Clinical education is a method that is applied to formal nurse education as a step to provide real and direct learning experiences in the nursing environment correctly and effectively. The success of education in a clinical setting certainly requires the support of teaching nurses (clinical instructors) who have credibility and competence in terms of knowledge, attitudes and skills and are actively involved in professional activities. The diversity of backgrounds of nurses and students, including patients, certainly contributes to a shift in paradigms and perspectives for the nursing environment both in education and in clinical settings in health services. Responding to this cultural diversity, it is important to prepare knowledge and understanding related to transcultural nursing issues, intercultural communication and clinical education which explores the socio-cultural elements in the implementation of staff, students and patients. Purpose: The purpose of this literature review is to identify the extent to which nurse educators play a role by including socio-cultural and transcultural aspects in efforts to develop the quality of education in clinical practice environments in the millennium era. Method: The method of writing this article uses 11 literature review, the publication year period 2019,2020 and 2021 with sources from 4 databases such as science Direct, Scopus, ProQues and Elsevier. The review guidelines used are based on Prisma and the Joanna Briggs Institutute. The level of eligibility is identified through the title, abstract, research methodology as well as the type of scholarly journal and full text. Results: The results of the reviews found are presented in a narrative form. The results of the review study found that there were 11 articles explaining the competence of clinical education based on the socio-cultural approach, which is an educational strategy in the clinical area that integrates transcultural elements of nursing, intercultural communication, collaboration, self-directed with the principles of openness, honesty, and mutual respect in the implementation of team interaction and collaboration. The development of interpersonal relationships is also an important role that educators must have in helping to introduce the nurse orientation process to the organizational environment and other professional teams so that the achievement of satisfaction with clinical education is able to improve the performance of nurses and students perfectly. Conclusion: Clinical education which is supported by the competence of nurse educators (clinical instructors) who have individual and professional competences has a role to play in improving clinical learning outcomes by both students and nurses with a socio-cultural and transcultural strategic approach that will create satisfaction with the achievement of clinical competence and performance effectively.

The virtually complete loss of intestinal worms, known as helminths, from Western society has resulted in elimination of a range of helminth-induced morbidities. Unfortunately, that loss has also led to inflammation-associated deficiencies in immune function, ultimately contributing to widespread pandemics of allergies, autoimmunity, and neuropsychiatric disorders. Several socio-medical studies have examined the effects of intentional reworming, or self-treatment with helminths, on a variety of inflammation-related disorders. In this study, the latest results from ongoing socio-medical studies are described. The results point toward two important factors that appear to be overlooked in some if not most clinical trials. Specifically, (a) the method of preparation of the helminth can have a profound effect on its therapeutic efficacy, and (b) variation between individuals in the effective therapeutic dosage apparently covers a 10-fold range, regardless of the helminth used. These results highlight current limits in our understanding of the biology of both hosts and helminths, and suggest that information from self-treatment may be critical for clinical evaluation of the benefits and limits of helminth therapy.

Background: Good clinical practice (GCP) training is the industry standard for ensuring the quality conduct of registrational clinical trials. However, concerns have been raised about whether the current structure and delivery of GCP training sufficiently prepares clinical investigators and their delegates to conduct clinical trials. Methods: We conducted qualitative semi-structured interviews with 13 clinical investigators and 10 research sponsors to 1) examine characteristics of the quality conduct of sponsored clinical trials, including critical tasks and concerns perceived as essential for trial quality, 2) identify key knowledge and skills required to perform critical tasks, and 3) identify gaps and redundancies in GCP training and areas of improvement to ensure the quality conduct of clinical trials. We used applied thematic analysis to analyze the data. Results: The top three tasks identified as critical for the quality conduct of clinical trials were obtaining informed consent, ensuring protocol compliance, and protecting participants’ health and safety. Respondents acknowledged that GCP principles address each of these critical tasks; however, they described many challenges and burdens of GCP training, including high training frequency and repetitive content. Respondents suggested moving beyond GCP training as a mere check-box activity by making it more effective, engaging, and interactive. They also emphasized that applying GCP principles in a real-world, skills-based environment would increase the relevance of GCP training to investigators and their delegates. Conclusion: Our findings indicate that although investigators and sponsors recognize that GCP training addresses critical tasks necessary to the quality conduct of clinical trials, they articulated the need for significant improvement in the design, content, and presentation of GCP training.

This study aimed to determine clinical instructors’ perceptions of the assessments used to evaluate the clinical knowledge of undergraduate nursing students. This study uses a descriptive phenomenological approach. Purposive sampling was used to recruit sixteen clinical instructors for semi-structured interviews between August to December 2019. All interviews were audio-recorded and transcribed verbatim. Data were analyzed using Colaizzi’s seven-step method. Four criteria were used to ensure the study’s validity: credibility, transferability, dependability, and confirmability. Three themes were identified in the clinical instructors’ views on evaluating the clinical performance of student nurses: familiarity with students, patchwork clinical learning, and differing perceptions of the same scoring system. Study results suggest the need for a reliable, valid, and consistent approach to evaluating students’ clinical knowledge. If the use of patchwork clinical internships for student nurses is unavoidable, a method for assessing student nurses’ clinical performance that requires instructor consensus is necessary.

Background In this study, we describe our clinical experience with the fifth-generation of a breast implant with a smooth, fine surface from a Korean manufacturer (BellaGel^Ò SmoothFine; HansBiomed Co. Ltd., Seoul, Korea) in Asian women. Methods We analyzed 223 women (mean age=35.28±9.45 years and mean follow-up period=12.03±2.48 months), comprising 118 bilateral cases and 109 unilateral ones, who received breast augmentation using the BellaGel^Ò SmoothFine at our hospital between June 4, 2018 and February 28, 2019. For safety assessment, we analyzed frequencies of postoperative complications and overall survival of the BellaGel^Ò SmoothFine. Results Postoperatively, complications (12 cases, 5.38%) include asymmetry (3 cases, 1.35%), hematoma (2 cases, 0.90%), hypertrophic scars (2 cases, 0.90%), wound disruption (2 cases, 0.90%), rippling (1 case, 0.45%), capsular contracture (1 case, 0.45%), stretch deformities with skin excess (1 case, 0.45%). In addition, time-to-events were calculated as 10.94±0.64 months (95% CI 9.69-12.19) and the survival rate reached 0.290±0.168 (95% CI 0.094-0.901) at 12 months postoperatively. Conclusions Here, we describe our clinical experience with the BellaGel^Ò SmoothFine. Our results are of significance in that this is the first report about the fifth-generation of a breast implant with a smooth, fine surface from a Korean manufacturer in Asian women.

The Clinical Trials Transformation Initiative (CTTI) Investigator Qualification Project addresses the need for a more efficient and effective means of identifying qualified clinical investigators and delegates. Selection of investigators and delegates who are qualified by training and experience to conduct clinical trials is essential to safeguarding protections for study participants and ensuring data quality and integrity. Sponsors generally document investigator qualification through training on the principles of good clinical practice (GCP), as defined by the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH), adopted by regulatory authorities in the US, Japan and the European Union. Although these GCP principles provide an important foundation for promoting the conduct of quality clinical trials, the industry standard “one-size-fits-all” GCP training may not fully prepare investigators and delegates for conducting quality clinical trials. Routine GCP training alone may not be sufficient to prepare an inexperienced member of a site team, while repeating such training is unlikely to enhance the qualifications of an experienced researcher. The CTTI project team used findings from qualitative research activities, as well as input from an expert meeting with multiple stakeholders, to identify gaps and redundancies in the current training of investigators and their delegates and recommend practical, action-based solutions. CTTI provides recommendations on how to implement a more efficient and effective means of qualification for investigators and delegates, determine whether a site team is a good fit for a particular protocol, and improve the quality of clinical trial conduct.

The primary focus of this review is to explore the application and significance of coping strategies within the domains of clinical psychology and neuropsychology. These strategies consist of a variety of techniques, behaviors, and cognitive interventions, and their critical role in reinforcing resilience and facilitating adaptive responses to stressors has been highlighted. At the core of this exploration, the intricate neuropsychological relationship between brain stress pathways and the application of coping mechanisms has been analyzed. The neural aspects of stress, and how they can be influenced by adaptive strategies, are detailed, illustrating the profound impact these coping mechanisms have at a neurobiological level. Delving into the neuropsychological underpinnings, this review will shed light on how stress response pathways in the brain interact with, and can be modulated by, various coping strategies. These mechanisms are particularly salient when addressing the multifaceted challenges faced by individuals with neuropsychological or mental health issues. While these strategies span a broad spectrum, from introspection and cognitive reframing to behavioral activation and social support seeking, their integration and application remain diverse within clinical contexts. This review endeavors to elucidate the theoretical underpinnings of these strategies, their empirical support, and their practical implications within therapeutic interventions. Furthermore, the intricate interplay between individualized coping techniques and structured therapeutic methodologies will be examined, emphasizing the potential for a holistic treatment paradigm, thereby enhancing therapeutic outcomes and fostering individual resilience.

Objectives: This study aims to identify, report, and analyze registered and published clinical trials and observational studies for the pharmacological treatment of COVID-19 conducted in China. Methods: A strategic search was conducted via the Chinese Clinical Trial Registry to identify and extract clinical trials and observational studies registered and conducted in China for the pharmacological treatment of COVID-2019 between January 1^st, 2020 and March 21^st, 2020. This was further supplemented by searches conducted via the China National Knowledge Infrastructure (CNKI) database, the MEDLINE database, the World Health Organization (WHO) database, and MedRxiv and BioRxiv electronic platforms for preprint articles, published up until April 8^th, 2020. Studies available in Chinese and English were included in the searches and extracted. A primary descriptive analysis was performed for registered clinical trials and observational studies identified in the Chinese Clinical Trial Registry based on the extraction of the following clinical study information: trial ID, planned date of enrollment, recruitment status, study design, population, sample size, intervention/exposure group, control /reference group, dosage, and primary outcomes. A secondary descriptive analysis was performed for published clinical trials and observational studies identified from the supplementary databases based on the extraction of the following published clinical study information: study design, population, intervention/exposure group, control /reference group and main results as appropriate. Results: A total of 221 clinical trials and observational studies were included from all databases searched. From the Chinese Clinical Trial Registry, 195 registered clinical studies including 170 clinical trials and 25 observational studies were identified and included for primary analysis. From the supplementary databases, 26 published clinical studies including 8 clinical trials and 18 observational studies were included for secondary analysis. Of these 26 published clinical studies, 18 studies, including 3 clinical trials and 15 observational studies were identified from CNKI, 2 studies including 1 clinical trial and 1 observational study from MEDLINE, 2 including 1 clinical trials and 1 observational studies from the WHO database, and 4 including 3 clinical trials and 1 observational studies from MedRxiv and BioRxiv platforms. In the primary analysis, among the 170 clinical trials included from the Chinese Clinical Trial Registry, 101 investigated western medicines (WMs), while 15 investigated Traditional Chinese Medicines (TCMs), and 54 investigated a combination of TCMs and WMs. Among the 25 included observational studies from the Chinese Clinical Trial Registry, 2 investigated WMs, 2 investigated TCMs, and 21 investigated a combination of TCMs and WMs. The total number of exposed patients in all 195 clinical studies from the Chinese Clinical Trial Registry amounted to 24,500. In the secondary analysis, treatment with Lopinavir-ritonavir and treatment with Hydroxychloroquine was not associated with a difference from standard of care in the rate of RT-PCR negativity; treatment with a combination of Lopinavir-ritonavir, interferon α, and Lian-Hua-Qing-Wen capsule was found to significantly improve the effective rate of treatment compared with Interferon α combined with Lian-Hua-Qing-Wen capsule. Conclusions: China is generating a massive source of evidence that is critical for defeating the COVID-19 pandemic. Not only the clinical experience, but also the scientific evidence should be shared with the global scientific community.

Increasing rates of infection by antibiotic resistant bacteria have led to a resurgence of interest in bacteriophage (phage) therapy. Several phage therapy studies in animals and humans have been completed over the last two decades. We conducted a systematic review of safety and toxicity data associated with phage therapy in both animals and humans reported in English-language publications from 2008 – 2021. Overall, 69 publications met our eligibility criteria including 20 animal studies, 35 clinical case reports or case series, and 14 clinical trials. After summarizing safety and toxicity data from these publications, we discuss potential approaches to optimizing safety and toxicity monitoring with the therapeutic use of phage moving forward. In our systematic review of the literature, we found few, but no serious, adverse events associated with phage therapy. Comprehensive and standardized reporting of potential toxicities associated with phage therapy has generally been lacking in the published literature. Structured safety and tolerability endpoints are necessary when phages are administered as anti-infective therapeutics.

COVID-19 was identified in Wuhan, China in in December 2019, and rapidly spread worldwide, being declared global pandemic one month later on 30 January 2020. Since its emergence, COVID-19 has raised global concerns associated with drastic measures that were never adopted in any previous outbreak, to contain the situation as early as possible. The 2019 novel corona virus (2019-nCoV) or SARS-CoV-2 is the causative agent of COVID-19. 2019-nCoV genetic sequence was rapidly identified within few days since the first reported cases and RT-PCR kits became available for COVID-19 diagnosis. However, RT-PCR diagnosis carries a risk of false-negative results, therefore additional serologic test are needed. The most important approach in the battle against COVID-19 is rapid diagnosis of suspicious cases, timely therapeutic intervention and isolation to avoid community spread. In this review, we summarize the clinical scenario that raises suspicion of COVID-19 and available laboratory diagnostics.

Background: There is a high bureaucratic and administrative burden associated with health care tasks (test requesting, visits scheduling, supporting documents provision) that has historically largely fallen on health care professionals, which is one among the factors contributing to low job satisfaction and lower productivity. Incorporating new professional roles that help to better respond to the needs of both patients and professionals can increase the quality and efficiency of service provision. Objective: To evaluate the impact of the clinical assistant’s introduction in the Sant Joan de Déu Barcelona Children’s Hospital’s pediatric oncology department, in terms of displacement of activity loads carried out by this new professional role and the consequent time freed up for physicians. Methodology: Observational and retrospective study using administrative data based on the analysis of the type of activity performed by clinical assistants and the measurement of the time freed up in favor of the physicians, based on in situ timekeeping, to approximate the potential skill mix productivity increase. Results: Since its implementation in the pediatric oncology department, clinical assistants have performed 13,553 requests (69.93% of the total), representing a total saving of 266.83 hours or 6.67 workweeks of 40 hours. They performed 74.25% of outpatient surgical requests in the oncology department, 87.5% of day hospital requests and 54.13% of total requests in the outpatient consultations area. Conclusion: The introduction of clinical assistants in the oncology department could be efficient to the extent that it displaces a good part of the bureaucratic and administrative tasks previously performed by health care professionals. This delegation allows them to work more closely to the maximum of their competences and the physicians to have more time for higher added value clinical tasks. In terms of efficiency, this role change enables to optimize the clinical process, reducing the cost by 56% compared to the conventional model.

Lymphoma diagnoses in the U.S. are substantial, with an estimated 89,380 new cases in 2023, necessitating innovative treatment approaches. Phase 1 clinical trials play a pivotal role in this context. We developed a binary predictive model to assess trial adherence to expected average durations, analyzing 1,089 completed Phase 1 lymphoma trials from clinicaltrials.gov. Using machine learning, the Random Forest model demonstrated high efficacy with an accuracy of 0.7248 and ROC-AUC of 0.7701 for lymphoma trials. Importantly, this model maintained an accuracy of 0.7405 when applied to lung cancer trials, showcasing its versatility. A key insight is the correlation between higher predicted probabilities and extended trial durations, offering nuanced insights beyond binary predictions. Our research contributes to enhanced clinical research planning and potential improvements in patient outcomes in oncology.

