Implications of potential clinically relevant interactions between COVID-19 vaccines and concomitant medications.

COVID-19 was announced as a global pandemic in 2020. Several types of COVID-19 vaccines are available such as mRNA vaccines, adenovirus vector vaccines, and protein subunit or inactivated virus vaccines. Vaccines are often administered in patients with chronic diseases who are likely to be treated with several drugs. A growing number of clinical observations indicated the possibility of interactions between COVID-19 vaccines and drugs. A hyperinflammatory state may spark significant imbalances in drug metabolism that may result in the alteration of drug pharmacokinetics and therapeutic response. Furthermore, interactions may result in additive or antagonistic or synergistic vaccine immune response. Information about COVID-19 vaccine-drug interactions is needed by physicians and pharmacists to make rational drug-use decisions. In this review, several individual and categorical evidence-based potential COVID-19 vaccine-drug interactions of clinical importance are described. Vigilance is needed to detect previously unreported COVID-19 drug interactions and to further assess known interactions. The clinical significance of which is not fully determined. Evidence suggests that adverse events to some drugs are rare after COVID-19 vaccination and their possibility should not affect vaccination of patients at risk. Clinicians prescribing medications should be aware of the likely risk of interaction with COVID-19 vaccines and may benefit from taking into account present recommendations of the best measures to avoid consequences of such interactions to preserve vaccine efficacy and patient safety.

The Potential of Natural Products in the Management of COVID-19.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was identified as the novel coronavirus that caused a life-threatening viral illness (COVID-19) at the end of 2019. Within a short period of time, this virus spread leading to tremendous loss of life and economic damage. Medications to treat this virus are not yet established, and the process of implementing new strategies for medications is time-consuming. Recent clinical studies revealed the abandonment of the most promising candidates, who later became potential leads. Only through comprehensive study for safety and efficacy the medications, which have already received approval, be repurposed for use in different therapeutic purposes. Natural sources are being used arbitrarily as antiviral drugs and immunity boosters because there are no clear therapies on the horizon. It has long been known that most natural compounds have strong antiviral properties including SARS-CoV-2. Natural remedies have been demonstrated to have inhibitory effects on MERS-CoV and SARS-CoV infections. The non-structural proteins of the virus, such as PLPRO, MPRO, and RdRp, as well as structural proteins like the spike (S) protein, have been demonstrated to have a substantial binding affinity and an inhibitory effect by a variety of natural products, according to in silico research. The virus also demonstrates to be a legitimate target for therapeutic development since it makes use of the host cell's transmembrane ACE2 receptor. In this chapter, we highlight on the potential of alkaloids, phenolic and polyphenolic compounds, flavonoids, terpenoids, cardiac glycosides, and natural products from marine sources against the human coronavirus via different mode of actions. Most of the studied metabolites act either by inhibiting virus replication or by blocking the active site of the protein of the virus either in silico or ex vivo. This review serves as a topic for further study and to discover other secondary metabolites for COVID-19 management.

A comprehensive review on lipid nanocarrier systems for cancer treatment: fabrication, future prospects and clinical trials.

Over the last few decades, cancer has been considered a clinical challenge, being among the leading causes of mortality all over the world. Although many treatment approaches have been developed for cancer, chemotherapy is still the most utilized in the clinical setting. However, the available chemotherapeutics-based treatments have several caveats including their lack of specificity, adverse effects as well as cancer relapse and metastasis which mainly explains the low survival rate of patients. Lipid nanoparticles (LNPs) have been utilized as promising nanocarrier systems for chemotherapeutics to overcome the challenges of the currently applied therapeutic strategies for cancer treatment. Loading chemotherapeutic agent(s) into LNPs improves drug delivery at different aspects including specific targeting of tumours, and enhancing the bioavailability of drugs at the tumour site through selective release of their payload, thus reducing their undesired side effects on healthy cells. This review article delineates an overview of the clinical challenges in many cancer treatments as well as depicts the role of LNPs in achieving optimal therapeutic outcomes. Moreover, the review contains a comprehensive description of the many LNPs categories used as nanocarriers in cancer treatment to date, as well as the potential of LNPs for future applications in other areas of medicine and research.

