Search results for: clinical leadership
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 4421

Search results for: clinical leadership

3221 Regulating Nanocarrier and Mononuclear Phagocyte System Interactions through Esomeprazole-Based Preconditioning Strategy

Authors: Zakia Belhadj, Bing He, Hua Zhang, Xueqing Wang, Wenbing Dai, Qiang Zhang

Abstract:

Mononuclear phagocyte system (MPS) forms an abominable obstacle hampering the tumor delivery efficiency of nanoparticles. Passively targeted nanocarriers have received clinical approval over the past 20 years. However, none of the actively targeted nanocarriers have entered clinical trials. Thus it is important to endue effective targeting ability to actively targeted approaches by overcoming biological barriers to nanoparticle drug delivery. Here, it presents that an Esomeprazole-based preconditioning strategy for regulating nanocarrier-MPS interaction to substantially prolong circulation time and enhance tumor targeting of nanoparticles. In vitro, the clinically approved proton pump inhibitor Esomeprazole “ESO” was demonstrated to reduce interactions between macrophages and subsequently injected targeted vesicles by interfering with their lysosomal trafficking. Of note, in vivo studies demonstrated that ESO pretreatment greatly decreased the liver and spleen uptake of c(RGDm7)-modified vesicles, highly enhanced their tumor accumulation, thereby provided superior therapeutic efficacy of c(RGDm7)-modified vesicles co-loaded with Doxorubicin (DOX) and Gefitinib (GE). This MPS-preconditioning strategy using ESO provides deeper insights into regulating nanoparticles interaction with the phagocytic system and enhancing their cancer cells' accessibility for anticancer therapy.

Keywords: esomeprazole (ESO), mononuclear phagocyte system (MPS), preconditioning strategy, targeted lipid vesicles

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3220 The Impact of Streptococcus pneumoniae Colonization on Viral Bronchiolitis

Authors: K. Genise, S. Murthy

Abstract:

Introductory Statement: The results of this retrospective chart review suggest the effects of bacterial colonization in critically ill children with viral bronchiolitis, currently unproven, are clinically insignificant. Background: Viral bronchiolitis is one of the most prevalent causes of illness requiring hospitalization among children worldwide and one of the most common reasons for admission to pediatric intensive care. It has been hypothesized that co-infection with bacteria results in more severe clinical outcomes. Conversely, the effects of bacterial colonization in critically ill patients with bronchiolitis are poorly defined. Current clinical management of colonized patients consists primarily of supportive therapies with the role of antibiotics remaining controversial. Methods: A retrospective review of all critically ill children admitted to the BC Children’s Hospital Pediatric Intensive Care Unit (PICU) from 2014-2017 with a diagnosis of bronchiolitis was performed. Routine testing in this time frame consisted of complete pathogen testing, including PCR for Streptococcus pneumoniae. Analyses were performed to determine the impact of bacterial colonization and antibiotic use on a primary outcome of PICU length-of-stay, with secondary outcomes of hospital length-of-stay and duration of ventilation. Results: There were 92 patients with complete pathogen testing performed during the assessed timeframe. A comparison between children with detected Streptococcus pneumoniae (n=22) and those without (n=70) revealed no significant (p=0.20) differences in severity of illness on presentation as per Pediatric Risk of Mortality III scores (mean=3.0). Patients colonized with S. pneumoniae had significantly shorter PICU stays (p=0.002), hospital stays (p=0.0001) and duration of non-invasive ventilation (p=0.002). Multivariate analyses revealed that these effects on length of PICU stay and duration of ventilation do not persist after controlling for antibiotic use, presence of radiographic consolidation, age, and severity of illness (p=0.15, p=0.32). The relationship between colonization and duration of hospital stay persists after controlling for these variables (p=0.008). Conclusions: Children with viral bronchiolitis colonized with S. pneumoniae do not appear to have significantly different PICU length-of-stays or duration of ventilation compared to children who are not colonized. Colonized children appear to have shorter hospital stays. The results of this study suggest bacterial colonization is not associated with increased severity of presenting illness or negative clinical outcomes.

