Developments in treatment for middle east respiratory syndrome coronavirus (MERS-CoV).

INTRODUCTION: An important respiratory pathogen that has led to multiple hospital outbreaks both inside and outside of the Arabian Peninsula is the Middle East Respiratory Syndrome Coronavirus (MERS-CoV). Given the elevated case fatality rate, there exists a pressing requirement for efficacious therapeutic agents. AREAS COVERED: This is an updated review of the developments in MERS treatment approaches. Using databases like PubMed, Embase, Cochrane, Scopus, and Google Scholar, a thorough search was carried out utilizing keywords like 'MERS,' 'MERS-CoV,' and 'Middle East respiratory syndrome' in conjunction with 'treatment' or 'therapy' from Jan 2012 to Feb 2024. EXPERT OPINION: MERS-CoV is a highly pathogenic respiratory infection that emerged in 2012 and continues to pose a significant public health threat. Despite ongoing efforts to control the spread of MERS-CoV, there is currently no specific antiviral treatment available. While many agents have been tested both in vivo and in vitro, none of them have been thoroughly examined in extensive clinical trials. Only case reports, case series, or cohort studies have been made available as clinical studies. However, there is a limited number of randomized-controlled trials. Because cases are irregular and sporadic, conducting a large prospective randomized trials for establishing an efficacious treatment might be difficult.

RNA therapeutics for diarrhea.

Diarrhea is caused by a variety of bacterial and viral agents, inflammatory conditions, medications, and hereditary conditions. Secretory diarrhea involves several ion and solute transporters, activation of the cyclic nucleotide and Ca2+ signaling pathways, as well as intestinal epithelial secretion. In many cases of secretory diarrhea, activation of Cl- channels, such as the cystic transmembrane conduction regulator and the Ca2+stimulated Cl- channel fibrosis, promote secretion while concurrently inhibiting Na+ transport expressing fluid absorption. Current diarrhea therapies include rehydration and electrolyte replacement via oral rehydration solutions, as well as medications that target peristalsis or fluid secretion. The rising understanding of RNA function and its importance in illness has encouraged the use of various RNAs to operate selectively on "untreatable" proteins, transcripts, and genes. Some RNA-based medications have received clinical approval, while others are currently in research or preclinical studies. Despite major obstacles in the development of RNA-based therapies, many approaches have been investigated to improve intracellular RNA trafficking and metabolic stability.

Evidence for transmission of SARS-CoV-2 at religious mass gatherings: A systematic review.

Background: Transmission of SARS-CoV-2 at major mass gatherings (MGs) has been observed during the COVID-19 pandemic. Methods: In this systematic review done according to the PRISMA guidelines, PubMed and Scopus databases were searched for relevant studies to describe the epidemiology of SARS-CoV-2 in relation to major religious MGs including the Grand Magal of Touba (GMT), Hajj, Umrah, Kumbh Mela, Arbaeen and Lourdes pilgrimage during the COVID-19 pandemic. Results: Ten articles met the inclusion criteria and were included.No cases of SARS-CoV-2 were detected at 2020 and 2021 GMT or at the 2020 Hajj. In a small study, 7 % of tested individuals were positive after the 2022 GMT. SARS-CoV-2 prevalence during the 2021-2022 Hajj and Umrah seasons varied from 0 to 15 % in different studies. At the 2021 Kumbh Mela, 0.4 million COVID-19 cases were diagnosed among returning pilgrims across India and 1 % tested positive during a one-day survey conducted on participants. During the 2021 Arbaeen pilgrimage, 3 % pilgrims were tested positive. No relevant data were found in relation to SARS-CoV-2 transmission at the 2021 Arbaeen and Lourdes pilgrimages. Conclusion: The transmission of the SARS-CoV-2 virus during religious MG events depends on many factors such as: the number and density of pilgrims, the intensity of circulation of the virus in the hosting country and in countries sending international participants at the time of the event, the transmissibility of virus variants at the time of the event, the various preventive measures adopted, and the immune status of the pilgrims.

The impact of antibiotic use in gastrointestinal tumors treated with immune checkpoint inhibitors: systematic review and meta-analysis.

