Clinical Presentations and Risk Factors of Gastrointestinal Bleeding in the Emergency Department: A Multicenter Retrospective Study.

BACKGROUND AND AIMS: Gastrointestinal bleeding is a major healthcare burden and is associated with significant morbidity and mortality. This study aimed to assess the prevalence, clinical presentation, and risk factors of patients presenting with gastrointestinal bleeding in the emergency department. MATERIALS AND METHODS: This retrospective study was conducted in two tertiary care hospitals in Riyadh, Saudi Arabia. The medical records of patients who presented to the emergency department with gastrointestinal bleeding between January 2010 and January 2020 were reviewed. Patients aged 18 years or older, with gastrointestinal bleeding (upper or lower) regardless of underlying cause, lifestyle, location of bleeding, health status, or medication use, were included. Demographic characteristics, initial vital signs, medical history, physical examination findings, comorbidities, medications, laboratory and radiological investigations, cause and stage of liver disease, management, and complications were recorded. Endoscopic findings and management of the bleeding site were collected according to the presenting symptoms. RESULTS: A total of 760 patients were included. The mean age was 62.7 ± 17.8 years, and 61.4% were males. The most common comorbidities at presentation were hypertension (54.1%), diabetes mellitus (51.2%), and ischemic heart disease (18.2%). The origins of the bleeding were lower gastrointestinal in 52% and upper gastrointestinal in 48% of patients. CONCLUSIONS: Lower gastrointestinal bleeding was found to be more common than upper gastrointestinal bleeding. Hemorrhoids, polyps, diverticular disease, and colonic ulcers were the major risk factors for lower gastrointestinal bleeding. In contrast, upper gastrointestinal bleeding was predominantly caused by esophageal varices, gastritis, and peptic ulcers.

Green Synthesis of Uncoated and Olive Leaf Extract-Coated Silver Nanoparticles: Sunlight Photocatalytic, Antiparasitic, and Antifungal Activities.

The circular economy, which attempts to decrease agricultural waste while also improving sustainable development through the production of sustainable products from waste and by-products, is currently one of the main objectives of environmental research. Taking this view, this study used a green approach to synthesize two forms of silver nanoparticles: coated silver nanoparticles with olive leaf extract (Ag-olive) and uncoated pure silver nanoparticles (Ag-pure), which were produced by the calcination of Ag-olive at 550 °C. The extract and the fabricated nanoparticles were characterized by a variety of physicochemical techniques, including high-performance liquid chromatography (HPLC), thermal gravimetric analysis (TGA), X-ray diffraction (XRD), scanning electron microscopy (SEM), and transmission electron microscopy (TEM). Adult ticks (Hyalomma dromedarii) (Acari: Ixodidae) were used in this study to evaluate the antiparasitic activity of synthesized nanoparticles and extract. Furthermore, the antifungal activity was evaluated against Aspergillus aculeatus strain N (MW958085), Fuserium oxysporum (MT550034), and Alternaria tenuissiuma (MT550036). In both antiparasitic and antifungal tests, the as-synthesized Ag-olive showed higher inhibition activity than Ag-pure and olive leaf extract. The findings of this research suggest that Ag-olive may be a powerful and eco-friendly antiparasitic and antifungal agent. Ag-pure was also evaluated as a photocatalyst under sunlight for the detoxification of Eri-chrome-black T (EBT), methylene blue (MB), methyl orange (MO), and rhodamine B (RhB).

Phytosynthesis via wasted onion peel extract of samarium oxide/silver core/shell nanoparticles for excellent inhibition of microbes.