Keywords: bronchiolitis, colonization, critical care, pediatrics, pneumococcal, infection

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3219 Engaging Medical Students in Research through Student Research Mentorship Programme

Authors: Qi En Han, Si En Wai, Eugene Quek

Abstract:

As one of the two Academic Medical Centres (AMCs) in Singapore, SingHealth Duke-NUS AMC strives to improve patients’ lives through excellent clinical care, research and education. These efforts are enhanced with the establishment of Academic Clinical Programmes (ACPs). Each ACP brings together specialists in a particular discipline from different institutions to maximize the power of shared knowledge and resources. Initiated by Surgery ACP, the student research mentorship programme is a programme designed to facilitate engagement between medical students and the surgical faculty. The programme offers mentors not only the opportunity to supervise research but also to nurture future clinician scientists. In turn, medical students acquire valuable research experience which may be useful in their future careers. The programme typically lasts one year, depending on the students’ commitment. Surgery ACP matches students’ research interests with the mentor's area of expertise whenever possible. Surgery ACP organizes informal tea sessions to bring students and prospective mentors together. Once a match is made, the pair is required to submit a project proposal which includes the title, proposed start and end dates, ethical and biosafety considerations and project details. The mentees either think of their own research question with guidance from the mentors or join an existing project. The mentees may participate in data collection, data analysis, manuscript writing and conference presentation. The progress of each research project is monitored through half-yearly progress report. The mentees report problems encountered or changes made to existing proposal on top of the progress made. A total of 18 mentors were successfully paired with 36 mentees since 2013. Currently, there are 23 on-going and 13 completed projects. The mentees are encouraged to present their projects at conferences and to publish in peer-reviewed journals. Six mentees have presented their completed projects at local or international conferences and one mentee has her work published. To further support student research, Surgery ACP organized a Research Day in 2015 to recognize their research efforts and to showcase their wide-range of research. Surgery ACP recognizes that early exposure of medical students to research is important in developing them into clinician scientists. As interest in research take time to develop and are usually realized during various research attachments, it is crucial that programmes such as the student research mentorship programme exist. Surgery ACP will continue to build on this programme.

Keywords: academic clinical programme, clinician scientist, medical student, mentoring

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3218 A Case of Osteopetrosis Diagnosed with Nystagmus

Authors: Zerrin Orbak, Busra Demir

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Osteopetrosis is a rare genetic disease characterized by impaired bone resorption and increased bone sclerosis. Clinical presentation is very different in osteopetrosis. It can be asymptomatic or can be seen with typical symptoms. Here, a case of osteopetrosis was presented when evaluated for nystagmus. She was 10 months old. Parents were second-degree relatives. On physical examination, pigeon chest deformity and horizontal nystagmus were observed. There was a failure of thrive but no fracture. The cardiovascular examination was normal. Cranial, vertebral and long bone roentgenograms revealed characteristic deformities of osteopetrosis and diffuse sclerosis. The diagnosis was confirmed by genetic testing. A Homozygous mutation was detected in the TNFRSF11A gene (c.508A>G p.(Arg170Gly)). RANKL is encoded by the tumor necrosis factor ligand superfamily member 11 (TNFSF11) gene, and the binding to its receptor RANK, encoded by the TNFRSF11A gene, determines the activation of the downstream pathway that drives osteoclast differentiation and activation (51). The complete absence of osteoclasts is the key feature of the osteoclast-poor form of osteopetrosis (46). Patients are characterized by the absence of TRAP-positive osteoclasts in bone biopsies. The osteoclast-poor subtype of osteopetrosis caused by mutations in TNFSF11 gene is ultra-rare in humans. Clinical presentation is usually severe, with onset in early infancy or in fetal life. But here, a case was presented with horizontal nystagmus. A case presented with horizontal nystagmus, which was evaluated by neurology and diagnosed incidentally, was shared.

Keywords: osteopetrosis, nystagmus, bone, osteoclast-poor

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3217 Structural and Functional Correlates of Reaction Time Variability in a Large Sample of Healthy Adolescents and Adolescents with ADHD Symptoms

Authors: Laura O’Halloran, Zhipeng Cao, Clare M. Kelly, Hugh Garavan, Robert Whelan

Abstract:

Reaction time (RT) variability on cognitive tasks provides the index of the efficiency of executive control processes (e.g. attention and inhibitory control) and is considered to be a hallmark of clinical disorders, such as attention-deficit disorder (ADHD). Increased RT variability is associated with structural and functional brain differences in children and adults with various clinical disorders, as well as poorer task performance accuracy. Furthermore, the strength of functional connectivity across various brain networks, such as the negative relationship between the task-negative default mode network and task-positive attentional networks, has been found to reflect differences in RT variability. Although RT variability may provide an index of attentional efficiency, as well as being a useful indicator of neurological impairment, the brain substrates associated with RT variability remain relatively poorly defined, particularly in a healthy sample. Method: Firstly, we used the intra-individual coefficient of variation (ICV) as an index of RT variability from “Go” responses on the Stop Signal Task. We then examined the functional and structural neural correlates of ICV in a large sample of 14-year old healthy adolescents (n=1719). Of these, a subset had elevated symptoms of ADHD (n=80) and was compared to a matched non-symptomatic control group (n=80). The relationship between brain activity during successful and unsuccessful inhibitions and gray matter volume were compared with the ICV. A mediation analysis was conducted to examine if specific brain regions mediated the relationship between ADHD symptoms and ICV. Lastly, we looked at functional connectivity across various brain networks and quantified both positive and negative correlations during “Go” responses on the Stop Signal Task. Results: The brain data revealed that higher ICV was associated with increased structural and functional brain activation in the precentral gyrus in the whole sample and in adolescents with ADHD symptoms. Lower ICV was associated with lower activation in the anterior cingulate cortex (ACC) and medial frontal gyrus in the whole sample and in the control group. Furthermore, our results indicated that activation in the precentral gyrus (Broadman Area 4) mediated the relationship between ADHD symptoms and behavioural ICV. Conclusion: This is the first study first to investigate the functional and structural correlates of ICV collectively in a large adolescent sample. Our findings demonstrate a concurrent increase in brain structure and function within task-active prefrontal networks as a function of increased RT variability. Furthermore, structural and functional brain activation patterns in the ACC, and medial frontal gyrus plays a role-optimizing top-down control in order to maintain task performance. Our results also evidenced clear differences in brain morphometry between adolescents with symptoms of ADHD but without clinical diagnosis and typically developing controls. Our findings shed light on specific functional and structural brain regions that are implicated in ICV and yield insights into effective cognitive control in healthy individuals and in clinical groups.

Keywords: ADHD, fMRI, reaction-time variability, default mode, functional connectivity

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3216 The Injection of a Freshly Manufactured Hyaluronan Fragment Promotes Healing of Chronic Wounds: A Clinical Study

Authors: Dylan Treger, Lujia Zhang, Xiaoxiao Jia, Jessica H. Hui, Munkh-Amgalan Gantumur, Mizhou Hui, Li Liu

Abstract:

Hyaluronic acid (HA) is involved in wound healing via inflammation, granulation, and re-epithelialization mechanisms. The poor physical properties of natural high-molecular-weight polymers limit their direct use in the medical field. In this clinical study, we investigated whether the local injection of a tissue-permeable 35 kDa HA fragment (HA35) could favor the healing process in patients with chronic wounds accompanied by neuropathic pain. The HA35 fragments were freshly manufactured by degradation of high-molecular-weight HA with bovine testis-derived hyaluronidase PH20. Twenty patients in this study had nonhealing wounds and wound-related pain for more than 3 months. Freshly produced HA35 was locally injected into healthy skin immediately surrounding chronic wounds once a day for 10 days. Wound-associated pain and the degree of wound healing were evaluated. The injection of HA35 relieved the pain associated with chronic wounds in 24 hours. HA35 treatment significantly promoted the healing of chronic wounds, including expanded fresh granulation tissue on the wounds; reduced darkness or redness, dryness, and damaged areas on the surface of the skin surrounding the wounds; and decreased the size of the wound area. It can be concluded that the topical injection of tissue-permeable HA35 around chronic wounds has great potential to promote wound healing.

Keywords: 35 kDa hyaluronan fragment HA35, chronic wound, wound healing, tissue permeability

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3215 Nanoliposomes in Photothermal Therapy: Advancements and Applications

Authors: Mehrnaz Mostafavi

Abstract:

Nanoliposomes, minute lipid-based vesicles at the nano-scale, show promise in the realm of photothermal therapy (PTT). This study presents an extensive overview of nanoliposomes in PTT, exploring their distinct attributes and the significant progress in this therapeutic methodology. The research delves into the fundamental traits of nanoliposomes, emphasizing their adaptability, compatibility with biological systems, and their capacity to encapsulate diverse therapeutic substances. Specifically, it examines the integration of light-absorbing materials, like gold nanoparticles or organic dyes, into nanoliposomal formulations, enabling their efficacy as proficient agents for photothermal treatment Additionally, this paper elucidates the mechanisms involved in nanoliposome-mediated PTT, highlighting their capability to convert light energy into localized heat, facilitating the precise targeting of diseased cells or tissues. This precise regulation of light absorption and heat generation by nanoliposomes presents a non-invasive and precisely focused therapeutic approach, particularly in conditions like cancer. The study explores advancements in nanoliposomal formulations aimed at optimizing PTT outcomes. These advancements include strategies for improved stability, enhanced drug loading, and the targeted delivery of therapeutic agents to specific cells or tissues. Furthermore, the paper discusses multifunctional nanoliposomal systems, integrating imaging components or targeting elements for real-time monitoring and improved accuracy in PTT. Moreover, the review highlights recent preclinical and clinical trials showcasing the effectiveness and safety of nanoliposome-based PTT across various disease models. It also addresses challenges in clinical implementation, such as scalability, regulatory considerations, and long-term safety assessments. In conclusion, this paper underscores the substantial potential of nanoliposomes in advancing PTT as a promising therapeutic approach. Their distinctive characteristics, combined with their precise ability to convert light into heat, offer a tailored and efficient method for treating targeted diseases. The encouraging outcomes from preclinical studies pave the way for further exploration and potential clinical applications of nanoliposome-based PTT.

