The Impact of Serum Levels of Reactive Oxygen and Nitrogen Species on the Disease Severity of COVID-19.

Elucidation of the redox pathways in severe coronavirus disease 2019 (COVID-19) might aid in the treatment and management of the disease. However, the roles of individual reactive oxygen species (ROS) and individual reactive nitrogen species (RNS) in COVID-19 severity have not been studied to date. The main objective of this research was to assess the levels of individual ROS and RNS in the sera of COVID-19 patients. The roles of individual ROS and RNS in COVID-19 severity and their usefulness as potential disease severity biomarkers were also clarified for the first time. The current case-control study enrolled 110 COVID-19-positive patients and 50 healthy controls of both genders. The serum levels of three individual RNS (nitric oxide (NO•), nitrogen dioxide (ONO-), and peroxynitrite (ONOO-)) and four ROS (superoxide anion (O2•-), hydroxyl radical (•OH), singlet oxygen (1O2), and hydrogen peroxide (H2O2)) were measured. All subjects underwent thorough clinical and routine laboratory evaluations. The main biochemical markers for disease severity were measured and correlated with the ROS and RNS levels, and they included tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), the neutrophil-to-lymphocyte ratio (NLR), and angiotensin-converting enzyme 2 (ACE2). The results indicated that the serum levels of individual ROS and RNS were significantly higher in COVID-19 patients than in healthy subjects. The correlations between the serum levels of ROS and RNS and the biochemical markers ranged from moderate to very strongly positive. Moreover, significantly elevated serum levels of ROS and RNS were observed in intensive care unit (ICU) patients compared with non-ICU patients. Thus, ROS and RNS concentrations in serum can be used as biomarkers to track the prognosis of COVID-19. This investigation demonstrated that oxidative and nitrative stress play a role in the etiology of COVID-19 and contribute to disease severity; thus, ROS and RNS are probable innovative targets in COVID-19 therapeutics.

Assessment of Public Knowledge about Chronic Kidney Disease and Factors Influencing Knowledge Levels: A Cross-Sectional Study.

Background and Objectives: Chronic kidney disease (CKD) poses a significant risk for end-stage renal disease (ESRD), cardiovascular diseases, and premature death. The study aims to assess CKD knowledge and predictive variables among the general public. Materials and Methods: A cross-sectional study was conducted among the general public in Al Medina Al-Munawara, Saudi Arabia, utilizing a 21-item questionnaire-based approach over a 4-month period from January 2023 to April 2023. The developed questionnaire was validated for readability by experts and refined in light of the feedback received from the experts and the final version was prepared. The reliability of the questionnaire was 0.71, which shows an acceptable level of internal consistency. The data analysis was performed using IBM SPSS software (version 25). Results: A total of 777 complete surveys were received after applying the exclusion criteria. The study results revealed that the majority of the respondents had poor knowledge 505 (65%), 203 (26.1) had moderate knowledge, and 69 (8.9%) had good knowledge. Gender (p = 0.004), age (<0.001), education level (p = 0.039), marital status (p = 0.003), and occupation (p = 0.002) play significant roles in shaping participants' knowledge levels regarding CKD. Lower odds of good knowledge were associated with females with an OR (95% CI) of 0.448 (0.263-0.764) and intermediate or higher secondary school level of education displayed an OR (95% CI) of 0.39 (0.18-0.89). Higher odds of good knowledge levels were associated with the age group of 18-27 with an OR (95% CI) of 5.077 (1.21-21.38) and being employed with an OR of 3.555 (1.04-12.21). Conclusions: A significant proportion of respondents had poor knowledge about CKD. Several demographic factors were associated with CKD knowledge. Further research is needed to explore these knowledge disparities and develop targeted interventions to improve CKD knowledge among the general public.

Assessment of risk factors associated with multidrug-resistant organism infections among patients admitted in a tertiary hospital - a retrospective study.