The aqueous onion peel extract (OPE) was used to synthesize silver nanoparticles (Ag-onion), samarium oxide nanoparticles (Sm2O3-onion), and silver/samarium oxide core/shell nanoparticles (Ag@Sm2O3-onion). The produced nanoparticles were characterized by thermal gravimetric analysis (TGA), infrared spectra (FT-IR), absorption spectra (UV-Vis), energy band gap, X-ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD), zeta potential, and transmission electron microscopy (TEM). OPE and NPs were tested for the disinfection of some water microbes. XRD analysis exhibited an amorphous structure of samarium oxide in both Sm2O3-onion and Ag@ Sm2O3-onion. The isolated bacteria from the water sample were Bacillus subtilis (OQ073500) and Escherichia coli (MW534699), while the isolated fungi were Alternaria brassicae (MZ266540), Aspergillus flavus (MT550030), Aspergillus penicillioides (MW957971), Pythium ultimum (MW830915), Verticillium dahlia (MW830379), Fusarium acuminatum (MZ266538), Candida albicans (MW534712), and Candida parapsilosis (MW960416). High levels of antimicrobial activity were seen in both the nanoparticles and the aqueous onion peel extract. Based on experimental results, Ag@Sm2O3 demonstrated the highest activity as an effective disinfectant, indicating the effectiveness of the modification process.

Photocatalytic Degradation of Rhodamine-B and Water Densification via Eco-Friendly Synthesized Cr2O3 and Ag@Cr2O3 Using Garlic Peel Aqueous Extract.

The purification and densification of wastewater play an important role in water recycling, especially if the materials used in water recycling are other types of recycled waste. Therefore, considering this view in this study, the biosynthesis of silver-decorated chromium oxide nanoparticles utilizing a wasted Allium sativum (garlic) peel extract is investigated. The aqueous extract of garlic peel (GPE) was treated with silver nitrate, chromium nitrate, and a mixture of silver nitrate and chromium nitrate to synthesize silver nanoparticles (Ag-garlic), chromium oxide nanoparticles (Cr2O3-garlic), and silver-decorated chromium oxide nanoparticles (Ag@Cr2O3-garlic), respectively. The synthesized nanoparticles were elucidated via thermal gravimetric analysis (TGA), infrared spectra (FT-IR), absorption spectra (UV-Vis), scanning electron microscopy (SEM), energy dispersive X-ray analysis (EDX), X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), and transmission electron microscopy (TEM). Antimicrobial activity studies were conducted against waterborne germs, bacterial strains (Bacillus subtilis, Enterococcus faecium, Escherichia coli, and Pseudomonas aeruginosa), and fungal strains (Alternaria porri, Aspergillus flavus, Aspergillus niger, Fuserium oxysporum, and Trichoderma longibrachiatum) and showed significant levels of antimicrobial activity. The results revealed that Ag@Cr2O3 significantly improved antimicrobial activity due to their synergistic effect. The photocatalytic activity of nanoparticles was assessed using Rhodamine B dye (5 ppm) under solar irradiation. Cr2O3-garlic exhibited the best activity as a photocatalyst among the studied nanoparticles, with 97.5% degradation efficiency under optimal conditions.

Design and construction of novel pyridine-pyrimidine hybrids as selective COX-2 suppressors: anti-inflammatory potential, ulcerogenic profile, molecular modeling and ADME/Tox studies.

NSAIDs represent a mainstay in pain and inflammation suppression, and their actions are mainly based on inhibiting COX-1 and COX-2 enzymes.Due to the adverse effects of these drugs, especially on the stomach and heart, scientists efforts have been directed to manufacture selective COX-2 without cardiovascular side effects and with minimal effects on the stomach. The cardiovascular side effects are thought to be related to the chemical composition rather than mechanism of action of these drugs.Novel pyridopyrimidines, 9a-j, were prepared and their chemical structures were confirmed by NMR, mass and IR Spectra, and elemental analysis. The effect of the 9a-j compounds on COX-1 and COX-2 was assessed and it was found that 2-hydrazino-5-(4-methoxyphenyl)-7-phenyl-3H-pyrido[2,3-d)pyrimidin-4-one (9d) was the most potent COX-2 inhibitor (IC50 = 0.54 uM) compared to celecoxib (IC50 = 1.11 uM) with selectivity indices of 6.56 and 5.12, respectively.The in vivo inhibition of paw edema of novel compounds 9a-j was measured using carrageenan-induced paw edema method, and that 2-hydrazino-5-(4-methoxyphenyl)-7-phenyl-3H-pyrido[2,3-d)pyrimidin-4-one (9d) showed the best inhibitory activity in comparison with the other compounds and celecoxib.The gastroprotective effect of the potent derivatives 9d, 9e, 9f, 9 g and 9h was investigated. 2-Hydrazino-5-(4-methoxyphenyl)-7-phenyl-3H-pyrido[2,3-d)pyrimidin-4-one (9d) and 7-(chlorophenyl)-hydrazino-5-(4-methoxyphenyl)-3H-pyrido[2,3-d)pyrimidin-4-one (9e) showed ulcer indices comparable to celecoxib (1 and 0.5 vs 0.5, respectively). Docking studies were carried out and they confirmed the mechanistic action of the designed compoundsCommunicated by Ramaswamy H. Sarma.