Suppressive effects of thymoquinone on the initiation stage of diethylnitrosamine hepatocarcinogenesis in rats.

Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related death globally. Chemoprevention is the most effective technique for reducing HCC incidence. Thymoquinone (TQ), the main bioactive constituent of Nigella sativa, exhibits anti-inflammatory and antineoplastic activities against various cancers. Therefore, TQ was tested as an inhibitor of the initial phase of diethylnitrosamine (DEN)-induced HCC in rats. Twenty-four male Wistar albino rats were randomly placed into four equal groups. Group 1 received saline and acted as the negative control; Group 2 received TQ; Group 3 received DEN; and Group 4 received TQ for 7 days and DEN on the 8th day. After 24 h of fasting, blood samples were taken from the slaughtered rats. Additionally, each rat's liver was dissected and separated into two halves for histological and biochemical investigation. DEN-induced hepatotoxicity was detected by elevated hepatic enzymes and HCC biomarkers reduced antioxidant and proapoptotic statuses. DEN administration caused a significant increase in the levels of glutathione, superoxide dismutase, malondialdehyde, caspase-3, alpha-fetoprotein (AFP), AFPL3, glypican 3, and the expression of BAX. However, DEN significantly decreased glutathione peroxidase, catalase, and CYP2E1 and the expression of BCl-2. Furthermore, it caused histological changes and showed a strong positive GSH S-transferase P expression in the hepatic parenchyma. Pretreatment with TQ prevented the histopathological and most of the biochemical changes and improved the antioxidant status. TQ supplementation appears to suppress the development of DEN-initiated liver cancer by reducing oxidative stress, activating the intrinsic mitotic apoptosis pathway, and retaining the antioxidant enzymes.

Enhanced antitumor activity of combined methotrexate and histone deacetylase inhibitor valproic acid on mammary cancer in vitro and in vivo.

Histone deacetylase inhibitors (HDACIs) act as antiproliferative agents by promoting differentiation and inducing apoptosis. Valproic acid (VPA) is a HDACI that shows promising chemotherapeutic effect in a number of tumor cells. The present study aimed to investigate the inhibitory effect of VPA on the viability of mammary cancer cells and its enhancing effect with methotrexate (MTX) in vitro and in vivo. Treatment with VPA or MTX alone induced concentration-dependent cytotoxic effects in two breast cancer cell lines. Valproic acid increased significantly the cytotoxicity of MTX three times against MCF7. Valproic acid addition to MTX, however, did not produce any significant changes on MTX cytotoxicity against MDA-MB231. VPA (150 and 200 mg/kg) significantly inhibited the growth of Ehrlich ascites carcinoma (EAC) and solid Ehrlich carcinoma (SEC) tumor mouse models and improved results were achieved for tumor inhibition when VPA was combined with MTX (1 and 2 mg/kg) in vivo. The antitumor activity was not associated with a significant increase in toxicity or mice mortality rate. All these findings suggest that the combination of MTX and VPA may have clinical and (or) adjuvant therapeutic application in the treatment of mammary cancer.

Thymoquinone Suppresses Angiogenesis in DEN-Induced Hepatocellular Carcinoma by Targeting miR-1-3p.