Background: Bacterial resistance has become a global health concern. To treat suspected multidrug resistant organisms (MDROs), physicians first use broad-spectrum antibiotics; however, this increases the chance of developing antimicrobial resistance. Thus, defining the risk factors for MDROs could aid in the selection of the ideal initial antimicrobial therapy and improve clinical outcomes. Objective: This study aimed to identify the common risk factors for MDRO infection among patients admitted to King Fahad Hospital (KFH) and to analyze the comorbidity factors associated with MDRO infections. Methods: This retrospective, observational, case-control study included adult patients ≥ 18 years old admitted to KFH between 1st of January to 31st of March 2021, with positive microbial culture. Pediatric patients, outpatients, or patients with only positive fungal cultures were excluded. Data were obtained from the KFH laboratory MDRO documenting database. Results: Two hundred and seventy patients were included in this study: 136 in the study group and 134 in the control group. Among patients, 167 (61.9 %) were males and 184 (68.1%) were 18 to 65 years old. The use of drugs such as cotrimoxazole, amikacin, and imipenem (OR = 4.331, C. I. of OR:1.728, 10.855, p = 0.002) were significantly associated with MDRO infections, whereas cefazolin was associated with a lower risk of MDRO infections (OR = 0.080, C.I. of OR:0.018, 0.347, p < 0.001). The intensive care unit showed higher odds of significant association with MDRO infections than those of the surgical unit (odds ratio [OR] = 8.717, 95% C.I. of OR: 3.040, 24.998, p < 0.001). Patients who previously consumed acid-suppressive medications showed higher odds of developing MDRO infections (OR = 5.333, C.I. of OR: 2.395, 11.877, p < 0.001). Conclusion: The most significant comorbidities were diabetes, hypertension, antibiotic use prior to hospitalization and the use of cotrimoxazole, amikacin and imipenem among other antibtiotics was mostly associated with MRDO infections. This study revealed an increasing trend of MDRO infections and a positive correlation with the incidence of strokes and mortality, which highlights the importance of understanding the risk factors for MDRO infections.

Prognostic factors for predicting severity and mortality in hospitalized COVID-19 patients.

BACKGROUND: Coronavirus disease 2019, COVID-19, has reached all the corners of the world and was declared by the WHO as a global pandemic and public health emergency of international concern on the January 31, 2020. Allocating quick and specific biomarkers to predict the disease severity upon admission to hospital became a crucial need. This study, therefore, aimed at exploring the relationship between laboratory results in COVID-19 patients admitted to hospital and the final outcome in these patients. METHODS: Retrospective analysis was performed on the medical records of 310 COVID-19-positive patients admitted to Uhod Hospital, the referral hospital in the area of Madinah, Kingdom of Saudi Arabia, between the April 13 and the July 29, 2020. The association of laboratory results with the survival/mortality outcomes was studied. RESULTS: It was demonstrated that lymphopenia, prolonged aPTT, high INR, high D. dimer and high CK are valuable prognostic predictors of the severity of the disease at early stages that can determine the outcome. Based on the results of the multiple logistic regression, the variables that are associated with death outcome are aPTT, HR, RR, ALT and CK level CONCLUSION: It is proposed to perform these tests on admission to hospital for moderate to severe COVID-19 patients to improve the management of those cases and reduce mortality.

Sensitivity improvement for spectrofluorimetric determination of commonly used antifungal drug 'nystatin': application for oral suspension.

In this paper, two simple, rapid and highly sensitive spectrofluorimetric methods were developed and validated for nystatin determination in its pure form and pharmaceutical dosage form (oral suspension). The first method was based on measuring the nystatin native fluorescence after dilution with isopropyl alcohol at 407 nm (excitation 303 nm). The fluoresence intensity was linearly dependant on the nystatin concentration within the specified range 50-500 ng ml-1 . The second was based on micellar enhancement of nystatin fluorescence using sodium dodecyl sulphate (SDS). In the presence of 2% w/v SDS, an ~1.9-fold enhancement could be achieved in the relative fluorescence intensity of nystatin. The linear range for the second method was 20-100 ng ml-1 . The limits of quantification and detection were found to be 43.23 ng ml-1 and 14.27 ng ml-1 (Method I), 6.08 ng ml-1 and 2.0 ng ml-1 (Method II). According to percentage recoveries and relative standard deviations (RSDs) obtained, the proposed methods were precise (RSDs were less than 2%), reproducible, and accurate and could be successfully applied for quantitative estimation of nystatin in its dosage form. The statistical results of this method were compared with that of the reported method and showed excellent agreement with respect to accuracy and precision.