The use of machine learning (ML) approaches to target clinical problems is called to revolutionize clinical decision-making. The success of these tools is subjected to the understanding of the intrinsic processes being used during the classical pathway by which clinicians make decisions. In a parallelism with this pathway, ML can have an impact at four levels: for data acquisition, predominantly by extracting standardized, high-quality information with the smallest possible learning curve; for feature extraction, by discharging healthcare practitioners from performing tedious measurements on raw data; for interpretation, by digesting complex, heterogeneous data in order to augment the understanding of the patient status; and for decision support, by leveraging the previous step to predict clinical outcomes, response to treatment or to recommend a specific intervention. This paper discusses the state-of-the-art, as well as the current clinical status and challenges associated with each of these tasks, together with the challenges related to the learning process, the auditability/traceability, the system infrastructure and the integration within clinical processes.

COVID-19 is causing major turmoil around the globe, and the clinical trial industry is likely to face unprecedented challenges to health and business sectors. In an effort to find a suitable treatment and prevention options for COVID-19, several COVID-19 clinical trials are being planned and initiated, while a large number of clinical trials for non- COVID-19 indications are suffering delays. With over more than 1000 trials being disrupted and more trials being added to this category daily, there is a direct impact on trial site activation and patient enrolment. This analysis deals with the specific impacts of the COVID-19 pandemic on the clinical trial and pharmaceutical industry. The objective of this study is to provide an updated information of the disrupted clinical trials and its impact on various therapeutic areas and different drugs. Among the severely affected clinical trials, oncology and CNS trials are the hardest hit therapy areas.This article will certainly emphasize the need for advanced and innovative approaches to maintain the health of the clinical trial ecosystem by continuing the existing trials and the start of the new studies. We have to take and follow necessary actions to guarantee that the initiatives will not be locked during the COVID-19 pandemic, both for the treatment of patients and for the researchers to conduct decision-relevant clinical trials.

Background The coronavirus pandemic has led to the creation of clinical guidelines by a large number of professional medical communities. However, the quality and methodology of development of Russian clinical guidelines has been little studied. The continued relevance of studying the use of DOACs in patients with COVID-19 was the basis for conducting this study. Aim The objective of this study was to assess DOACs consumption and expenditures in Russian Federation during COVID-19 pandemic and to analyse domestic evidence base for the use of DOACs in COVID-19 patients through identifying all publicly available Russian-produced CPGs for the treatment of COVID-19 and assessing their quality as the source of recommendations for the use of oral anticoagulants for the prevention of thrombotic complications in COVID-19 patients. Methods We searched Russian databases for CPGs, published between 2020 and 2023. We identified 7 relevant documents that met our inclusion criteria. Three authors analyzed Russian clinical guidelines using a AGREE II questionnaire. We calculated DOACs DDD consumption according to Russian clinical guidelines and DDD consumption in patients with COVID-19 for the period 2020-2022. Results 7 clinical CPGs were analyzed with the AGREE II tool, it was revealed that experts gave the highest scores for the sections scope and purpose (from 62.98% to 100%), clarity of presentation (from 96.30% to 100%). The lowest scores were given for the sections stakenholder involment (33.33% to 64.81%), rigour of development (from 0% to 49.31%), applicability (from 23.61% to 50%), editory independence ( from 0% to 50%). When comparing the total score, it was found that two clinical guidelines received the highest scores - ROPNIZ (Livzan), ROPNIZ (Drapkina). The minimum score is registered with the NIIOZMM (Khripun) clinical guideline. No guideline received a total score of more than 70%. According to clinical recommendations, the consumption of apixaban and rivaroxaban is 15 DDD (30-day course of therapy), 22.5 DDD (45-day course of therapy). Consumption of apixaban in the Russian Federation in 2020 and 2021 corresponds to the indicators presented in clinical recommendations (in 2020 – 26.59 DDD per patient with COVID-19; in 2021 – 15.75 DDD per patient with COVID-19), and in 2022 – 10.67 DDD, which is below the recommended values. In 2020, consumption of rivaroxaban in the Russian Federation was 26.59 which corresponds to data from clinical recommendations; in 2021, consumption decreased to 7.87 DDD; in 2022 – 5.48 DDD, which is 2.74 times less than recommended.

Traumatic events, especially massive trauma resulting from catastrophic incidents, wars, or severe abuse, can elicit significant neuropsychological alterations, with profound implications for cognitive, emotional, and behavioral functioning. This mini review delineates the primary neural changes post-trauma and underscores the importance of timely neuropsychological and clinical interventions. Specific brain regions, including the amygdala and prefrontal cortex, undergo physiological changes that can lead to memory impairments, attention deficits, and emotional disturbances. PTSD, a commonly diagnosed condition post-trauma, exemplifies the intricate relationship between trauma and memory processing. Furthermore, the concept of neuroplasticity, the brain's inherent ability to adapt and rewire, offers hope for recovery. Current clinical interventions, such as cognitive-behavioral therapy, mindfulness practices, and biofeedback, leverage this neuroplastic potential to foster healing. The review underscores the vital importance of early intervention to mitigate long term neuropsychological impacts, emphasizing the role of timely and targeted clinical interventions. The synthesis of this knowledge is crucial for clinicians, allowing for informed therapeutic approaches that holistically address both the physiological and psychological dimensions of trauma.

Introduction: Leprosy, caused by Mycobacterium leprae is one of the oldest infectious diseases in human history and its eradication is linked to poverty control, lack of basic sanitation, the fragility of health, and education services. Objective: To evaluate the frequency of blood groups (ABO/Rh) and the sociodemographic and clinical profile of Angolan patients with Leprosy treated at the Anti-Tuberculosis and Leprosy Dispensary in Luanda, the capital city of Angola. Methodology: A descriptive, introspective, cross-sectional study with a quantitative approach was carried out with 102 patients of Luanda, in the second half of 2021. Results: Of the 102 patients included in the study, the majority belonged to the ORh+ group (51.9%), followed by the BRh+ group (27.4%) and ARh+ (18.6%), most were under 51 years of age ( 87.3%), with low education (54.9%), coming from urban areas (44.1%). As for clinical conditions, most had a multibacillary infection (93.1%), diagnosed mainly by smear microscopy (75.5%) without other infection (79.4%), some of them with complications (28.4%) and individuals with non-O blood group showed changes in the blood count. Conclusion: Leprosy seems to be common in ORh+ individuals, it continues to affect especially those residing in areas of population agglomerations and with low education, presenting itself as a multibacillary infection, where changes in the blood count are greater in non-O individuals.

Objectives: Data sharing has become a requirement of many funding bodies and is becoming a scientific standard in many disciplines. In medical research, however, data sharing can conflict with clinicians’ obligation to protect patients’ privacy. General recommendations on data sharing exist also for clinical research, but so far lack practical and Swiss-specific aspects. The objective of this document is to provide practical recommendations for all relevant aspects of data sharing in agreement with legislation in Switzerland. Methods: This document was written by members of the Swiss CTU Network, a network of academic clinical trial units. The process did not follow a formalized Delphi process. After an internal consensus round, this report is now published as pre-print for external review. A second version will incorporate external comments. We plan to publish this document as a text in progress, as we expect relevant changes in related fields such as the development of further dedicated medical repositories or methodological advances in anonymization techniques. Results: We developed principles and practical recommendations with respect to informed consent, data management plan, anonymization, data structure and format, coding of variables, metadata and documentation, version control, selection of repository, requesting and use of data. We also provide a summary of legal aspects relevant for the Swiss context. Conclusions: The intension to share data has an impact not only after a clinical trial or an observational study is completed, but also during the planning period, the conduct and the analysis phase. Clinical researchers need to be aware at the beginning of a study on how to inform patients and at least the amount of work related to preparing data for sharing, metadata, and any further documentation. This report provides details of aspects to be considered, suggests decision criteria, and provides examples and checklists, in order to support data sharing in practice.

Glioblastoma (GBM) is the most lethal form of brain tumor, characterized by rapid growth and surrounding tissue invasion. The current standard treatment is surgery followed by radiotherapy, and concurrent chemotherapy, typically with temozolomide. Although extensive research has been performed over the past years to develop an effective therapeutic strategy for the treatment of GBM, efforts have not provided major improvements in the overall survival of patients with GBM. Thus, new therapeutic approaches are urgently needed. A major challenge in the development of therapies for central nervous system (CNS) disorders is overcoming the blood–brain barrier (BBB). In this context, the intranasal (IN) route of drug administration has been proposed as a non-invasive alternative route to directly targeting the CNS. In fact, this route of drug administration may bypass the blood-brain barrier and reduce systemic side effects. Recently, formulations have been developed to further enhance nose-to-brain transport, mainly with the use of nano-sized and nanostructured drug delivery systems. The focus of this review will be on the strategies developed to deliver a number of anticancer compounds for the treatment of GBM using the nasal administration. In particular, the specific properties of nanomedicines proposed for the nose-to-brain delivery will be critically evaluated. The number of preclinical and clinical data reviewed support the idea that nasal delivery of anticancer drugs might represent a breakthrough advancement in the fight against GBM.

Glioblastoma (GBM), the most common and aggressive primary brain tumor in adults, remains one of the least treatable cancers. Current standard of care—combining surgical resection, radiation, and alkylating chemotherapy—results in a median survival of only 15 months. Despite decades of investment and research into the development of new therapies, most candidate anti-glioma compounds fail to translate into effective treatments in clinical trials. One key issue underlying this failure of therapies that work in pre-clinical models to generate meaningful improvement in human patients is the profound mismatch between drug discovery systems—cell cultures and mouse models—and the actual tumors they are supposed to imitate. Indeed, current strategies that evaluate the effects of novel treatments on GBM cells in vitro fail to account for a wide range of factors known to influence tumor growth. These include secreted factors, the brain’s unique extracellular matrix, circulatory structures, the presence of non-tumor brain cells, and nutrient sources available for tumor metabolism. While mouse models provide a more realistic testing ground for potential therapies, they still fail to account for the full complexity of tumor-microenvironment interactions, as well as the role of the immune system. Based on the limitations of current models, researchers have begun to develop and implement novel culture systems that better recapitulate the complex reality of brain tumors growing in situ. A rise in the use of patient derived cells, creative combinations of added growth factors and supplements, may provide a more effective proving ground for the development of novel therapies. This review will summarize and analyze these exciting developments in 3D culturing systems. Special attention will be paid to how they enhance the design and identification of compounds that increase the efficacy of radiotherapy, a bedrock of GBM treatment.

Electronic health records (EHRs) are becoming a vital source of data for healthcare quality improvement, research, and operations. However, much of the most valuable information contained in EHRs remains buried in unstructured text. The field of clinical text mining has advanced rapidly in recent years, transitioning from rule-based approaches to machine learning and, more recently, deep learning. With new methods come new challenges, however, especially for those new to the field. This review provides an overview of clinical text mining for those who are encountering it for the first time (e.g. physician researchers, operational analytics teams, machine learning scientists from other domains). While not a comprehensive survey, it describes the state of the art, with a particular focus on new tasks and methods developed over the past few years. It also identifies key barriers between these remarkable technical advances and the practical realities of implementation at health systems and in industry.

The emergence of M. tuberculosis strains resistant to Isoniazid (INH) and Rifampicin (RIF), the two most potent drugs of first-line anti-TB therapy is termed multidrug drug-resistant TB (MDR-TB). Multidrug-resistant tuberculosis has been a serious medical and epidemic problem all over the world. We present here a series of clinical cases consist of two patients diagnosed with isoniazid resistant tuberculosis. Histopathological examination supports the diagnosis of tuberculous granulomas. And the pathology molecular examination revealed the presence of Isoniazid-resistant Mycobacterium tuberculosis1,2 via the following mutation c.947G>A; p.Gly316Asp. Isoniazid-resistance is associated with mutations in the furA-katG and fabG1-inhA operons, as well as mutations in the ahpC gene. 64% of the isoniazid-resistance phenotypes were associated with the katG315 mutation worldwide. The second most common mutation is inhA-15, and it has been reported in 19% of the Isoniazid-resistant isolates. The significant association between the two mutations, inhA c-15 and katG 315 respectively, and the high-level resistance is of interest in the interpretation of current and future molecular diagnostic testing, as an early prediction of the level of Isoniazid-resistance is essential to decide the benefit of high-dose Isoniazid use.

The traditional nomenclature system for classifying Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV), based on clinical phenotype, described Granulomatosis with Polyangiitis (GPA), Eosinophilic Granulomatosis with Polyangiitis (EGPA) and Microscopic Polyangiitis (MPA) as distinct clinical entities. This classification has proved its expedience in clinical trials and every day clinical practice, yet, a substantial overlap in clinical presentation still exists, and often causes difficulties in prompt definition and clinical distinction. Additionally, new insights into the AAV pathogenesis point out that PR3 and MPO-AAV may not represent expressions of the same disease spectrum but rather two distinct disorders, as they display significant differences. Thus, it is supported that a classification based on ANCA serotype (PR3-ANCA, MPO-ANCA or ANCA-negative), could be more accurate and also closer to the nature of the disease, instead of the phenotype-based one. This review aims to elucidate the major differences between PR3 and MPO-AAV, in terms of epidemiology, pathogenesis, histological and clinical manifestations, and response to therapeutic approaches.

Background: Kawasaki disease (KD) is a form of vasculitis that primarily affects children under the age of 5 years old. Patients may be missed diagnosis when initial clinical symptoms do not fulfill the traditional criteria. We aimed to analyze factors that clinicians could use to differentiate febrile children suspected of KD. Method: We retrospectively enrolled a total of 83 febrile children who were initially suspected of KD, but they did not meet the American Heart Association (AHA) criteria for a diagnosis. However, some of these patients were diagnosed with KD during their second visit. We analyzed patients' characteristics, clinical symptoms, and laboratory data. Results: In total, 50 patients were enrolled in the study. Of those, ten patients were diagnosed with KD on their second visit (group 1), while the other 40 patients still did not fit a KD diagnosis (group 2). A patient with a neutrophil to lymphocyte ratio greater than 1.33 combined with a C-reactive protein more than 33 mg/L was more likely to have KD. Conclusion: Among patients suspected of KD that did not initially meet the criteria, clinicians should pay special attention to elevated neutrophil-to-lymphocyte ratios and CRP levels and closely follow up such patients.

Background: Transient Hypogammaglobulinemia of Infancy (THI) is a primary immunodeficiency caused by a temporary decline of serum levels of immunoglobulin G (IgG) greater than 2 standard deviations below the mean age-specific reference values in an infant between 5 and 24 months of age. Preterm infants are particularly susceptible to THI, as, in the third trimester of pregnancy, IgG is transferred across the placenta from mother to infant.Objective: To systematically review the diagnostic criteria of Transient Hypogammaglobulinemia of infants.Design & Methods: Systematic Review. Manual searching of 3 electronic databases (PubMed, Medline, & Google Scholar) from September 2021 – April 2022. Abstracts were screened to assess fit to the inclusion criteria. Data was extracted from the selected studies by using an adapted extraction tool from Cochrane.org. Studies were then assessed for bias by using an assessment tool also adapted from Cochrane.org.Results: Of the 215 articles identified, 16 were eligible for examining the diagnostic criteria of THI. These studies were also assessed for bias in 6 domains. 5 studies (31%) had a low risk of bias, while 4 studies (25%) had a high risk of bias, & 7 studies (44%) were unclear for bias.Conclusion: We can conclude that THI is only definitively diagnosed after the abnormal IgG levels have normalized, hence THI is mostly a benign condition, but must be monitored for subsequent recurrent infections. The diagnostic criterion also includes vaccine & isohaemagglutinin responses to differentiate against other immunological disorders in infants.