Hepatocellular carcinoma (HCC) is characterized by its high vascularity and metastasis. Thymoquinone (TQ), the main bio-active constituent of Nigella sativa, has shown anticancer and hepatoprotective effects. TQ's anticancer effect is mediated through miRNA regulation. miR-1-3p plays a significant role in various cancers but its role in HCC invasiveness remains poorly understood. Bio-informatics analysis predicted that the 3'-UTR of TIMP3 is a target for miR-1-3p; Rats were equally divided into four groups: Group 1, the negative control; Group 2 received TQ; Group 3 received DEN; and Group 4 received DEN after pretreatment with TQ. The expression of TIMP3, MMP2, MMP9, and VEGF in rats' liver was determined immunohistochemically. RT-qPCR was used to measure the miR-1-3p level in rats' liver, and TIMP3, MMP2, MMP9, and VEGF in the HepG2 cells after being transfected with miR-1-3p mimic or inhibitor; In rats pretreated with TQ, a decreased expression of MMP2, MMP9 and VEGF, and increased expression levels of TIMP3 and miR-1-3p were detected. Treating the HepG2 cells with miR-1-3p mimic led to the upregulation of TIMP3 and downregulation of MMP2, MMP9, and VEGF, and showed a significant delay in wound healing; These results suggested that the anti-angiogenic effect of TQ in HCC may be mediated through the regulation of miR-1-3p.

Pharmacogenomics and COVID-19: clinical implications of human genome interactions with repurposed drugs.

The outbreak of Coronavirus disease 2019 (COVID-19) has evolved into an emergent global pandemic. Many drugs without established efficacy are being used to treat COVID-19 patients either as an offlabel/compassionate use or as a clinical trial. Although drug repurposing is an attractive approach with reduced time and cost, there is a need to make predictions on success before the start of therapy. For the optimum use of these repurposed drugs, many factors should be considered such as drug-gene or dug-drug interactions, drug toxicity, and patient co-morbidity. There is limited data on the pharmacogenomics of these agents and this may constitute an obstacle for successful COVID-19 therapy. This article reviewed the available human genome interactions with some promising repurposed drugs for COVID-19 management. These drugs include chloroquine (CQ), hydroxychloroquine (HCQ), azithromycin, lopinavir/ritonavir (LPV/r), atazanavir (ATV), favipiravir (FVP), nevirapine (NVP), efavirenz (EFV), oseltamivir, remdesivir, anakinra, tocilizumab (TCZ), eculizumab, heme oxygenase 1 (HO-1) regulators, renin-angiotensin-aldosterone system (RAAS) inhibitors, ivermectin, and nitazoxanide. Drug-gene variant pairs that may alter the therapeutic outcomes in COVID-19 patients are presented. The major drug variant pairs that associated with variations in clinical efficacy include CQ/HCQ (CYP2C8, CYP2D6, ACE2, and HO-1); azithromycin (ABCB1); LPV/r (SLCO1B1, ABCB1, ABCC2 and CYP3A); NVP (ABCC10); oseltamivir (CES1 and ABCB1); remdesivir (CYP2C8, CYP2D6, CYP3A4, and OATP1B1); anakinra (IL-1a); and TCZ (IL6R and FCGR3A). The major drug variant pairs that associated with variations in adverse effects include CQ/HCQ (G6PD; hemolysis and ABCA4; retinopathy), ATV (MDR1 and UGT1A1*28; hyperbilirubinemia; and APOA5; dyslipidemia), NVP (HLA-DRB1*01, HLA-B*3505 and CYP2B6; skin rash and MDR1; hepatotoxicity), and EFV (CYP2B6; depression and suicidal tendencies).

Cross-Sectional Study on Awareness and Knowledge of COVID-19 Among Senior pharmacy Students.