Fabric phase sorptive extraction coupled with UPLC-ESI-MS/MS method for fast and sensitive quantitation of tadalafil in a bioequivalence study.

The current study coupled fabric phase sorptive extraction (FPSE) with ultraperformance liquid chromatography method with electrospray ionization and tandem mass detection (UPLC-ESI-MS/MS) for fast and sensitive determination of tadalafil (TAD) in a bioequivalence study. Fabric phase sorptive extraction allowed direct extraction of TAD from the sample matrix with improved selectivity, repeatability, and recoveries. A sol-gel Carbowax 20 M (CX-20 M) coated FPSE membrane revealed the best extraction efficiency for TAD because of its strong affinity for analytes via intermolecular interactions, high mass transfer rate to FPSE membrane, and high permeability. An automated multiple reaction monitoring (MRM) optimizer was employed for the best selection of the precursor and product ions, ion breakdown profile, the fine adjustment of the fragmentor voltages for each precursor ions, and the collision energies for the product ions. The chromatographic separation was conducted using a mobile phase A: 5.0 mM ammonium acetate with 0.1 % formic acid in water and mobile phase B: formic acid (0.1%) in acetonitrile in ratio (55:45, v/v) through isocratic elution mode on an Agilent EclipsePlus C18 (50 × 2.1 mm, 1.8 µm) column and the flow rate was adjusted at 0.4 mL min-1. The total run time per sample was 1.0 min. The method was validated by FDA standards for bioanalytical method validation over a concentration range of 0.1-100 ng mL-1 with a correlation coefficient of 0.9993 and the lower limit of quantitation (LLOQ) was 0.1 ng mL-1 in rat plasma. Intra- and inter-assay precision (%RSD) were lower than 4.1% and accuracy (%RE) was within 2.4%. The developed FPSE-UPLC-ESI-MS/MS method was effectively used in a randomized, two-way, single-dose, crossover study to compare the bioequivalence of two TAD formulations from different companies in male rats and verified to be bioequivalent.

Parallel artificial liquid membrane extraction coupled with UPLC-ESI-MS/MS method for high-throughput quantitation of repaglinide in diabetic patients.

A high-throughput therapeutic monitoring method was developed for repaglinide (RPG) in diabetic patients, combining parallel artificial liquid membrane extraction (PALME) with ultraperformance liquid chromatography electrospray ionization tandem mass spectrometry (UPLC-ESI-MS/MS). PALME was performed using a 96-well donor plate comprising a donor solution containing a plasma sample, 50 mM phosphate buffer (pH = 8.0), and cetirizine (CTZ) as internal standard. A polypropylene (PP) porous membrane served as a selective support for the liquid membrane (SLM), preventing nonspecific binding produced by other membranes. The extraction was accomplished across SLM made of PP membrane with dodecyl acetate and 1 % trioctylamine (w/w), and the acceptor solution comprised DMSO and 200 mM formic acid (50:50, v/v). The simple workflow for PALME provided analyte enrichment, highly efficient sample cleanup, high throughput analysis, and excellent reproducibility. Method validation met FDA criteria, with a linear plasma calibration range (0.1-100 ng mL-1, r = 0.9995) and a lower limit of quantitation (LLOQ) of 0.1 ng mL-1. Recovery results at 98.9 % affirmed method reliability. The ability to analyze 198 samples per hour, coupled with a reduced amount of solvents, underscores the method's high throughput and eco-friendly profile. The PALME-UPLC-ESI-MS/MS method was successfully applied to therapeutic drug monitoring of RPG in diabetic patients following 2 mg RPG tablet administration, establishing its effectiveness.