Background: Primary cardiac sarcomas (PCS) are extremely rare malignant tumors involving the heart. Only isolated case reports have been described. There is a paucity of data on the epidemiological characteristics of PCS. This study has the objective of investigating the epidemiologic characteristics, survival outcomes, and independent prognostic factors of PCS. Methods: We enrolled a total of 362 patients with PCS, between 2000 and 2017, by retrieving the Surveillance, Epidemiology, and End Results (SEER) database. We analyzed demographics, clinical characteristics, and overall mortality (OM) as well as cancer-specific mortality (CSM) of PCS. Variables with a p-value < 0.1 in the univariate Cox regression were incorporated into the multivariate Cox model to determine the independent prognostic factors, with a hazard ratio (HR) of greater than 1 representing adverse prognostic factors. Results: Crude analysis revealed a high OM in age 80+ (HR=5.958, 95% CI 3.357-10.575, p=0), followed by age 60-79 (HR=1.429, 95% CI 1.028-1.986, p=0.033); and PCS with distant metastases (HR=1.888, 95% CI 1.389-2.566, p=0). Patients that underwent surgical resection of the primary tumor and patients with malignant fibrous histiocytomas (HR=0.657, 95% CI 0.455-0.95, p=0.025) had a better OM (HR=0.606, 95% CI 0.465-0.791, p=0). The highest cancer-specific mortality was observed in age 80+ (HR=5.037, 95% CI 2.606-9.736, p=0) and patients with distant metastases (HR=1.953, 95% CI 1.396-2.733, p=0). Patients with malignant fibrous histiocytomas (HR=0.572, 95% CI 0.378-0.865, p=0.008) and those who underwent surgery (HR=0.581, 95% CI 0.436-0.774, p=0) had a lower CSM. Multivariate Cox proportional hazard regression analyses revealed higher OM in the age group 80+ (HR=13.261, 95% CI 5.839-30.119, p=0) and advanced disease with distant metastases (HR=2.013, 95% CI 1.355-2.99, p=0.001). Lower OM was found in patients with rhabdomyosarcoma (HR=0.364, 95% CI 0.154-0.86, p=0.021) and widowed patients (HR=0.506, 95% CI 0.263-0.977, p=0.042). Multivariate Cox proportional hazard regression analyses of CSM also revealed higher mortality in the same groups, and lower mortality in patients with Rhabdomyosarcoma. Conclusion: In this United States population-based retrospective cohort study using the SEER database, we found that cardiac rhabdomyosarcoma was associated with the lowest CSM and OM. Furthermore, as expected, age and advanced disease at diagnosis were independent factors predicting poor prognosis. Surgical resection of the primary tumor showed lower CSM and OM in the crude analysis but when adjusted for covariates in the multivariate analysis, it did not significantly impact the overall mortality or the cancer-specific mortality. These findings allow for treating clinicians to recognize patients that should be referred to palliative/hospice care at the time of diagnosis and avoid any surgical interventions as they did not show any differences in mortality. Surgical resection in patients with poor prognoses should be reserved as a palliative measure rather than an attempt to cure the disease.

Scrub typhus (ST) is one of the most neglected tropical diseases, a leading cause of acute undifferentiated febrile illness in areas of the ‘tsutsugamushi triangle’, diagnosed frequently in South Asian countries. The bacteria Orientia tsutsugamushi is the causative agent of the disease, which enters to human body through the bite of trombiculid mite (Chigger) of the genus Leptotrombidium deliense.The diagnosis of the disease becomes challenging as its early symptoms mimic other febrile illnesses like dengue, influenza, and corona viruses. Lack of rapid, reliable, and cost-effective diagnostic methods further complicates the identification process. Northeast India, a mountainous region with a predominantly rural tribal population, has witnessed a resurgence of scrub typhus cases in recent years. Various ecological factors, including rodent population, habitat characteristics, and climatic conditions, influence its prevalence. Entomological investigations have confirmed the abundance of vector mites, highlighting the importance of understanding their distribution and the probability of transmission of scrub typhus in the region. Proper diagnosis, awareness campaigns, and behavioral interventions are essential for controlling scrub typhus outbreaks and reducing its impact on public health in Northeast India. Further research and community-based studies are necessary to accurately assess the disease burden and implement effective prevention strategies.

Genetic testing allows for identification of germline DNA variations which are associated with a significant increase in risk of developing breast and ovarian cancer. Detection of a BRCA1 or BRCA2 pathogenic variant triggers several clinical management actions, which may include increased surveillance and prophylactic surgery for healthy carriers or treatment with PARP inhibitor therapy for carriers diagnosed with cancer. Thus, standardized validated criteria for annotation of BRCA1 and BRCA2 variants according to their pathogenicity are necessary to support clinical decision making and ensure improved outcomes. Upon detection, variants whose pathogenicity can be inferred by the genetic code are typically classified as pathogenic, likely pathogenic, likely benign, or benign. Variants whose impact on function cannot be directly inferred by the genetic code are labeled as Variants of Uncertain Clinical Significance (VUS) and are evaluated by multifactorial likelihood models that use personal and family history of cancer, segregation data, prediction tools, and co-occurrence with a pathogenic BRCA variant. Missense variants, coding alterations that replace a single amino acid residue with another, are a class of variants for which determination of clinical relevance is particularly challenging. Here, we discuss current issues in variant classification by following a typical life cycle of a BRCA1 missense variant through detection, annotation and information dissemination. Advances in massively parallel sequencing have led to a substantial increase in VUS findings. Although comprehensive assessment and classification of missense variants according to their pathogenicity remains the bottle neck, new developments in functional analysis, high throughput assays, data sharing, and statistical models are rapidly changing this scenario.

BACKGROUND: Retinoblastoma is a malignant tumour that develops from the immature cells of the retina. It is the most frequent type of paediatric intraocular cancer and is curable. Clinical and histological findings after enucleation of the affected eye dictate not only the patient's secondary care but also their prognosis. We assessed the clinical and histopathologic predictors of survival among children with retinoblastoma from two tertiary health facilities in Uganda. METHODS: This retrospective research utilized archived formalin fixed & paraffin embedded blocks of eye specimens enucleated between 2014 to 2016 at Mbarara University, pathology department and Ruharo Eye Centre. The specimens were then processed and stained with haematoxylin and eosin. The confirmation of retinoblastoma was made to include histologic stage and features of the tumor. Biographic data of the patients and the clinical features such as leukocoria, proptosis, phthisis, staphyloma, buphthalmos were retrieved from the records.RESULTS: Males (55.1%) dominated the study population (N=78). The median age was 31 months. The commonest clinical sign was leukocoria (69.2%) and the most abundant histopathological stage was stage 1 (41%). Optic nerve invasion 39.5%, choroidal invasion 29.5%, scleral invasion 7.7% and orbital extension 16.7% were seen. Flexner-Wintersteiner rosettes were seen in 24.6%. Necrosis was a prominent feature (71.2%). The two-year survival was estimated to be 62%. Leukocoria (RR 1.1), female gender (RR 1.4), intralaminar optic nerve invasion (RR 7.6) and a lack of orbital extension (RR- 7) were significant predictors of survival.CONCLUSION: Leukocoria and proptosis are noticeable clinical signs of retinoblastoma. Most patients present while in stage one although stage four presentation is also common. Leukocoria, optic nerve invasion, orbital extension, and gender are significant factors predictive of survival in patients with retinoblastoma.

The World Health Organization has identified antimicrobial resistance as a public health emergency and developed a global priority pathogens list of antibiotic-resistant bacteria that can be summarized in the acronym ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacterales species), reminding us of their ability to escape the effect of antibacterial drugs. We previously tested new heteroaryl-ethylene compounds in order to define their spectrum of activity and antibacterial capability. Now, we focus our attention on PB4, a compound with promising MIC and MBC values in all conditions tested. In the present study, we evaluate the activity of PB4 on selected samples of ESKAPE isolates from nosocomial infections: 14 S. aureus, 6 E. faecalis, 7 E. faecium, 12 E. coli and 14 A. baumanii. Furthermore, an ATCC control strain was selected for all species tested. MICs were performed according to the standard method, with some modifications. PB4 MIC values were within very low ranges regardless of bacterial species and resistance profiles: from 0,12 to 2 mg/L for S. aureus, E. faecalis, E. faecium and A. baumannii. For E. coli, the MIC values obtained were slightly higher (4-64 mg/L), butstill promising. The PB4 heteroaryl-ethylenic compound was able to counteract the bacterial growth of both high-priority Gram-positive and Gram-negative clinical strains. In the future, it would be interesting to evaluate the activity of PB4 in animal models to test for its toxicity.

Effective healthcare relies on accurate and timely diagnosis; however, obtaining large amounts of training data while maintaining patient privacy remains challenging. This study introduces a novel approach utilizing federated learning (FL) and a cross-device multi-modal model for clin-ical event classification using vital signs data. Our architecture leverages FL to train machine learning models, including Random Forest, AdaBoost, and SGD ensemble model, on vital signs data from a diverse clientele at a Boston hospital (MIMIC-IV dataset). The FL structure preserves patient privacy by training directly on each client's device without transferring sensitive data. The study demonstrates the potential of FL in privacy-preserving clinical event classification, achieving an impressive accuracy of 98.9%. These findings underscore the significance of FL and cross-device ensemble technology in healthcare applications, enabling the analysis of large amounts of sensitive patient data while safeguarding privacy.

Immune checkpoint inhibitors (ICIs) are a class of drug that produces durable and sustained anti-tumour responses in a wide variety of malignancies. The exponential rise in their use has been mirrored by a rise in immune-related adverse events (irAEs). Knowledge of such toxicities, as well as effective management algorithms for these toxicities, is essential to optimize clinical efficacy and safety. Currently, the guidelines for management of the irAEs are based largely on retrospective studies and case series. In this article, we review the current landscape of clinical trials investigating the management of irAEs with an aim to develop standardized, randomized controlled trial-based management algorithms for ICI-related toxicities.

Many clinical trials end uninformatively. Informativeness, in the context of clinical trials, defines whether a study’s results definitively answer its research questions with meaningful next steps. One subset of these trials are those focused on global health set in low-resource settings. Global health clinical trials benefitting people in low-resource settings are funded primarily by a limited number of large foundations, pharmaceutical firms (“industry”), and national governments. While clinical trial protocols are required to go through reviews in regulatory and ethical domains, outside of industry-funded trials, funders rarely require focused scientific design reviews. There are no documented standards and processes, or even best practices, for funders to perform scientific reviews after the funding commitment. Considering the investment in and standardization of ethical and regulatory reviews, and the prevalence of studies ending without clarity or never finishing, it may be that scientific reviews of trial designs with a focus on informativeness offer the best chance for improved outcomes and return on investments in clinical trials. A maturity model is a helpful tool for knowledge transfer to help grow capabilities in a new area, or for those looking to perform a self-assessment in an existing area. Such a model is offered for scientific design reviews of clinical trial protocols: a valuable and often-neglected governance step for funders or sponsors, among others. This maturity model includes 11 process areas and 5 maturity levels. Each of the 55 process area levels is populated with descriptions on a continuum toward an optimal state to improve trial protocols in the area of risk of failure. This tool allows for prescriptive guidance on next investments to improve attributes of post-funding reviews of trials, with a focus on informativeness.

Various tissue resident stem cells are receiving attention from basic scientists and clinicians as they hold certain promise for regenerative medicine. This paper is intended to clarify and facilitate the understanding, development and adoption of regenerative medicine in general and specifically of therapies based on unmodified, autologous adipose-derived regenerative cells (UA-ADRCs). To this end, results of landmark experiments on stem cells and stem cell therapy performed in the labs of the authors are summarized, the most intriguing of which are the following: (i) vascular associated mesenchymal stem cells (MSCs) can be isolated from different organs (adipose tissue, heart, skin, bone marrow and skeletal muscle) and differentiated into ectoderm, mesoderm and endoderm, providing significant support for the hypothesis of the existence of a small, ubiquitously distributed, universal vascular associated stem cell with full pluripotency; (ii) the orientation and differentiation of MSCs are driven by signals of the respective microenvironment; and (iii) these stem cells irrespective of the tissue origin exhibit full pluripotent differentiation potential without any prior genetic modification or the need for culturing. They can be obtained from a small amount of adipose tissue when using the appropriate technology for isolating the cells, and can be harvested from and re-applied to the same patient at the point of care without the need for complicated processing, manipulation, culturing, expensive equipment, or repeat interventions. These findings demonstrate the potential of UA-ADRCs for triggering the development of an entire new generation of medicine for the benefit of patients and of healthcare systems.

This study focused on the development and implementation of an educational simulation program based on Korean Triage and Acuity Scale (KTAS) for nurses in emergency medical centers who completed KTAS training. We also examined its educational effects based on the evaluation of clinical decision-making ability, job satisfaction, and customer orientation. The study participants were 30 nurses in the emergency medical center of a general hospital. Data were collected from May 3 to 24, 2017, and analyzed using SPSS 22.0. There was a significant difference in the mean scores in clinical decision-making ability, job satisfaction, and customer orientation before and after simulation education. In other words, emergency nurses who received KTAS-based simulation education program improved their clinical decision making ability, job satisfaction, and customer orientation. Based on the results of this study, it is expected that it can be used for KTAS education, and it was found that simulation-based education is a useful learning method for triage nurses in emergency medical center.

Chikungunya is a mosquito-borne viral disease caused by Chikungunya virus (CHIKV. We conducted this study determine the seroprevalence and clinical presentation of Chikungunya infection among outpatients seeking healthcare in Mzuzu City, Malawi. Blood samples were collected from malaria negative and non-septic febrile outpatients with fevers ≥38 °C, for not more than 5 days. The enzyme- linked immunosorbent assay (ELISA) test was used to detect anti-CHIKV IgM antibodies and its results were used to determine seroprevalence of Chikungunya. A total of 119 serum samples were tested, of these, 73 (61.3%) tested positive for anti-CHIKV IgM antibodies by ELISA. Laboratory requisition forms were used to capture demographic information such as age, sex, clinical signs and symptoms presented by the enrolled patients. Age groups of 1-9, 10- 19, 20- 29, 30- 39, 40- 49, and ≥50 years had 17.8% (n= 13), 12.3 %,( n=9), 15.1%) (n=11), 19.2%; (n=14), 17.8% (n=13) and 17.8% (n=13) proportion of seroprevalence respectively. Most of the CHIKV infected individuals presented with fever (52.05%), joint pain (45.21%) and abdominal pain (42.67%). The presence of anti- CHIKV IgM antibodies suggest the presence of recent CHIKV infection and therefore accurate laboratory assays are highly recommended for CHIKV diagnosis and appropriate management of febrile patients.

The coronavirus disease 2019 (COVID-19) pandemic has caused considerable global disruption to clinical practice. This article will review the impact that the pandemic has had on oncology clinical trials. It will assess the effect of the COVID-19 situation on the initial presentation and investigation of patients with suspected cancer. It will also discuss the impact of the pandemic on the subsequent management of cancer patients and how clinical trial approval, recruitment and conduct were affected during the pandemic. An intriguing aspect of the pandemic is that clinical trials investigating treatments for COVID-19 and vaccinations against the causative virus, SARS-CoV-2, have been approved and conducted at unprecedented speed. In light of this, this re-view will also discuss the potential that this enhanced regulatory environment could have on the running of oncology clinical trials in the future.