Dual activity of indolin-2-ones containing an arylidene motif: DNA and BSA interaction.

Applying a multistep approach, novel indolin-2-ones (IND) that possess an arylidene motif have been synthesized. Eight compounds were chosen for different biological tests (antimicrobial and cytotoxicity). IND containing 2-thienyl (4h) fragment have been found to exhibit good antimicrobial activity against B. cereus. Molecules that have 3-aminophenyl (4d) or 2-pyridyl (4g) groups have shown the best antifungal activities against all tested fungi. These compounds have also been noticed as promising pharmaceuticals against MCF-7 cancer cell lines. Experimental outcomes from the investigation of the interaction of 4d with DNA implied its moderate binding to DNA (KSV = 1.35 × 104 and 3.05 × 104 M-1 for EB and Hoechst binder, respectively). However, considerably stronger binding of 4d to BSA has been evidenced (Ka = 6.1 × 106 M-1). In summary, IND that contains m-aminobenzylidene fragment (4d) exhibits a good dual biological activity making it a promising candidate for further investigation in the drug discovery sector.

Evaluation of Outreach of Community Pharmacists in Public Health Services in Al-Jouf Region of Saudi Arabia: Findings and Implications.

BACKGROUND: Diversifying the conventional role of community pharmacists from dispensing to involvement in public health services could help in optimized patient care and ultimately good health practices. The current study aimed to ascertain the involvement of community pharmacists, barriers to involvement, their preparedness towards the provision of public health services in the future, and effective strategies to improve their existing role, especially in remote areas of the Kingdom of Saudi Arabia. METHODS: A cross-sectional study was conducted in the Al-Jouf region of Saudi Arabia (KSA), between January to April 2023. A convenient sampling technique was used to recruit community pharmacists (CPs). A self-designed and validated questionnaire was used for data collection. The relative importance index (RII) was utilized to rank the barriers to participation in public health services. Data were subjected to statistical analysis using SPSS. RESULTS: This study recruited 119 participants (mean age: 32.2 ± 7.9; male gender: 67.2%). Of these, 91.6% were involved in the provision of public health services at community pharmacies. Majority of CPs (n = 114/119, 95.8%) provided drug use-related written information to the patients, and the least practiced service was screening of dyslipidemia (n = 81; 68.1%). According to RII, the major barrier was the lack of time given by patients (RII: 0.812). Overall, the majority of the pharmacists (n = 94/119; 79%) were willing to provide public health services. Most of the CPs reported that empowerment through education and awareness (n = 100/119; 84%) is most effective strategy to enhance the involvement of pharmacists in public health services. CONCLUSIONS: Findings of the present study underscored the adequate participation of community pharmacists in public health activities. Further studies are required in other remote regions of KSA to get a clear insight into the overall participation of community pharmacists in public health services and generalize the findings.

Appraisal of anti-inflammatory and immunomodulatory potential of ramipril against Freund's adjuvant-provoked arthritic rat model.

