Non-Hodgkin's lymphoma complicated with human coronavirus HKU1 pneumonia: A case report and literature review.

Objective: To analyze the clinical manifestations, diagnostic methods and treatment process of the patients with non-Hodgkin's lymphoma complicated with human coronavirus(HCoV)-HKU1 pneumonia and improve the clinical medical staff's awareness of the disease, and to reduce the occurrence of clinical adverse events. Method(s): The clinical data of a patient with non-Hodgkin's lymphoma complicated with HCoV-HKU1 pneumonia with hot flashes and night sweats, dry cough and dry throat as the main clinical features who were hospitalized in the hospital in January 2021 were analyzed, and the relevant literatures were reviewed and the clinical manifestations and diagnosis of HCoV-HKU1 were analyzed. Result(s): The female patient was admitted to the hospital due to diagnosed non-Hodgkin's lymphoma for more than 2 months. The physical examination results showed Karnofsky score was 90 points;there was no palpable enlargement of systemic superfical lymph nodes;mild tenderness in the right lower abdomen, no rebound tenderness, and slightly thicker breath sounds in both lungs were found, and a few moist rales were heard in both lower lungs. The chest CT results showed diffuse exudative foci in both lungs, and the number of white blood cells in the urine analysis was 158 muL-1;next generation sequencing technique(NGS) was used the detect the bronchoalveolar lavage fluid, and HCoV-HKU1 pneumonia was diagnosed. At admission, the patient had symptoms such as dull pain in the right lower abdomen, nighttime cough, and night sweats;antiviral treatment with oseltamivir was ineffective. After treatment with Compound Sulfamethoxazole Tablets and Lianhua Qingwen Granules, the respiratory symptoms of the patient disappeared. The re-examination chest CT results showed the exudation was absorbed. Conclusion(s): The clinical symptoms of the patients with non-Hodgkin's lymphoma complicated with HCoV-HKU1 pneumonia are non-specific. When the diffuse shadow changes in the lungs are found in clinic, and the new coronavirus nucleic acid test is negative, attention should still be paid to the possibility of other HCoV infections. The NGS can efficiently screen the infectious pathogens, which is beneficial to guide the diagnosis and treatment of pulmonary infectious diseases more accurately.Copyright © 2023 Jilin University Press. All rights reserved.

Changes in state policy for promoting a healthy lifestyle. (A historical aspect).

Healthy lifestyle promotion from the perspective of state policy, journalism, healthcare, sociology, and psychology was analyzed. The objective of the study was to analyze changes in the financial and agitation state policy aimed at increasing the motivational activity of citizens of the Russian Federation towards a healthy lifestyle (HLS) in the Soviet era and at the post-Soviet stage and assess the effectiveness of these measures. The effectiveness of the Soviet propaganda of healthy lifestyles among the population was evaluated. Crisis phenomena in public health, low persuasiveness of the media presentation of the healthy lifestyle value, the COVID-19 pandemic, difficulties in implementing corporate health promotion programs in the workplace at individual en-terprises, and ignoring gender stereotypes in attitudes to health are the reasons that contribute to the adherence of Russian workers to unhealthy behaviors, that cause an increase in the incidence of chronic non-communicable diseases. The historical aspect of changes in state policy for health promotion made it possible to determine the tasks in developing health-saving programs.Copyright © 2023, Media Sphera Publishing Group. All rights reserved.

Food Insecurity and COVID-19 Diagnosis: Findings from a National United States Sample

This study explores the association between experiencing food insecurity and COVID-19 diagnosis in the United States, and what sociodemographic characteristics moderate this relationship. We analyzed a national sample of adults in the United States (n = 6,475). Multiple logistic regression results revealed respondents experiencing food insecurity had an approximately 3.0 times significantly higher odds of a positive COVID-19 diagnosis (odds ratio [OR] = 2.95, 95% confidence interval [CI] = 1.38-6.32, p < 0.01), which remained significant after adjusting for sociodemographics and COVID-19 mitigation behaviors (OR = 2.59, 95% CI = 1.09-6.18, p < 0.05). Age group had a significant moderating effect (OR = 42.55, 95% CI = 3.13-579.15, p < 0.01). Results indicate experiencing food insecurity is associated with contracting COVID-19.Copyright © 2022 Taylor & Francis Group, LLC.