Extraordinary actions have been implemented in an effort to control the rapid spread of the ongoing COVID-19 epidemic in Egypt. People's adherence to control measures is influenced by their knowledge, attitudes and practices towards the disease. Therefore, in the present study we assessed pharmacy senior students' knowledge, attitudes and practices towards the COVID-19 pandemic. An online questionnaire was created and it consisted of 12 questions testing their knowledge about COVID-19 clinical characteristics, transmission routes and prevention and control steps. Among senior pharmacy students (n = 238), 70% were females and 63% were living in greater Cairo. Their main source of information included social media (70%), published articles (48%) and television (48%). The overall correct knowledge score was 83%. Most of the students displayed a good COVID-19 knowledge level (72.5% of the students). The students were least informed when trying to answer questions about hyper-coagulation, as a major cause for death in patients with severe COVID-19, and about the timings on the necessity to wear masks. Assessment of students' attitudes and practices towards COVID-19 reflected that 87% of them were confident that health care teams and scientists could win the fight against the virus. In addition, 72% of students agreed that COVID-19 will be controlled successfully. The greater the students' knowledge, the more confident they felt that COVID-19 will be controlled successfully (OR 2.2, 95% confidence interval [CI] 1.03-4.72). Good behavioral practice towards COVID-19 control was confirmed when 87% of students answered that they didn't go out to any crowded place. Females were 3.6 times (95% confidence interval [CI] 1.03-3.11) more likely to avoid going out than males. Bad behavioral practice became evident when approximately 50% of students admitted that they did not wear masks when they left their house. Therefore, more efforts should be taken to protect future pharmacists from this pandemic.

EVESOR, a model-based, multiparameter, Phase I trial to optimize the benefit/toxicity ratio of everolimus and sorafenib.

AIM: This novel multiparameter Phase I study aimed to optimize doses/dosing schedules of everolimus and sorafenib drug combination, based on modeling/simulation (NCT01932177). PATIENTS & METHODS: About 26 patients with solid tumors were treated in four different dosing schedules. Everolimus once daily + sorafenib twice daily were given continuously in arms A and B, and intermittently in arms C (alternating every other week) and D (everolimus continuous and sorafenib 3 days on/4 days off). RESULTS: Continuous schedules exhibited higher toxicity risks than intermittent schedules (64.1 vs 35.9%; p < 0.0001), and trends for lower disease control rates (80 vs 100%). No significant pharmacokinetic interaction was identified. CONCLUSION: Feasibility of EVESOR trial is demonstrated. Intermittent schedules might provide better tolerance and efficacy than continuous schedules.

Implementation of clinical pharmacy services in a pediatric dialysis unit.

BACKGROUND: End-stage renal disease patients on hemodialysis are on complex drug regimens consisting of multiple medications, many of which are administered in several doses per day. Consequently, such patients are at high risk for developing drug therapy-related problems (DTRPs). The aim of this study was to detect DTRPs in children undergoing hemodialysis and to assess and evaluate the impact of interventions by the clinical pharmacist on the clinical outcome of children undergoing hemodialysis. METHODS: Fifty hemodialysis outpatients were randomly divided into two groups (25 each): the control group and the test group. During the 9-month study period, patients in the control group received the usual medical care, and those in the test group received pharmaceutical care 3 times weekly in addition to the usual medical care. RESULTS: After 9 months of pharmaceutical care implementation, the test group showed a significant decline in systolic and diastolic blood pressure (p = 0.0001), serum phosphorus level (p = 0.006) and parathyroid hormone level (p = 0.001) versus their baseline values and versus the control. The serum Ca*P product level of the test group decreased (p = 0.001) after intervention versus baseline. Serum calcium level significantly increased in test group (p = 0.02) and decreased in the control group (p = 0.001) versus the respective baseline values. Satisfaction with the renal treatment significantly improved in the test group (p = 0.0001) versus the control group after 9 months of pharmaceutical care implementation based on Renal Treatment Satisfaction Questionnaire scores. CONCLUSIONS: Pharmacist-initiated pharmaceutical care improved the satisfaction and biochemical findings of patients on hemodialysis.

Correlation of Genetic Polymorphism of CYP3A5 to Cyclophosphamide Efficacy and Toxicity in Rhabdomyosarcoma Pediatric Egyptian Cancer Patients.

