Repositioning of anti-infective compounds against monkeypox virus core cysteine proteinase: a molecular dynamics study.

Monkeypox virus (MPXV) core cysteine proteinase (CCP) is one of the major drug targets used to examine the inhibitory action of chemical moieties. In this study, an in silico technique was applied to screen 1395 anti-infective compounds to find out the potential molecules against the MPXV-CCP. The top five hits were selected after screening and processed for exhaustive docking based on the docked score of ≤ -9.5 kcal/mol. Later, the top three hits based on the exhaustive-docking score and interaction profile were selected to perform MD simulations. The overall RMSD suggested that two compounds, SC75741 and ammonium glycyrrhizinate, showed a highly stable complex with a standard deviation of 0.18 and 0.23 nm, respectively. Later, the MM/GBSA binding free energies of complexes showed significant binding strength with ΔGTOTAL from -21.59 to -15 kcal/mol. This report reported the potential inhibitory activity of SC75741 and ammonium glycyrrhizinate against MPXV-CCP by competitively inhibiting the binding of the native substrate.

The Association between Self-Care Activities and Depression in Adult Patients with Type 2 Diabetes in Saudi Arabia: A Cross-Sectional Web-Based Survey Study.

This study examined the level of adherence to self-care behaviors among individuals with type 2 diabetes in Saudi Arabia and its connection with depression and demographic factors. A cross-sectional survey was conducted among diabetes patients using the Patient Health Questionnaire (PHQ-9) to measure depression and the Summary of Diabetes Self-Care Activities (SDSCA) to evaluate diabetes self-care activities. Among the 252 participants who completed the survey, 43.2% were older than 55 and 59% were men. The ordinal regression model showed an association between the PHQ-9 and SDSCA scores with an OR of 0.83 (95% CI: 0.71 to 0.96, p = 0.013). The PHQ-9 score was significantly associated with blood sugar monitoring (OR: 0.90 [95% CI: 0.82 to 0.99, p = 0.003]), exercise (OR: 0.88 [95% CI: 0.79 to 0.98, p = 0.002]), and diet (OR: 0.94 [95% CI: 0.85 to 1.03, p = 0.045]). Of all the diabetes-related factors, only a history of hospitalization and receiving diabetes education were found to be associated with improved self-care behaviors. In conclusion, a negative association was found between PHQ-9 scores and the SDSCA mean score and most daily diabetic self-care behavior components.

Bioprospecting of Meliaceae family phytomolecules for the treatment of monkeypox virus infection: a QSAR modeling and MD simulation approach.

Recent monkeypox virus (MPXV) infections show the risk of MPXV transmission that persists today and the significance of surveillance and quick response methods to stop the virus's spread. Currently, the monkeypox virus infection is not specifically treated. In this study, QSAR models were designed using known inhibitors of cysteine proteinase from the vaccinia virus, where the Random Forest model and Ridge model had showed the best correlation between predicted and observed EC50. These models were used to screen Maliaceae family phytochemicals against MPXV cysteine proteinase. The compound, IMPHY010637 was detected in top 5 from both the QSAR screening models and showed best docked score (-8.6 kcal/mol) and thus selected for further investigation. Further, the IMPHY010637 showed interaction with the catalytic residue His241 of the protein as reported in earlier studies. The ADMET analysis of the compound showed the acceptable drug-like properties of IMPHY010637. However, these properties could be improved after experimental validation of protein-ligand binding. Both docked complex and poses created in 100 ns MD simulation of the protein-ligand complex showed the presence of multiple hydrogen bonds. RMSD and conformation analysis showed stable binding of IMPHY010637 with the cysteine proteinase of MPXV at its active site. Compared to the known inhibitor, IMPHY010637 showed better binding with the protein as observed by the PCA and MM/GBSA analysis. This study concluded IMPHY010637 as a potential inhibitor for the cysteine proteinase of MPXV using computational methods that could be tested in in-vitro experiments.Communicated by Ramaswamy H. Sarma.