A nutritional approach could be a promising strategy to prevent or slow the progression of neurodegenerative diseases such as Parkinson’s and Alzheimer’s disease, since there is no effective therapy for these diseases so far. The beneficial effects of omega-3 fatty acids are now well established by a plethora of studies through their involvement in multiple biochemical functions, including synthesis of antinflammatory mediators, cell membrane fluidity, intracellular signalling and gene expression. This systematic review will consider epidemiological studies and clinical trials that assessed the impact of supplementation or dietary intake of omega-3 polyunsaturated fatty acids on neurodegenerative diseases such as Parkinson’s and Alzheimer’s diseases. Indeed, treatment with omega-3 fatty acids, being safe and well tolerated, represent a valuable and biologically plausible tool in the management of neurodegenerative diseases in their early stages.

Purpose: Expanded carrier screening (ECS) informs couples of their risk of having offspring affected by certain genetic conditions. Limited data exists assessing the actions and reproductive outcomes of at-risk couples (ARCs). We describe the impact of ECS on planned and actual pregnancy management in the largest sample of ARCs studied to date. Methods: Couples who elected ECS and were found to be at high risk of having a pregnancy affected by at least one of 176 genetic conditions were invited to complete a survey about their actions and pregnancy management. Results: Three hundred ninety-one ARCs completed the survey. Among those screened before becoming pregnant, 77% planned or pursued actions to avoid having affected offspring. Among those screened during pregnancy, 37% elected prenatal diagnostic testing (PNDx) for that pregnancy. In subsequent pregnancies that occurred in both the preconception and prenatal screening groups, PNDx was pursued in 29%. The decision to decline PNDx was most frequently based on the fear of procedure-related miscarriage, as well as the belief that termination would not be pursued in the event of a positive diagnosis. Conclusions: ECS results impacted couples’ reproductive decision-making and led to altered pregnancy management that effectively eliminates the risk of having affected offspring.

Introduction: An epidemic of Coronavirus Disease 2019 (COVID-19) begun in December 2019 in China, causing a Public Health Emergency of International Concern. Among raised questions, clinical, laboratory, and imaging features have been partially characterized in some observational studies. No systematic reviews have been published on this matter. Methods: We performed a systematic literature review with meta-analysis, using three databases to assess clinical, laboratory, imaging features, and outcomes of COVID-19 confirmed cases. Observational studies, and also case reports, were included and analyzed separately. We performed a random-effects model meta-analysis to calculate the pooled prevalence and 95% confidence interval (95%CI). Results: 660 articles were retrieved (1/1/2020-2/23/2020). After screening by abstract/title, 27 articles were selected for full-text assessment. Of them, 19 were finally included for qualitative and quantitative analyses. Additionally, 39 case report articles were included and analyzed separately. For 656 patients, fever (88.7%, 95%CI 84.5-92.9%), cough (57.6%, 40.8-74.4%) and dyspnea (45.6%, 10.9-80.4%) were the most prevalent manifestations. Among the patients, 20.3% (95%CI 10.0-30.6%) required intensive care unit (ICU), with 32.8% presenting acute respiratory distress syndrome (ARDS) (95%CI 13.7-51.8), 6.2% (95%CI 3.1-9.3) with shock and 13.9% (95%CI 6.2-21.5%) of hospitalized patients with fatal outcomes (case fatality rate, CFR).Conclusion: COVID-19 brings a huge burden to healthcare facilities, especially in patients with comorbidities. ICU was required for approximately 20% of polymorbid, COVID-19 infected patients and this group was associated with a CFR of over 13%. As this virus spreads globally, countries need to urgently prepare human resources, infrastructure, and facilities to treat severe COVID-19.

The 2019 COVID-19 pandemic caused by SARS-CoV-2 has resulted in many fatalities worldwide. Despite various types of supportive care, mortality rates for patients with comorbidities remain high. To explore alternative treatment options, interferons (IFNs) have emerged as promising therapeutic drugs for SARS-CoV-2. This review aims to investigate the potential of IFNs as a drug with details on their mechanisms of action, and available data on their use with ongoing clinical trials, results, potential limitations, and challenges. Recently published research articles, which were systematically searched through online databases, have been selected and found that IFNs have colossal potential in treating SARS-CoV-2 infection by modulating the host's immune response and inhibiting viral replication and decreasing the severity of disease and hospitalization (p = 0.03, ±0.05) and (p = 0.04, ±0.05) respectively. However, due to less available data, more controlled and randomized trials are needed to confirm the efficacy and safety of IFN therapy. The optimal dosing and duration of IFN therapy also remain to be determined. Although further research is needed the wait for ongoing clinical trial results under investigation is also important for a better understanding of IFN therapy.

Background: Effectiveness of Anastrozole and levonorgestrel-releasing intrauterine device (LNG-IUD, Mirena®) in the treatment of endometriosis. Methods: Randomized clinical trial. Elegibility criteria: Endometriomas >3×4 cm, CA-125>35 U/mL and symptoms suggestive of endometriosis. Thirty-one women were randomized to anastrozole+Mirena®+Conservative Surgery(CS) (n=8), anastrozole+Mirena®+transvaginal ultrasound-guided puncture-aspiration(TUGPA) (n=7), Mirena®+CS (n=9), or Mirena®+TUGPA (n=7). Interventions: Anastrozole 1 mg/day and/or only Mirena® for 6 months. CS or TUGPA one month after starting medical treatment. Results: A significant improvement in symptoms during the treatment (difference of 43%, 95% CI 29.9-56.2) occurred, which was maintained at 1 and 2 years. It was more significant in patients treated with anastrozole. For CA-125, the most significant decrease was observed without anastrozole. After CS for endometriosis, a reduction of findings of endometriomas and long-term recurrences occurred, with or without anastrozole, although anastrozole seems to delay recurrences. At 4,2±1,7 years, 88% of the patients who underwent CS were asymptomatic, compared to only 21% if TUGPA was performed, with or without anastrozole (p=0.019). Conclusion: Dosing anastrozole for 6 months, starting one month before CS of endometriosis, reduces more significantly the painful symptoms and delays recurrences, but has no other significant advantages over the single insertion of LNG-IUD (Mirena®) during the same time.

Hepatitis B Virus (HBV) is a challenge for global health services, affecting millions and leading hundreds to end-stage liver disease each year. This comprehensive review explores the interactions between HBV and the host, examining their impact on clinical outcomes. HBV infection encompasses a spectrum of severity, ranging from acute hepatitis B to chronic hepatitis B, which can potentially progress to cirrhosis and hepatocellular carcinoma (HCC). Occult hepatitis B infection (OBI), characterized by low HBV DNA levels in hepatitis B surface antigen-negative individuals, can reactivate and cause acute hepatitis B. The identification of diverse HBV genotypes reveals distinct geographical distributions and associations with clinical outcomes. Moreover, single nucleotide polymorphisms (SNPs) within the host genome have been linked to several clinical outcomes, including cirrhosis, HCC, OBI, hepatitis B reactivation, and spontaneous clearance. The immune response plays a key role in controlling HBV infection by eliminating infected cells and neutralizing HBV in the bloodstream. Furthermore, HBV can modulate host metabolic pathways involved in glucose and lipid metabolism and bile acid absorption, further influencing disease progression. HBV clinical outcomes correlate with three levels of viral adaptation. In conclusion, the clinical outcomes of HBV infection could result from complex immune and metabolic interactions between the host and HBV. These outcomes can vary among populations and are influenced by HBV genotypes, host genetics, environmental factors, and lifestyle. Understanding the degrees of HBV adaptation is essential for developing region-specific control and prevention measures.

It is currently recognized that an injudicious strategy in the last decades has been not only focusing of research typically on caries in children, but also the narrow focusing on fluoride, because despite sufficient availability of fluoride in water and oral healthcare products, caries levels escalate steadily as people get older and caries remain a main public health issue to be settled. In the last two decades the scientific community intensified efforts of exploring other products for caries prevention, herbal products being one of these approaches. Because preliminary evidence indicated that clinical trials for caries prevention with herbal products are heterogeneous in design, quality and products evaluated, we performed a scoping review intended to explore the main characteristics of such clinical trials. From an initial collection of 1986 unique papers from different literature databases, 56 articles satisfied the inclusion and exclusion criteria. The species investigated, dosage forms, study designs, duration of intervention, controls, endpoints, quality of reporting and risk of bias are discussed. 85.71% of the trials reviewed here reported positive results but given the methodological flaws and biases affecting them, it is difficult to conclude on the efficacy of those products based on the studies published thus far.

Background: Given the potential for additional development to clarify a better knowledge of the overall impact of COVID-19 on the pediatric population, the clinical symptoms of SARS-CoV-2 infection in children and adolescents are still being explored. Morbidity in children is characterized by a variable clinical course. Our study's goal was to compare clinical aspects of 230 pediatric patients who tested positive for SARS-CoV-2 and were hospitalized between April 2020 and March 2022. Methods: In a retrospective analysis, we compared two groups hospitalized in the infectious diseases clinical ward IX at the National Institute for Infectious Diseases "Prof. Dr. Matei Bals," Bucharest, Romania. The first group of 88 patients was admitted between (April–December 2020) and their clinical manifestations were compared with the second group of 142 children followed between July 2021 and March 2022. Results: Of 230 children, the median age was 4.5 (interquartile range 0.6-17) years, 53.9% were male. 88 (36.21%) patients (first group) were admitted during the second wave in Romania, mostly aged < 5 years old, and experienced digestive manifestations like fever (p=0.001), and diarrhoea (p=0.004). The second group experienced different clinical signs when compared with the first group, with higher temperature and increased respiratory symptoms analogous to those of acute respiratory viral infections. The proportion in the second group increased, and 64.5% had symptoms for a median interval of 5 days; age (0-4 -years old) and length of stay were both proportionally inversely (p<0.01) and with correlation with hospital admission (p = 0.04). We report two Paediatric Inflammatory Multisystem Syndrome (PIMS) in the second group, with favourable evolution under treatment. Comorbidities were risk factors for complications appear (p < 0.001) in both groups. All paediatric cases admitted to our clinic evolved favourably and no death was recorded. Conclusions: In the first group children experienced digestive symptoms, whereas the second group experienced mild and moderate respiratory symptoms. We confirmed risk factors for severe cases as manifestations across the age spectrum, 0-4 (digestive symptoms) and 5-12 years old (for respiratory symptoms), associated comorbidities, fever, and male gender. The potential effects of COVID-19 infection in children older than 5 years should encourage caregivers to vaccinate and improve the prognosis among pediatric patients at risk.

Probiotics have been widely used in gastroenteritis due to acute and chronic illnesses. However, evidence supporting the effectiveness of probiotics in different health conditions are inconclusive and conflicting. The aim of the study was to review existing literature on the effects of probiotics in gastroenteritis among adults. Only original articles on clinical trials that demonstrated the effects of probiotics in adults with gastroenteritis were used for this analysis. Multiple databases such as PubMed, Google Scholar, MEDLINE and Scopus databases were searched for the data. The study followed standard procedures for data extraction using PRISMA flow chart. A quality appraisal of the selected studies was conducted using CADIMA. Finally, a meta-analysis was conducted. Thirty-five articles met the selection criteria; of them, probiotics were found effective in the treatment and/or prevention of chronic inflammatory bowel disease (IBD) including ulcerative colitis and Crohn’s disease in 17 (49%), and the treatment of pouchitis in 4 (11.4%), antibiotic-induced diarrhea in 3 (8.6%), Helicobacter pylori infection in 2 (5.7%) and diverticulitis in 1 (2.9%), while the remaining 7 (20%) were ineffective and 1 study results were inconclusive. Meta-analysis, on the contrary, didn’t demonstrate any significant protective effects of probiotics. Having a τ² value of zero and I² of 6%, the studies were homogeneous and had minimum variances. Further studies are suggested to evaluate the beneficial effects of probiotics in IBDs and other chronic bowel diseases.

Fumaric acid esters (FAEs) are small molecules with anti-oxidative, anti-inflammatory and immune-modulating effects. Dimethyl fumarate (DMF) is the best characterised FAE and is approved and registered for the treatment of psoriasis and Relapsing-Remitting Multiple Sclerosis (RRMS). Psoriasis and RRMS share an immune-mediated aetiology, driven by severe inflammation and oxidative stress. DMF, as well as monomethyl fumarate and diroximel fumarate, are commonly prescribed first-line agents with favourable safety and efficacy profiles. The potential benefits of FAEs against other diseases that appear pathogenically different but share the pathologies of oxidative stress and inflammation are currently investigated.

Porous tantalum (Ta) is a promising biomaterial and has been applied in orthopedics and dentistry for nearly two decades. The high porosity and interconnected pore structure of porous Ta promise fine bone ingrowth and new bone formation within the inner space, which further guarantee rapid osteointegration and bone-implant stability in long term. Porous Ta has high wettability and surface energy that can facilitate adherence, proliferation and mineralization of osteoblasts. Meanwhile, low elastic modulus and high friction coefficient of porous Ta can effectively avoid stress shield effect, minimize marginal bone loss and ensure primary stability. Accordingly, the satisfactory clinical application of porous Ta based implants or prostheses are mainly derived from its excellent biological and mechanical properties. With the advent of additive manufacturing, personalized porous Ta based implants or prostheses have shown their clinical value in the treatment of individual patient who need specially designed implant or prosthesis. In addition, many modification methods have been introduced to enhance the bioactivity and antibacterial property of porous Ta with promising in vitro and in vivo research results. In any case, choosing suitable patients is of great importance to guarantee surgical success after porous Ta insertion.

The abnormal accumulation of cells in the human brain, if left untreated, may cause brain damage. Management and treatment of these tumours require an early and accurate diagnosis, while their prognostic characterisation can also be beneficial in the choice of care planning for the patient. CDSSs are being continuously developed and integrated into routine clinical practice as they assist clinicians and radiologists to deal with an enormous amount of medical data, reduce clinical errors, and improve diagnostic capabilities. They assist detection, classification, and grading of brain tumours as well as alerting physicians of requirement of change in treatment plans. The aim of this systematic review is to identify various CDSSs used in brain tumour diagnosis and prognosis, that rely on data captured by any imaging modality. Based on the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol, the literature search was conducted in PubMed and Engineering Village Compendex databases. This review examines various CDSS tool types, system features, techniques used, accuracy, and outcome, to provide the latest evidence available in the field of neuro-oncology. An overview of different types of CDSSs used to support clinical decision-making in the management and treatment of brain tumours, along with highlighting their benefits, challenges, and future perspectives has been provided.

Clinical trials are research studies performed on people that are aimed at evaluating a medical, surgical, or behavioural intervention. It is a primary way that researchers find out if a new treatment, like a new drug or diet, or medical device is safe and effective in people. In this paper blockchain technology is embedded in a digital twin aiming to improve the quality of clinical trials through the boost of data integrity among the quality-related activities, and to promote participants' safety. First, a blockchain-embedded quality-enabled digital twin is proposed and the interactions among the enablers and peers are highlighted. Then, a prototype of the proposed system is developed, and the data of a pilot trial is used to justify the applicability of the system. The results showed that the proposed system is efficient, and hence it is feasible to adopt into a clinical trial. With the successful development of the proposed system, it is promising to provide effective data integration and knowledge management for improving participant safety.