Improving fluorescence emission of cyproheptadine by hindering its intramolecular photoinduced electron transfer (PET): Application to content uniformity testing and human plasma.

The ability to determine antihistaminic drugs in biological matrices is critical for the medication adherence assessment. Among these antihistaminic medications, cyproheptadine (CPD); that is acting as a potent first-generation antihistaminic drug that has been extensively prescribed for allergic patients. Most of the established approaches for CPD detection are not appropriate for this purpose owing to their weak sensitivity, lack of rapidity, and complicated experimental procedures. Herein, we present a very fast, highly sensitive, and reproducible approach for the detection of CPD in its pure form, tablet formulation, and spiked human plasma. The photoluminescence approach depends on hindering the intramolecular photoinduced electron transfer (PET) effect of the lone pair of the N-atom present on the piperidine ring of CPD by making the surrounding medium acidic using 1.0 M acetic acid. Based on blocking PET, the target CPD drug has been sensitively detected from 5.0 to 500 ng mL-1 with a very low detection and quantitation limit of 7.01 and 21.25 ng mL-1, respectively. Moreover, the established approach was used for checking the tablet content uniformity testing for each tablet and spiked human plasma, and noteworthy, the matrices interference was insignificant.

Repaglinide-Solid Lipid Nanoparticles in Chitosan Patches for Transdermal Application: Box-Behnken Design, Characterization, and In Vivo Evaluation.

Background: Repaglinide (REP) is an antidiabetic drug with limited oral bioavailability attributable to its low solubility and considerable first-pass hepatic breakdown. This study aimed to develop a biodegradable chitosan-based system loaded with REP-solid lipid nanoparticles (REP-SLNs) for controlled release and bioavailability enhancement via transdermal delivery. Methods: REP-SLNs were fabricated by ultrasonic hot-melt emulsification. A Box-Behnken design (BBD) was employed to explore and optimize the impacts of processing variables (lipid content, surfactant concentration, and sonication amplitude) on particle size (PS), and entrapment efficiency (EE). The optimized REP-SLN formulation was then incorporated within a chitosan solution to develop a transdermal delivery system (REP-SLN-TDDS) and evaluated for physicochemical properties, drug release, and ex vivo permeation profiles. Pharmacokinetic and pharmacodynamic characteristics were assessed using experimental rats. Results: The optimized REP-SLNs had a PS of 249±9.8 nm and EE of 78%±2.3%. The developed REP-SLN-TDDS demonstrated acceptable characteristics without significant aggregation of REP-SLNs throughout the casting and drying processes. The REP-SLN-TDDS exhibited a biphasic release pattern, where around 36% of the drug load was released during the first 2 h, then the drug release was sustained at around 80% at 24 h. The computed flux across rat skin for the REP-SLN-TDDS was 2.481±0.22 µg/cm2/h in comparison to 0.696±0.07 µg/cm2/h for the unprocessed REP, with an enhancement ratio of 3.56. The REP-SLN-TDDS was capable of sustaining greater REP plasma levels over a 24 h period (p<0.05). The REP-SLN-TDDS also reduced blood glucose levels compared to unprocessed REP and commercial tablets (p<0.05) in experimental rats. Conclusion: Our REP-SLN-TDDS can be considered an efficient therapeutic option for REP administration.

Sitagliptin ameliorates L-arginine-induced acute pancreatitis via modulating inflammatory cytokines expression and combating oxidative stress.