A survey of drive-thru pharmacy services: Evaluating the acceptance and perspectives of community pharmacists in Saudi Arabia.

Background: The practice of dispensing drugs in primary healthcare centers has shifted to community pharmacies in Saudi Arabia. These changes increase demand and mandate improving their services; one such is establishing pharmacy drive-thru services. To explore the effects of drive-thru services on the pharmacy profession, this study aimed to measure community pharmacists' acceptance, perception, and satisfaction regarding drive-thru services. Methods: This cross-sectional study design was conducted in Saudi Arabia between January 2023 and May 2023-comparing the perception, acceptance, and satisfaction of pharmacists who work in a community pharmacy that provides a drive-thru service versus no drive-thru service. Community pharmacists were invited to complete an online questionnaire consisting of four sections developed from previous studies with some modifications. Descriptive statistical analysis and an independent t-test were utilized to test the difference between the two groups (providing drive-thru service vs. non) in their responses. Results: This study included 380 community pharmacists, of whom 33 % provided drive-thru services and 67 % did not. Pharmacists' perceptions of drive-thru services differed significantly. Those with drive-thru services perceived lower convenience for delivering drug information and patient counseling, and they were concerned about the potential impact on their health effects (M = 3.15, SD = 1.34) compared to those without (M = 3.58, SD = 1.10), t (3 7 8) = -3.32, p < 0.01). However, they recognized the convenience of serving sick patients, the elderly, disabled individuals, and mothers with children in cars (M = 3.71, SD = 1.17), which was higher than those without (M = 4.04, SD = 1.21), t (3 7 8) = -2.70, p < 0.01). Regarding the current pharmacy layout suitability, pharmacists with drive-thru services found it more suitable (M = 3.13, SD = 1.14) than those without (M = 2.49, SD = 1.14), t (3 7 8) = 5.1, p < 0.01). However, the two groups had no significant difference in overall satisfaction. Conclusion: Pharmacists working in pharmacies offering drive-thru services recognized certain benefits but also expressed concerns about health effects and decreased convenience for counseling. These findings provide valuable insights for policymakers and pharmacy management, highlighting the nuanced views of pharmacists in adopting drive-thru services.

Investigation of Zika virus methyl transferase inhibitors using steered molecular dynamics.

Zika virus (ZIKV) spread is considered a major public health threat by the World Health Organization (WHO). There are no vaccines or drugs available to control the infection of the Zika virus, therefore a highly effective medicinal molecule is urgently required. In this study, a computationally intensive investigation was performed to identify a potent natural compound that could inhibit the ZIKV NS5 methyltransferase. This research approach is based on target-based drug identification principles where the native inhibitor SAH (S-adenosylhomocysteine) of ZIKV NS5 methyltransferase was selected as a reference. High-throughput virtual screening and tanimoto similarity coefficient were applied to the natural compound library for ranking the potential candidates. The top five compounds were selected for interaction analysis, MD simulation, total binding free energy through MM/GBSA, and steered MD simulation. Among these compounds, Adenosine 5'-monophosphate monohydrate, Tubercidin, and 5-Iodotubercidin showed stable binding to the protein compared to the native compound, SAH. These three compounds also showed less fluctuations in RMSF in contrast to native compound. Additionally, the same interacting residues observed in SAH also made strong interactions with these three compounds. Adenosine 5'-monophosphate monohydrate and 5-Iodotubercidin had greater total binding free energies than the reference ligand. Moreover, the dissociation resistance of all three compounds was equivalent to that of the reference ligand. This study suggested binding properties of three-hit compounds that could be used to develop drugs against Zika virus infections.Communicated by Ramaswamy H. Sarma.

Immunoinformatics-Driven Strategies for Advancing Epitope-Based Vaccine Design for West Nile Virus.