Clinical pharmacists are employed at many hospital departments in Denmark, but not yet on the Faroe Islands. The purpose of this study was to test feasibility of a clinical pharmacist-led medication review service at the surgical ward of the National Hospital on the Faroe Islands. Hospitalised surgical patients were offered a medication review service by a clinical pharmacist. Identified drug related problems (DRPs) were classified according to the Pharmaceutical Care Network Europe (PCNE) model. The qualitative inputs from the ward’s staff were collected. In total, 42 patients with 171 identified DRPs were included. The majority of the DRPs concerned suboptimal effect and the safety of the drug treatment. The 49.6 % of the proposed medication changes were accepted by the ward physicians. According to the qualitative inputs, the interest for the service was greater among the younger physicians compared to the older ones, and among nurses compared to physicians. Identified barriers for the optimal service implementation were an absence of medication ordinations and poor visibility of pharmacist’s notes in electronic health records. For a successful implementation of the service, work on the physicians’ interest in an interdisciplinary cooperation and optimization of the electronic health records are warranted.

Simulation-Based Medical Education that uses Virtual Patients has become increasingly important during the COVID-19 pandemic. With the need for social distancing and minimizing contact, medical simulation technology has provided a valuable tool for healthcare professionals to practice and improve their skills without the need for face-to-face interactions. MedSIM is a medically accurate simulation platform with Virtual Patients designed for undergraduate medical education. Our study involved two groups of students. The PreCOVID group, before the pandemic, underwent conventional teaching methods. The COVID group, during the pandemic, had students exposed to conventions skills taught earlier and were taught again with MedSIM. Students indicated high satisfaction with the clinical skills demonstrated by the Virtual Patients. More than half agreed that MedSIM had enabled them to perform all kinds of procedures on patients (PreCOVID group 68.8%, COVID group 71.3%), showed cues and consequences much like those in natural clinical environments (PreCOVID 68.4%, COVID 71.3%). Also, MedSIM allowed them to have a repetitive practice that helps in critical skills transfer to actual patients (PreCOVID 72.7%, COVID 74.7%). MedSIM met the expectations of most of the students. Students from both groups rated the online performance of the MedSIM simulator as "Very good." Analysis from a customized word cloud indicated that most students found MedSIM to be good and of educational value. MedSIM platform enhances healthcare professionals' skills and knowledge, leading to better patient outcomes and increased access to healthcare, supporting SDG 3 (Good Health and Well-being). It also provides a safe and controlled environment for healthcare professionals to learn and practice essential skills, supporting SDG 4 (Quality Education).

Globally, the COVID-19 pandemic has brought the world to a standstill with the infected cases surpassing millions. The causative agent of COVID-19, the SARS-CoV-2 is a novel coronavirus that emerged from the wet animal market in Wuhan, China in early December 2019. Soon after, human-to-human transmission increased the rate of infection making the disease widespread with new hotspots emerging around the world.The epidemiological reports based on clinical characteristics including age, gender, symptoms (both severe and non-severe), and the conditions requiring intensive medical care, along with case fatality revealed that people with co-existing health conditions like diabetes, hypertension, cigarette smoking, and others with cardiovascular and kidney diseases were more susceptible to COVID-19 infection with poor prognosis in cases related to the severity of symptoms and requiring ICU, medical ventilators with a high fatality rate. Even people with immunosuppressed conditions like HIV and cancer, alongwith old age and pregnant women are vulnerable to COVID-19 infection and can cause severe health complications.It is extremely important to have a comprehensive idea of the underlying pathophysiology related to these health conditions which makes them more susceptible to contract SARS-CoV-2 infection in correlation with the development of severe symptoms. This review will provide an extensive viewpoint related to COVID-19 patients having coexisting health conditions together with the association between the prognosis of the disease and the pathogenesis of the SARS-CoV-2 infection, based on the current information available.

The purpose of this systematic review is to examine the various articles published in the field of neuropsychology of anxiety research in terms of publication type and volume, methodology, and subject matter. The significance of this topic derives from the clinical and functional consequences of cognitive symptoms. Generalized anxiety disorder refers to the cluster of clinical symptoms characterized by predominant anxious anticipation and difficulty controlling worry. In order for the review to be systematic and reproducible, a search of the PsycINFO, Scopus, PubMed, Elsevier databases and an analysis using the PRISMA method are suggested. After analyzing the research data, empirical studies evaluating the clinical neuropsychology of generalized anxiety disorder are discussed.

Background: Laryngopharyngeal reflux (LPR) is a common disease in otolaryngology characterized by an inflammatory reaction of the mucosa of the upper aerodigestive tract caused by digestive refluxate enzymes. LPR has been identified as etiological or favoring factor of laryngeal, oral, sinonasal or otological diseases. In this case-series, we reported atypical clinical presentation of LPR in patients presenting in our clinic with reflux. Methods: A retrospective medical chart review of 351 patients with LPR treated in the European Reflux Clinic in Brussels, Poitiers and Paris was performed. In order to be included, patients had to report atypical clinical presentation of LPR, consisting of symptoms or findings that are not described in reflux symptom score and reflux sign assessment. The LPR diagnosis was confirmed with 24-hour hypopharyngeal-esophageal impedance pH-study and patients were treated with a combination of diet, proton pump inhibitors and alginates. The atypical symptoms or findings had to be resolved from pre- to posttreatment Results: From 2017 to 2021, 21 patients with atypical LPR were treated in our center. The clinical presentation consisted of recurrent aphthosis or burning mouth (N=9), recurrent burps and abdominal disorders (N=2), posterior nasal obstruction (N=2), recurrent acute suppurative otitis media (N=2), severe vocal fold dysplasia (N=2), and recurrent acute rhinopharyngitis (N=1), tearing (N=1), aspirations (N=1) or tracheobronchitis (N=1). Abnormal upper aerodigestive tract reflux events were identified in all of these patients. Atypical clinical findings resolved and did not recur after an adequate anti-reflux treatment. Conclusion: LPR may present with various clinical presentations including mouth, eye, tracheobronchial, nasal or laryngeal findings, which may all regress with an adequate treatment. Future studies are needed to better specify the relationship between LPR and these atypical findings through analyses identifying gastroduodenal enzyme in the enflamed tissue.

Background and Objectives: Clinical trials are a critical step in the development of new medicines and medical devices, testing the efficacy and safety of new treatment regimens. However, if the results of clinical trials are not made public, the evidence base on interventions is incomplete and possibly distorted, which lead to suboptimal treatment choices and negatively affect public health. This study analyses and contrasts the laws and regulations governing clinical trial registration and reporting in China and the United States. Methods: We used desk research to compile, assess and compare current laws, regulations, compliance patterns, and enforcement mechanisms and actions in China and the United States (U.S.). Policy documents were downloaded from Chinese and U.S. government websites. A spreadsheet analysis was utilized for direct comparison. Results: Both China and the U.S. have laws and regulations governing clinical trial registration and reporting. Chinese legislation covers a broader range of trials. In the U.S. trial results must be disclosed to both the national regulator and the public, while Chinese law mandates disclosure to the regulator alone. Cross-country comparisons of regulatory compliance by trial sponsors are impossible due to the opacity of the Chinese data platform. Neither country effectively ensures that all clinical trial results are made public as required by the Declaration of Helsinki and recommended by the WHO. Interpretation: While neither country is perfect, both may be able to learn from each other. There is a major gap in the literature regarding the extent of non-publication of clinical trial results by sponsors operating in China.

In order to harness the potential of mobile technologies to enhance the quality of clinical research, it is critical to first understand how to engage patients and research sites when planning and conducting mobile clinical trials. The Clinical Trials Transformation Initiative has developed the first comprehensive, evidence-based set of recommendations for incorporating patient and site perspectives in mobile clinical trials, which can aid in engaging stakeholders, addressing site challenges, and maximizing value for participants.

Hemoglobin is one of the proteins that are more susceptible to S-glutathionylation and the levels of its modified form, glutathionyl hemoglobin, increase in several human pathological conditions. The scope of the present review is to provide knowledge about how hemoglobin is subjected to be S-glutathionylated and how this modification affects its functionality. The different diseases that showed increased levels of glutathionyl hemoglobin and the methods used for its quantification in clinical investigations will be also outlined. Since there is a growing need for precise and reliable methods of markers of oxidative stress in human blood, this review highlights how glutathionyl hemoglobin is more and more emerging as a good indicator of severe oxidative stress but also as a key pathogenic factor in several diseases.

Clinical trials for Alzheimer’s disease (AD) face multiple challenges, such as the high screen failure rate and even allocation of heterogeneous participants. Artificial intelligence (AI), which has become a potent tool of modern science with the expansion in the volume, variety, and velocity of biological data, offers promising potential to address these issues in AD clinical trials. In this review, we introduce the current status of AD clinical trials and topic of machine learning. Then, a comprehensive review is focused on the potential applications of AI in the steps of AD clinical trials, including the prediction of AD biomarkers and differential diagnosis of AD in the prescreen during eligibility assessment and the likelihood stratification of patients who will progress to AD dementia and fast cognitive decline group from the slow decline group in randomization. Finally, this review provides challenges, developments and the future outlook on the integration of AI into AD clinical trials.

All the available botulinum type A neurotoxins for clinical uses are of A1 subtype. We developed a subtype A2 low molecular weight (150kD) neurotoxin (A2NTX), with less spread and faster entry into the motor nerve terminal than A1 in vitro and in vivo. Preliminary clinical studies showed its efficacy superior to A1 toxins. We conducted an open study exploring its safety and tolerability profile in comparison with A1LL (onabotulinumtoxinA) and low molecular weight (150kD) A1 neurotoxin (A1NTX). Those who had been using A1LL (n=90; 50-360 mouse LD50 units) or A1NTX (n=30; 50-580 units) were switched to A2NTX (n=120; 25-600 units) from 2010 till 2018 (number of sessions ~ 27, cumulative doses ~11,640 units per patient). Adverse events for A2NTX included weakness (n=1, ascribed to alcoholic polyneuropathy), dysphagia (1), local weakness (4), spread to other muscles (1), whereas those for A1LL or A1NTX comprised weakness (n=2, A1NTX), dysphagia (8), ptosis (6), local weakness (7) and spread to other muscles (15). After injections, 89 out of 120 patients preferred A2NTX to A1 for the successive sessions. The present study demonstrated that A2NTX had the clinical safety up to the dose of 500 units, and was well tolerated compared to A1 toxins.

The Swiss Personalized Health Network (SPHN) is a Swiss research infrastructure initiative that aims to facilitate the exchange of health-related data in a FAIR manner. The SPHN Dataset and SPHN RDF Schema form an essential part of the SPHN Semantic Interoperability Framework, which currently covers mostly clinical routine data. To facilitate the integration of omics data produced by the SPHN National Data Streams, a genomics extension was developed. This was done in close collaboration with clinicians, researchers, bioinformaticians, and data managers, from Swiss university hospitals, academic research groups and the omics platforms. Here, we present the genomics extension of the SPHN RDF Schema, which can be used to semantically describe genomics experiments and covers both clinical and research domains. The schema centers around the general omics process flow, with concepts that denote the individual steps, such as sample processing, assay, and data processing. Genomics-specific specializations are provided, such as library preparation, sequencing assay, and sequencing analysis. The schema also facilitates in capturing other important omics metadata, such as information about the sequencing instrument, standard operating procedure, and quality control metrics. The extension aligns with existing semantic data models and reuses common biomedical vocabularies, such as EDAM, OBI and FAIR genomes, as value sets, thereby facilitating semantic interoperability. It will be used to FAIRify data that is produced within the Swiss network and to facilitate sharing this data as one knowledge graph for reuse among its participants.

The emergence of new type of viral pneumonia cases in China, on December 31, 2019; identified as the cause of human coronavirus, labeled as "COVID-19," took a heavy toll of death and reported cases of infected people all over the world, with the potential to spread widely and rapidly, achieved worldwide prominence but arose without the procurement guidance. There is an immediate need for active intervention and fast drug discovery against the 2019-nCoV outbreak. Herein, the study provides numerous candidates of drugs (either alone or integrated with another drugs) which could prove to be effective against 2019-nCoV, are under different stages of clinical trials. This review will offer rapid identification of a number of repurposable drugs and potential drug combinations targeting 2019-nCoV and preferentially allow the international research community to evaluate the findings, to validate the efficacy of the proposed drugs in prospective trials and to lead potential clinical practices.

Chimeric antigen receptor and T-cell receptor (CAR-T/TCR) cellular immunotherapies have shown remarkable success in the treatment of some refractory B-cell malignancies, with potential to provide durable clinical response for other types of cancer. In this paper, we look at all available FDA CAR-T/TCR clinical trials for the treatment of cancer, and analyze them with respect to different disease tissues, targeted antigens, products, and originator locations. We found that 627 of 1,007 registered are currently active and of those 273 (44%) originated in China and 280 (45%) in the US. Our analysis suggests that the rapid increase in the number of clinical trials is driven by the development of different CAR-T products that use a similar therapeutic approach. We coin the term bioparallels to describe such products. Our results suggest that one feature of the CAR-T/TCR industry may be a robust response to success and failure of competitor products.

A cross-sectional study was carried out to determine the prevalence of subclinical mastitis (SCM) among medium to large scale household dairy farms in southwestern district, Jhenaidah, Bangladesh during July to December 2019. A total of 78 (n=100) lactating cows from household dairy farms (N=32) having three or more dairy cows were selected randomly as sampled populations. Milk samples were screened for SCM by using Surf Field Mastitis Test (SFMT). The prevalence of SCM varied among farm level [71.9% (95% CI: 53.3-86.3)], individual animal level [67.9% (95% CI: 56.4-86.3)] and quarter level [29.5% (95% CI: 24.5-34.9)]. Descriptive statistics represented the farmers and farm demography, characteristics of the sampled population, and overall management feature. Random Effect Logistic Regression identified, Body Condition Score (BCS) [OR=3.8 and 2.9, at cows level and quarter level respectively (BCS-2 vs. BCS-≥3)], and breed [OR=5.1 and 2.9, at cows level and quarter level respectively (HF× Sahiwal vs. HF × Local)] as potential risk factors. This study shows that SCM is highly prevalent in the study area, which is a major threat to the dairy industry's production performance. Regular screening by SFMT, proper hygiene, improve the management system, and farmer’s awareness is required to control the disease.

Background: Cardiomyopathy is commonly observed disease that may occurs due to mutations in either susceptible genes or modifier gene. People with broad age group are affected either attributable to spontaneous or inherited mutations of these genes. Various gene mutations are reported so far but only few of them were studied in detail. Methods: In the current study, we evaluated epidemiological variables like age, sex, familial status, parental consanguinity. We also described specific clinical symptoms associated with the cardiomyopathy condition in Indian population. Results: Our studies on mutation screening of phospholamban gene revealed two transitions (4880 C/T, 4887 T/G) in 5’ flanking region which might cause inherited dilated cardiomyopathy with refractory congestive heart failure are We further deliberated the gene polymorphism of renin angiotensin system gene angiotensin-1-converting enzyme as an associated marker/ modifier in cardiomyopathy patients and their family members. Conclusions: Information on epidemiological, clinical statistics, phospholamban gene mutation analysis and angiotensin-1-converting enzyme gene polymorphism is essential to guide the successful execution for future therapies and benefits us to identify those patients at risk for faster disease progression, congestive heart failure, and arrhythmia.