OBJECTIVES: Rhabdomyosarcoma (RMS) accounts for 50% of soft tissue sarcomas and 7% of pediatric malignancies. Cyclophosphamide (CPA) is the cornerstone of therapy and is a prodrug that is activated by the highly polymorphic drug-metabolizing enzyme CYP3A5. We aim to examine the possible CYP3A5 polymorphism association with CPA efficacy, survival outcomes, and toxicity in Egyptian pediatric RMS patients. METHODS: The three non-functional SNPs, CYP3A5*3 rs776746 (C_26201809_30), CYP3A5*6 rs10264272 (C_30203950_10), and CYP3A5*7 rs41303343 (C_32287188_10) were genotyped by real-time PCR. We conducted a cohort retrospective study of 150 pediatric RMS patients treated with CPA-based first-line treatment to analyze the association between these genotypes and CPA efficacy/toxicities in RMS patients. KEY FINDINGS: The frequency of having normal, intermediate, and poor metabolizers was 4.7%, 34%, and 61.3%, respectively. There was an association between these different phenotypes, genotypes, and CPA efficacy/toxicity. Hemorrhagic cystitis and pancytopenia were present in all patients, while nephrotoxicity incidence was 87.3%. There was a notable difference in the occurrence of hemorrhagic cystitis among CYP3A5 intermediate metabolizers *1/*3, *1/*6, and poor metabolizers *3/*3, *3/*6 with a significance level of p<0.05. Neither CYP3A5*7 polymorphism nor *6/*6 genotype was identified in our study. CONCLUSION: Our results demonstrate that CYP3A5*3 (rs776746) and CYP3A5*6 (rs10264272) have a great association with CPA efficacy and toxicity in RMS patients.

Efficacy and Toxicity of Vincristine and CYP3A5 Genetic Polymorphism in Rhabdomyosarcoma Pediatric Egyptian Patients.

BACKGROUND: Rhabdomyosarcoma (RMS) is a rare cancer that develops in soft tissue, particularly skeletal muscle tissue and occasionally hollow organs like the bladder or uterus. Vincristine (VCR) is the main therapy used in treatment of RMS, it is an alkaloid produced from vinca and it is one of the most commonly prescribed drugs in pediatric oncology for the treatment of a number of tumors. The CYP3A5 enzyme is responsible for vincristine metabolism. The effect of CYP3A5 genetic polymorphism on the efficacy and toxicity of VCR on RMS patients still needs further research. METHODS: Genotyping for CYP3A5 SNPs rs776746, rs10264272 and rs41303343 was performed using Taqman Real-Time PCR assays in a retrospective cohort study of 150 RMS pediatric patients treated with vincristine. The relationship between these genotypes and RMS survival was then examined. RESULTS: We found that patients with CYP3A5*3/*3 had the highest incidence of vincristine-induced neuropathy reaching 61.3%. Patients with CYP3A5*1/*3, CYP3A5*3/*6 and the normal metabolizers with CYP3A5*1/*1 had frequencies of 22%, 10.7%, and 4.7%. patients with the lowest frequency of 1.3% were those with the CYP3A5*1/*6 genotype. There was no correlation between the genotypes of CYP3A5*3, CYP3A5*6, CYP3A5*7, and RMS survival. Initial risk, metastasis, response, convulsions, unsteady gait and hepatotoxicity grade had a significant effect on overall survival with p<0.05. CONCLUSION: CYP3A5*1/*1 have less severe vincristine-induced neuropathy than CYP3A5 *1/*3, CYP3A5 *1/*6 and CYP3A5 *3/*3, CYP3A5 *3/*6. There is a significant influence of CYP3A5 mutation on neuropathy grade and assist of ADL as a part of neurotoxicity.

The clinical outcome of adjuvant therapy with black seed oil on intractable paediatric seizures: a pilot study.