The West Nile virus (WNV) is the causative agent of West Nile disease (WND), which poses a potential risk of meningitis or encephalitis. The aim of the study was to design an epitope-based vaccine for WNV by utilizing computational analyses. The epitope-based vaccine design process encompassed WNV sequence collection, phylogenetic tree construction, and sequence alignment. Computational models identified B-cell and T-cell epitopes, followed by immunological property analysis. Epitopes were then modeled and docked with B-cell receptors, MHC I, and MHC II. Molecular dynamics simulations further explored dynamic interactions between epitopes and receptors. The findings indicated that the B-cell epitope QINHHWHKSGSSIG, along with three T-cell epitopes (FLVHREWFM for MHC I, NPFVSVATANAKVLI for MHC II, and NAYYVMTVGTKTFLV for MHC II), successfully passed the immunological evaluations. These four epitopes were further subjected to docking and molecular dynamics simulation studies. Although each demonstrated favorable affinities with their respective receptors, only NAYYVMTVGTKTFLV displayed a stable interaction with MHC II during MDS analysis, hence emerging as a potential candidate for a WNV epitope-based vaccine. This study demonstrates a comprehensive approach to epitope vaccine design, combining computational analyses, molecular modeling, and simulation techniques to identify potential vaccine candidates for WNV.

Exploration of phytochemical compounds against Marburg virus using QSAR, molecular dynamics, and free energy landscape.

Marburg virus disease (MVD) is caused by the Marburg virus, a one-of-a-kind zoonotic RNA virus from the genus Filovirus. Thus, this current study employed AI-based QSAR and molecular docking-based virtual screening for identifying potential binders against the target protein (nucleoprotein (NP)) of the Marburg virus. A total of 2727 phytochemicals were used for screening, out of which the top three compounds (74977521, 90470472, and 11953909) were identified based on their predicted bioactivity (pIC50) and binding score (< - 7.4 kcal/mol). Later, MD simulation in triplicates and trajectory analysis were performed which showed that 11953909 and 74977521 had the most stable and consistent complex formations and had the most significant interactions with the highest number of hydrogen bonds. PCA (principal component analysis) and FEL (free energy landscape) analysis indicated that these compounds had favourable energy states for most of the conformations. The total binding free energy of the compounds using the MM/GBSA technique showed that 11953909 (ΔGTOTAL = - 30.78 kcal/mol) and 74977521 (ΔGTOTAL = - 30 kcal/mol) had the highest binding affinity with the protein. Overall, this in silico pipeline proposed that the phytochemicals 11953909 and 74977521 could be the possible binders of NP. This study aimed to find phytochemicals inhibiting the protein's function and potentially treating MVD.

Pooled rates and demographics of POTS following SARS-CoV-2 infection versus COVID-19 vaccination: Systematic review and meta-analysis.

PURPOSE: To address recent concerns of postural orthostatic tachycardia syndrome (POTS) occurring after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and coronavirus disease 2019 (COVID-19) vaccination. METHODS: We searched PubMed, Web of Science, and Scopus as of 1st June 2023. We performed a systematic review and meta-analysis of pooled POTS rate in SARS-CoV-2-infected and COVID-19-vaccinated groups from epidemiological studies, followed by subgroup analyses by characteristic. Meta-analysis of risk ratio was conducted to compare POTS rate in infected versus uninfected groups. Meta-analysis of demographics was also performed to compare cases of post-infection and post-vaccination POTS from case reports and series. RESULTS: We estimated the pooled POTS rate of 107.75 (95 % CI: 9.73 to 273.52) and 3.94 (95 % CI: 0 to 16.39) cases per 10,000 (i.e., 1.08 % and 0.039 %) in infected and vaccinated individuals based on 5 and 2 studies, respectively. Meta-regression revealed age as a significant variable influencing 86.2 % variance of the pooled POTS rate in infected population (P < 0.05). Moreover, POTS was 2.12-fold more likely to occur in infected than uninfected individuals (RR = 2.12, 95 % CI: 1.71 to 2.62, P < 0.001). Meta-analyzed demographics for cases of post-infection (n = 43) and post-vaccination (n = 17) POTS found no significant differences in several variables between groups, except that the time from exposure to symptom onset was shorter for cases of post-vaccination POTS (P < 0.05). CONCLUSION: Although evidence is limited for post-vaccination POTS, our study showed that POTS occur more frequently following SARS-CoV-2 infection than COVID-19 vaccination.