Background: Immune checkpoint inhibitors (ICI) have improved overall survival in patients with different cancer types. However, treatment efficacy varies between patients depending on several factors. Recent research suggested that antibiotic-induced dysbiosis can impair ICI efficacy. Here we review the impact of antibiotic use in clinical outcome of patients with gastrointestinal cancer treated with ICI. Methods: This is a systematic review and utilized a thorough search of MEDLINE, Cochrane, Scopus, EB-SCO, Web of Science of studies published till September 2023. The aim of the study is to determine the association between antibiotic use and ICI treatment efficacy in patients with gastrointestinal cancers (GI). We utilized a meta-analysis of the association between the use of antibiotics and overall survival and progression-free survival. Results: Nine studies met the inclusion criteria with a total of 2,214 patients. The most common type of cancers was hepatocellular carcinoma (HCC). The majority of the studies were retrospective, and one was collective of clinical trials. The use of antibiotics was associated with decreased both overall survival [haz-ard ratio (HR) 1.92, 95% confidence interval (CI) 1.41, 2.63] and progression-free survival [HR 1.81, 95% CI 1.29, 2.54]. Conclusion: The use of antibiotics may affect clinical outcomes in patients with GI cancers treated with ICI. Further prospective studies are needed to improve the understanding of this phenomenon. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023462172.

Middle East Respiratory Syndrome Coronavirus Could be a Priority Pathogen to Cause Public Health Emergency: Noticeable Features and Counteractive Measures.

Middle East respiratory syndrome (MERS) is caused by a specific strain of the 6 types of human coronaviruses (HCoV). MERS-CoV has spread unchecked since it was first discovered in Saudi Arabia in 2012. The virus most likely spreads through nosocomial and zoonotic channels. Genetic analyses suggest that bats were the initial hosts and that the disease spread to camels. Person-to-person transmission occurs with varying frequency, being most prevalent in clinical settings and the least common among the general population and among close relatives. Due to the severity of the illness, high fatality rate, potential for epidemic spread, and lack of adequate medical countermeasures, the World Health Organization (WHO) continues to list MERS-CoV as a priority pathogen. While no specific antiviral medicines exist, a combination of antivirals has shown promise in recent clinical trials. Vaccines against MERS-CoV are critically needed and are currently being developed. Early diagnosis and implementing appropriate infection control measures are keys to preventing hospital-associated outbreaks. Preventive measures include avoiding raw or undercooked meats and other animal products, ensuring proper hand hygiene in healthcare settings and around dromedaries, educating the public and healthcare personnel about the disease, and adhering to other recommended practices. Countries with a high prevalence of MERS should adhere to regulations designed to limit the transmission of the virus. The recent spread of MERS-CoV highlights the importance of public awareness regarding the significance of reporting symptoms so that appropriate control measures can be adopted. The narrative review discusses the incidence of MERS, its clinical presentation, potential transmission routes, recent reports, preventative and control measures, and current therapeutic options.

Perceived Knowledge, Guidelines Concordance, and Practices of Physicians for Management of Recurrent Urinary Tract Infections in Women.

Background: Recurrent urinary tract infections (rUTIs) are common complaints that burden the healthcare system. Reporting perceived knowledge and guidelines in concordance regarding the management of (rUTI) is essential for providing better healthcare and higher treatment rate. This study assesses the perceived knowledge, guidelines concordance, and physicians' practices toward treatment of (rUTI) among physicians with different specialties. Study Design: This questionnaire-based survey included residents, fellows, and consultants of various specialties across several regions in Saudi Arabia. Results: A total of 419 physicians were included in the final analysis. In terms of age distribution, the majority were 28-38 years of age (159, 37.9%), followed by 18-28 years (99, 23.6%). Gender distribution was nearly balanced. The sample included a significant number of residents (182, 43.4%), consultants (173, 41.3%), and fellows (64, 15.3%). OBS/GYNE shows a significant presence of females (40.6%) and is notably represented in private hospitals or clinics (52.5%) and among fellows (40.6%) and consultants (32.4%). Infectious disease physicians had the highest perceived knowledge scores (3.83 ± 0.09), followed closely by urologists/urogynecologists (3.67 ± 0.48). Urologists/urogynecologists also reported the highest satisfaction (4.24 ± 0.83) and familiarity (2.89 ± 1.11) with new rUTI guidelines. Infectious disease physicians were most confident (3.50 ± 0.71) in communicating with patients about rUTI treatment options. In terms of practices and guideline adherence, obstetricians/gynaecologists were more likely to repeat urine sample tests for suspected contamination (3.73 ± 1.00) and less likely to treat asymptomatic bacteriuria (1.33 ± 0.59) the same as UTIs compared to other physicians. They also scored highest in conducting post-treatment tests for asymptomatic patients (3.21 ± 1.37) and recommending vaginal estrogen therapy for peri- and post-menopausal women to prevent UTIs (3.59 ± 1.06) among all specialties. Conversely, urologists and urogynecologists were more likely to discuss antibiotic prophylaxis (3.79 ± 0.89) and cranberry prophylaxis (3.71 ± 0.73) with their rUTI patients. Conclusion: The findings highlight variations in knowledge, satisfaction, familiarity with guidelines, confidence in communication, and guideline concordance among different physician specialities regarding the management of UTIs and rUTIs.

