Characterization of recurrent cytomegalovirus reactivations post allogenic stem cell transplantation in a population with high seropositivity.

OBJECTIVES: This study aimed to characterize incidences of CMV reactivations within one year post-allo-SCT and identify risk factors for CMV second reactivation episode in population with high seropositivity where first CMV reactivation episode deemed to be high. METHODS: This retrospective cohort study analyzed data from 359 allo-SCT patients aged 14 and older admitted to a tertiary academic hospital. Data on demographic and clinical factors, CMV serostatus, conditioning regimens, graft-versus-host disease prophylaxis, engraftment time, and CMV reactivations were collected. RESULTS: First and second CMV reactivations occurred in 88.9% and 18.4% of post-allo-SCT patients respectively. Patients were stratified into two groups based on primary disease necessitating allo-SCT, patients with malignant (Group 1) and non-malignant (Group 2) hematological disease. Factors associated with the second reactivation included cord blood as a stem cell source, human leukocyte antigen mismatch, acute graft-versus-host disease, and hematological malignancies. Patients with non-malignant hematological disease displayed better outcomes, including a higher rate of spontaneous clearance of first CMV reactivation (70% versus 49.4%) and lower rates of second CMV reactivation (9.6% versus 31%) than those with malignant hematological disease. The one-year overall survival rate was 87.7% (95.5% in non-malignant hematological disease and 78.13% in malignant hematological disease). CONCLUSION: Our findings are concordant with previous local study in regard to high rate of first CMV reactivation post-allo-SCT. It appears that patients with nonmalignant hematological disease had better outcomes, such as lower second CMV reactivation and higher survival rates compared to patients with malignant hematological disease. Further investigation is needed to identify other factors affecting recurrent CMV reactivations in allo-SCT in patients with malignant hematological disease.

Effectiveness of oral antibiotics in managing extended-spectrum B-lactamase urinary tract infections: A retrospective analysis.

Background: Urinary tract infections caused by extended-spectrum beta-lactamase organisms pose a significant concern worldwide. Given the escalating prevalence of drug resistance and the limited data on the effectiveness of oral antibiotics in treating these infections, this study aimed to assess the clinical outcomes in adult patients with extended-spectrum beta-lactamase urinary tract infections treated with oral antibiotics. Methods: A retrospective observational cohort study was conducted at King Abdulaziz Medical City, Saudi Arabia, from January 2018 to December 2021. It included patients ⩾18 years with complicated or uncomplicated urinary tract infections from extended-spectrum beta-lactamase Enterobacterales and treated with oral antibiotics as step-down or mainstay therapy. All-cause clinical failure within 30 days post-discharge was evaluated as the efficacy outcome. Statistical analyses were performed using SPSS software. Results: Out of 643 screened patients, 152 patients met the inclusion criteria. The patients were divided into oral step-down therapy (51.3%) and oral-only (48.7%) groups. The majority (69.1%) were females, with a mean age of 62 years. Complicated urinary tract infections were diagnosed in (75.5%) of cases, and the predominant pathogen was E. coli (79.6%). Clinical failure was observed in 23.1% in the oral step-down group and 13.5% in the oral-only group, with no significant difference (p = 0.128). Total antibiotics duration was significantly lower in the oral-only group (8 days vs. 12.2 days; p < 0.001). Binary logistic regression identified elder age, diabetes mellitus history, and prior extended-spectrum beta-lactamase infection as predictors of clinical failure. Conclusion: This study suggests that both step-down or primary oral antibiotic treatment yielded similar clinical outcomes in managing patients with extended-spectrum beta-lactamase urinary tract infections. Further prospective studies are required to validate these findings.

Abelacimab: A leap forward in anticoagulation with FXI and FXIa Inhibition.

Direct Oral Anticoagulants (DOACs) have revolutionized the treatment of thromboembolic disorders, offering targeted, effective, and safer alternatives to traditional anticoagulants like heparins and vitamin K antagonists (VKAs). Despite their benefits, DOACs have drawbacks, including an increased risk of gastrointestinal bleeding and unsuitability for patients with mechanical heart valves. Recent research has highlighted Factor XI (FXI) as a promising anticoagulation target due to its significant role in pathological thrombosis and minor involvement in normal hemostasis. Abelacimab, an antibody that inhibits FXI, has shown potential in transforming anticoagulation therapy by sparing hemostasis. This review provides a comprehensive analysis of abelacimab, examining its clinical pharmacology and its pharmacokinetic and pharmacodynamic properties. It scrutinizes abelacimab's safety profile and key monitoring parameters. The current evidence supporting its use and potential future research strengthening its position in anticoagulant therapy is also discussed. The objective is to enhance understanding and contribute to discussions around developing safer anticoagulants, particularly for patients at risk for thrombosis.