Microbiological trends and mortality risk factors of central line-associated bloodstream infections in an academic medical center 2015-2020.

BACKGROUND: Despite tremendous efforts to prevent central line-associated bloodstream infections, they still remain life-threatening complications among hospitalized patients with significant morbidity and mortality worldwide. The emerging antibiotic-resistant bacteria and other risk factors, including patient comorbidities, complicate patient management. METHODS: A single-center retrospective observational study was conducted at King Fahad Hospital of the University, Eastern Province, Saudi Arabia. Hospitalized patients with confirmed central line-associated bloodstream infections between January 2015 and December 2020 were included. The primary objectives were to investigate the trends in antibiotic susceptibility patterns of the causative agents, coexisting comorbid conditions, and other risk factors associated with mortality. RESULTS: A total of 214 patients with confirmed central line-associated bloodstream infections were included (CLABSI). The overall 30-day mortality rate was 33.6%. The infection rates per 1000 central line days for medical, surgical, and pediatric intensive care units were 4.97, 2.99, and 4.56 per 1000 CL days, respectively. The overall microbiological trends showed a predominance of Gram-negative agents, a steady increase of fungal CLABSI up to 24.0% in 2020, and a high prevalence of multidrug resistance up to 47% of bacterial CLABSI. In addition, the study indicates a significant negative surviving correlation with diabetes mellitus, cardiovascular disease, lung disease, chronic kidney disease, and the presence of ≥ 3 comorbidities (P < 0.05). CONCLUSION: The microbiological trends of the study population demonstrated a steady increase of CLABSI caused by Candida spp. with a predominance of Gram-negative pathogens. Stratifying the patients according to relevant mortality risk factors, including patient comorbidities, will help reduce CLABSI rates and improve patient outcomes.

Prevalence of Hepatocellular Carcinoma in Hepatitis B Population within Southeast Asia: A Systematic Review and Meta-Analysis of 39,050 Participants.

BACKGROUND AND AIM: Hepatocellular carcinoma (HCC) is a significant complication of hepatitis B and still poses a global public health concern. This systematic review and meta-analysis provide adequate details on the prevalence of HCC in the HBV population within Southeast Asian countries. METHOD: Following the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) criteria, a thorough search for literature discussing the prevalence of HCC in the HBV population within southeast Asia was performed. Eligible studies were subjected to a meta-analysis utilising a DerSimonian and Laird approach and a random effect model. A protocol was registered with PROSPERO (CRD42023423953). RESULT: Our study meticulously recovered 41 articles from seven countries in Southeast Asia, namely Cambodia, Indonesia, Malaysia, the Philippines, Singapore, Thailand, and Vietnam. A total of 39,050 HBV patients and 7479 HCC cases in southeast Asia were analysed. The pooled prevalence of HCC in HBV cases within southeast Asia was 45.8% (95% CI, 34.3-57.8%, I2 = 99.51%, p < 0.001). Singapore (62.5%, CI: 42.4-79.1) had the highest pooled prevalence of HCC in the HBV population compared to Vietnam, with the lowest estimate (22.4%, CI: 9.9-44.9). There was a drop in the pooled prevalence of HCC in HBV from 2016 until now (37.6%, CI: 19.2-60.5). CONCLUSION: The findings of this review reveal a high pooled prevalence of HCC in the HBV population and therefore stir the need for routine screening, management, and surveillance.

Deep and Transfer Learning Approaches for Automated Early Detection of Monkeypox (Mpox) Alongside Other Similar Skin Lesions and Their Classification.