The impact of COVID-19 and other factors on the usage status of the biologic drug therapies for rheumatoid arthritis: A study from Vietnam.

OBJECTIVES: To describe the status of using biological Disease Modifying Anti Rheumatic Drugs (bDMARDs) to treat rheumatoid arthritis (RA) and related factors. In addition, the study determined the impact of COVID-19 on the usage of bDMARDs. METHODS: This is a cross-sectional study and included 219 RA patients over 18 years old. The Kaplan-Meier method and the log-rank test (p<0.05) were used to estimate the retention time and compare between different times. Cox regression analysis was used to determine the factors affecting the retention time of biological drugs (p<0.05). RESULTS: Out of 1967 courses of treatment, there were 149 (7.6%) drug discontinuations, 760 (38.6%) doses extensions and 64 (3.3%) drug switch. Moderate disease level and choosing tumor necrosis factor (TNF) inhibitors initially were associated with retention time of COVID-19. Drug discontinuations and dose extensions increased after COVID-19 emergence. The retention time during COVID-19 was significantly different from that of pre-COVID-19. Gender, type of first-used bDMARD, conventional synthetic DMARDs (csDMARDs) and corticoid usage status, disease activity levels were associated with retention time. CONCLUSION: The presence of COVID-19 has a significant effect on usage status of the biologic drug. Further longitudinal studies are needed to clarify the relationship between COVID-19 and drug usage as well as related factors.

ChatGPT-3.5 System Usability Scale early assessment among Healthcare Workers: Horizons of adoption in medical practice.

Artificial intelligence (AI) chatbots, such as ChatGPT, have widely invaded all domains of human life. They have the potential to transform healthcare future. However, their effective implementation hinges on healthcare workers' (HCWs) adoption and perceptions. This study aimed to evaluate HCWs usability of ChatGPT three months post-launch in Saudi Arabia using the System Usability Scale (SUS). A total of 194 HCWs participated in the survey. Forty-seven percent were satisfied with their usage, 57 % expressed moderate to high trust in its ability to generate medical decisions. 58 % expected ChatGPT would improve patients' outcomes, even though 84 % were optimistic of its potential to improve the future of healthcare practice. They expressed possible concerns like recommending harmful medical decisions and medicolegal implications. The overall mean SUS score was 64.52, equivalent to 50 % percentile rank, indicating high marginal acceptability of the system. The strongest positive predictors of high SUS scores were participants' belief in AI chatbot's benefits in medical research, self-rated familiarity with ChatGPT and self-rated computer skills proficiency. Participants' learnability and ease of use score correlated positively but weakly. On the other hand, medical students and interns had significantly high learnability scores compared to others, while ease of use scores correlated very strongly with participants' perception of positive impact of ChatGPT on the future of healthcare practice. Our findings highlight the HCWs' perceived marginal acceptance of ChatGPT at the current stage and their optimism of its potential in supporting them in future practice, especially in the research domain, in addition to humble ambition of its potential to improve patients' outcomes particularly in regard of medical decisions. On the other end, it underscores the need for ongoing efforts to build trust and address ethical and legal concerns of AI implications in healthcare. The study contributes to the growing body of literature on AI chatbots in healthcare, especially addressing its future improvement strategies and provides insights for policymakers and healthcare providers about the potential benefits and challenges of implementing them in their practice.