Background: Acute pancreatitis (AP) is an inflammatory condition that resolves spontaneously, but occasionally, develops into systemic inflammation, organ failure and mortality. Oxidative stress and activation of inflammatory pathways represent major players in AP pathogenesis. Current management of AP relies on attenuating injuries to the pancreas and putting the inflammatory process under control. In this study, we investigated the role of sitagliptin in modulating L-arginine-induced AP in rats. Methods: Swiss rats were subdivided into a healthy control group, AP group (a single dose of L-arginine 250 mg/100 g, intraperitoneal), and sitagliptin + L-arginine-treated group (10 mg sitagliptin/kg body weight/day, orally). Sitagliptin treatment started 1 hour after L-arginine injection and continued for 3days. Biochemical and histopathological investigations were performed on serum and tissue samples collected from test animals. Results: L-arginine increased pancreatic meyloperoxidase and serum amylase- and lipase activities and serum levels of TNF-α, LT-α, IFN-γ, IL-1α/ß, IL-6, IL-10, IL-12, and IL-15. AP animals showed elevated MDA and NO and decreased GSH and serum calcium levels. Histopathological changes were observed by H&E staining. Sitagliptin treatment significantly ameliorated these biochemical and histological changes diminishing the signs of AP. Conclusion: Sitagliptin treatment was effective in ameliorating L-arginine-induced AP which can be regarded to its anti-inflammatory and antioxidant effect.

Evaluation of Health Literacy and Associated Factors Among Adults Living in Saudi Arabia: A Cross-Sectional Study.

In this westernized culture, maintaining a healthy lifestyle has become a major health concern internationally. Health literacy is an emerging concept and requires effective measures and reform to improve the health status and health of individuals at both national and international levels, and has become one of the important determinants of individual health and healthcare service. This study aimed to assess health literacy among adults in Saudi Arabia. A cross-sectional study was conducted among a randomly selected population using a structured validated questionnaire over 4 months in 2021. The questionnaires designed for the study included 26 items divided into 5 domains assessed on a five-point Likert scale. Data were analyzed using IBM SPSS Statistics 26 (IBM Inc., Chicago, IL, USA) and IBM SPSS 26 (IBM Inc.). The mean score for reading, access to information, understanding, appraisal, and decision-making was 12.01 ± 4.37, 20.16 ± 7.17, 24.84 ± 8.37, 11.85 ± 4.90, and 36.94 ± 10.41 respectively. The mean scores of reading and understanding domains were found to have significant differences concerning gender (P < .05). Additionally, participants' age was significantly associated with the mean score of reading and decision-making (P < .006 and P < .049). The findings reported a prevalence of inadequate HL in the population of Saudi Arabia was 54.4%, and the determinants associated with the scores of HL were age, gender, and education.

Utilization of a TiO2-CuO Bimetallic/Polyaniline Nanocomposite as a Transducer in a Solid Contact Potentiometric Sensor for the Determination of Vildagliptin.

Current fundamental electrochemical research shows the potential of utilizing polymeric nanostructured materials as ion-to-electron transducers. In this paper, aniline was polymerized in the presence of TiO2 and CuO nanoparticles to yield a bimetallic/PANI nanocomposite. It was applied as a transducer in a carbon paste electrode for the potentiometric determination of vildagliptin in the presence of 18-crown-6-ether as a recognition element. The electrode's potentiometric performance was studied according to the IUPAC guidelines. It exhibited a wide linearity range of 1 × 10-2 M to 1 × 10-8 M, remarkable sensitivity (LOD of 4.5 × 10-9 M), and a fast response time of 10 s ± 1.3. The sensor did not show any potential drift due to the absence of the water layer between the carbon paste and the metallic conductor. This endowed the sensor with high stability and a long lifetime, as 137 days passed without the need to change the carbon paste surface. The electrode was utilized for the determination of the concentration of vildagliptin in bulk, pharmaceutical tablets, and human plasma, with average recovery ranging from 97.65% to 100.03%.

Migraine Management in Community Pharmacies: Knowledge, Attitude and Practice Patterns of Pharmacists in Saudi Arabia.