The world faces multiple public health emergencies simultaneously, such as COVID-19 and Monkeypox (mpox). mpox, from being a neglected disease, has emerged as a global threat that has spread to more than 100 nonendemic countries, even as COVID-19 has been spreading for more than 3 years now. The general mpox symptoms are similar to chickenpox and measles, thus leading to a possible misdiagnosis. This study aimed at facilitating a rapid and high-brevity mpox diagnosis. Reportedly, mpox circulates among particular groups, such as sexually promiscuous gay and bisexuals. Hence, selectively vaccinating, isolating, and treating them seems difficult due to the associated social stigma. Deep learning (DL) has great promise in image-based diagnosis and could help in error-free bulk diagnosis. The novelty proposed, the system adopted, and the methods and approaches are discussed in the article. The present work proposes the use of DL models for automated early mpox diagnosis. The performances of the proposed algorithms were evaluated using the data set available in public domain. The data set adopted for the study was meant for both training and testing, the details of which are elaborated. The performances of CNN, VGG19, ResNet 50, Inception v3, and Autoencoder algorithms were compared. It was concluded that CNN, VGG19, and Inception v3 could help in early detection of mpox skin lesions, and Inception v3 returned the best (96.56%) classification accuracy.

Pharmacist-led education curriculum for fourth-year medical students: a single-center experience

Background: Doctors are usually challenged by the transition between theoretical basic science knowledge and actual clinical practice. Thus, a critical educational intervention is the early incorporation of pharmacists into the pharmacotherapy courses for undergraduate medical students from their college years and moving to the practice setting. Objective: We sought to determine if a pharmacist-led education course would improve medical students’ knowledge of general pharmacotherapy topics. Methods: All fourth-year female medical students were invited to enroll in the pharmacy practice curriculum between January and March 2022. The program was divided into three main domains: formal lectures, a hands-on prescription writing skills session, and on-site pharmacy practice sessions. The pharmacy practice session was divided into three sections: first section pharmacy practice, second section pharmacy innovation, and the third section clinical pharmacy. Those who completed the curriculum were requested to complete preand post-session assessments and curriculum evaluations. Results: One hundred fourteen medical students enrolled in the pharmacy practice module. One hundred eleven (97.4%) completed the pre-and post-course assessment. After completing the module, the medical students’ knowledge scores improved from pre- to post-course. A significant difference in the overall knowledge was observed between the pre-course and post-course scores (9.51 versus 16.04; p<0.001). The difference between the pre-course and post-course scores was also significant when comparing the knowledge per each part of the assessment, showing an average score of 2.78 versus 4.05 (p<0.001) for the first section; 3.39 versus 5.49 (p<0.001) for the second section; 3.34 versus 6.48 (p<0.001) for the third section. The program received overall positive feedback; the experience was rated overall as “Excellent” by 73% of the participants. (AU)

Extended infusion versus intermittent infusion of Piperacillin/ tazobactam: altering current methods to optimize future outcome

Due to worldwide bacterial resistance, researchers and clinicians were required to optimize existing antimicrobials by influencing the pharmacokinetics and pharmacodynamics (PK/PD) features. Piperacillin/tazobactam (PIP/TZB) is one of the most frequently empirical antibiotics prescribed globally. The aim of the review was to evaluate the use of an extended infusion (EI) versus an intermittent infusion (II) of PIP/TZB in hospital settings in terms of patient safety and efficacy. Several PK/PD studies assessed the use of an extended infusion of PIP/TZB to reach different minimum inhibitory concentration (MIC) levels for many microorganisms including Pseudomonas aeruginosa. One of the main parameters to define the size of the effect of PIP/TZB to various microorganisms is the percentage of time the free drug concentration above MIC (%fT > MIC). Many studies have compared extended infusion (EI) versus intermittent infusion (II) in terms of mortality rate, clinical cure or efficacy, length of stay whether in an intensive care unit (ICU) or hospital, duration of therapy, and cost. The clinical data reviewed in this article include PK/PD studies, prospective trials, systematic reviews, and meta-analysis. The review emphasized the role of an extended infusion in a population with altered pharmacokinetics including patients on continuous renal replacement therapy (CRRT), critically ill patients with augmented renal clearance, and patients with cystic fibrosis. Our review reports a positive trend when using an extended infusion of PIP/TZB which encourages the adoption and implementation of the extended infusion to achieve positive patient outcomes. Nevertheless, more studies are required to attain generalizable and reliable data to determine whether an extended infusion improves patient outcomes. (AU)

Cheminformatics and machine learning approaches for repurposing anti-viral compounds against monkeypox virus thymidylate kinase.