Because of evident role of renin-angiotensin system in the etiology of rheumatoid arthritis, the current study's objective was to assess the anti-arthritic efficacy of ramipril through CFA-instigated arthritic model. The drug has been shown to have anti-inflammatory potential. CFA-instigated arthritic model assessed the anti-arthritic efficacy of ramipril by estimating different parameters, including paw volume, arthritic index scoring, haematological and biochemical attributes, histological and radiographic analyses, and various cytokines level. Ramipril significantly (p < 0.001) reduced paw volume and the arthritic index especially at the dose of 4mg/kg. The biochemical and haematological changes were likewise restored to normal by ramipril administration with an increase in anti-inflammatory cytokines while reducing pro-inflammatory cytokines level. Ramipril's ability to prevent arthritis by preserving the normal architecture of arthritis-induced joints is further supported by radiographic and histological investigation. The study's findings demonstrated ramipril's considerable anti-arthritic activity. To identify the precise mechanism of action, however, thorough mechanistic studies are still needed.

Synthesis, Characterization, and Biological Evaluation of Meldrum's Acid Derivatives: Dual Activity and Molecular Docking Study.

In the presented study, eight novel Meldrum's acid derivatives containing various vanillic groups were synthesized. Vanillidene Meldrum's acid compounds were tested against different cancer cell lines and microbes. Out of nine, three showed very good biological activity against E. coli, and HeLa and A549 cell lines. It is shown that the O-alkyl substituted derivatives possessed better antimicrobial and anticancer activities in comparison with the O-acyl ones. The decyl substituted molecule (3i) has the highest activity against E. coli (MIC = 12.4 µM) and cancer cell lines (HeLa, A549, and LS174 = 15.7, 21.8, and 30.5 µM, respectively). The selectivity index of 3i is 4.8 (HeLa). The molecular docking study indicates that compound 3i showed good binding affinity to DNA, E. coli Gyrase B, and topoisomerase II beta. The covalent docking showed that 3i was a Michael acceptor for the nucleophiles Lys and Ser. The best Eb was noted for the topoisomerase II beta-LYS482-3i cluster.

Biochemical association of regulatory variant of KLF14 genotype in the pathogenesis of cardiodiabetic patients.

Background and purpose: The study focuses on examining the relationship between a single nucleotide polymorphism (SNP) in KLF14 rs4731702 and risk of type 2 diabetes mellitus (T2DM) and dyslipidemia in different ethnic populations. The purpose of this study was to evaluate the association between KLF14 rs4731702 and serum lipid profile and to determine the frequency distribution of KLF14 rs4731702 among T2DM and cardiometabolic patients. Methods: A total of 300 volunteers were recruited, consisting of three groups: 100 healthy individuals, 100 individuals diagnosed with T2DM, and 100 individuals diagnosed with cardiometabolic disorders. Biochemical analysis of blood samples was conducted to assess various biomarkers related to glycemic control and lipid profile. This involved measuring levels of glucose, triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and ApoA1. Genotyping analysis was performed to investigate KLF14 rs4731702 polymorphism. The Tetra ARMS-PCR method was employed for genotyping analysis. Results: The results of biochemical profiling revealed a significant association between altered glycemic biomarkers and lipid profile in diseased patients compared to healthy participants. The frequencies of KLF14 rs4731702 alleles and genotypes were compared between the control group and T2DM group. A statistically significant difference was observed, indicating a potential association between KLF14 rs4731702 and T2DM. In the dominant inheritance model of KLF14 rs4731702 SNP, a statistically significant difference [odds ratio (95% confidence interval)] of 0.56 (0.34 -0.96) was found between the control and T2DM subjects. This suggests that the presence of certain genotypes influences the risk of T2DM. In T2DM patients, individuals carrying the C allele exhibited compromised insulin sensitivity, decreased HDL-C and ApoA1 levels, and increased serum glucose, TG, and LDL-C concentrations. Conversely, TT genotype carriers demonstrated increased levels of HDL-C and ApoA1, lower insulin resistance, serum glucose, LDL-C, and TG levels. Conclusion: The study's findings indicate that dyslipidemia in T2DM patients is associated with reduced KLF14 functionality due to CC and CT genotypes, leading to insulin resistance and an increased risk of cardiovascular diseases. Additionally, risk of KLF14 rs4731702 polymorphism was found to increase with age and was more prevalent in female than in male individuals. These insights contribute to understanding genetic factors influencing the development and progression of T2DM and dyslipidemia in different ethnic populations.