In Saudi Arabia, community pharmacies offer healthcare services for different conditions. However, clarity of the competence of pharmacists in managing migraines is lacking. This study aimed to explore the current knowledge, attitude, and practice patterns of community pharmacists concerning migraine management in the northwestern part of Saudi Arabia. A cross-sectional study was carried out between June and September 2022 among 215 Saudi community pharmacists. Data analysis was performed by descriptive and inferential statistics using SPSS version 27. Most community pharmacists (87.9%) feel that migraine management is essential to their practice, and 83.3% suggest between one and five over-the-counter (OTC) migraine products daily. Among the study pharmacists, 83.7% feel migraine patients should try OTC before prescription medications. Only 9.3% of the community pharmacists do not believe that migraine is a neurological disorder. The medications most prescribed for migraine were triptans, representing 52.1% of prescriptions. There were significant differences between the gender of the pharmacists and their knowledge, attitude, and practice overall score (p-value = 0.04). Male pharmacists exhibited higher knowledge, attitude, and practice scores than female pharmacists. Although many community pharmacists acknowledge their expertise and involvement in managing migraines, there is a requirement for further education and training to enhance their capacity to offer complete care to migraine patients. Pharmacists should also consider non-pharmacological interventions and complementary therapies when treating migraine symptoms.

Alpha-Mangostin ameliorates acute kidney injury via modifying levels of circulating TNF-α and IL-6 in glycerol-induced rhabdomyolysis animal model.

Alpha mangostin (AM), isolated from G. mangostana, showed beneficial effects in several disorders due to its antioxidant and anti-inflammatory properties. Acute kidney injury (AKI) due to different etiologies can develop into severe complications, resulting in high mortality rates. In this work, AM is tested for its ability to alleviate AKI in glycerol-induced AKI rat model, where 30 Male Sprague-Dawley rats were assigned to a healthy group, glycerol-treated group and AM-treated group. Glycerol- and AM groups received a single dose of glycerol (per IM, 50% glycerol in saline, 8 ml/kg), whereas control group was injected with saline. AM treatment (a single daily dose, per IP, 175mg/kg) was accomplished for three days. Animals were executed to collect blood samples and kidney tissue for biochemical and histological examination. It was found that glycerol induced increase in serum creatinine, blood urea nitrogen (BUN), lipid peroxidation, serum magnesium, TNF-α and IL-6. It also induced renal edema and hypocalcemia along with histopathological renal damage. AM treatment improved renal histological features and alleviated increase in serum creatinine, BUN, serum magnesium, TNF-α and IL-6 levels, as well as renal edema and lipid peroxidation but did not affect serum calcium levels. This suggests AM as a potential therapeutic agent for treating AKI mainly via its antioxidant and anti-inflammatory properties.

Uptake, Safety and Attitudes Towards COVID-19 Vaccination: A Cross-Sectional Study on First and Second Doses Among the General Public.

Objective: To investigate public uptake, attitudes and the safety of the first and second doses of COVID-19 vaccination. Methods: This was a cross-sectional web-based survey study. A self-administered questionnaire was prepared from a literature search and information about COVID-19 available at various resources. The developed questionnaire was validated for readability by experts and refined in light of the feedback received from the experts and the final version was prepared. The reliability of the questionnaire was 0.7 which shows an acceptable level of scale internal consistency. The data analysis was performed using IBM SPSS software (version 25). Results: A total of 513 participants completed the survey, including 311 (60.6%) women and 202 (39.4%) men. The mean age was (31.5±12.8) years. It was found that 493 (96.1%) took the first and second doses of COVID-19 and 376 (73.3%) suffered from side effects, of these 14% (56/376) reported the side effects to the health authorities. The most common side effects were fatigue (51.5%), fever (42.3%), headache (39.5%), and injection site pain (37.6%). Half of the participants (50.5%) had a positive attitude towards COVID-19 preventive measures. Females had higher odds of experiencing side effects than males OR (95% CI); 2.002 (1.312-3.056). Individuals living in urban areas had lower odds of experiencing side effects than those living in rural areas OR (95% CI); 0.364 (0.142-0.933). Conclusion: Vaccine uptake was massive and side effects due to the COVID-19 vaccine were common but minor. The majority of the participants had positive attitudes towards recommended COVID-19 preventive measures. Being female and living in rural areas were associated with experiencing side effects.