One of the emerging epidemic concerns is Monkeypox disease which is spreading globally. This disease is caused by the monkeypox virus (MPXV), with an increasing global incidence with an outbreak in 2022. One of the novel targets for monkeypox disease is thymidylate kinase, which is involved in pyrimidine metabolism. In this study, docking-based virtual screening and molecular dynamics techniques were employed in addition to the machine learning (ML) model to investigate the potential anti-viral natural small compounds to inhibit thymidylate kinase of MPXV. Several potential hits were identified through high-throughput virtual screening, and further top three candidates were selected, which ranked using the ML model. These three compounds were then examined under molecular dynamics simulation and MM/GBSA-binding free energy analysis. Among these, Chlorhexidine HCl showed high potential for binding to the thymidylate kinase with stable and consistent conformation with RMSD < 0.3 nm. The MM/GBSA analysis also showed the minimum binding free energy (ΔGTOTAL) of -62.41 kcal/mol for this compound. Overall, this study used structure-based drug design complemented by machine learning-guided ligand-based drug design to screen potential hit compounds from the anti-viral natural compound database.

Experimental drugs in randomized controlled trials for long-COVID: what's in the pipeline? A systematic and critical review.

INTRODUCTION: Over three years have passed since the emergence of coronavirus disease 2019 (COVID-19), and yet the treatment for long-COVID, a post-COVID-19 syndrome, remains long overdue. Currently, there is no standardized treatment available for long-COVID, primarily due to the lack of funding for post-acute infection syndromes (PAIS). Nevertheless, the past few years have seen a renewed interest in long-COVID research, with billions of dollars allocated for this purpose. As a result, multiple randomized controlled trials (RCTs) have been funded in the quest to find an effective treatment for long-COVID. AREAS COVERED: This systematic review identified and evaluated the potential of current drug treatments for long-COVID, examining both completed and ongoing RCTs. EXPERT OPINION: We identified four completed and 22 ongoing RCTs, investigating 22 unique drugs. However, most drugs were deemed to not have high potential for treating long-COVID, according to three pre-specified domains, a testament to the ordeal of treating long-COVID. Given that long-COVID is highly multifaceted with several proposed subtypes, treatments likely need to be tailored accordingly. Currently, rintatolimod appears to have modest to high potential for treating the myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) subtype, LTY-100 and Treamid for pulmonary fibrosis subtype, and metformin for general long-COVID prevention.

Postrenal transplant anemia and its effects on patients and graft outcomes: Seven years follow-up.

Introduction: Post-transplant anemia (PTA) is a common serious complication following kidney transplantation. It affects graft and patient survival. Anemia that presents within six months post-transplantation is defined as an early PTA. Late PTA is when anemia occurs more than six months following transplantation. Despite this, there are limited studies on the long-term impact of anemia on patient survival and graft function in kidney transplants. We conducted a retrospective study with long-term follow-up to investigate the effect of early and late PTA on patient and graft function within seven years and to estimate the prevalence of PTA at six months, two, four, and seven years postrenal transplantation along with the associated risk factors. Method: A retrospective chart review of 145 adult patients who had kidney transplants from January 1 to December 31, 2015, and were followed up until December 31, 2022. Anemia was defined according to the World Health Organization (WHO) criteria of hemoglobin<12 gm/dl in females and<13 mg/dl in males. Pretransplant, six months, two, four, and seven years postrenal transplantation medications and laboratory data were obtained. Patients were excluded if they were pediatrics or had missing data. Result: 180 patients were screened, and 145 patients met the inclusion criteria. The prevalence of early PTA was 8.3%. Trimethoprim-sulfamethoxazole was significantly associated with anemia within six months. The prevalence of anemia increased at two, four-, and seven-years post-transplant (24.8%, 24.8%, and 27.6%, respectively). Graft failure was significantly associated with late PTA at four and seven years (p-value < 0.001). P < 0.005, respectively). Death was reported for 3 patients, and it was significantly associated with late transplant anemia (p-value < 0.005), Cytomegalovirus was associated with anemia at 6 months and 2 years post-transplant and significantly associated with graft failure (p-value < 0.037). Conclusion: The results of this study indicate that post-transplant anemia is associated with graft failure and patient mortality. Therefore, managing anemia post-transplant should be addressed more carefully.