Advancing the understanding of venetoclax in t(11;14)-positive multiple myeloma: a comprehensive review of clinical evidence and future prospects.

Venetoclax is a selective inhibitor of the anti-apoptotic protein B-cell lymphoma 2 (BCL2), as a targeted therapy for multiple myeloma (MM) patients. It was initially approved by the United States Food and Drug Administration for the treatment of chronic lymphocytic leukemia in April 2016 and later for acute myeloid leukemia in October 2020. However, venetoclax is used as an off-label in a subset group of relapsed and refractory multiple myeloma (RRMM) patients with the presence of translocation t(11;14). Preclinical and clinical studies have highlighted the potential of venetoclax in the management of MM patients, with a specific focus on t(11;14) as a predictive biomarker for initiating venetoclax-based treatment. Later, several studies in RRMM patients that used venetoclax in combination with dexamethasone or/and proteasome inhibitors have shown promising results, in which management guidelines have included venetoclax as one of the options to treat MM patients. Hence, this review focuses on the use of venetoclax in RRMM, clinical efficacy, safety, dosing strategies, and predictive biomarkers for initiating venetoclax. Additionally, we discuss ongoing studies that are investigating different combination of venetoclax regimens in MM patients.

Zanubrutinib in Mantle Cell Lymphoma Management: A Comprehensive Review.

Purpose: The pharmacology, pharmacokinetics, pharmacodynamics, clinical efficacy, and safety of zanbrutinib are described. Summary: Mantle cell lymphoma (MCL) is a mature B-cell lymphoma that is typically associated with unfavorable outcomes, and virtually all patients with MCL have refractory or relapsed disease despite aggressive treatment. The treatment paradigm for MCL has transformed dramatically over the past decade owing to rapid advancements in immunotherapy and molecular-targeted therapies. Zanubrutinib, a second-generation Bruton's tyrosine kinase inhibitor (BTKI) designated for mature B-cell non-Hodgkin's lymphoma (NHL), has drastically improved the survival outcomes in relapsed/refractory (R/R) MCL patients. This selective BTKI is a small molecule that functions by forming a covalent bond in the active site of BTK. The inhibition of BTK activity is essential for the signaling of B-cell antigen receptor (BCR) and cytokine receptor pathways. In a preclinical study, zanubrutinib inhibited malignant B-cell proliferation and reduced tumor growth. Zanubrutinib was granted FDA-accelerated approval based on the results of Phase I and II trials. The investigator-assessed overall response rate was 83.7%, of which 78% of patients achieved complete response. The median duration of response was 19.5 months, and the median progression-free survival was 22.1 months. The most common (≥20%) all-grade adverse events were low neutrophil count (46.5%), upper respiratory tract infection (38.4%), rash (36.0%), low white blood cell count (33.7%), and low platelet count (32.6%). Conclusion: Zanubrutinib is a selective, next-generation, orally active, irreversible BTK inhibitor. The selectivity of zanubrutinib and its superior efficacy, with a well-tolerated safety profile, have proven to be attractive options for other malignancies.

Assessing the influence of COVID-19 on influenza prevalence: A multicenter time series study.

BACKGROUND: During the COVID-19 pandemic, countries around the world implemented various interventions to manage the spread of respiratory illnesses, including influenza. However, there is a lack of studies that have assessed the influence of COVID-19 on influenza prevalence in Saudi Arabia. In this study, we aimed to evaluate the prevalence of positive influenza cases before and during the COVID-19 pandemic in relation to the mitigation measures and policy initiatives in Saudi Arabia. METHODS: A multicenter, time-series cross-sectional study was conducted to evaluate influenza prevalence before and during the COVID-19 pandemic between 01/01/2017 and 31/12/2021. This study included all patients who were screened for influenza infection at healthcare facilities across Saudi Arabia using polymerase chain reaction (PCR). The primary outcome was to determine the prevalence of influenza infections before and during the COVID-19 pandemic, while the secondary outcome was to describe the demographic data and comorbidities of the included patients in both periods. RESULTS: During the study period, 5238 cases were identified based on a positive PCR result for influenza virus. The yearly number of influenza cases in the pre-COVID-19 period was 1123 (2.03 %), 1075 (1.63 %), and 1883 (2.20 %) cases in 2017, 2018, and 2019, respectively. On the other hand, the number of cases during the COVID-19 pandemic was 417 (0.63 %) and 740 (1.27 %) in 2020 and 2021, respectively, with a comparable number of performed tests. Patients infected with the influenza virus between 2020 and 2021 were older than patients who were infected before the COVID-19 pandemic. CONCLUSION: The study found a lower number of influenza cases during the COVID-19 pandemic, with no clear peak during November and December 2020 and 2021.