Defining and supporting a professional role for pharmacists associated with traditional and complementary medicines: a cross-country survey of pharmacists.

Introduction: An estimated 80% of the world's population use traditional and complementary medicine (T&CM) products as part of their healthcare, with many accessed through pharmacy. This cross-cultural study posed a set of professional practice responsibilities and actions to pharmacists related to T&CM products, with a view toward developing consensus, safeguarding, and promoting the health of the public. Methods: Data were collected from 2,810 pharmacists across nine countries during 2022 via a cross-sectional online survey reported in accordance with the guidelines of STrengthening the Reporting of OBservational studies in Epidemiology (STROBE) and the Checklist for Reporting Results of Internet E-Surveys (CHERRIES). Results: Of the 2,810 participants from nine countries, 2,341 completed all sections of the survey. Of these, most agreed (69%) that T&CM product use was common in the community they served, but most did not have adequate training to support consumer needs. Over 75% acknowledged that there were known and unknown safety risks associated with T&CM use. Of 18 professional responsibilities posed, 92% agreed that pharmacists should be able to inform consumers about potential risks, including T&CM side effects and drug-herb interactions. The provision of accurate scientific information on the effectiveness of T&CM products, skills to guide consumers in making informed decisions, and communication with other healthcare professionals to support appropriate and safe T&CM product use were all ranked with high levels of agreement. In order to effectively fulfill these responsibilities, pharmacists agreed that regulatory reforms, development of T&CM education and training, and access to quality products supported by high-quality evidence were needed. Conclusion: General agreement from across nine countries on eighteen professional responsibilities and several stakeholder actions serve as a foundation for the discussion and development of international T&CM guidelines for pharmacists.

An evaluation of the impact of antibiotic stewardship on reducing the use of high-risk antibiotics and its effect on the incidence of Clostridium difficile infection in hospital settings.

OBJECTIVES: To evaluate the impact of a high-risk antibiotic stewardship programme on reducing antibiotic use and on hospital Clostridium difficile infection (CDI) incidence rates. A secondary objective was to present the possible utility of time-series analysis as an antibiotic risk classification tool. METHODS: This was an interventional, retrospective, ecological investigation in a medium-sized hospital over 6.5 years (January 2004 to June 2010). The intervention was the restriction of high-risk antibiotics (second-generation cephalosporins, third-generation cephalosporins, fluoroquinolones and clindamycin). Amoxicillin/clavulanic acid and macrolides were classified as medium-risk antibiotics based on time-series analysis findings and their use was monitored. The intervention was evaluated by segmented regression analysis of interrupted time series. RESULTS: The intervention was associated with a significant change in level of use of high-risk antibiotics (coefficient -17.3, P < 0.0001) and with a borderline significant trend change in their use being reduced by 0.156 defined daily doses/100 bed-days per month (P = 0.0597). The reduction in the use of high-risk antibiotics was associated with a significant change in the incidence trend of CDI (P = 0.0081), i.e. the CDI incidence rate decreased by 0.0047/100 bed-days per month. Analysis showed that variations in the incidence of CDI were affected by the age-adjusted comorbidity index with a lag of 1 month (coefficient 0.137051, P = 0.0182). Significant decreases in slope (coefficient -0.414, P = 0.0309) post-intervention were also observed for the monitored medium-risk antibiotics. CONCLUSIONS: The restriction of the high-risk antibiotics contributed to both a reduction in their use and a reduction in the incidence of CDI in the study site hospital. Time-series analysis can be utilized as a risk classification tool with utility in antibiotic stewardship design and quality improvement programmes.

An ultrasensitive UHPLC-ESI-MS/MS method augmented with a controlled microwave derivatization reaction for quantitation of vitamin D3 and its major metabolites in COVID-19 patients.