Highlights on the Development, Related Patents, and Prospects of Lenacapavir: The First-in-Class HIV-1 Capsid Inhibitor for the Treatment of Multi-Drug-Resistant HIV-1 Infection.

The multidrug-resistant (MDR) human immunodeficiency virus 1 (HIV-1) infection is an unmet medical need. HIV-1 capsid plays an important role at different stages of the HIV-1 replication cycle and is an attractive drug target for developing therapies against MDR HIV-1 infection. Lenacapavir (LEN) is the first-in-class HIV-1 capsid inhibitor approved by the USFDA, EMA, and Health Canada for treating MDR HIV-1 infection. This article highlights the development, pharmaceutical aspects, clinical studies, patent literature, and future directions on LEN-based therapies. The literature for this review was collected from PubMed, authentic websites (USFDA, EMA, Health Canada, Gilead, and NIH), and the free patent database (Espacenet, USPTO, and Patent scope). LEN has been developed by Gilead and is marketed as Sunlenca (tablet and subcutaneous injection). The long-acting and patient-compliant LEN demonstrated a low level of drug-related mutations, is active against MDR HIV-1 infection, and does not reveal cross-resistance to other anti-HIV drugs. LEN is also an excellent drug for patients having difficult or limited access to healthcare facilities. The literature has established additive/synergistic effects of combining LEN with rilpivirine, cabotegravir, islatravir, bictegravir, and tenofovir. HIV-1 infection may be accompanied by opportunistic infections such as tuberculosis (TB). The associated diseases make HIV treatment complex and warrant drug interaction studies (drug-drug, drug-food, and drug-disease interaction). Many inventions on different aspects of LEN have been claimed in patent literature. However, there is a great scope for developing more inventions related to the drug combination of LEN with anti-HIV/anti-TB drugs in a single dosage form, new formulations, and methods of treating HIV and TB co-infection. Additional research may provide more LEN-based treatments with favorable pharmacokinetic parameters for MDR HIV-1 infections and associated opportunistic infections such as TB.

Effect of Broad-Spectrum Antibiotic De-escalation on Critically Ill Patient Outcomes: A Retrospective Cohort Study.

PURPOSE: Antibiotic de-escalation (ADE) in critically ill patients is controversial. Previous studies mainly focused on mortality; however, data are lacking about superinfection. Therefore, we aimed to identify the impact of ADE versus continuation of therapy on superinfections rate and other outcomes in critically ill patients. METHODS: This was a two-center retrospective cohort study of adults initiated on broad-spectrum antibiotics in the intensive care unit (ICU) for ≥ 48 h. The primary outcome was the superinfection rate. Secondary outcomes included 30-day infection recurrence, ICU and hospital length of stay, and mortality. RESULTS: 250 patients were included, 125 in each group (ADE group and continuation group). Broad spectrum antibiotic discontinuation occurred at a mean of 7.2 ± 5.2 days in the ADE arm vs. 10.3 ± 7.7 in the continuation arm (P value = 0.001). Superinfection was numerically lower in the ADE group (6.4% vs. 10.4%; P = 0.254), but the difference was not significant. Additionally, the ADE group had shorter days to infection recurrence (P = 0.045) but a longer hospital stay (26 (14-46) vs. 21 (10-36) days; P = 0.016) and a longer ICU stay (14 (6-23) vs. 8 (4-16) days; P = 0.002). CONCLUSION: No significant differences were found in superinfection rates among ICU patients whose broad-spectrum antibiotics were de-escalated versus patients whose antibiotics were continued. Future research into the association between rapid diagnostics with antibiotic de-escalation in the setting of high resistance is warranted.