Overview of the Healthcare Systems of the Maghreb Countries: Issues and Progress

Objectives: To provide an update overview on the current status of healthcare systems in the Maghreb region (Algeria, Morocco, and Tunisia) and to emphasize the progress made in the midst of the challenges facing these countries. Method(s): A descriptive comparative approach of healthcare systems in the three countries, based on data from sources with an established methodology, including descriptive healthcare data from the WHO database. Result(s): The population of the Maghreb will increase from 102 million to 132 million by 2050. The current population is mostly centered in Algeria and Morocco, accounting for 77%. Annual healthcare expenditure per capita is 447.9$, 776.8$ and 854.6$ in Morocco, Tunisia and Algeria, respectively. The average infant mortality rate per 1000 live improved to 10.9 in Tunisia, 16.8 in Morocco and 18.9 in Algeria. Maternal mortality rates have dropped to 43 and 48.5/100 000 births in Tunisia and Algeria, respectively while remaining relatively high in Morocco: 72.6. Number of hospital beds/1000 inhabitants is only 1.1 in Morocco, 1.9 and 2.9 in Algeria and Tunisia, respectively. The number of physicians/1000 people was 0.73 in Morocco, 1.3 in Tunisia and 1.72 in Algeria. This remains considerably low compared to the 3.9/1000 in Europe. The Maghreb countries are currently facing an exodus of physicians, mainly to France, which represents 7.1% and 10.7% of Tunisians and Moroccans, respectively, and more than 24% for Algerians. The Maghreb countries were very early mobilized (governments, ministries of health, civil society) to fight against COVID-19 and have successfully controlled the pandemic, according to pre-established control strategies and the strongly commitment of health professional. Conclusion(s): Despite the considerable progress made, the Maghreb countries still face major challenges. Physicians migration, rising cost of care and endemic infectious disease outbreaks constitute a huge hurdle on the already overburdened and resilient healthcare systems.Copyright © 2023

The Sociocultural and Economic Barriers to Self-Care Culture for COVID-19 Control in Developing Societies: The Case of Iran

There are natural and unnatural problems for human beings. Communicable and incommunicable diseases are common issues in human life. The prevalence of COVID-19 since December 2019 is an ongoing and mysterious danger, and its control is a critical concern. According to the traits and dangerous consequences of COVID-19, self-care plays an inevitable role in its control. This chapter has reviewed the sociocultural and economic barriers to self-care for COVID-19 control in developing societies with an emphasis on Iran. Using the documentary method, databases about concepts, research, theories, and economic, social, and cultural indexes were reviewed. The most used databases were PubMed, Magiran, Noormags, Google Scholar, Sid, Iran Statistic Center, Trading Economics, and World Meters. Reviewing data on life expectancy, mortality, and other indexes among developed and less developed societies, the most barriers for developing societies such as Iran were introduced. Findings showed that the most important barriers are short-term (economic factors), medium-term (social factors), and long-term (cultural factors) barriers. In each time/subject period, two levels, micro and macro, are presented. The macro-economic barriers are economic poverty, economic recession, and inflation. The micro-economic barriers are malnutrition, lack of financial ability to use health-care facilities, lack of living facilities, and the work time in epidemiological conditions. The macro-social barriers are social inequality, lack of attention to prevention, weakness of social organization, and family size in less developed areas while the micro-social barriers are a weakness of education and socialization, and unstable job conditions. The macro-cultural barriers are fate-orientation, weakness of preventive insight, application of common beliefs, low social trust, social traps, and traditional habitus in health care while the micro-cultural barriers are poverty of knowledge and living awareness, self-medication belief, self-healthy imagination, misunderstanding of disease risks, social indifference, and social irresponsibility. As a result, cultural factors are the most important barriers to the self-care culture for the control of pandemic diseases such as COVID-19. © 2023, The Author(s), under exclusive license to Springer Nature Switzerland AG.

The influence of the Covid-19 pandemic on the shunt revision rate

Introduction: During the first year of the Covid-19 pandemic we observed a decrease of our shunt revision rate. In order to investigate a possible correlation with an assumingly lower general infection rate in children in times of lock down and homeschooling, we performed a detailed analysis of our shunt and general pediatric patient population. Method(s): Electronic patient charts retrieval for children admitted for shunt revision or infectious diseases was performed for four time periods (study period April 2020 - March 2021, control periods from three previous years). A detailed analysis of all shunt revision and infectious cases including age and season specific evaluation followed. Possible correlations were investigated. Result(s): A total of 318 shunt revision and 13,919 pediatric cases have been evaluated. The shunt revision rate during the study period was 29% less compared to the average rate of three previous years (p 0.061), the number of pediatric cases with main diagnosis infection dropped significantly (p < 0.05), whereas other pediatric admissions remained stable. Significant age or seasonal influences did not exist. The number of shunt revisions in association with a documented systemic infection or a primary shunt infection dropped significantly during the study period (p<0.05 each). This was not the case for underdrainage, overdrainage (p>0.05 each) or other indications. In general, infections of upper and lower airways, the gastrointestinal and nervous system decreased during the pandemic, urinary infection rates remained stable. Conclusion(s): The decreased shunt revision rate during the first year of the pandemic seems correlate with a decrease of the general infection rate in children and adolescents at the same time. Infectionassociated shunt failures showed a significant decrease during this period compared to previous years.