Revolutionizing healthcare: the role of artificial intelligence in clinical practice.

INTRODUCTION: Healthcare systems are complex and challenging for all stakeholders, but artificial intelligence (AI) has transformed various fields, including healthcare, with the potential to improve patient care and quality of life. Rapid AI advancements can revolutionize healthcare by integrating it into clinical practice. Reporting AI's role in clinical practice is crucial for successful implementation by equipping healthcare providers with essential knowledge and tools. RESEARCH SIGNIFICANCE: This review article provides a comprehensive and up-to-date overview of the current state of AI in clinical practice, including its potential applications in disease diagnosis, treatment recommendations, and patient engagement. It also discusses the associated challenges, covering ethical and legal considerations and the need for human expertise. By doing so, it enhances understanding of AI's significance in healthcare and supports healthcare organizations in effectively adopting AI technologies. MATERIALS AND METHODS: The current investigation analyzed the use of AI in the healthcare system with a comprehensive review of relevant indexed literature, such as PubMed/Medline, Scopus, and EMBASE, with no time constraints but limited to articles published in English. The focused question explores the impact of applying AI in healthcare settings and the potential outcomes of this application. RESULTS: Integrating AI into healthcare holds excellent potential for improving disease diagnosis, treatment selection, and clinical laboratory testing. AI tools can leverage large datasets and identify patterns to surpass human performance in several healthcare aspects. AI offers increased accuracy, reduced costs, and time savings while minimizing human errors. It can revolutionize personalized medicine, optimize medication dosages, enhance population health management, establish guidelines, provide virtual health assistants, support mental health care, improve patient education, and influence patient-physician trust. CONCLUSION: AI can be used to diagnose diseases, develop personalized treatment plans, and assist clinicians with decision-making. Rather than simply automating tasks, AI is about developing technologies that can enhance patient care across healthcare settings. However, challenges related to data privacy, bias, and the need for human expertise must be addressed for the responsible and effective implementation of AI in healthcare.

Ocular toxicities associated with antibody drug conjugates and immunotherapy in oncology: clinical presentation, pathogenesis, and management strategies.

INTRODUCTION: The development of molecularly targeted anticancer therapies and immunotherapy continues to revolutionize the treatment of cancer. FDA accelerated approvals of novel targeted therapies allowed for introduction of these agents into the clinic at a rapid rate. On-and off-target ocular toxicities are prevalent treatment-related adverse events of newer therapies including antibody drug conjugates (ADCs) and immunotherapy. Ocular toxicities associated with ADCs and immunotherapy have heterogeneous presentations and pathogenesis requiring unique and often complex monitoring, and management. AREAS COVERED: In this article, we provide an updated review of treatment-emergent ocular toxicity associated with new and novel oncologic therapies and summarize guidelines and best practice strategies for prevention, monitoring and management. A literature search was performed through PubMed, ClinicalTrials.gov, and FDA website (1 January 2017 to 10 May 2023) to identify relevant information. EXPERT OPINION: The implementation of a strategy for monitoring, prevention, and management of treatment-related ocular toxicities involves a multi-disciplinary, often cross-center approach. Communication with infusion nursing leadership, clinic staff, and eye care providers is crucial to the successful implementation of eye care plans to prevent and manage ocular toxicity.

Late-onset cardiotoxicity in patients with HER2-positive metastatic breast cancer receiving trastuzumab-based therapy.