Keywords: nanoliposomes, photothermal therapy, light absorption, heat conversion, therapeutic agents, targeted delivery, cancer therapy

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3214 Lessons from Implementation of a Network-Wide Safety Huddle in Behavioral Health

Authors: Deborah Weidner, Melissa Morgera

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The model of care delivery in the Behavioral Health Network (BHN) is integrated across all five regions of Hartford Healthcare and thus spans the entirety of the state of Connecticut, with care provided in seven inpatient settings and over 30 ambulatory outpatient locations. While safety has been a core priority of the BHN in alignment with High Reliability practices, safety initiatives have historically been facilitated locally in each region or within each entity, with interventions implemented locally as opposed to throughout the network. To address this, the BHN introduced a network wide Safety Huddle during 2022. Launched in January, the BHN Safety Huddle brought together internal stakeholders, including medical and administrative leaders, along with executive institute leadership, quality, and risk management. By bringing leaders together and introducing a network-wide safety huddle into the way we work, the benefit has been an increase in awareness of safety events occurring in behavioral health areas as well as increased systemization of countermeasures to prevent future events. One significant discussion topic presented in huddles has pertained to environmental design and patient access to potentially dangerous items, addressing some of the most relevant factors resulting in harm to patients in inpatient and emergency settings for behavioral health patients. The safety huddle has improved visibility of potential environmental safety risks through the generation of over 15 safety alerts cascaded throughout the BHN and also spurred a rapid improvement project focused on standardization of patient belonging searches to reduce patient access to potentially dangerous items on inpatient units. Safety events pertaining to potentially dangerous items decreased by 31% as a result of standardized interventions implemented across the network and as a result of increased awareness. A second positive outcome originating from the BHN Safety Huddle was implementation of a recommendation to increase the emergency Narcan®(naloxone) supply on hand in ambulatory settings of the BHN after incidents involving accidental overdose resulted in higher doses of naloxone administration. By increasing the emergency supply of naloxone on hand in all ambulatory and residential settings, colleagues are better prepared to respond in an emergency situation should a patient experience an overdose while on site. Lastly, discussions in safety huddle spurred a new initiative within the BHN to improve responsiveness to assaultive incidents through a consultation service. This consult service, aligned with one of the network’s improvement priorities to reduce harm events related to assaultive incidents, was borne out of discussion in huddle in which it was identified that additional interventions may be needed in providing clinical care to patients who are experiencing multiple and/ or frequent safety events.

Keywords: quality, safety, behavioral health, risk management

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3213 Coping Techniques, Repertoire, and Flexibility in Parental Adjustment to Pediatric Cancer

Authors: Michael Dolgin, Oz Hamtzani, Talma Kushnir

Abstract:

A literature review has shown that while parents of children with cancer experience increased levels of psychological distress associated with their child's medical condition, considerable variability in parental adjustment is evident. Of the factors that may account for this variability, little attention has been devoted to the simultaneous interaction of three coping constructs and their role in parental adjustment: (1) Coping techniques employed, (2) Repertoire of coping techniques, and (3) Flexibility in applying coping techniques. While these constructs have been studied individually in relation to adjustment in general, studies to date have not included them together within a single conceptual model and research design and evaluated them in a clinical population. The objective of the current study was to determine how these three coping technique constructs interact to impact parental adjustment to pediatric cancer. A cross-sectional sample of 145 parents of children in active cancer treatment completed standardized measures of coping techniques, repertoire, flexibility, and parental distress. A hierarchical multiple regression analysis demonstrated that 37% of the variance in parental distress was predicted by the use of avoidance-focused coping techniques [F(1,118)=69.843, p<.001], with an additional 3% predicted by coping repertoire [F(2,117)=7.63, p=.00] for a total of 40% variance explained. Coping flexibility was found to mediate the relationship between coping repertoire and parental distress. These findings suggest that coping techniques employed by parents (problem/emotion-focused vs. avoidance-focused), as well as coping repertoire, significantly impact parental adjustment. Flexibility in applying coping techniques within one’s coping repertoire further contributes to parental adjustment. Implications for further study and clinical intervention will be presented.