Smart microfluidics: Synergy of machine learning and microfluidics in the development of medical diagnostics for chronic and emerging infectious diseases

The COVID-19 pandemic, emerging/re-emerging infections as well as other non-communicable chronic diseases, highlight the necessity of smart microfluidic point-of-care diagnostic (POC) devices and systems in developing nations as risk factors for infections, severe disease manifestations and poor clinical outcomes are highly represented in these countries. These POC devices are also becoming vital as analytical procedures executable outside of conventional laboratory settings are seen as the future of healthcare delivery. Microfluidics have grown into a revolutionary system to miniaturize chemical and biological experimentation, including disease detection and diagnosis utilizing muPads/paper-based microfluidic devices, polymer-based microfluidic devices and 3-dimensional printed microfluidic devices. Through the development of droplet digital PCR, single-cell RNA sequencing, and next-generation sequencing, microfluidics in their analogous forms have been the leading contributor to the technical advancements in medicine. Microfluidics and machine-learning-based algorithms complement each other with the possibility of scientific exploration, induced by the framework's robustness, as preliminary studies have documented significant achievements in biomedicine, such as sorting, microencapsulation, and automated detection. Despite these milestones and potential applications, the complexity of microfluidic system design, fabrication, and operation has prevented widespread adoption. As previous studies focused on microfluidic devices that can handle molecular diagnostic procedures, researchers must integrate these components with other microsystem processes like data acquisition, data processing, power supply, fluid control, and sample pretreatment to overcome the barriers to smart microfluidic commercialization.Copyright © 2023 by Begell House, Inc.

Digital Contact Tracing for COVID-19: Overview of Existing Systems and Framework for Future Innovation

Background: The COVID-19 pandemic catalyzed innovation in infection control measures, including widespread deployment of digital contact tracing systems. However, these technologies were not well understood by the general public and were complex for the public health community to implement, hampering adoption. Objective(s): To provide an overview of existing digital contact tracing systems, creating a framework for understanding design elements that impact their effectiveness as public health tools and offering a rubric for decision-makers to evaluate different systems for selection and implementation. Method(s): Scientific literature and publicly available information from relevant health authorities and other stakeholders was reviewed. Information was synthesized to develop a conceptual framework explaining how key design elements impact effectiveness of digital contact tracing systems and highlighting opportunities for future improvement. Result(s): A range of digital contact tracing interventions were deployed by governments worldwide and several professional sports leagues. Key design elements of the systems include: (1) data architecture (i.e., centralized versus decentralized systems, impacting privacy guarantees and data availability);(2) proximity detection technology (e.g., type of device signaling);(3) alert logic and timing (e.g., time- and distance-based criteria affecting sensitivity and specificity of alerts;real-time proximity alerts and/or bidirectional contact tracing, determining scope of infection prevention);(4) population (eligibility and availability);and (5) the structural and public health context of intervention (e.g., availability and timeliness of testing). Several systems demonstrated effectiveness in preventing transmission during COVID-19, though numerous limitations have also been documented in the literature. Conclusion(s): Digital contact tracing systems have the potential to mitigate the economic and public health impact of future infectious disease outbreaks, reducing community transmission and detecting potential cases earlier in the disease course. Lessons learned from solutions deployed during the COVID-19 pandemic provide an opportunity to improve multiple aspects of these systems, enhancing preparedness for future outbreaks.Copyright © 2023

Mesenchymal Stem/Stromal Cells: HUMAN MESENCHYMAL STEM CELL THERAPY IN SEVERE COVID-19 PATIENTS: 2-YEAR FOLLOW-UP RESULTS OF A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL

Background & Aim: The long-term effects of human mesenchymal stem cell (MSC) treatment on COVID-19 patients have not been fully characterized. The aim of this study was to evaluate the safety and efficacy of a MSC treatment administered to severe COVID-19 patients enrolled in a randomized, double-blind, placebo-controlled clinical trial (NCT 04288102). Methods, Results & Conclusion(s): A total of 100 patients experiencing severe COVID-19 received either MSC treatment (n = 65, 4x107 cells per infusion) or a placebo (n = 35) combined with standard of care on days 0, 3, and 6. Patients were subsequently evaluated 18 and 24 months after treatment to evaluate the long-term safety and efficacy of the MSC treatment. The outcomes measured included: 6-minute walking distance (6-MWD), lung imaging, quality of life according to the Short Form 36 questionnaire, COVID-19-related symptoms, titers of SARS-CoV-2 neutralizing antibodies, MSC-related adverse events (AEs), and tumor markers. Two years after treatment, a marginally smaller proportion of patients had a 6-MWD below the lower limit of the normal range in the MSC group than in the placebo group (OR = 0.19, 95% CI: 0.04-0.80, Fisher's exact test, p = 0.015). On the SF-36 questionnaire, a marginally higher general health score was received by the MSC group at month 18 compared with the placebo group (50.00 vs. 35.00;95% CI: 0.00-20.00, Wilcoxon rank sum test, p = 0.016). In contrast, there were no differences in the total severity score of lung imaging or the titer of neutralizing antibodies between the two groups. Meanwhile, there were no MSC-related AEs reported at the 18- or 24-month follow-ups. The serum levels of most of the tumor markers examined remained within normal ranges and were similar between the MSC and placebo groups. Long-term safety was observed for the COVID-19 patients who received MSC treatment. Yet few sustained efficacy of MSC treatment was observed at the end of the 2-year follow-up period. Funding(s): The National Key Research and Development Program of China (2022YFA1105604, 2020YFC0860900), the specific research fund of The Innovation Platform for Academicians of Hainan Province (YSPTZX202216) and the Fund of National Clinical Center for Infectious Diseases, PLA General Hospital (NCRCID202105,413FZT6). [Figure presented]Copyright © 2023 International Society for Cell & Gene Therapy

24th Collegium Ramazzini Statement: Prevention of Work-Related Infection in the COVID-19 Pandemic

Background: Workers whose occupations put them in contact with infected persons and the public are at increased risk of coronavirus disease (COVID-19) infection. Recommendations: The Collegium Ramazzini calls on governments at all levels to protect worker health by strengthening public health systems;maintaining comprehensive social insurance systems;establishing policies that presume all COVID-19 infections in high-risk workers are work-related;enforcing all occupational health standards;and developing pandemic preparedness plans. The Collegium Ramazzini calls on all employers-large and small, public and private-to protect the health of all workers by developing disease preparedness plans;implementing basic infection control measures;establishing disease identification and isolation policies;reducing hazardous exposures;supporting personal protective equipment (PPE) programs;and restricting unnecessary travel. Conclusion(s): Governments and employers have legal obligations to protect worker health. They are not relieved of these duties during pandemics.Copyright © 2020 American College of Occupational and Environmental Medicine.

Case study from Kosovo - repetitive COVID-19 infection and pregnancy

A 25-year-old woman, gravida 2, with no medical history of cardiovascular nor other chronic diseases, came to the gynaecologist and described symptoms of a flu-like disease, including very high fever. The gyneacologist prescribed her antibiotics and paracetamol to calm down the fever. At 37 week of gestation she was admitted to the provincial COVID-19 treatment center for isolation and health care in University Clinical Center of Kosovo in Gynecology/Obstetrics department. All bacteriological tests, including hemocultures and cultures of urines were negative. She received antipyretics (acetaminophen), antispasmodics trimethylphloroglucinol and antibiotics (oral azithromycin for 5 days and intravenous ceftriaxone). Despite this treatments, fever and uterine contractions persisted therefor the commission of doctors decided to deliver the baby via ceserean section. The peritoneal cavity and uterus were found to be very inflamed. Fetal appendages as well as the bladder were strewn with eruptive, vesicular lesions bleeding on contact. After few hours after the delivery her temperature (36.5 degreeC) and blood pressure (120/60 mmHg) were normal. The baby was healthy and tested negative on the COVD-19 tests performed. The patients after 2 weeks of treatment and a negative COVID-19 result she was released to go home and was counselled to eat healthy and prescribed multivitamins for her immune system and regular follow ups with the gynecologist. In a period of 8 months the patient became pregnant again and got infected with the COVID-19 again at 25 weeks pregnant. This time the symptoms were not severe and she was followed up at home. The delivery was planned with cesarean section and the baby was in healthy conditions. The patient got vaccinated with Astra Zeneca COVID-19 vaccine after the delivery. Because of their changed physiology, susceptibility to infections, and weakened mechanical and immunological processes, pregnant women are a particularly vulnerable group in any infectious disease outbreak. The requirement to protect the fetus adds to the difficulty of controlling their health. Keywords: COVID-19, pregnant women, cesarean section, Kosovo, astra-zeneca vaccineCopyright © 2023