Performance of CURB-65 and ISARIC 4C mortality scores for hospitalized patients with confirmed COVID-19 infection in Saudi Arabia.

Background: The COVID-19 pandemic continues with new waves that could persist with the arrival of new SARS-CoV-2 variants. Therefore, the availability of validated and effective triage tools is the cornerstone for proper clinical management. Thus, this study aimed to assess the validity of the ISARIC-4C score as a triage tool for hospitalized COVID-19 patients in Saudi Arabia and to compare its performance with the CURB-65 score. Material and methods: This retrospective observational cohort study was conducted between March 2020 and May 2021 at KFHU, Saudi Arabia, using 542 confirmed COVID-19 patient data on the variables relevant to the application of the ISARIC-4C mortality score and the CURB-65 score. Chi-square and t-tests were employed to study the significance of the CURB-65 score and the ISARIC-4C score variables considering the ICU requirements and the mortality of COVID-19 hospitalized patients. In addition, logistic regression was used to predict the variables related to COVID-19 mortality. In addition, the diagnostic accuracy of both scores was validated by calculating sensitivities, specificities, positive predictive value, negative predictive value, and Youden's J indices (YJI). Results: ROC analysis showed an AUC value of 0.834 [95% CI; 0.800-0.865]) for the CURB-65 score and 0.809 [95% CI; 0.773-0.841]) for the ISARIC-4C score. The sensitivity for CURB-65 and ISARIC-4C is 75% and 85.71%, respectively, while the specificity was 82.31% and 62.66%, respectively. The difference between AUCs was 0.025 (95% [CI; -0.0203-0.0704], p = 0.2795). Conclusion: Study results support external validation of the ISARIC-4C score in predicting the mortality risk of hospitalized COVID-19 patients in Saudi Arabia. In addition, the CURB-65 and ISARIC-4C scores showed comparable performance with good consistent discrimination and are suitable for clinical utility as triage tools for hospitalized COVID-19 patients.

Effect of zinc supplementation on symptom reduction and length of hospital stay among pediatric patients with Coronavirus disease 2019 (COVID-19).

Objectives: Zinc is considered an essential multipurpose trace element because of its ability to act as a cofactor and signaling molecule. As reported in earlier studies of pediatric respiratory infection management, zinc exhibits potent immunoregulatory and antiviral properties, but its effects on pediatric patients with COVID-19 remain unknown. The aim of this study was to determine the extent to which zinc supplementation improves COVID-19 symptoms, length of hospitalization and, to determine how zinc supplementation impacts ICU admission, in-hospital mortality, need for ventilation, duration of ventilation, need for vasopressors, development of liver injury, or respiratory failure. Methods: Pediatric patients younger than 18 years with confirmed COVID-19 infection during the study period (March 1, 2020, to December 31, 2021) were recruited for this retrospective cohort study. The study population was divided into two arms (zinc/no zinc supplementation as an adjunct to standard therapy). Results: Of 169 hospitalized patients who were screened, 101 met the inclusion criteria. No statistically significant association was found between the administration of zinc as adjunctive therapy and symptom reduction, intensive care unit (ICU) admission, or mortality (p = 0.105; p = 0.941, and p = 0.073, respectively). However, zinc supplementation was associated with a statistically significant reduction in respiratory failure and length of hospitalization (p = 0.004 and p = 0.017, respectively), also, zinc administration was associated with elevated serum creatinine (p = 0.01*). Conclusions: Among pediatric patients with COVID-19, zinc supplementation was associated with shorter hospital stay. However, there was no significant difference between the two groups in terms of symptom improvement, in-hospital mortality, or ICU admission. In addition, the study raises question about the possibility of kidney injury as indicated by high levels of serum creatinine.