The FDA has concluded that a biosimilar candidate capable of demonstrating pharmacodynamic biomarkers in a healthy subject need not be tested for clinical efficacy in patients, regardless of if the biomarker correlates with clinical response. Since monoclonal antibodies (mAbs) do not trig-ger pharmacodynamic response, they can be substituted with robust functional disqualifying them for this waiver that can be overcome by allowing comparison of functional properties that eventually result in clinical response. This suggestion is based on the FDA's preference for more sensitive testing methods. However, clinical efficacy testing in patients is the least sensitive method, as confirmed by statistical modeling, a fact that regulatory agencies need to admit. In this paper, I present a logical and rational argument to establish the biosimilarity of products that do not have pharmacodynamic biomarkers based on their orthogonally proven functional bio-similarity. This understanding will significantly lower the development cost of biosimilars, a goal that the FDA outlined in all its guidance. Keywords: biosimilarity 1; biosimilars 2; pharmacodynamic biomarkers 3; monoclonal antibodies 4; FDA 5; clinical efficacy testing in healthy subjects 6; clinical efficacy testing in patients 7; functional assays 8; receptor binding 9.

Clopidogrel is one of the most prescribed antiplatelet drugs for cardiovascular diseases prevention. Clopidogrel is a prodrug metabolised by CYP2C19 in active metabolites with anti-aggregant effect. Pharmacogenetic variants such as CYP2C19*2 variant can alter the anti-aggregant effect of clopidogrel leading to a higher risk of cardiovascular disease relapse. The aim of this study was to evaluate the prescription characteristics of CYP2C19 pharmacogenetics in patients on clopidogrel treatment, based on a specific query in a clinical data warehouse. We evaluated the demographics of patients, prescribers, medical indications, CYP2C19 pharmacogenetic tests and therapeutic changes. Neurologists were the main prescribers of CYP2C19 pharmacogenetic tests associated with clopidogrel treatment in a context of suspicion of stroke relapse. Pharmacogenetic tests were mainly prescribed a posteriori to clopidogrel prescription. Clopidogrel pharmacogenetic resistance was associated with the prescription of lysine acetylsalicylate in substitution of clopidogrel. Clear clinical practice guidelines are needed to position CYP2C19 pharmacogenetic testing for patients on clopidogrel treatment.

Over a year into the COVID-19 pandemic, there is growing evidence that SARS-CoV-2 infections among dogs are more common than previously thought. In this study, the prevalence of SARS-CoV-2 antibodies was investigated in two dog population. The first group was comprised of 1069 dogs admitted to the Veterinary Teaching Hospital for any given reason. The second group included dogs that shared households with confirmed COVID-19 cases in humans. This study group numbered 78 dogs. In COVID-19 infected households, 43.9% tested ELISA positive, and neutralisation antibodies were detected in 25.64% of dogs. Those data are comparable with the secondary attack rate in the human population. With 14.69% of dogs in the general population testing ELISA positive, there was a surge of SARS-CoV-2 infections within the dog population amid the second wave of the pandemic. Noticeably seroprevalence of SARS-CoV-2 in the dog and the human population did not differ at the end of the study period. Male sex, breed and age were identified as significant risk factors. This study gives strong evidence that while acute dog infections are mostly asymptomatic, they can pose a significant risk to dog health. Seropositive dogs had a 1.97 times greater risk for developing central nervous symptoms.

Implementing the methodology of clinical simulation in the nursing degree course is a necessity in the European framework of higher education to acquire competences. The objectives of this research were to evaluate the strategies and techniques used during the simulations, identify the contents learned, and determine which of them are transferred to the nursing practice. We performed an observational, descriptive, and cross-sectional study from the nursing students’ perspective during the 2020-21-year course. On the one hand, our results show that the DASH scale helped us to obtain an internal validity of the simulations obtaining a mean score of 6.61 out of 7. On the other hand, the Ad Hoc scale, based on the competences were acquired in the simulations were transferred to the care practices. In conclusion, it is possible to improve care practices by integrating knowledge through clinical simulations.

The widely spread CoronaVirus Disease (COVID)- 19 is one of the worst infectious disease outbreaks in history and has become an emergency of primary international concern. As the pandemic evolves, academic communities have been actively involved in various capacities, including accurate epidemic estimation, fast clinical diagnosis, policy effectiveness evaluation and development of contract tracing technologies. There are more than 23,000 academic papers on the COVID-19 outbreak, and this number is doubling every 20 days while the pandemic is still on-going [1]. The literature, however, at its early stage, lacks a comprehensive survey from a data analytics perspective. In this paper, we review the latest models for analyzing COVID19 related data, conduct post-publication model evaluations and cross-model comparisons, and collect data sources from different projects.

Management of Juvenile idiopathic arthritis (JIA) has improved tremendously in recent years due to the introduction of new drug therapies but remains complex also in terms of non-pharmaceutical issues. In order to determine the direction of scientific progress by characterizing the current spectrum of ongoing clinical research in JIA, we analyzed all ongoing studies in the field of JIA registered in clinicaltrials.gov and clinicaltrialsregister.eu concerning sponsoring, enrollment, duration, localization, and particularly objectives. Close of database was 7 January 2021. After identifying doubled-registered studies, N=72 went into further analysis. Of these, 61.1% were academia-sponsored and 37.5% by pharma industry. The majority of studies was of interventional type (77.8%), while others (22.2%) were observational. Median planned enrollments were 100 participants (interventional studies) and 175 participants (observational studies), respectively. Duration differed remarkably from one month to more than 15 years with a median of 42.5 months. 61.1% of studies were located in a single country, 38.9% were in several. Europe and North America clearly dominated study localizations. Study objectives were DMARDs (56.9%), followed by diagnostics and disease activity measurement (18.1%), and medication other than DMARD (12.5%), besides others. Studies on DMARDs were mainly sponsored by industry, predominantly interventional studies on established and novel biologics, with several on specific issues like systemic JIA and others. The spectrum of registered studies is currently centered on drug therapy and diagnostics, while other issues in JIA play a subordinated role.

Managing blood cholesterol levels is important for the treatment and prevention of diabetes, cardiovascular disease, and obesity. An easy-to-use, portable cholesterol blood test will accelerate more frequent testing by patients and at-risk populations. We aim to evaluate the performance of smartphone-based point-of-care cholesterol blood tests as compared to that of hospital-grade laboratory tests. We used smartphone systems that are already familiar to many people. Because smartphone systems can be carried around everywhere, blood can be measured easily and frequently. We compared the results of cholesterol tests with those of existing clinical diagnostic laboratory methods. We found that smartphone-based point-of-care lipid blood tests are as accurate as hospital-grade laboratory tests (N=116, R>0.97, P<0.001 for all 3 cholesterol blood tests: total cholesterol, high density lipoprotein, and triglyceride). Our system will be useful for those who need to manage blood cholesterol levels to motivate them to track and control their behavior.

Bovine mastitis is the most impacting disease of dairy industry, and it is characterized by a complexity of causal agents, which have revealed a geographical variation among regions and countries. The mastitis-related pathogens have been traditionally classified as contagious or environmental, based on habits of the microorganisms and transmission routes. In addition, the severity of mammary infections has been associated with the virulence of the pathogens, and immune and nutritional status of the hosts. Considering this scenario, we investigated the etiological nature, clinical severity scores, and days in milk (DIM) data in 4,273 clinical cases of bovine mastitis among ten large-dairy farms located in the Southeast region of Brazil. Streptococcus dysgalactiae (283/4,273=6.6%), Escherichia coli (190/4,273=4.4%), Prototheca spp. (112/4,273=2.6%), and Streptococcus uberis (95/4,273=2.2%) were the predominant pathogens isolated, all from the environmental origin. Among 4,273 clinical cases, clinical gravity score was available in 43.8% (1,871/4,273) animals. From these, 69.8% (1,306/1,871), 27.3% (510/1,871) and 2.9% (55/1,871) were scored as mild, moderate, and severe, respectively. Most of isolation of pathogens were observed in the first 100 days in milk, and their clinical severity scored as mild (3,612/4,273=84.5%). Our results contribute to the etiological identification, clinical severity scoring, and milking aspects of bovine clinical mastitis in dairy farms with a history of clinical mammary infections.

Background. Until now, cost of allergy treatment in insured public health care system and non-insured self-financing private health care system in Indonesia has not been well documented and published, as well as the cost of allergy treatment with subcutaneous immunotherapy. Objective. To evaluate the clinical and cost benefits of allergic rhinitis treatment in children with subcutaneous immunotherapy in non-insured self-financing private health care system. Methods. A retrospective cohort study conducted from 2015 until 2020, compared clinical improvement and health care costs over 18 months in newly diagnosed AR children who received SCIT versus matched AR control subjects who did not receive SCIT, with each group consisting of 1,098 subjects Results. Decrease of sp-HDM-IgE level (kU/ml) from 20.5 + 8.75 kU/ml to 12.1 + 3.07 kU/ml had been observed in the SCIT group. To reduce the symptom score of allergic rhinitis by 1.0 with SCIT it costs IDR 21,753,062.7 per child, for non SCIT it costs IDR 104,147,878.0 per child. Meanwhile, to reduce the medication score (MS) by 1.0 with SCIT it costs Rp. 17,024,138.8 while with non SCIT it costs Rp. 104,147,878.0. Meanwhile, to lower combination symptoms and medication score (CSMS) by 1.0, with SCIT it costs IDR 9,550,126.6, while with non SCIT it costs IDR 52,073,938.9. Conclusion. In conclusion, this first Indonesia-based study demonstrates substantial health care cost savings associated with SCIT for children with AR in an uninsured private health care system and provides strong evidence for the clinical benefits and cost-savings benefits of AR treatment in children.

Patients with non-union fractures spend extended periods in the hospital following poor healing. Patients have to make several follow-up visits for medical and rehabilitation purposes. However, the clinical pathways and quality of life of these patients are unknown. This prospective study aimed to identify the clinical pathways (CPs) of 22 patients with lower limb non-union fractures whilst determining their quality of life. Data were collected from hospital records on admission through discharge, utilising a CP questionnaire. We used the same questionnaire to track patients' follow-up frequency, involvement in activities of daily living, and outcomes at six months. We used the short form-36 questionnaire to assess patients’ initial quality of life. The Kruskal-Wallis test compared the quality of life domains across different fracture sites. We examined CPs using medians and inter-quantile ranges. During the six-month follow-up period, 12 patients with lower limb non-union fractures were readmitted. All of the patients had impairments, limited activity, and participation restrictions. Lower limb fractures can have a substantial impact on emotional and physical health, and lower limb non-union fractures may have an even greater effect on the emotional and physical health of patients, necessitating a more holistic approach to patient care.

We sought to evaluate the effects of non-surgical periodontal treatment (NSPT) on periodontal clinical parameters, systemic blood pressure (BP) and plasma levels of systemic inflammation markers in patients with combined refractory arterial hypertension (RAH) and stage III grade B periodontitis. Twenty-seven participants with RAH and periodontitis received NSPT. The analyzed clinical parameters were probing depth (PD), clinical attachment level (CAL), bleeding on probing (BOP), and plaque index (PI). An assessment was performed for systemic BP, complete blood count, coagulogram, creatinine measurement, C-reactive protein (CRP), glycated hemoglobin, cholesterol, glutamic oxaloacetic transaminase, glutamate pyruvic transaminase, waist-hip ratio, and body mass index. In the follow-up period, twenty-two patients were evaluated at baseline and after 90 and 180 days. The data were submitted to statistical analysis (α=0.05%). As expected, the clinical results showed a significant improvement in the percentages of PI, BOP, PD and CAL, which were statistically significant at 90 and 180 days (p&lt;0.0001). Importantly, NSPT significantly reduced the blood level of CRP (p&lt;0.02). However, no significant reduction in BP parameters was noted in the evaluated follow-up periods. NSPT, despite the benefits in periodontal clinical parameters, reduced the plasma level of CRP but not the BP in patients with combined RAH and periodontitis.

Dietzia natronolimnaea C79793-74 has emerged as a potential probiotic strain with implications for managing Crohn's disease. This study evaluates the safety profile of D. natronolimnaea C79793-74 as a probiotic sup-plement. Genotypic characterization involved a 16S rRNA gene and genomic sequencing and genome an-notation. The safety assessment included interrogation of the assembled genome for antibiotic resistance genes and virulence factors, utilizing the CARD and VFDB databases. Notably, the analysis revealed an ab-sence of antibiotic resistance or virulence factors in Dietzia natronolimnaea C79793-74. The safety and tol-erability of D. natronolimnaea C79793-74 were further investigated in an 8-week double-blind, place-bo-controlled clinical trial involving healthy adult participants. A daily dose of 5 x 109 CFU of the probiotic strain was administered. This clinical trial represents the first assessment of the safety of D. natronolimnaea C79793-74 in human subjects. Results demonstrated that participants in both the Dietzia and Placebo groups maintained clinical and hematologic markers within the normal range throughout the study. More-over, the probiotic strain was well-tolerated, with nearly all participants experiencing no severe or medium adverse events. Collectively, the comprehensive data obtained in this study support the inference that Dietzia natronolimnaea C79793-74 is safe and well-tolerated as a nutritional supplement for human con-sumption

Validation and verification are the critical requirements in the knowledge acquisition method for the clinical decision support system (CDSS). After acquiring the medical knowledge from diverse sources, the rigorous validation and formal verification process are required before creating the final knowledge model. Previously, we have proposed a hybrid knowledge acquisition method for acquiring medical knowledge from clinical practice guidelines (CPGs) and patient data in the Smart CDSS for treatment of oral cavity cancer. The final knowledge model was created by combining knowledge models obtained from CPGs and patient data after passing through a rigorous validation process. However, detailed analysis shows that due to lack of formal verification process, it involves various inconsistencies in knowledge relevant to the formalism of knowledge, conformance to CPGs, quality of knowledge, and complexities of knowledge acquisition artifacts. Therefore, it is required to enhance a hybrid knowledge acquisition method that thwarts the inconsistencies using formal verification. This paper presents the verification process using the Z formal method and its outcome as an enhanced acquisition method – known as the refined knowledge acquisition (ReKA) method. The ReKA method adopted verification method and explored the mechanism of theorem proving using the Z notation. It enables to identify inconsistencies in the validation process used for hybrid knowledge acquisition. Additionally, it refines the hybrid knowledge acquisition method by discovering the missing steps in the current validation process at the acquisition stage. Consequently, ReKA adds a set of nine additional criteria to be used to have a final valid refined clinical knowledge model. The criteria ensure the validity of final knowledge model concerning formalism of knowledge, conformance to GPGs, quality of the knowledge, usage of stringent conditions and treatment plans, and inconsistencies possibly resulting from the complexities. Evaluation, using four medical knowledge acquisition scenarios, shows that newly added knowledge in CDSS due to the addition of criteria by ReKA method always produces a valid knowledge model. The final knowledge model was also evaluated with 1229 oral cavity patient cases, which outperformed with an accuracy of 72.57\% compared to a similar approach with an accuracy of 69.7\%. Furthermore, ReKA method identified a set of decision paths (about 47.8%) in the existing approach, which results in a final knowledge model with low quality, non-conformed from standard CPGs. In conclusion, ReKA is formally proved method which always yields valid knowledge model having high quality, supporting local practices, and influenced from standard guidelines.