AIM: To evaluate the effect of black seed oil, as add-on treatment to antiepileptic drugs (AEDs), on seizure frequency and severity as well as oxidative stress in intractable epilepsy patients. METHODS: A prospective, randomised, single-blinded, controlled, crossover pilot study. Five healthy children were included as controls. Thirty intractable epileptic children were randomly assigned to either Group I or II. Group I received placebo for four weeks, followed by a two-week washout period, and subsequently black seed oil for four weeks. Group II received the same intervention but in the reverse order. All patients received AEDs throughout the study period. Prior to allocation, all patients underwent a neurological assessment and evaluation of oxidative stress markers; total antioxidant capacity (TAC) and malondialehyde (MDA). Patients were assessed at Weeks 4 and 10 for oxidative stress markers and seizure frequency and severity. RESULTS: At baseline, both groups (I, II) had significantly lower serum TAC levels relative to healthy controls (p=0.007), while MDA levels were unchanged. After the 4-week period of black seed oil administration, there was no significant difference between the two groups with regards to seizure frequency, severity, or oxidative stress markers (TAC and MDA; p>0.05). Eight patients had >50% reduction in seizure frequency/severity after black seed oil versus placebo. CONCLUSION: Children with intractable epilepsy show evidence of oxidative stress. Administration of 40-80 mg/kg/day of black seed oil as add-on therapy did not alter either oxidative stress markers or seizure frequency or severity in intractable epileptic patients.

Protective effects of butylated hydroxytoluene on the initiation of N-nitrosodiethylamine-induced hepatocellular carcinoma in albino rats.

Diethylnitrosamine (DEN), a hepatocarcinogen, is found in a variety of smoked and fried foods and was reported to be hepatotoxic in mice. Butylated hydroxytoluene (BHT) is a potent antioxidant used in cosmetic formulations and as a food additive and preservative. As a result, BHT was studied as a potential inhibitor in the early stages of diethylnitrosamine (DEN)-induced HCC. Male Wistar albino rats (n = 24) were equally subdivided. Group 1 was the negative control; Group 2 and 3 administered BHT and DEN, respectively; Group 4 received BHT followed by DEN. Blood samples and rat livers were taken for biochemical and histological investigation. Hepatotoxicity was assessed by increased liver enzymes and HCC indicators, along with reduced antioxidant and pro-apoptotic factors. AFP, AFPL3, GPC3, GSH, SOD, MDA, CASP3 and BAX expression increased significantly after DEN treatment. DEN also reduced GPx, CAT, and CYP2E1 activity, and BCl-2 expression. Moreover, in the hepatic parenchyma, the DEN caused histological alterations. Pretreatment with BHT enhanced antioxidant status while preventing histopathological and most biochemical alterations. BHT pretreatment suppresses DEN-initiated HCC by decreasing oxidative stress, triggering intrinsic mitotic apoptosis, and preventing histopathological changes in liver tissue.

Probiotics mixture and taurine attenuate L-arginine-induced acute pancreatitis in rats: Impact on transient receptor potential vanilloid-1 (TRPV-1)/IL-33/NF-κB signaling and apoptosis.

Acute pancreatitis (AP) is an inflammatory disorder of acinar cells. It may develop into severe chronic pancreatitis with a significant mortality rate. The current study aimed to assess the therapeutic effect of a Lactobacillus (LAB) mixture against rat AP. Six groups were created including control, taurine (300 mg/kg; i.p.) for 7 days, LAB mixture for 7 days, L-arginine (2.5 g/kg; i.p.) 2 doses with 1 h interval on 1st day, L-arginine+taurine, and L-arginine+LAB. Serum amylase and lipase activities were measured. Pancreatic tissue was used for histopathological examination, oxidative stress biomarkers including malondialdehyde (MDA) and reduced glutathione (GSH), and inflammatory biomarkers including myeloperoxidase (MPO) and interleukin (IL)-33 assessment. qRT-PCR was used for transient receptor potential vanilloid-1 (TRPV-1) investigation and Western blot analysis for measuring nuclear factor kappa-B (NF-κBp65) and the apoptosis biomarker; caspase-3. Taurine and LAB reduced lipase and significantly ameliorated induced oxidative stress by normalizing MDA and GSH contents. They counteracted inflammation by reducing MPO, IL-33, NF-κBp65, and TRPV-1. In addition, taurine and LAB counteracted apoptosis as proved by reduced caspase-3 expression. Taken together, these findings indicate that taurine and the use LAB mixture can mitigate AP by L-arginine via influencing TRPV-1/IL-33/NF-κB signaling together with exhibiting potent antioxidant and anti-inflammatory effects.