COVID-19 self-medication treatment: Media's adverse effect based on people's level of education.

OBJECTIVE: Self-medication has become a major concern among nonmedical professionals during the treatment of COVID-19. Such concerns have been attributed to the adverse effect of information shared via media outlets. Here, a survey was undertaken among nonhealthcare professionals to find out the adverse effect of media on self-medication for treating COVID-19. METHODS: A questionnaire-based survey was conducted electronically among nonmedical professionals (270 respondents). The questionnaire comprised three main components: demographic, education, and factor for self-medication. Statistical analysis of the data was made using analysis of variance to determine the degree of agreement between the response of participants with education below and above graduation. RESULTS AND CONCLUSION: Most of the respondents agreed that they get information about the COVID-19 medicines from different media. However, most of them do not visit the reliable source like World Health Organization (WHO) website to get information about COVID-19. The respondents were aware of the usage of medications such as Remdesvir, azithromycin, vitamins, herbal preparations, paracetamol, and cetirizine for COVID-19. The usage of herbal preparation may be due to their promotion in the media as over the counter drugs (OTC) products. It has been proposed to create more awareness and warning signs for the patients in and around pharmacy and hospital. Media campaign to create awareness for the prevention of COVID-19 spread should also be added with a caution line not to use any medication for treatment without prior consultation with physician. The matter of concern is that only a small fraction of the respondents follow WHO website to get information regarding COVID-19, which mandates to create awareness among the public regarding the role of WHO in healthcare. A significant agreement was noted between below graduates and post-graduates regarding questions such as visiting WHO website and the safety of taking medicine without consulting physician. Media is a contributing factor to self-medication, and measures of caution are highly imperative.

Enalapril attenuated CFA provoked arthritic manifestation by modulating proinflammatory and anti-inflammatory cytokine network.

Enalapril with documented anti-inflammatory potential was evaluated in current investigation to explore its anti-arthritic efficacy. For anti-arthritic evaluation of enalapril, CFA-instigated arthritic model was employed after which various parameters comprising paw volume, body weight, arthritic index, hematological and biochemical parameters, radiographic analysis and level of various cytokines were estimated. Enalapril demonstrated significant (p˂0.001) anti-arthritic activity by suppressing paw volume, arthritic index while preserved CFA instigated weight loss. Likewise, enalapril also normalized the hematological and biochemical alterations, suppressed the level of proinflammatory cytokines with elevation of anti-inflammatory cytokines. Radiographic and histopathological analysis also further validates the anti-arthritic attribute of enalapril where enalapril preserved the normal architecture of arthritis induced joints. Outcomes of the study pointed out a notable anti-arthritic activity of enalapril. However detailed mechanistic studies are still required to point out the exact mechanism of action.

Biochemical Association of MTHFR C677T Polymorphism with Myocardial Infarction in the Presence of Diabetes Mellitus as a Risk Factor.

Myocardial infarction (MI) is a cardiovascular disease that occurs due to the blockage of the coronary artery. Subsequently, cardiac muscles receive a lower oxygen supply, which leads to the death of cardiac muscles. The etiology of MI is linked to various environmental, occupational, and genetic factors. Various studies have been conducted on the polymorphism of genes involved in MI. Previous studies have shown that different variants of the methylene tetrahydrofolate reductase (MTHFR) gene are involved in causing MI by altering the metabolism of folate and homocysteine. However, the genetic polymorphism of MTHFR C677T (rs1801133) and its association with MI in the presence of diabetes mellitus (DM) as a risk factor still needs to be investigated. This study recruited 300 participants who were divided into three groups, i.e., the control, MI, and MI-DM. The blood samples collected from the study participants were subjected to various biochemical tests and their clinical parameters were monitored. MTHFR C677T (rs1801133) genotyping was performed by Tetra ARMS PCR using predetermined primers. The MTHFR C677T (rs1801133) polymorphism was associated with MI in the presence of DM as a risk factor among the participants. The MTHFR C677T (rs1801133) T/T homozygous genotype was found to be significant among MI patients in the presence of DM as a risk factor.