Epidemiology, clinical presentation, and outcome of mpox: A study of 381 cases in Saudi Arabia.

Objectives: There are limited data on the clinical and epidemiological aspects of mpox in Saudi Arabia. This study investigates the characteristics of Mpox cases from May to September 2023. Methods: A total of 381 cases of Mpox were included in this study, diagnosed based on a combination of clinical symptoms and laboratory testing. Results: The majority of mpox cases were males (91.1%), with a mean age of (±SD) of 32.4 (±8.3) years; 356 (93.4%) did not report travel, 277 (72.7%) denied engaging in extra-marital sex, and 379 (99.5%) were not linked to secondary cases. Fever was reported in 371 (97.4%), whereas headache was present in 314 (82.4%). Cough (1.3%) and conjunctivitis (0.5%) were rare. The most commonly affected areas in terms of lesions were the palms and soles (297 cases, 78%), followed by the genitals (206 cases, 54%), face (198 cases, 52%), and mouth (160 cases, 42%). Of the 1325 identified contacts, 1134 (85.5%) were hospital contacts, and 191 (14.5%) were community contacts, and 393 (29.6%) were high-risk contact. Of the high-risk contacts, 284 (72.3%) accepted post-exposure vaccination. The genotyped samples were all subclade IIb (formerly the West Africa clade). Conclusions: This study provides valuable insights into mpox characteristics in Saudi Arabia. The genome of monkeypox virus belonged to subclade IIb of the West Africa clade. Further analysis of the global tree sublineage is needed.

Virtual Objective Structured Clinical Examination (OSCE) Training in the Pandemic Era: Feasibility, Satisfaction, and the Road Ahead.

INTRODUCTION: Objective Structured Clinical Examinations (OSCEs) are essential assessments for evaluating the clinical competencies of medical students. The COVID-19 pandemic caused a significant disruption in medical education, prompting institutions to adopt virtual formats for academic activities. This study analyzes the feasibility, satisfaction, and experiences of pediatric board candidates and faculty during virtual or electronic OSCE (e-OSCE) training sessions using Zoom video communication (Zoom Video Communications, Inc., San Jose, USA). METHODS: This is a post-event survey assessing the perceptions of faculty and candidates and the perceived advantages and obstacles of e-OSCE. RESULTS: A total of 142 participants were invited to complete a post-event survey, and 105 (73.9%) completed the survey. There was equal gender representation. More than half of the participants were examiners. The overall satisfaction with the virtual e-OSCE was high, with a mean score of 4.7±0.67 out of 5. Most participants were likely to recommend e-OSCE to a friend or colleague (mean score 8.84±1.51/10). More faculty (66.1%) than candidates (40.8%) preferred e-OSCE (P=0.006). CONCLUSION: Transitioning to virtual OSCE training during the pandemic proved feasible, with high satisfaction rates. Further research on virtual training for OSCE in medical education is recommended to optimize its implementation and outcomes.

Dynamic Patterns and Predominance of Respiratory Pathogens Post-COVID-19: Insights from a Two-Year Analysis.

INTRODUCTION: Respiratory tract infections (RTIs) stand out as the most frequent causes leading to visits to the emergency department and hospitalizations. This study aims to assess the types and prevalence of respiratory infections across two years following the end of the COVID-19 pandemic. METHODS: Patients presenting with an influenza-like illness (ILI) were tested using multiplex RT-PCR (QIAstat-Dx, Qiagen). The multiplexed RT- PCR test detects 21 respiratory viruses and bacteria. RESULTS: During the study period, PCR test was done on a total of 1,790 samples were tested, and 712 (40%) were positive for a total of 796 pathogens. The mean age (± SD) of the participants was 20.1 ± 28.4 years in 2022 and 21.9 ± 27.6 years in 2023. Among the detected pathogens, the most prevalent were Rhinovirus/Enterovirus 222 (12.4%), followed by RSV A&B (103 cases, 5.7%), and H1N1 Influenza (77 cases, 4.3%). Additionally,  Influenza A/B constituted 172 (9.6%) while parainfluenza constituted (58, 3.2%). SARS-CoV-2 was identified in 3.97% of the samples. Over the two-year period, the monthly pattern of the identified pathogens exhibited fluctuations in the prevalence. Furthermore, variations were observed in the detected pathogens across different age groups. CONCLUSION: In addition to adding significant knowledge to the field of respiratory viral infections, this study emphasizes the necessity of ongoing research and surveillance for the detection and characterization of respiratory viruses, particularly those with the potential for emergence. Such studies would also require setting up a strategy for genotyping and/or sequencing of viruses.