Disseminated Mucormycosis in a patient on long term immunosuppression: Severe fungal infections as multi-system disorders

Introduction: Mucormycosis is a rare, severe fungal infection with an incidence of 0.005 to 0.17 per million.1 but incidence has risen recently, particularly in the Asian subcontinent, due to use of immunosuppression for Covid19.2 Presentations can vary and are classified into: rhino-orbito-cerebral, pulmonary, cutaneous, disseminated, renal and gastrointestinal. Risk factors include diabetes, immunosuppression, iron overload, malnutrition, and prematurity.1,3 Although mucormycosis has an extremely high mortality rate and disseminated infection is usually fatal, treatment options exist if diagnosed early and surgical debridement may be curative. Objective(s): We present a case of mucormycois in a female patient in her 40s who was immunosuppressed with methotrexate for rheumatoid disease. This case is discussed to increase awareness of critical illness caused by opportunistic invasive fungal infections in immunosuppressed patients and promote timely identification and management. Method(s): We detail the clinical context and management of a patient with mucormycosis and discuss relevant literature. Result(s): A female patient in her 40s who had been experiencing upper respiratory tract symptoms for several weeks, including cough and brown sputum, was admitted with a presumptive diagnosis of methotrexate toxicity after a full blood count performed by the general practitioner demonstrated pancytopenia. Initially, National Early Warning System 2 score (NEWS2) was 2 but became intensely hypertensive during blood transfusion and then profoundly shocked with an escalating NEWS2. Broad-spectrum antibiotics and fluconazole were commenced for neutropenic sepsis and the patient was referred to critical care in multiple organ failure. Computerised tomography (CT) scan of the chest, abdomen and pelvis showed "left upper lobe consolidation, which with neutropenia might represent an angioinvasive aspergillosis". She had multiple areas of skin discolouration and desquamation. Haematology and Infectious Diseases opinions were sought, and a bone marrow biopsy was performed which showed severe toxic effects consistent with sepsis/life threatening infection. Progressive proptosis was noted, and CT scan of her head was requested. Sadly, she was never stable enough for CT transfer. Beta D Glucan and aspergillus antigen serology was negative. Broncho-alveolar lavage demonstrated Candida albicans and then, later, Rhizopus arrhizus was isolated and anti-fungal treatment changed to voriconazole and then amphotericin B. Upon reviewing the notes in light of the positive culture for Rhizopus, the patient had likely been exhibiting symptomatic Mucormycosis sinus infection for some time prior to this admission with disseminated infection. The patient's condition continued to deteriorate and she sadly died. Conclusion(s): * The Early Warning Score significantly underestimated how unwell the patient was upon arrival in ED, a systems-based assessment would have demonstrated that the patient had multiple system dysfunction and significant potential to deteriorate suddenly despite having stable observations * The methotrexate level has no clinical value in diagnosing or refuting a diagnosis of methotrexate toxicity * A full examination of the immunosuppressed patient including ENT is a necessity when searching for a source of infection * Invasive fungal infections can cause multi-system symptoms and atypical presentations * As a greater proportion of patients have received systemic immunosuppression for Covid-19, vigilance for more unusual pathogens, including Mucormycosis by clinicians is advised.

A comprehensive knowledgebase of known and predicted human genetic variants associated with COVID-19 susceptibility and severity