Phthalazone tethered 1,2,3-triazole conjugates: In silico molecular docking studies, synthesis, in vitro antiproliferative, and kinase inhibitory activities.

New phthalazone tethered 1,2,3-triazole derivatives 12-21 were synthesized utilizing the Cu(I)-catalyzed click reactions of alkyne-functionalized phthalazone 1 with functionalized azides 2-11. The new phthalazone-1,2,3-triazoles structures 12-21 were confirmed by different spectroscopic tools, like IR; 1H, 13C, 2D HMBC and 2D ROESY NMR; EI MS, and elemental analysis. The antiproliferative efficacy of the molecular hybrids 12-21 against four cancer cell lines was evaluated, including colorectal cancer, hepatoblastoma, prostate cancer, breast adenocarcinoma, and the normal cell line WI38. The antiproliferative assessment of derivatives 12-21 showed potent activity of compounds 16, 18, and 21 compared to the anticancer drug doxorubicin. Compound 16 showed selectivity (SI) towardthe tested cell lines ranging from 3.35 to 8.84 when compared to Dox., that showed SI ranged from 0.75 to 1.61. Derivatives 16, 18 and 21 were assessed towards VEGFR-2 inhibitory activity and result in that derivative 16 showed the potent activity (IC50 = 0.123 µM) in comparison with sorafenib (IC50 = 0.116 µM). Compound 16 caused an interference with the cell cycle distribution of MCF7 and increased the percentage of cells in S phase by 1.37-fold. In silico molecular docking of the effective derivatives 16, 18, and 21 against vascular endothelial growth factor receptor-2 (VEGFR-2) confirmed the formation of stable protein-ligand interactions within the pocket.

The anticancer and EGFR-TK/CDK-9 dual inhibitory potentials of new synthetic pyranopyrazole and pyrazolone derivatives: X-ray crystallography, in vitro, and in silico mechanistic investigations.

Treatment options for the management of breast cancer are still inadequate. This inadequacy is attributed to the lack of effective targeted medications, often resulting in the recurrence of metastatic disorders. Cumulative evidence suggests that epidermal growth factor receptor (EGFR-TK) and cyclin-dependent kinases-9 (CDK-9) overexpression correlates with worse overall survival in breast cancer patients. Pyranopyrazole and pyrazolone are privileged options for the development of anticancer agents. Inspired by this proven scientific fact, we report here the synthesis of two new series of suggested anticancer molecules incorporating both heterocycles together with their characterization by IR, 1H NMR, 13C NMR, 13C NMR-DEPT, and X-ray diffraction methods. An attempt to get the pyranopyrazole-gold complexes was conducted but unexpectedly yielded benzylidene-2,4-dihydro-3H-pyrazol-3-one instead. This unexpected result was confirmed by X-ray crystallographic analysis. All newly synthesized compounds were assessed for their anti-proliferative activity against two different human breast cancer cells, and the obtained results were compared with the reference drug Staurosporine. The target compounds revealed variable cytotoxicity with IC50 at a low micromolar range with superior selectivity indices. Target enzyme EGFR-TK and CDK-9 assays showed that compounds 22 and 23 effectively inhibited both biological targets with IC50 values of 0.143 and 0.121 µM, respectively. Molecular docking experiments and molecular dynamics simulation were also conducted to further rationalize the in vitro obtained results.Communicated by Ramaswamy H. Sarma.

Covalent Organic Frameworks (COFs) as Multi-Target Multifunctional Frameworks.

Covalent organic frameworks (COFs), synthesized from organic monomers, are porous crystalline polymers. Monomers get attached through strong covalent bonds to form 2D and 3D structures. The adjustable pore size, high stability (chemical and thermal), and metal-free nature of COFs make their applications wider. This review article briefly elaborates the synthesis, types, and applications (catalysis, environmental Remediation, sensors) of COFs. Furthermore, the applications of COFs as biomaterials are comprehensively discussed. There are several reported COFs having good results in anti-cancer and anti-bacterial treatments. At the end, some newly reported COFs having anti-viral and wound healing properties are also discussed.