Coronavirus Disease 2019 (COVID-19), caused by a novel coronavirus named Severe Acute Respiratory Syndrome - Coronavirus-2 (SARS-CoV-2), emerged in early December 2019 in China and attained a pandemic situation worldwide by its rapid spread to nearly 167 countries with 287.239 confirmed cases and 11.921 human deaths with a case fatality rate (CFR) of around 4 per cent. Bats were considered as the reservoir host, and the search of a probable intermediate host is still going on. Animals have anticipated culprit of SARS-CoV-2 as of now. The disease is mainly manifested by pneumonia and related respiratory signs and symptoms, but the involvement of the gastrointestinal system and nervous system is also suggested. The severe form of the disease associated with death is mainly reported in older and immune-compromised patients with pre-existing disease history. Death in severe cases is attributed to respiratory failure associated with hyperinflammation. Cytokine storm syndrome associated with rampant inflammation in response to SARS-CoV-2 infection is considered as the leading killer of COVID-19 patients. COVID-19 patients were reported with higher levels of many pro-inflammatory cytokines and chemokines like IFN-g, IL-1b, IP-10, and MCP-1. Furthermore, severe cases of COVID-19 revealed higher levels of TNF-α, G-CSF, and MIP-1A. Blood profile of the COVID-19 patients exhibits lymphopenia, leucopenia, thrombocytopenia and RNAaemia along with increased levels of aspartate aminotransferase. SARS-CoV-2 infection in pregnant women does not lead to fetus mortalities unlike other zoonotic coronaviruses like SARS-CoV and MERS-CoV, with no evidence of intrauterine transmission to neonates. Rapid and confirmatory diagnostics have been developed, and high efforts are being made to develop effective vaccines and therapeutics. In the absence of any virus-specific therapeutic, internationally health care authorities are recommending adoption of effective prevention and control measures to counter and contain this pandemic virus. This paper is an overview of this virus and the disease with a particular focus on SARS-COV-2 / COVID-19 clinical pathology, pathogenesis and immunopathology along with a few recent research developments.

: Background: Parkinson’s disease (PD) is a chronic, progressive illness with a profound impact on health-related quality of life, and it is crucial to know what factors influence quality of life throughout the course of the disease. This study aimed to evaluate PD patients’ motor and non-motor symptoms to compare symptom severity between PD clinical phenotypes and to assess the impact of disease symptoms on quality of life in a cohort of Latvian patients. Methods: We evaluated 43 patients with Parkinson’s disease. Fourteen patients had tremor-dominant (TD) PD, twenty-five patients had postural instability/gait difficulty (PIGD), and four patients had a mixed phenotype. Results: The patients’ mean age was 65.21 years, and the disease’s mean duration was 7 years. The most common non-motor symptoms were fatigue (95.3%), sleep disturbance (83.7%), daytime sleepiness (83.7%), and pain and other sensations (81.4%). PIGD patients had a higher prevalence of depressed mood, daytime sleepiness, constipation, light headedness on standing, cognitive impairment, and severe gastrointestinal and urinary disturbances (as assessed using the SCOPA-AUT domains) compared with TD patients. A high prevalence of fatigue was assessed in both disease subtypes. Health-related quality of life significantly statistically correlated with MDS-UPDRS parts III and IV (r = 0.704), the Hoehn and Yahr scale (r = 0.723), as well as the SCOPA-AUT scale’s gastrointestinal (r = 0.639), cardiovascular (r = 0.586), thermoregulatory (r = 0.566) and pupillomotor domains (r = 0.597). Conclusion: The severity of motor symptoms, as well as non-motor symptoms, such as fatigue, apathy, sleep problems and daytime sleepiness, pain, and disturbances in gastrointestinal and cardiovascular function, negatively affect PD patients’ health-related quality of life. Thermoregulatory and pupillomotor symptoms also significantly affect PD patients’ well-being.

The overall objective of this mixed-method digital-based observational study was to determine the mental health impact among CTU staff working during the COVID-19 pandemic. The Qualtrics Core XM platform was used to deploy the questionnaire where a quantitative analysis was conducted. The qualitative part of the study used the Microsoft Teams digital application to complete the interviews. Various validated mental health assessments were administered: Vancouver Index of Acculturation (VIA), Hospital Anxiety and Depression Scale (HADS), Insomnia Severity Index (ISI), Pandemic Stress Index (PSI), Burnout Assessment Tool-12 (BAT-12), General Self Efficacy Scale (GSE) and The Everyday Discrimination Scale (EDS). A total of 485 participants took part, of which 73.4% were female and 70.1% of the sample were white British. A high prevalence of anxiety, exhaustion and depression were identified across all participants. A significant mental health impact was identified among the CTU workforce where wellbeing was compromised during the course of the COVID-19 pandemic.

Malignant gliomas are heterogeneous neoplasms. Glioma stem-like cells (GSCs) are undifferentiated and self-renewing cells that develop and maintain these tumors. These cells are the main population that resist current therapies. Genomic and epigenomic analyses has identified various molecular subtypes. Bone morphogenetic protein 4 (BMP4) reduces the number of GSCs through differentiation and induction of apoptosis, thus increasing therapeutic sensitivity. However, the short half-life of BMP4 impedes its clinical application. We have previously reviewed BMP4 signaling in central nervous system development and glioma tumorigenesis and its’ potential as a treatment target in human gliomas. Recent advances in understanding both adult and pediatric malignant gliomas highlight critical roles of BMP4 signaling pathways in the regulation of tumor biology, and indicate its’ potential as a therapeutic molecule. Furthermore, significant progress has been made on synthesizing BMP4 biocompatible delivery materials, which can bind to and markedly extend BMP4 half-life. Here, we review current research associated with BMP4 in brain tumors, especially in pediatric malignant gliomas. We also summarize BMP4 delivery strategies, with a focus on biocompatible BMP4 binding peptide amphiphile nanostructures as promising novel delivery platforms for treatment of these devastating tumors.

Objectives: The aim of our current study was to analyze whether the use of important measures of methodological quality and reporting of randomized clinical trials published in the field of cardiovascular disease research have changed over time. Further aim was to investigate whether there was an improvement over time in the ability of these trials to provide a good estimate of the true intervention effect. Methods We conducted two searches in the Cochrane Central Register of Controlled Trials (CENTAL) database to identify cardiovascular clinical research trials published in either 2012 or 2017. Randomized clinical trials (RCTs) trials in cardiovascular disease research with adult participants were eligible to be included. We randomly selected 250 RCTs for both publication year 2012 and 2017. Trial characteristics, data on measures of methodological quality and reporting were extracted and risk of bias for each trial was assessed. Results As compared to 2012 in 2017 there were significant improvements in the reporting of the presence of a data monitoring committee (42.0% in 2017 compared to 34.4% in 2012), and a positive tendency of registering cardiovascular disease research RCTs in clinical trial registries (83.6% in 2017 compared to 72.0% in 2012). On the other hand, we also observed that significantly fewer RCTs reported sample size calculation (60.4% in 2017 compared to 98.4% in 2012) in 2017 as compared to 2012. RCTs in 2017 were more likely to have low overall risk of bias ( RoB ) than in 2012 (29.2% in 2017compared to 21.2% in 2012). Conclusion: As compared to 2012 in 2017 there were significant improvement in some, but not all the important measures of methodological quality. Although more trials in the field of cardiovascular disease research had a lower overall RoB in 2017, the improvement over time was not consistently perceived in all RoB domains.

Background. It is unclear whether the use of clinical prediction rules is sufficient to rule out infective endocarditis (IE) in patients with Staphylococcus aureus bacteremia (SAB) without an echocardiogram evaluation, either transthoracic (TTE) and/or transesophageal (TEE). Our primary purpose was to test the usefulness of PREDICT, POSITIVE and VIRSTA scores to rule out IE without echocardiography. Our secondary purpose was to evaluate whether not performing an echocardiogram evaluation is associated with higher mortality. Methods. We conducted a unicentric retrospective cohort including all patients with a first SAB episode from January 2015 to December 2020. IE was defined according to modified Duke criteria. We predefined threshold cut-off points to consider that IE was ruled out by means of the mentioned scores. To assess 30-day mortality, we used a multivariable regression model considering performing an echocardiogram as covariate. Results. Out of 404 patients, IE was diagnosed in 50 (12.4%). Prevalence of IE within patients with negative PREDICT, POSITIVE and VIRSTA scores was: 3.6% (95% CI 0.1-6.9%), 4.9% (95% CI 2.2-7.7%), and 2.2% (95% CI 0.2-4.3%), respectively. Patients with negative VIRSTA and negative TTE had an IE prevalence of 0.9% (95% CI 0-2.8%). Performing an echocardiogram was independently associated with lower 30-day mortality (OR 0.24 95%CI 0.10-0.54, p=0.001). Conclusion. PREDICT and POSITIVE scores were not sufficient to rule out IE without TEE. In patients with negative VIRSTA score, it was doubtful if IE could be discarded with a negative TTE. Not performing an echocardiogram was associated with worse outcomes, which might be related to presence of occult IE. Further studies are needed to assess the usefulness of clinical prediction rules in avoiding echocardiographic evaluation in SAB patients.

(1) Background: the NGS based mutational study of hereditary cancer genes is crucial to design tailored prevention strategies in subjects with different hereditary cancer risk. The ease of amplicon-based NGS library construction protocols contrasts with the greater uniformity of enrichment provided by capture-based protocols and so with greater chances for detecting larger genomic rearrangements and copy-number variations. Capture-based protocols, however, are characterized by a higher level of complexity of sample handling, extremely susceptible to human bias. Robotics platforms may definitely help dealing with these limits, reducing hands-on time, limiting random errors and guaranteeing process standardization. (2) Methods: We implemented and validated the complete automation of the SOPHiA GENETICS’ CE-IVD Hereditary Cancer Solution™ (HCS) libraries preparation workflow on the Hamilton’s STARlet platform. (3) Results: We demonstrate that this automated workflow, used for more than 1000 samples achieved the same performances of manual setup in terms of coverages and reads uniformity, with extremely lower variability of reads mapping rate onto the regions of interest. (4) Conclusions: This automated solution offers same reliable and affordable NGS data, but with the essential advantages of a flexible, automated and integrated framework, minimizing possible human errors and depicting a laboratory’s walk-away scenario.

Objective: To examine the burnout syndrome among the healthcare personnel in Puerto Rico during the COVID-19 pandemic. Methods: Descriptive study that pursues to understand burnout syndrome in the clinical personnel in Puerto Rico. The Maslach Burnout Inventory (MBI) was sent via email to healthcare professionals around the island. Furthermore, open questions were asked to the participants. Results: The overall burnout level on the clinical personnel was found to be moderate. Nonetheless, in physicians, 12.1% had severe burnout levels compared to a 13.1% score in nurses. Additionally, 92.4% of physicians and 100% of nurses had moderate to severe burnout. In the three subscales, nurses scored high levels in all of them, and physicians were high in Emotional Exhaustion and moderate level in Depersonalization and Personal Accomplishment at Work. There were high levels of burnout syndrome of the clinical personnel in Puerto Rico. Conclusion: Since the beginning of the COVID-19 pandemic, over 90% of healthcare professionals in Puerto Rico have been working with moderate to severe burnout syndrome, being the nurses the most affected. Key Words: Burnout syndrome, MBI, Clinical personnel, COVID-19, SARS-CoV-2

Objective: The objective of this study is to determine the epidemic dynamics and clinical features of COVID-19 in southern Hainan Island, China, and provide experience for other tropical areas of the world. Methods: This retrospective study included confirmed cases of COVID-19 in southern Hainan. All enrolled patients were treated in Sanya, and data on epidemiological and clinical features of the disease and infection prevention and control measures adopted by the local government during the epidemic were collected. Results: Of the 74 cases, 71 (95.95%) were imported from Wuhan, Hubei Province (47, 63.51%), other cities in Hubei Province (11, 14.86%), or provinces other than Hubei and Hainan (13, 17.57%). Three (4.06%) patients were infected in southern Hainan, including one autochthonous case in Sanya. Fifty-four cases (72.97%) were detected in Sanya, and 27 cases (27.03%) were diagnosed in other cities. The rate of severe or critical cases was 28.38% (21/74), and mortality was 2.7% (2/74). The serum lactate levels and base excess of severe-critical patients were higher than those of patients with mild-moderate disease. Multivariate logistic regression analysis showed that chronic conditions were risk factors for severe and critical COVID-19. Seventy-four patients were diagnosed with COVID-19 over a 22-day period in Sanya, and the epidemic period in the city was 48 days. The outbreak was controlled rapidly because the local government adopted strict infection prevention and control measures. Conclusions: The clinical characteristics of COVID-19 in Hainan Island were similar to those reported in other regions. In Sanya, the rate of severe and very severe cases was higher than in other regions; however, most cases were imported, and there was only one autochthonous case. The rapid control of the outbreak in Sanya may be related to the tropical climate, adoption of strict infection prevention and control measures, daily reporting of new cases, increased public awareness about the epidemic, and other emergency actions implemented by the local government.

Since the effects of renin–angiotensin–aldosterone system (RAAS) inhibitors on the clinical outcomes of coronavirus disease-19 (COVID-19) have been conflicting in different studies, we performed this meta-analysis. A systematic search of published articles was performed in PubMed and EMBASE from January-May 5, 2020. Studies that reported the clinical outcomes of patients with COVID-19, stratified by the class of concomitant antihypertensive drug therapy, were included. The Mantel-Haenszel random effects model was used to estimate pooled odds ratio (OR). A total of 6,997 hypertensive patients with COVID-19 were included. The overall risk of poor patient outcomes (severe COVID-19 or death) was lower in patients taking RAAS inhibitors (OR=0.84, 95% CI: [0.73, 0.96]; P=0.017) compared with those receiving non-RAAS inhibitor antihypertensives. Patients taking angiotensin-I-converting enzyme inhibitors (ACEIs) were less likely to experience poor clinical outcomes (OR=0.73, 95% CI: [0.58-0.92]; P=0.01) compared with those receiving angiotensin-II receptor blockers (ARBs). Compared to all other antihypertensives, ACEIs decreases the risk poor COVID-19 outcomes (OR=0.77, 95% CI: [0.63-0.93]) while ARBs did not (OR=1.13, 95% CI: [0.95-1.35]). The risk of poor patient outcomes from COVID-19 was lower in patients who received RAAS inhibitors compared with those who took non-RAAS inhibitors. Unlike ARBs, ACEIs might help in decreasing the severity and mortality of COVID-19.

Background: A growing number of clinical practice guidelines (CPGs) with regards to non-pharmacological interventions for breast cancer survivors are available. However, given the limitations in guideline development methodologies and inconsistency of recommendations, it remains uncertain how best to design and implement such non-pharmacological strategies to tailor interventions for breast cancer survivors with varied health conditions, healthcare needs, and preferences. Aim: To critically appraise and summarise available non-pharmacological interventions for symptom management and health promotion that can be self-managed by breast cancer survivors based on the recommendations of the CPGs. Methods: Clinical practice guidelines which were published between January 2016 and September 2021 and described non-pharmacological interventions for breast cancer survivors were systematically searched in six electronic databases, nine relevant guideline databases, and five cancer care society websites. The quality of the included CPGs was assessed by four evaluators using the Appraisal of Guidelines for REsearch and Evaluation, second edition tool. Content analysis was conducted to synthesise the characteristics of the non-pharmacological interventions that were recommended by the included CPGs, such as the intervention’s form, duration and frequency, level of evidence, grade of recommendation, and source of evidence. Results: Fourteen CPGs were identified and analysed. Of the 14 CPGs appraised, only five were rated as high quality. The domain with the highest standardised percentage was “scope and purpose” (84.61%), while the “applicability” domain had the lowest standardised percentage (51.04%). Five guidelines were assessed as “recommended”, seven were rated as “recommended with modifications”, and the remaining two were considered “not recommended”. Regarding the content analysis, physical activity/exercise, meditation, hypnosis, yoga, music therapy, stress management, relaxation, massage, and acupressure were the common self-managed non-pharmacological interventions recommended by the 14 CPGs. Physical activity/exercise was the only self-managed non-pharmacological intervention that was mostly recommended for psychological and physical symptom management by the included CPGs. However, there were significant disparities in terms of level of evidence and grade of recommendation in the included CPGs. Conclusion: The recommendations for the self-managed non-pharmacological interventions were varied and limited among the 14 CPGs, and some were based on medium- and low-quality evidence. More rigorous methods are required to develop high-quality CPGs in order to guide clinicians in offering high-quality and tailored breast cancer survivorship care.