Host genetic susceptibility is a key risk factor for severe illness associated with COVID-19. Despite numerous studies of COVID-19 host genetics, our knowledge of COVID-19-associated variants is still limited, and there is no resource comprising all the published variants and categorizing them based on their confidence level. Also, there are currently no computational tools available to predict novel COVID-19 severity variants. Therefore, we collated 820 host genetic variants reported to affect COVID-19 susceptibility by means of a systematic literature search and confidence evaluation, and obtained 196 high-confidence variants. We then developed the first machine learning classifier of severe COVID-19 variants to perform a genome-wide prediction of COVID-19 severity for 82,468,698 missense variants in the human genome. We further evaluated the classifier's predictions using feature importance analyses to investigate the biological properties of COVID-19 susceptibility variants, which identified conservation scores as the most impactful predictive features. The results of enrichment analyses revealed that genes carrying high-confidence COVID-19 susceptibility variants shared pathways, networks, diseases and biological functions, with the immune system and infectious disease being the most significant categories. Additionally, we investigated the pleiotropic effects of COVID-19-associated variants using phenome-wide association studies (PheWAS) in ~40,000 BioMe BioBank genotyped individuals, revealing pre-existing conditions that could serve to increase the risk of severe COVID-19 such as chronic liver disease and thromboembolism. Lastly, we generated a web-based interface for exploring, downloading and submitting genetic variants associated with COVID-19 susceptibility for use in both research and clinical settings (https://itanlab.shinyapps.io/COVID19webpage/). Taken together, our work provides the most comprehensive COVID-19 host genetics knowledgebase to date for the known and predicted genetic determinants of severe COVID-19, a resource that should further contribute to our understanding of the biology underlying COVID-19 susceptibility and facilitate the identification of individuals at high risk for severe COVID-19.Copyright © 2023 Elsevier Inc.

The Analysis of Dynamic Processes of Virus Transmission: How Could Diagnostic Tests and Vaccinations Can Stop COVID-19 Pandemic?

Objectives: COVID-19 reached its fourth year of pandemic since 2020. The repeated waves of infections have been driven by multiple factors such as pathological traits of variants, diagnostic accuracy, and vaccination conditions. This study revisits and analyzes the dynamic processes of viral transmission to generate new scientific knowledge. Method(s): A cascade model of viral transmission from one case to another was developed, and theoretically analyzed how the number of infected cases at time t, D+[t], can be changed at time t+1, D+[t+1], considering six parameters: 1) k:level of transmission, 2) Rt: effective reproduction number, 3) rho: capture rate of infected cases, 4) theta: immunity protection rate in individuals, 5) epsilon: evasion rate from vaccines, and 6) Sn: test sensitivity. Result(s): The formula which associates D+[t] with D+[t+1] was given as follows: D+[t+1] = K.D+[t], where K = {(1-Sn) + (1-rho) / rho}{1-Rtk (1-theta(1-epsilon))k} / {1-Rt (1-theta(1-epsilon))}. Also, assuming K be smaller than 1, the lower limit of test sensitivity to stop the viral transmission was formulated: Sn > {Rt (1-theta(1-epsilon))-Rtk(1-theta(1-epsilon))k} / {(1-Rtk(1-theta(1-epsilon))k)rho}. In example computations, the formula indicated that a one-off PCR test with the sensitivity of 85% would not be sufficient to contain highly contagious infections such as the Omicron variants, and that it would be practically impossible to control the situation with the immune-evasive sub-variants in circulation. Conclusion(s): The theory developed in this study broadens the science on evidence-based public health and will be useful for outcomes studies and informed decisions on public policy for pandemic control.Copyright © 2023

Perceived Attitudes Toward Vaccines, Trust and Vaccination Behaviors

Objectives: The decision-making process for taking vaccination is influenced by a multitude of factors such as individual beliefs concerning vaccinations, trust in contextual forces, and sociodemographic. This study established a model to understand the relationship between people's beliefs in the safety, importance and effectiveness of vaccines, their trust in the medical advice from the government and doctors and their behaviors of having their children vaccinated from infectious diseases in low-and-middle-income countries (LMIC). Method(s): We structured a structural equation model with two latent variables, Motivation and Trust, and their relationships with the vaccination taking behavior. Motivation is constructed by people's beliefs in the safety, importance and effectiveness of vaccines and trust is constructed by people's trust in government, medical providers and scientists. This study used the 2018 Wellcome Global Monitor dataset and focused on people in 80 LMIC. The countries were divided into eight geographic regions: Eastern Africa, Central & Southern Africa, Norther Africa & Middle East, Western Africa, Central Asia, Southeast Asia, South Asia and Southern& Eastern Europe. Result(s): The latent variable Motivation is significantly positively associated with parental vaccination behaviors in all geographic areas except for South Asia and Western Africa. South Asia is the only area where the trust in government and medical system, providers had a significant association with vaccination behavior and such association is positive. Conclusion(s): In most LMIC, positive attitudes about vaccines are associated with an improved vaccine rate. Increasing people's belief in vaccines' importance, safety and effectiveness will be essential both for boosting vaccination rates and scaling up a vaccine for COVID-19. In South Asia, trust in the government and the public health system are important in deciding taking vaccines. In these countries, policymakers need to think of ways to improve people's trust in the public health system and further effectively communicate important health messages.Copyright © 2023