A Pediatric Case of Spinal Intradural Epidermoid Cyst: A Rare Encounter.

Intradural epidermoid cysts of the spine are rare congenital lesions. Their etiology is thought to stem from ectodermal remnants during embryonic development. They result in a diverse clinical presentation, often marked by an insidious onset and variable neurological deficits. Timely diagnosis is crucial for optimizing patient outcomes. We present the case of a 10-year-old male child presenting a six-month history of worsening back pain, intermittent leg weakness, and urinary incontinence. The physical examination revealed tenderness over the lower thoracic and lumbar spine, lower limb weakness, hyperreflexia, and sensory deficits. The diagnostic work-up, including cerebrospinal fluid analysis and magnetic resonance imaging, confirmed the presence of an intradural epidermoid cyst in the lumbosacral region. Surgical excision resulted in complete resection, with subsequent improvement in neurological deficits. This pediatric case underscores the importance of maintaining a high index of suspicion for unexplained neurological deficits. Characteristic imaging findings played a pivotal role in the diagnosis, guiding successful surgical intervention and achieving favorable outcomes.

Effect of Pirfenidone on Risk of Pulmonary Fibrosis in COVID-19 Patients Experiencing Cytokine Storm.

OBJECTIVES: Severe stages of COVID-19 infection have been associated with the excessive discharge of pro-inflammatory mediators such as cytokines, resulting in lung deterioration, which progresses rapidly to lung fibrosis leading to acute respiratory distress syndrome. In this investigation, the efficacy and safety of the novel antifibrotic and anti-inflammatory agent, Pirfenidone, were assessed in COVID-19 patients with pulmonary fibrosis secondary to cytokine storm. In this randomized controlled study, we assigned 100 adult COVID-19 patients cytokine storm and admitted to the intensive care isolation unit into either pirfenidone added to the standard therapy (n = 47), or the standard protocol only (n = 53). High-resolution computed tomography of the chest was performed in all patients to evaluate fibrotic lesions and their progression. The results showed that the percentage of patients who developed pulmonary fibrosis during cytokine storm onset in the pirfenidone group relative to the standard group was 29.8% and 35.8%, respectively, with no significant difference between the two groups; while there was a significant increase in the proportion of patients discharged from the isolation unit with pulmonary fibrosis without progression in fibrotic lesions in the pirfenidone group compared to the standard group (21.3% and 5.7%, respectively). Furthermore, there was a significant difference concerning liver enzyme elevation and GIT disturbance incidences in the studied groups (p = 0.006 and 0.01, respectively). Our findings show that Pirfenidone inhibits fibrosis advancement in COVID-19 patients with pulmonary fibrosis and is associated with hepatotoxicity and GI distress. It may be beneficial in patients with mild to moderate COVID-19-induced pulmonary fibrosis; however, additional research is necessary.

Surveillance of Side Effects after Two Doses of COVID-19 Vaccines among Patients with Comorbid Conditions: A Sub-Cohort Analysis from Saudi Arabia.