It is established that vitamin D deficiency is correlated with the disease severity in COVID-19 patients. However, the reliable and sensitive quantitation of vitamin D3 (D3) and its metabolites remains a difficult challenge. Herein, a novel ultrasensitive and reliable UHPLC-ESI-MS/MS method was developed and validated for the quantitation of D3 and its major metabolites in COVID-19 patients. The mass spectral sensitivity was augmented via controlled microwave-assisted derivatization reaction (CMDR) with 2-nitrosopyridine (Pyr-NO) at 65 °C for 2 min. CMDR hyphenation with UHPLC-MS/MS improves detection sensitivity while shortening separation and derivatization reaction times. The precursor to product ion transitions for D3, 25-hydroxy D3 (25(OH)D3), 1,25-dihydroxy D3 (1,25-(OH)2D3) and calcipotriol (CPT) as an internal standard were m/z 493.4 â†’ 231.3, m/z 509.4 â†’ 231.3, m/z 525.4 â†’ 247.3, and m/z 521.4 â†’ 247.3; respectively. The separation of the formed derivatives was conducted using a gradient elution mode with mobile phase A: formic acid (0.1%) in water and mobile phase B: formic acid (0.1%) in acetonitrile. The elution started with 40% (v/v) of B for 0.3 min then increased linearly to 90% (v/v) at 2 min on an Agilent EclipsePlus C18 (50 × 2.1 mm, 1.8 µm) column at a flow rate of 0.3 mL min-1. The method was validated using FDA standards for bioanalytical method validation over a concentration range of 0.02-50 ng mL-1 with correlation coefficient ≥0.9987 and the lower limit of quantitation (LLOQ) were 0.02-0.05 ng mL-1 in human plasma. The developed method has demonstrated excellent comparability to a well-established chemiluminescent immunoassay (CLIA) method for the analysis of D3 metabolites in human samples. The developed UHPLC-ESI-MS/MS method was implemented for routine and reliable quantitation of D3 and its major metabolites in COVID-19 patients.

Regen-Cov and Covid-19, Update on the Drug Profile and Fda Status: A Mini-Review and Bibliometric Study.

COVID-19 is caused by coronavirus (SARS-CoV-2) is a worldwide health crisis. This severe acute respiratory syndrome was declared an outbreak after the first case was reported in Wuhan, the capital city of Hubei Province in China. On March 11th, 2020, the World Health Organization (WHO) declared it as a pandemic. The pharmaceutical treatment of COVID-19 has garnered significant critical attention due to the unavailability of medications to treat COVID-19. Recently, researchers have shown an increased interest in the monoclonal antibody drugs to treat COVID-19 especially REGEN-COV (casirivimab and imde-vimab). This review aims to highlight the relation between the drug and COVID-19 and the recently updated information on the monoclonal antibody REGEN-COV from the U.S. Food and Drug Administration and other authorities. It is also designed to focus on the bibliometric data of REGEN-COV for the last three years (2020, 2021, and 2021) in PubMed and Google Scholar.

Re-Entrant Honeycomb Auxetic Structure with Enhanced Directional Properties.

This paper presents a modified re-entrant honeycomb auxetic structure. The structure is constructed by adding an additional horizontal member between the vertical and re-entrant member of the semi-re-entrant honeycomb model to increase the overall compliance of the structure in order to obtain higher values of negative Poisson's ratio (NPR). An analytical model of the structure is presented, taking into account the bending, shear, and axial deformations. The model is verified using finite element analysis (FEA) and tensile testing. The results of FEA and tensile testing corroborate the results of the presented mathematical model. The structure is also compared to the existing re-entrant honeycomb structure. The newly added strut has shown a direct effect on the directional properties of the overall structure. With an increase in the newly added strut to re-entrant lengths, NPR was significantly enhanced in the x-direction and reduced in the y-direction loadings. The structure shows an improved Young's modulus compared to solid material in both loading directions, especially for the low values of the new strut and re-entrant lengths ratio. The structure also shows that high NPR can be achieved for low relative density compared to semi re-entrant honeycomb structure.