Comparison of Knowledge and Practices among University Students of Allied Health Sciences and Engineering Departments in University of Lahore, Pakistan about Corona Virus Disease

Background: Corona Viruses is a group of viruses that cause diseases in both humans and mammals and are known to cause chronic respiratory diseases. The viruses among them include SARS, MERS and COVID-19. The most recent pandemic was a result of COVID-19. Older people and those with underlying medical problems are more likely to develop serious illness. Objective(s): To compare the knowledge and practices of Allied Health and Engineering students of the University of Lahore about Corona Virus Disease. Methodology: A cross-sectional questionnaire based survey was conducted on 326 students studying in Allied health Sciences and Engineering departments of UOL. The data was compiled in SPSS, version 24 for analysis. Result(s): The students of Allied Health Sciences had a better understanding and were more aware of COVID-19, its percussions and the methods to prevent its spread than of the Engineering Students. More than half of the Engineering students have found to have less understanding about the causative agent of the COVID-19 and similar trend was found in other categories. Health sciences students showed higher tendency towards hands hygiene practices than engineering students. Practical implication: Lessons learned from different outbreaks of infectious diseases suggested that knowledge and practices towards infectious diseases are associated with level of panic emotion among the population, which can further complicate attempts to prevent the spread of the disease. To facilitate outbreak management of COVID-19 in Lahore, Pakistan, there is an urgent need to understand the public's awareness of COVID-19. Keeping these considerations in mind this research was kicked-off to gauge the knowledge and practices of these medical and engineering students about Corona virus disease. Conclusion(s): The study shows that educational background plays a vital role in disease control and it will help in successful uptake of control interventions for prevention of COVID-19.Copyright © 2023 Lahore Medical And Dental College. All rights reserved.

Evaluation of the Updated French Autorisation D'Acces Precoce (AAP) Early Access Authorization Pathway

Objectives: To evaluate products reviewed by the Transparency Committee (TC) of the Haute Authorite de Sante (HAS) under the Autorisation d'Acces Precoce (AAP) Early Access Authorization (EAA) pathway and investigate any trends. Method(s): All 97 AAP submissions are publicly available from HAS and were evaluated on or before January 4th, 2023. The TC's opinion was reviewed to obtain the outcome, decision date, therapeutic area, and reasons for rejection. Results were tabulated and descriptive statistics were compiled. Result(s): In total, 79 of the 97 (81%) submissions evaluated were approved for EAA, including renewals of previously granted authorization (6 of 79);18 were rejected. Of the 97 submissions, 35% were indicated for the treatment of solid cancers, 14% for haematological cancers, 10% for ultra-rare diseases, 10% for infectious diseases, 4% for rare diseases, 4% for autoimmune diseases, 4% for skin diseases, and 2% for weight management. Notable approved submissions including those indicated for rare diseases, cancer, autoimmune diseases, and COVID-19, with 93%, 90%, 75%, and 63% of these submissions being granted EAA, respectively. Across the 18 unsuccessful submissions, the main reasons cited for rejection were insufficient efficacy and safety data (78%), lack of innovation compared to existing treatment options (61%), the availability of existing treatment options (56%), and the treatment not being rare enough to qualify for special consideration (28%). Conclusion(s): Since its inception in July 2021, the AAP has proven to be a popular program. As awareness of the program grows and more information becomes available about its benefits and eligibility criteria, it is likely that the number of submissions will continue to increase. However, given the link between submission success and the quality of available data (including a data collection plan), it is recommended manufacturers provide robust evidence to bolster their submissions.Copyright © 2023

EXPERIENCE WITH TIXAGEVIMAB AND CILGAVIMAB (EVUSHELD) IN 86 RHEUMATIC PATIENTS UNDERGOING ANTI-B CELL THERAPY WITH RITUXIMAB.