Background: Individuals with underlying chronic illnesses have demonstrated considerable hesitancy towards COVID-19 vaccines. These concerns are primarily attributed to their concerns over the safety profile. Real-world data on the safety profile among COVID-19 vaccinees with comorbid conditions are scarce. This study aimed to ascertain the side-effects profile after two doses of COVID-19 vaccines among chronic-disease patients. Methodology: A cross-sectional questionnaire-based study was conducted among faculty members with comorbid conditions at a public educational institute in Saudi Arabia. A 20-item questionnaire recorded the demographics and side effects after the two doses of COVID-19 vaccines. The frequency of side effects was recorded following each dose of vaccine, and the association of the side-effects score with the demographics was ascertained through appropriate statistics. Results: A total of 204 patients with at least one comorbid condition were included in this study. A total of 24 side effects were reported after the first dose and 22 after second dose of the COVID-19 vaccine. The incidence of at least one side effect was 88.7% and 95.1% after the first and second doses of the vaccine, respectively. The frequent side effects after the first dose were pain at the injection site (63.2%), fatigue (58.8%), fever (47.5%), muscle and joint pain (38.7%), and headache (36.3%). However, pain at the injection site (71.1%), muscle and joint pain (62.7%), headache (49.5%), fever (45.6%), and stress (33.3%) were frequent after the second dose. The average side-effects score was 4.41 ± 4.18 (median: 3, IQR: 1, 6) and 4.79 ± 3.54 (median 4, IQR: 2, 6) after the first and second dose, respectively. Female gender, diabetes mellitus, hypertension, hyperlipidemia, comorbidity > 2, family history of COVID-19, and the AstraZeneca vaccine were significantly associated with higher side-effect scores. Only 35.8% of study participants were satisfied with the safety of COVID-19 vaccines. Conclusions: Our analysis showed a high proportion of transient and short-lived side effects of Pfizer and AstraZeneca vaccines among individuals with chronic illnesses. However, the side-effects profile was comparable with the safety reports of phase 3 clinical trials of these vaccines. The frequency of side effects was found to be associated with certain demographics, necessitating the need for further investigations to establish a causal relationship. The current study's findings will help instill confidence in the COVID-19 vaccines among people living with chronic conditions, overcome vaccine hesitancy, and increase vaccine coverage in this population.

Barriers and facilitators of childhood COVID-19 vaccination among parents: A systematic review.

Background: The acceptance of vaccination against COVID-19 among parents of young children plays a significant role in controlling the current pandemic. A wide range of factors that influence vaccine hesitancy in adults has been reported worldwide, but less attention has been given to COVID-19 vaccination among children. Vaccine hesitancy is considered a major challenge in achieving herd immunity, and it is more challenging among parents as they remain deeply concerned about their child's health. In this context, a systematic review of the current literature is inevitable to assess vaccine hesitancy among parents of young children to ensure a successful ongoing vaccination program. Method: A systematic search of peer-reviewed English literature indexed in Google Scholar, PubMed, Embase, and Web of science was performed using developed keywords between 1 January 2020 and August 2022. This systematic review included only those studies that focused on parental concerns about COVID-19 vaccines in children up to 12 years without a diagnosis of COVID-19. Following PRISMA guidelines, a total of 108 studies were included. The quality appraisal of the study was performed by Newcastle-Ottawa Scale (NOS). Results: The results of 108 studies depict that vaccine hesitancy rates differed globally with a considerably large number of factors associated with it. The highest vaccine hesitancy rates among parents were reported in a study from the USA (86.1%) and two studies from Saudi Arabia (>85%) and Turkey (89.6%). Conversely, the lowest vaccine hesitancy rates ranging from 0.69 and 2% were found in two studies from South Africa and Switzerland, respectively. The largest study (n = 227,740) was conducted in Switzerland while the smallest sample size (n = 12) was represented by a study conducted in the USA. The most commonly reported barriers to childhood vaccination were mothers' lower education level (N = 46/108, 43%), followed by financial instability (N = 19/108, 18%), low confidence in new vaccines (N = 13/108, 12%), and unmonitored social media platforms (N = 5/108, 4.6%). These factors were significantly associated with vaccine refusal among parents. However, the potential facilitators for vaccine uptake among respondents who intended to have their children vaccinated include higher education level (N = 12/108, 11%), followed by information obtained through healthcare professionals (N = 9/108, 8.3%) and strong confidence in preventive measures taken by the government (N = 5/81, 4.6%). Conclusion: This review underscores that parents around the globe are hesitant to vaccinate their kids against COVID-19. The spectrum of factors associated with vaccine hesitancy and uptake varies across the globe. There is a dire need to address vaccine hesitancy concerns regarding the efficacy and safety of approved vaccines. Local context is inevitable to take into account while developing programs to reduce vaccine hesitancy. There is a dire need to devise strategies to address vaccine hesitancy among parents through the identification of attributing factors.