Ameliorative effects of resveratrol on liver injury in streptozotocin-induced diabetic rats.

The objective of this study was to investigate the ameliorative property and potential mechanism of resveratrol (RVT) in a dose of 10 mg/kg for 15 consecutive days against liver injury in streptozotocin-induced diabetic rats. Diabetic rats significantly (P < 0.05) exhibited liver injury manifested by increased aspartylaminotransferase, alanine aminotransferase, and bilirubin; disturbed liver weight to body weight; and confirmed by hematoxylin and eosin staining. Liver from diabetic rats exhibited significant increase in malondialdehyde level and significant decrease in reduced glutathione, glutathione-S-transferase, quinone reductase, catalase, and superoxide dismutase. Diabetic rats showed significant disturbance in serum lipid profile. Treatment with RVT significantly (P < 0.05) abrogated diabetes-induced perturbation in these parameters and liver histology. These data suggest that RVT treatment is associated with promising hepatoprotective effect against diabetes-induced liver damage via reduction of serum glucose level and oxidative damage and improving serum lipid profile.

Safety and Effectiveness of COVID-19 Vaccines: Results from a Cross-Sectional Survey among Staff, Workers and Students at an Egyptian University.

Mass vaccination is the most effective strategy against the spread of the COVID-19 pandemic. However, concerns about the vaccine's safety and effectiveness remain a huge obstacle to vaccine acceptance. The aim of the present study was to explore different COVID-19 vaccine outcomes, including the development of adverse events and/or COVID-19 infection following COVID-19 vaccination. A cross-sectional study was conducted by distributing an online survey targeting staff and students at the British university in Egypt. A total of 637 participants fully completed the survey. Of these, 609 (95.6%) participants received the COVID-19 vaccine. Only 12.6% of the total vaccinated participants reported COVID-19 infection after vaccination. Of these, only 2.8% reported having severe symptoms while 9.9% reported having no or mild symptoms. The most common side effects reported after the first vs. second dose were headache (36.3% vs. 14.6%), tiredness and fatigue (26.9% vs. 10.7), and fever (25.6% vs. 6.7%). In conclusion, the present study explored different COVID-19 vaccine outcomes where the overall incidence of side effects is higher after the first dose than after the second dose. There is a relationship between COVID-19 vaccines' side effects and gastrointestinal disorders, gender, and the type of COVID-19 vaccine. Post-vaccination symptoms were more frequently reported in women compared to men and more frequent with viral vector vaccines compared to other types. The effectiveness of different types of COVID-19 vaccines was confirmed by the lower incidence rate of post-vaccination COVID-19 infection.

An evaluation of relugolix/estradiol/norethindrone acetate for the treatment of heavy menstrual bleeding associated with uterine fibroids in premenopausal women.

INTRODUCTION: Uterine Fibroids (UFs) are the most predominant benign tumor in women who are coming of reproductive age, and causes intense economic load priced in billions of US dollars. Historically, surgery has been the main definitive treatment, albeit less attractive nowadays, especially for women with future fertility plans. Therefore, studies to explore the pharmacological treatment options are increasing especially as those that are currently available are limited for short-term use only. AREAS COVERED: This drug evaluation features the clinical results from previous and ongoing studies of relugolix, in combination with the add back therapy of estradiol (E2) and norethindrone acetate (NETA), as a novel, orally administered, nonpeptide antagonist of gonadotropin-releasing hormone (GnRH) for the management of heavy menstrual bleeding (HMB) in premenopausal women with UFs. EXPERT OPINION: The combination of relugolix/E2/NETA is an encouraging, well-tolerated and noninvasive pharmacological option for UFs patients. Relugolix induced a concentration-dependent decrease in HMB. However, it should be used with hormonal add-back therapy (E2+ NETA) to avoid induced hypoestrogenic side effects, importantly bone mineral density loss. Moreover, symptoms will likely resume shortly after the termination of the relugolix combination administration.