INTRODUCTION: Patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC) typically receive long-term trastuzumab treatment for several years. The aim of our study is to identify the incidence and characterize late-onset cardiotoxicity in patients with HER2-positive MBC receiving trastuzumab-based therapy. METHODS: We retrospectively reviewed charts of HER2-positive MBC patients who received >1 year of trastuzumab-based therapy at the Massachusetts General Hospital Cancer Center over three-year period. The primary endpoint was development of trastuzumab-induced cardiotoxicity (TIC). Secondary endpoints included time to TIC development, incidence/duration of trastuzumab interruption due to TIC, incidence of permanent discontinuation of trastuzumab due to TIC, clinic visit, or hospitalization due to TIC. RESULTS: Thirty-seven patients were included. Mean age was 56 years (range: 33-78 years, SD 9.5). Seven patients received prior doxorubicin and 14 patients received previous or concurrent breast irradiation. Mean duration of trastuzumab-based therapy was 57 months (range: 14-140 months, SD 39.3). Seven patients (18.9%) experienced TIC resulting in treatment interruption for two patients (28 and 78 days). The median time from starting trastuzumab therapy to TIC was 14 months (interquartile range: 11-29.5 months). The mean number of left ventricular ejection fraction (LVEF) assessment completed per year was 2.7 (range: 1.2-6.6, SD 1.1). CONCLUSION: Cardiotoxicity occurred in a minority of patients with HER2-positive MBC receiving trastuzumab-based therapy for more than one year. LVEF reductions to below the institutional lower limit of normal and therapy modifications were uncommon.

Identifying gaps in vaccination perception after mandating the COVID-19 vaccine in Saudi Arabia.

OBJECTIVE: The burden of COVID-19 pandemic affected the globe, and it is unclear how it has impacted the general perception of other vaccines. We aimed to investigate the public awareness, knowledge, and attitude towards other complementary vaccines after the mandate of the COVID-19 vaccine. METHODS: A cross-sectional study was conducted in Saudi Arabia using a survey distributed via several social media platforms in June 2022. The questionnaire had three main sections; awareness; attitudes; and demographic information. Descriptive analysis was mainly used and supplemented with Chi-square test for correlation. All individuals over the age of 18 were eligible to participate in the study. RESULTS: A total of 1,045 participants from Saudi Arabia completed the survey. Of the respondents, 55.9% were female, and 95% were Saudi citizens. Public awareness towards vaccines after the mandate of COVID-19 vaccine was the highest with the influenza vaccine (98.2%), followed by human papillomavirus (HPV) (40.7%), tetanus, diphtheria, and pertussis (Tdap) (37.2%), and lastly, pneumococcal vaccine (17%). More than 50% of the participants expressed their willingness to receive any of the four vaccines if they knew about the benefits related to these vaccines. CONCLUSION: The study showed that participants were willing to receive the vaccination if they were aware of the general benefits of vaccinations. Therefore, health education and campaigns toward recommended vaccines for high-risk group are essential and needed.

Assessing the Perception of Pharmacy Students on Launching a Doctor of Pharmacy/Master of Public Health Dual Degree Program in Saudi Arabia: A Multi-Institutional Cross-Sectional Study.

There is a lack of Doctor of Pharmacy (PharmD) and Master of Public Health (MPH) dual degree programs in Saudi Arabia. This study aims to examine current pharmacy students' perceptions regarding establishing such a program and the perceived limitations and advantages of pursuing such a degree. We conducted a cross-sectional web-based short survey to assess the feasibility of establishing a PharmD/MPH dual degree program in several randomly selected pharmacy schools in Saudi Arabia. Our cohort consisted of 657 students. Almost 56% were males, and nearly 58% were fourth-year pharmacy students. Close to 85% had a "very well" or "well" understanding regarding the pharmacist's role in the public health area, and almost 70% stated that they see themselves playing a role in public health as a future pharmacist. Nearly 93% reported that they are either "very likely" or "likely" to enroll in such a program if given the opportunity. Almost 80% felt it would increase their job opportunities. On the other hand, close to 70% felt it would increase workload and stress. This study highlights pharmacy students' positive perceptions regarding establishing a PharmD/MPH dual degree program in Saudi Arabia. The study results could be utilized as the starting point to propose and establish this program to health education policymakers in Saudi Arabia.

Evaluation of Emergency Department Visits by Oncology Patients: A Running Comparison to Admissions and ED Visits Under the CMS OP-35 Ruling.

