression of cell cycle regulatory proteins, pro-apoptotic and anti-apoptotic proteins, HMG-CoA reductase and pro-inflammatory mediators. α-Ionone and β-ionone derivatives exhibit anti-inflammatory, antimicrobial and anticancer effects, however the corresponding structure activity relationships are still inconclusive. Overall, data demonstrates that ionone is a promising scaffold for cancer, inflammation and infectious disease research and thus is more than simply a violet's fragrance.

Objectives: Hypertension (HTN) is a major risk factor for cardiovascular disease, it is an epidemic health problem with 1 billion people affected worldwide. Limited studies have examined the impact of HTN on physical, psychological and social functioning of HTN patients. Furthermore, little is known about factors that impair these domains among these patients. Thus, the aim of the present study is to assess health-related quality of life (HRQoL) and to explore predictors of poor HRQoL in patients with HTN in Jordan., Methods: Hypertensive patients visiting cardiology and internal medicine departments were recruited from three major hospitals in Jordan. Patients' Socio-demographics and medical data were collected via direct patient encounters and medical records. The validated Arabic version of EQ-5D tool was used to assess HRQoL. Simple linear regression was performed to explore the factors associated with poor HRQoL., Results: The mean score of the EQ-5D index of the 300 participants was 0.732 (SD = 0.29, range from -0.594 to 1.0). While extreme problems were only reported by 10% of the participants, most of them reported "some problems" through the five dimensions with the highest percentage (43.3%) for mobility dimension. Gender, monthly income, number of medical conditions, number of medications, number of HTN medications, duration of HTN and the presence of any atherosclerotic cardiovascular diseases were significantly associated with the EQ-5D index value (P-value <.05)., Conclusions: The current study highlights factors that negatively impact HRQoL in patients with HTN. Such findings should provide useful information for future pharmaceutical care intervention programmes aimed at improving HRQoL and other health outcomes in patients with HTN., (© 2020 John Wiley & Sons Ltd.)

Background: Measurement of the degree of adherence is a key element for the evaluation of treatment efficacy and safety; thus, adherence plays an important role in clinical research and practice. The aim of this study was to investigate medication adherence in children with inflammatory bowel disease (IBD) utilizing a multimethod assessment approach. A further aim was to examine factors that can influence adherence within this population., Methods: Medication adherence in 47 children (age range 3 to 17 years) with IBD in three centers in Northern Ireland and Jordan was assessed via subjective (parent and child versions of the Medication Adherence Report Scale (MARS) specific questionnaire) and objective methods, that is, high-performance liquid chromatography (HPLC) determination of the 6-mercaptopurine (6-MP) and azathioprine (AZA) metabolites in packed red blood cell samples taken during a clinic visit. Beliefs about prescribed medicines were also assessed in parents/guardians using the Beliefs about Medicines Questionnaire (BMQ)., Results: An overall nonadherence to AZA/6-MP therapy in children with IBD was found to be 36.17% (17 out of 47 patients were classified as nonadherent using at least one of the assessment methods). A total of 41 patients (91.1%) were classified as adherent to AZA or 6-MP using the blood sampling, while adherence rates using the MARS questionnaire completed by children and parents/guardians were 60.6% and 72.7%, respectively. The latter provides a more longitudinal measure of adherence. Child self-reported nonadherence rates were significantly higher than parent/guardian reported rates ( p =0.013). Binary logistic regression analysis identified age to be independently predictive of adherence, with adolescents (children aged ≥ 13 years old) more likely to be classified as nonadherent. Regarding the BMQ, when parental/guardian necessity beliefs outweighed concerns, that is, higher scores in the necessity-concern differential (NCD), adolescents were more likely to be classified as adherent., Conclusion: Results provide evidence for ongoing adherence challenges in the paediatric population with IBD. It is recommended that parents/guardians (particularly of older children) and older children themselves, should receive enhanced counselling and education about their prescribed medicines., Competing Interests: The authors declare that there are no conflicts of interest., (Copyright © 2020 Mervat M. Alsous et al.)