Reducing prescribing errors in the paediatric intensive care unit: an experience from Egypt.

AIM: To investigate the impact of different measures, implemented by clinical pharmacists, on prescribing error rates in a paediatric intensive care unit (PICU) in Cairo, Egypt. METHODS: We performed a pre-post study of prescribing errors in a 12 bed PICU. We utilized a chart review method for the detection of prescribing errors. The rate and potential severity of prescribing errors were determined before and then after the implementation of the medication error reducing measures. These measures included the use of a new structured medication order chart, physician education, provision of dosing assists and physician performance feedback. RESULTS: We evaluated 1417 medication orders for 139 patients preintervention and 1097 orders for 101 patients postintervention. Of preintervention orders, 1107 (78.1%) had at least one prescribing error. The intervention resulted in significant reduction in prescribing error rate to 35.2% postintervention (p < 0.001). The intervention resulted also in a significant reduction in the rate of potentially severe errors from 29.7% preintervention to 7% postintervention (p < 0.001) and the rate of potentially moderate errors from 39.8% preintervention to 24.2% postintervention (p < 0.001). Besides, rates of all types of prescribing errors were declined to different degrees as a result of the intervention. CONCLUSION: Clinical pharmacists' activities, focusing on improving physician-nurse communication, physician drug knowledge and awareness of errors, were shown effective in reducing the rate of prescribing errors and their potential severity in a PICU.

Thymoquinone: A Promising Natural Compound with Potential Benefits for COVID-19 Prevention and Cure.

COVID-19 has caused a major global health crisis, as excessive inflammation, oxidation, and exaggerated immune response in some sufferers can lead to a condition known as cytokine storm, which may progress to acute respiratory distress syndrome (ARDs), which can be fatal. So far, few effective drugs have emerged to assist in the treatment of patients with COVID-19, though some herbal medicine candidates may assist in the fight against COVID-19 deaths. Thymoquinone (TQ), the main active ingredient of black seed oil, possesses antioxidant, anti-inflammatory, antiviral, antimicrobial, immunomodulatory and anticoagulant activities. TQ also increases the activity and number of cytokine suppressors, lymphocytes, natural killer cells, and macrophages, and it has demonstrated antiviral potential against a number of viruses, including murine cytomegalovirus, Epstein-Barr virus, hepatitis C virus, human immunodeficiency virus, and other coronaviruses. Recently, TQ has demonstrated notable antiviral activity against a SARSCoV-2 strain isolated from Egyptian patients and, interestingly, molecular docking studies have also shown that TQ could potentially inhibit COVID-19 development through binding to the receptor-binding domain on the spike and envelope proteins of SARS-CoV-2, which may hinder virus entry into the host cell and inhibit its ion channel and pore forming activity. Other studies have shown that TQ may have an inhibitory effect on SARS CoV2 proteases, which could diminish viral replication, and it has also demonstrated good antagonism to angiotensin-converting enzyme 2 receptors, allowing it to interfere with virus uptake into the host cell. Several studies have also noted its potential protective capability against numerous chronic diseases and conditions, including diabetes, hypertension, dyslipidemia, asthma, renal dysfunction and malignancy. TQ has recently been tested in clinical trials for the treatment of several different diseases, and this review thus aims to highlight the potential therapeutic effects of TQ in the context of the COVID-19 pandemic.