Background: Cancer is the second leading cause of death in the United States. The incidence of emergency department (ED) visits by oncology patients has grown over the past years. Some ED visits are medically unnecessary and could be prevented with improved prevention measures. Objectives: To evaluate the incidence and causes of ED visits by cancer patients and evaluate outcomes and disposition of ED visits. Methods: This single-center, retrospective chart review was conducted in a tertiary medical hospital. We collected data using an electronic medical record and included oncology patients with active cancer who had ED visits from January 1, 2018, to December 31, 2018. Key data collection included baseline demographics; type of malignancy; main chief complaint; clinic visit history; current and past ED visits; treatment and supportive care data; and disposition status if admitted. Pregnant patients, patients without active cancer, and patients who received outpatient care at clinics other than the University of Arizona Cancer Center were excluded. Results: This chart review study screened 1,659 encounters and included 205 encounters. Approximately 70% of the encounters were solid tumor patients and 30% were hematologic malignancies. Nearly 50% of the patients with hematologic malignancies had preventable ED visits while 32.8% of solid tumor patients had preventable ED visits. The most common preventable ED visit reasons in both groups were pain, fever, nausea, vomiting, and dehydration. Almost 50% of the patients in both groups were hospitalized with a median length of stay of 3 days. The majority of admitted patients were discharged home in both the solid tumor (82.3%) and hematologic malignancy (83.8%) groups. Conclusion: This study showed that the rate of preventable visits was numerically higher in the hematologic cancer group compared with the solid tumor group. These findings highlight the potential need for implementing prevention measures in the future.

A long-distance rRNA base pair impacts the ability of macrolide antibiotics to kill bacteria.

While most of the ribosome-targeting antibiotics are bacteriostatic, some members of the macrolide class demonstrate considerable bactericidal activity. We previously showed that an extended alkyl-aryl side chain is the key structural element determining the macrolides' slow dissociation from the ribosome and likely accounts for the antibiotics' cidality. In the nontranslating Escherichia coli ribosome, the extended side chain of macrolides interacts with 23S ribosomal RNA (rRNA) nucleotides A752 and U2609, that were proposed to form a base pair. However, the existence of this base pair in the translating ribosome, its possible functional role, and its impact on the binding and cidality of the antibiotic remain unknown. By engineering E. coli cells carrying individual and compensatory mutations at the 752 and 2609 rRNA positions, we show that integrity of the base pair helps to modulate the ribosomal response to regulatory nascent peptides, determines the slow dissociation rate of the extended macrolides from the ribosome, and increases their bactericidal effect. Our findings demonstrate that the ability of antibiotics to kill bacterial cells relies not only on the chemical nature of the inhibitor, but also on structural features of the target.

Attitude and Perception of Physicians and Nurses Toward the Role of Clinical Pharmacists in Riyadh, Saudi Arabia: A Qualitative Study.

Clinical pharmacists are responsible for guiding pharmacotherapy and ensuring medication safety along with other health-care providers. This study highlighted barriers that physicians and nurses encounter when interacting with clinical pharmacists. Twenty-seven physicians and nurses were randomly invited to participate in focus-group discussions. Five focus-group discussions were recorded and then transcribed, and the transcripts were reviewed and coded. Three major themes were identified, which were the role of clinical pharmacists, interprofessional communication, and competency. The greatest challenge reported in this study was lack of consistent understanding of the role of clinical pharmacists which to some extent caused communication deficiencies and affected the level of involvement with multidisciplinary teams. Despite that, majority of the participants perceived pharmacists as beneficial in optimizing pharmacotherapy and improving quality of care. Clinical pharmacy services are perceived positively in impacting quality of care as expressed by majority of the study participants. However, there is a lack of common understanding of the role of clinical pharmacists by other health-care providers.

Awareness of venous thromboembolism and thromboprophylaxis among hospitalized patients: a cross-sectional study.

BACKGROUND: Patient awareness of venous thromboembolism (VTE) and thromboprophylaxis is essential for their safety. In this study, we evaluated patients' awareness of VTE and their perceptions of thromboprophylaxis. METHODS: We administered a cross-sectional survey to patients hospitalized at the King Abdulaziz Medical City, Riyadh, Saudi Arabia. RESULTS: Of 190 patients approached, 174 completed the survey, constituting a response rate of 95%. Most participants (72%) were receiving thromboprophylaxis. However, only 32 and 15% reported knowledge of deep vein thrombosis (DVT) and pulmonary embolism (PE), respectively. Fifty-five percent of participants with knowledge of DVT identified swelling of the leg as a symptom. Risk factors for blood clot development were correctly identified by about half of participants, although most agreed that blood clots can cause death (77%). The level of awareness of DVT or PE did not significantly differ by respondents' demographics. However, awareness of DVT or PE was significantly higher among those with a personal or family history of VTE. Participants had positive perceptions of thromboprophylaxis and were satisfied with treatment (> 69%), but perceived its adverse effects less favorably and reported lower satisfaction with the information provided about DVT and PE (46%). CONCLUSION: This study demonstrates the lack of awareness of VTE, DVT, and PE among hospitalized patients. More attention must be paid to patient education to ensure safe and high-quality patient care.