Background Frequent presenters (FPs) define a group of individual who visit hospital emergency depart-ment (ED) frequently for urgent care. Many among the group present with main diagnosis of mental health conditions. This group of individual tend to use ED resources disproportionally and significantly affect overall healthcare outcome. No previous reviews have examined the profiles of FPs with mental health conditions. Aims This study aims to identify the key socio-demographic and clinical characteristics of patients who frequently present to ED with mental health primary diagnosis by performing systemic review from existing literature. Method PRISMA guideline was used. PubMed, PsycINFO, Scopus and Web of Science (WOS) were searched in May 2023. A manual search on reference list of included articles were conducted at same time. Covidence was used to perform extraction and screening, completed by two authors independently. Inclusion and exclusion criteria were defined. Results The abstracts of 3341 non-duplicate articles were screened with 40 full texts assessed for eligi-bility. 20 studies were included from 2004-2022 conducted in 6 countries with total patient number of 25688 (52% male, 48% female, mean age 40.7 years old). 27% were unemployed, 20% married, 41% homeless, and 17% had tertiary or above education. 44% had history of substance abuse or alcohol dependence. Top 3 diagnosis are found to be anxiety disorders (44%), depressive disorders (39%) and schizophrenia spectrum and other psychotic disorders (33%). Conclusion On average, FPs are middle aged and equally prevalent in both gender. Current data lacks rep-resentation for gender diverse group. They are significantly associated with high rate of unem-ployment, homelessness, lower than average education level, and being single. Anxiety disor-der, depressive disorder, and schizophrenia spectrum disorders are the most common clinical diagnosis associated with the group.

This study aimed to explore how Indonesian clinical psychologists (CPs) address aspects of spirituality and religion (SR), particularly their attitudes towards and experience of it, on the mental health context. Semi-structured interviews were conducted with 43 CPs in public health centres in Yogyakarta Province, Indonesia. Data were anyalsed using deductive thematic analysis and they generated ten sub-themes which were merged into three central themes. The first theme was experiences related to SR, particularly in Indonesian sociocultural context. The second theme concentrated on participants’ clinical experience related to SR integration into clinical practice. The last theme highlighted the effort made by participants to create holistic mental health services. The originality of this study was represented by the interview quote in the title, “Doing my profession is also part of worship”. It was found that SR is part of culture and belief among Indonesian people, including CPs and mental health treatment clients. In summary, participants genuinely acknowledged that they were not able to completely detach SR from their professional practice. However, participants also pointed out that they were different with spiritual-religious healers (SRHs) and favourably welcomed future collaboration with credible SRHs. This positive attitude embodied a holistic care approach that recognises the diverse biopsycho-social-spiritual needs of clients. Therefore, professional organisations and psychology faculties should establish regulations and education of SR in psychology curricula and conventional psychotherapy to achieve this holistic mental health services in Indonesia.

Clinical metagenomics (CMg), referred to as the application of next-generation sequencing (NGS) to clinical samples, is a promising tool for the diagnosis of hospital-acquired pneumonia (HAP). Indeed, CMg allows identifying pathogens and antibiotic resistance genes (ARGs), thereby providing the information required for the optimization of the antibiotic regimen. Hence, provided that CMg would be faster than conventional culture, the probabilistic regimen used in HAP could be tailored faster, which should lead to an expected decrease of mortality and morbidity. While the inference of the antibiotic susceptibility testing from metagenomic or even genomic data is challenging, a limited number of antibiotics are used in the probabilistic regimen of HAP (namely beta-lactams, aminoglycosides, fluoroquinolones, glycopeptides and oxazolidinones). Accordingly in the perspective of applying CMg to the early diagnostic of HAP, we aimed at reviewing the performances of whole genomic sequencing (WGS) of the main HAP-causing bacteria (Enterobacteriaceae, Pseudomonas aeruginosa, Acinetobacter baumannii, Stenotrophomonas maltophilia and Staphylococcus aureus) for the prediction of susceptibility to the antibiotic families advocated in the probabilistic regimen of HAP.

Biosensors are measurement devices that can sense several biomolecules, and are widely used for the detection of relevant clinical pathogens such as bacteria and viruses, showing outstanding results. Because of the latent existing risk of facing another pandemic like the one we are living due to COVID-19, researchers are constantly looking forward to developing new technologies for diagnosis and treatment of infections caused by different bacteria and viruses. Regarding that, nanotechnology has improved biosensors design and performance through the development of materials and nanoparticles that enhance their affinity, selectivity, and efficacy in detecting these pathogens, such as employing nanoparticles, graphene quantum dots, and electrospun nanofibers. Therefore, this work aims to present a comprehensive review that exposes how biosensors work in terms of bacterial and viral detection, and the nanotechnological features that are contributing to achieving a faster yet still efficient COVID-19 diagnosis at the point-of-care.

Background: Chikungunya virus (CHIKV) diagnosis have become a challenge for primary care physicians in areas where zika virus and/or dengue virus are present. Case definitions for the three arboviral infections are overlapping. Methods: A cross-sectional analysis was carried out. A bivariate analysis was made using confirmed CHIKV infection as the outcome. Variables with significant statistical association were included in an agreement consensus. Agreed variables were analyzed in multiple regression model. The area under the receiver operating characteristic (ROC) curve was calculated to determine a cut-off value and performance. Results: 295 patients with confirmed CHIKV infection were included. A screening tool was made using symmetric arthritis (4 points), fatigue (3 points), rash (2 points) and ankle joint pain (1 point). The ROC curve identified a cut-off value and a score ≥ 5.5 was considered positive to identify CHIKV patients with a sensibility of 64.4% and a specificity of 87.4%, positive predictive value of 85.5%, negative predictive value of 67.7%, area under the curve of 0.72, and an accuracy of 75%. Conclusion: We developed a screening tool for CHIKV diagnosis using only clinical symptoms as well as proposed an algorithm to aid the primary care physician.

Objective: The purpose of this study was to determine if Porphyra tenera extract (PTE) has immune-enhancing effects and is safe in healthy adults. Methods: Subjects (3x10³ ≤ peripheral blood leukocyte levels < 8x10³ cells/μl) who met the inclusion criteria were recruited for this study. Enrolled subjects (n=120) were randomly assigned to either the PTE group (n=60) who were given 2.5 g/day of PTE (as Porphyra tenera extract) in capsule form or the placebo group (n=60) who were given crystal cellulose capsules with the identical appearance, weight, and flavor as the PTE capsules for 8 weeks. Outcomes were assessed by measuring natural killer cell (NK-cell) activity, cytokines, and upper respiratory infection (URI), and safety parameters were assessed at baseline and 8 weeks. Results: Compared to baseline, NK cell activity (%) increased for all effector cell to target cell ratios in the PTE group after 8 weeks, but there were no changes in the placebo group (p<0.1). Subgroup analysis of 101 subjects without an URI revealed that NK-cell activity in the PTE group tended to be increased for all E:T ratios (E:T=12.5:1 p=0.068; E:T=25:1 p=0.036; E:T=50:1 p=0.081) compared to the placebo group. There was a significant difference between these two groups for the E:T=25:1 ratio, which increased from 20.3±12.0% at baseline to 23.2±12.4% after 8 weeks in the PTE group (p=0.036). There was no significant difference in levels of cytokines between these two groups. Conclusions: PTE supplementation appears to enhance immune function by improving NK-cell activity without adverse effects in healthy adults.

Chronic lymphocytic leukemia (CLL) is a hematologic malignancy characterized by progressive accumulation of a rare population of CD5+ B lymphocytes in peripheral blood, bone marrow and lymphoid tissues. CLL exhibits remarkable clinical heterogeneity, with some patients presenting with indolent disease and others progressing rapidly to aggressive CLL. The significant heterogeneity of CLL underscores the importance of identifying novel prognostic markers. Recently, the RAS-related gene RRAS2 has emerged as both a driver oncogene and a potential marker for CLL progression, with higher RRAS2 expression associated with poorer disease prognosis. Although missense somatic mutations in the coding sequence of RRAS2 have not been described in CLL, this study reports the frequent detection of three somatic mutations in the 3' untranslated region (3'UTR) affecting positions +26, +53, and +180 downstream of the stop codon in the mRNA. An inverse relationship was observed between these three somatic mutations and RRAS2 mRNA expression, which correlated with lower blood lymphocytosis and better prognosis. These findings highlight the importance of RRAS2 overexpression in CLL development and prognosis and point to somatic mutations in its 3'UTR as novel mechanistic clues. Our results may contribute to the development of targeted therapeutic strategies and improved risk stratification for CLL patients.

Background: Areca nut and betel quid (ANBQ) chewing is a widespread carcinogenic habit. The BENIT (ClinicalTrials.gov - NCT02942745) is the first known randomized trial designed for ANBQ chewers. Methods: We compared intensive behavioral treatment intervention condition (IC) with control condition (CC) in the BENIT and included a 5-stage early stopping rule. We report the primary analysis at stage 3. English literate adults in Guam and Saipan who self-identified as ANBQ chewers with tobacco were enrolled between August 2016 and August 2020. IC participants (n=88) received five in-person sessions over 22 days and a brochure containing quitting advice. CC participants (n=88) received only the brochure. Participants were assessed at baseline and day-22 follow-up. Self-reported chewing status at day-22 was determined by a composite of two survey items with disparate wording and response options for cross-verification. Results: Cessation rates were 38.6% (IC) and 9.1% (CC). Proportional hazards regression revealed a p=0.0058, which met the Stage 3 criteria for significance and an estimated reduction in ANBQ chewing for IC compared to the CC of 71% (95% CI: 41%-88%). Conclusion: Robust self-reported intervention effects at day-22 suggests that intensive cessation programs such as BENIT should be further developed and implemented on a larger scale.

Pulmonary thromboembolism is a very common cardiovascular disease, with a still high mortality rate. Despite the clear guidelines, this disease still represents a great challenge both in diagnosis and treatment. Heterogeneous clinical picture, often without pathognomonic signs and symptoms, represents a huge differential diagnostic problem even for experienced doctors. The decision on the therapeutic regimen also represents a major dilemma in the group of patients who are hemodynamically stable at initial presentation and have signs of right ventricular (RV) dysfunction proven by echocardiography and positive biomarker values (pulmonary embolism of intermediate-high risk). Studies have shown conflicting results about the benefit of using fibrinolytic therapy in this group of patients until hemodynamic decompensation, due to the risk of major bleeding. The latest recommendations give preference to new oral anticoagulants (NOACs) compared to vitamin K antagonists (VKA), except for certain categories of patients (patients with antiphospholipid syndrome, mechanical valves, pregnancy). When using oral anticoagulant therapy, special attention should be paid to drug-drug interactions, which can lead to many complications, even to the death of the patient. Special population groups such as pregnant women, obese patients, patients with antiphospholipid syndrome and cancer represent a great therapeutic challenge in the application of anticoagulant therapy. In these patients, not only the effectiveness of the drugs must be taken into account, but great attention must be paid to their safety and possible side effects, which is why a multidisciplinary approach is emphasized in order to provide the best therapeutic option.

There is a growing number of evidence-based indications for pharmacogenetic (PGx) testing. We aimed to evaluate clinical relevance of a 16-gene panel test for PGx-guided pharmacotherapy. In an observational cohort study we included subjects tested with a PGx panel for variants of ABCB1, COMT, CYP1A2, CYP2B6, CYP3A4, CYP3A5, CYP2C9, CYP2C19, CYP2D6, CYP4F2, DPYD, OPRM1, POR, SLCO1B1, TPMT and VKORC1. PGx-guided pharmacotherapy management was supported by the PGx expert system SONOGEN XP. The primary study outcome was PGx-based changes and recommendations regarding current and potential future medication. PGx-testing was triggered by specific drug-gene pairs in 102 subjects, and by screening in 33. Based on PharmGKB expert guidelines we identified at least one “actionable” variant in all 135 (100%) tested patients. Drugs that triggered PGx-testing were clopidogrel in 60, tamoxifen in 15, polypsychopharmacotherapy in 9, opioids in 7, and other in 11 patients. Among those, PGx variants resulted in clinical recommendations to change PGx-triggering drugs in 33 (32.4 %), and other current pharmacotherapy in 23 (22.5%). Additional costs of panel vs. single gene tests are moderate, and the efficiency of PGx panel testing challenges traditional cost-benefit calculations for single drug-gene pairs. However, PGx-guided pharmacotherapy requires specialized expert consultations with interdisciplinary collaborations.

Orthohantaviruses can cause two types of human infections: hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS). HFRS is a zoonotic disease transmitted by multiple rodent species. Yunnan Province in southwest China is the natural foci of HFRS, and Dali Prefecture in Yunnan Province has the highest incidence of HFRS; however, the precise status of orthohantavirus infection in Dali Prefecture remains unknown. To this end, we obtained clinical data of HFRS patients from the medical records of the People's Hospital of Xiangyun County in Dali Prefecture from July 2019 to August 2021. We collected epidemiological data of HFRS patients through interviews and investigated host animals using the night clip or night cage method. We systematically performed epidemiological analyses of patients and host animals. The differences in the presence of rodent activity at home (2=8.75, P=0.031&lt;0.05), of rodent-proof equipment in the food (2=9.19, P=0.025&lt;0.05), and of rodents or rodent excrement in the workplace (2=10.35, P=0.014&lt;0.05) were statistically different in the four clinical types, including mild, medium, severe, and critical HFRS-associated diseases. Furthermore, we conducted molecular detection of orthohantavirus in host animals. The total orthohantavirus infection rate of rodents was 2.7% (9/331); the specific infection rate of specific animal species was 6.1% (5/82) for the Apodemus chevrieri, 100% (1/1) for the Rattus nitidus, 3.8% (2/53) for the Rattus norvegicus, and 12.5% (1/8) for the Crocidura dracula. In this study, a total of 21 strains of orthohantavirus were detected in patients and rodents. The 12 orthohantavirus strains from patients showed a closer relationship with Seoul orthohantavirus (SEOOV) L0199, DLR2, and GZRn60 strains; the six orthohantavirus strains from Rattus norvegicus and Apodemus chevrieri were closely related to SEOOV GZRn60 strain; One strains (XYRn163) from Rattus norvegicus and one strain (XYR.nitidus97) from Rattus nitidus were closely related to SEOOV DLR2 strain; the orthohantavirus strain from Crocidura dracula was closely related to the Luxi orthohantavirus (LUXV) LX309 strain. In conclusion, patients with HFRS in Xuangyun County of Dali Prefecture are predominantly affected by SEOOV, with multiple genotypes of orthohantavirus in host animals, and most importantly, these orthohantavirus strains constantly demonstrated zoonotic risk in humans.