Pattern of cephalosporin and carbapenem-resistant Pseudomonas aeruginosa: a retrospective analysis.

Objectives: Despite its financial cost on the world's health care system, Pseudomonas aeruginosa antibiotic resistance has been increasing. Therefore, the goal of this study was to assess the level of antimicrobial resistance to anti-pseudomonas medicines, specifically ß-lactam medications such as cephalosporin and carbapenems. In addition, we evaluate the prevalence of multi-drug resistance to P. aeruginosa, particularly during the years of the COVID-19 pandemic. Methods: This retrospective analysis covered the period from January 2019 to December 2022 and included cephalosporin- and carbapenem-resistant P. aeruginosa isolates. The real-time polymerase chain reaction Genexpert test (CARBA-R kit) was used for the detection of genes responsible for carbapenemase resistance. Results: During the time of the study, 1815 clinical isolates of P. aeruginosa were identified and 160 (9%) were resistant to carbapenems and cephalosporins. The resistance rates were 32.5% (13/597) in 2019, 11.2% (44/393) in 2020, 7% (26/369) in 2021, and 11% (50/456) in 2022. Of those isolates, multidrug-resistant rates were 6.7%, 86.3%, 57.7%, and 56%, per year over the study period. Using Genexpert test, 88 (93.6%) of multidrug-resistant P. aeruginosa were negative for carbapenemase genes. Conclusion: This study emphasizes the alarming patterns of carbapenem and cephalosporin resistance among P. aeruginosa clinical isolates. Furhter surviellance from different centers and different regions is required.

Infectious causes of fever of unknown origin in developing countries: An international ID-IRI study.

Background: Fever of unknown origin (FUO) in developing countries is an important dilemma and further research is needed to elucidate the infectious causes of FUO. Methods: A multi-center study for infectious causes of FUO in lower middle-income countries (LMIC) and low-income countries (LIC) was conducted between January 1, 2018 and January 1, 2023. In total, 15 participating centers from seven different countries provided the data, which were collected through the Infectious Diseases-International Research Initiative platform. Only adult patients with confirmed infection as the cause of FUO were included in the study. The severity parameters were quick Sequential Organ Failure Assessment (qSOFA) ≥2, intensive care unit (ICU) admission, vasopressor use, and invasive mechanical ventilation (IMV). Results: A total of 160 patients with infectious FUO were included in the study. Overall, 148 (92.5%) patients had community-acquired infections and 12 (7.5%) had hospital-acquired infections. The most common infectious syndromes were tuberculosis (TB) (n=27, 16.9%), infective endocarditis (n=25, 15.6%), malaria (n=21, 13.1%), brucellosis (n=15, 9.4%), and typhoid fever (n=9, 5.6%). Plasmodium falciparum, Mycobacterium tuberculosis, Brucellae, Staphylococcus aureus, Salmonella typhi, and Rickettsiae were the leading infectious agents in this study. A total of 56 (35.0%) cases had invasive procedures for diagnosis. The mean qSOFA score was 0.76±0.94 {median (interquartile range [IQR]): 0 (0-1)}. ICU admission (n=26, 16.2%), vasopressor use (n=14, 8.8%), and IMV (n=10, 6.3%) were not rare. Overall, 38 (23.8%) patients had at least one of the severity parameters. The mortality rate was 15 (9.4%), and the mortality was attributable to the infection causing FUO in 12 (7.5%) patients. Conclusions: In LMIC and LIC, tuberculosis and cardiac infections were the most severe and the leading infections causing FUO.