The problem of prevention of coronavirus disease 2019 (COVID-19) in patients with immune-mediated inflammatory rheumatic diseases (IMRD) remains highly relevant. The presence of IRD is associated with a high risk of disease and severe course of COVID-19 during immunosuppressive treatment, primarily anti-B cell therapy with rituximab (RTX), and a low level of post-vaccination response in such patients. A new strategy for the prevention and treatment of COVID-19 are virus-neutralizing monoclonal antibodies to coronavirus;currently, combined long-acting monoclonal antibodies tixagevimab and cilgavimab (Evusheld) are registered for prevention in the world and the Russian Federation. . Tixagevimab and cilgavimab (TC) show neutralizing activity against SARS-CoV-2, including the Omicron strain, primarily its variants BA.4, BA.5, BA.2.75 ("Centaur"). Objective - to evaluate the efficacy and safety of TC for pre-exposure prophylaxis of COVID-19 in rheumatic patients receiving RTX, based on a prospective observational study. Materials and methods. The main group included 86 patients with various IMRD receiving RTX: 50 of them had ANCA-associated systemic vasculitis (AAV), 15 - rheumatoid arthritis, 9 - Sjogren's syndrome (SS), 4 - IgG4-related disease, 3 - systemic lupus erythematosus (SLE), 3 - dermatomyositis (DM), 2 - systemic scleroderma (SSD). Median age was 59 (19-82) years;male: female ratio - 1:1,8. From March 26 to August 30 2022, patients received a single intramuscular injection of TC in a total dose of 300 mg, mainly after RTX (in 52% of cases, in 28% on the next day after RTX). The control group included 42 patients with AAV (median age - 45 (35-71) years;male: female ratio - 1:1), also treated with RTX, who did not receive pre-exposure prophylaxis of TC. The duration of observation was 7 months, until November 1 2022. At this time, 98% of confirmed cases of coronavirus in the Russian Federation were Omicron. A telephone and/or online survey of patient has been conducted to detect cases of COVID-19 and adverse reactions. Results. In the TC group, confirmed coronavirus infection have been detected in 17 (20%) patients (AAV - 10, SS - 3, SSD - 2, SLE - 1, DM - 1), with fever in 7 (8%), only in one case hospitalization was required (lung damage was not detected in computed tomography), in two cases, according to CT mild lung damage (CT 1-2), there were no deaths. Good TC's tolerability was noted, signs not associated with COVID-19 or progression of IMRD after administration of TC were observed in 8 (9%) patients (GPA - 3 MPA - 1, RA - 2, SLE - 1, IgG4-related disease - 1), adverse reactions definitely associated with the use of TC were not found. The most serious event not associated with coronavirus infection was the progression of polyneuropathy in a patient with RA. In the control group, 3 (7%) patients were diagnosed with COVID-19, one with severe lung injury (CT 3, pulmonary embolism) and death. Conclusions. The data of clinical studies and our own clinical experience evidence the effectiveness of the use of a combination of long-acting monoclonal antibodies TC (Evusheld), registered for indications for pre-exposure prophylaxis and treatment of COVID-19. Patients with IMRD treated with RTX have a favorable safety profile of TC. The introduction of virus-neutralizing monoclonal antibodies, a new drug class for the prevention and treatment of infectious diseases, opens significant prospects for improving the prognosis of patients with IRD.Copyright © 2023 Ima-Press Publishing House. All rights reserved.

Expansion of human T cells using xenogeneic free and gamma irradiated human platelet lysate

Commercially available human platelet lysate (hPL) is produced using expired human platelets obtained from accredited blood banks in the United States. These platelets were originally intended for use in patient transfusion. The safety of platelets used in transfusion is managed by the U.S. Food Drug Administration (FDA), as well as the American Association of Blood Banks (AABB). These organizations set standards, including testing for transmissible diseases. The United States record for blood safety is well established, with extremely low rates of disease transmission, making the platelet units used for hPL manufacture low risk. The Covid-19 pandemic has increased awareness of emerging infectious diseases, even though transmission of Covid-19 via blood transfusion has not been documented. For that reason, gamma irradiated hPL offers an additional safety measure in the clinic. Chimeric Antigen Receptor (CAR) expressing T-cells have demonstrated potent clinical efficacy in patients with hematological malignancies. In addition, there are several phase I clinical trials evaluating the use of CAR-T-cells for targeting of solid tumorassociated antigens. Some of the challenging issues found during production of CAR-T cells are the efficiency of T cell transduction to generate CAR-T cells, the expansion of T cells to clinically relevant numbers and the long-term survival in vivo of the therapeutic cells. The use of human platelet lysate has been demonstrated to improve these issues. Our data from experiments performed using human CD3+ from donors demonstrates that human platelet lysates offer an improved performance on T cell expansion versus serum derived products. hPL efficiently promotes T cell expansion, with higher cell yields and lower cell exhaustion rate. Additionally, we efficiently developed a protocol for suspension culture of T cells, which could facilitate the large-scale expansion of allogeneic CAR-T cells.