Keywords: coping techniques, repertoire, flexibility, adjustment

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3212 Development of Technologies for the Treatment of Nutritional Problems in Primary Care

Authors: Marta Fernández Batalla, José María Santamaría García, Maria Lourdes Jiménez Rodríguez, Roberto Barchino Plata, Adriana Cercas Duque, Enrique Monsalvo San Macario

Abstract:

Background: Primary Care Nursing is taking more autonomy in clinical decisions. One of the most frequent therapies to solve is related to the problems of maintaining a sufficient supply of food. Nursing diagnoses related to food are addressed by the nurse-family and community as the first responsible. Objectives and interventions are set according to each patient. To improve the goal setting and the treatment of these care problems, a technological tool is developed to help nurses. Objective: To evaluate the computational tool developed to support the clinical decision in feeding problems. Material and methods: A cross-sectional descriptive study was carried out at the Meco Health Center, Madrid, Spain. The study population consisted of four specialist nurses in primary care. These nurses tested the tool on 30 people with ‘need for nutritional therapy’. Subsequently, the usability of the tool and the satisfaction of the professional were sought. Results: A simple and convenient computational tool is designed for use. It has 3 main entrance fields: age, size, sex. The tool returns the following information: BMI (Body Mass Index) and caloric consumed by the person. The next step is the caloric calculation depending on the activity. It is possible to propose a goal of BMI or weight to achieve. With this, the amount of calories to be consumed is proposed. After using the tool, it was determined that the tool calculated the BMI and calories correctly (in 100% of clinical cases). satisfaction on nutritional assessment was ‘satisfactory’ or ‘very satisfactory’, linked to the speed of operations. As a point of improvement, the options of ‘stress factor’ linked to weekly physical activity. Conclusion: Based on the results, it is clear that the computational tools of decision support are useful in the clinic. Nurses are not only consumers of computational tools, but can develop their own tools. These technological solutions improve the effectiveness of nutrition assessment and intervention. We are currently working on improvements such as the calculation of protein percentages as a function of protein percentages as a function of stress parameters.

Keywords: feeding behavior health, nutrition therapy, primary care nursing, technology assessment

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3211 Prevalence and Pattern of Drug Usage among Youth in Ogbomoso, Nigeria

Authors: Samson F. Agberotimi, Rachel B. Asagba, Choja Oduaran

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Disturbing rate of use of different substances such as cannabis, alcohol, as well as pharmaceutical drugs among Nigerian youth in recent times has been affirmed in the literature. There is, however, a paucity of literature addressing the pattern of usage of such drugs, especially for clinical relevance and intervention planning. The present study investigated the prevalence and pattern of drug usage among youth in Ogbomoso, Nigeria. A cross-sectional survey involving 92 purposively selected participants comprising of 82 males and 10 females aged between 15 and 24 years was conducted. A measure of drug involvement and demographic characteristics was administered to the participants. Descriptive analysis was done using the SPSS v.21. Cannabis (79.4%), alcohol (77.2%), codeine (70.7%), tobacco (65.2%) and tramadol (47.8%) are the five most frequently used substances. However, the majority of the users of tobacco (68.3%) and alcohol (62.0%) are casual users indicating a mild level of use of the substances among the participants. On the other hand, 49.2% of the codeine users, 27.3% of the tramadol users, and 21.9% of the cannabis users reported harmful/intensive levels of use. Furthermore, the results revealed individuals at the pathological level of use as 28.8% for cannabis, 25.0% for tramadol, and 21.6% for codeine, and thus require clinical/therapeutic intervention. In conclusion, cannabis remains the most frequently used substance among youths. However, there appears to be a shift from the use of conventional psychoactive substances to pharmaceutical/prescription drugs such as codeine and tramadol. The findings of this study raised the need for both preventive and therapeutic interventions addressing the problem of substance use disorder among youth in contemporary society.

Keywords: Ogbomoso, pattern of drug use, prevalence of drug use, youth

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3210 A Neuropsychological Investigation of the Relationship between Anxiety Levels and Loss of Inhibitory Cognitive Control in Ageing and Dementia

Authors: Nasreen Basoudan, Andrea Tales, Frederic Boy

Abstract:

Non-clinical anxiety may be comprised of state anxiety - temporarily experienced anxiety related to a specific situation, and trait anxiety - a longer lasting response or a general disposition to anxiety. While temporary and occasional anxiety whether as a mood state or personality dimension is normal, nonclinical anxiety may influence many more components of information processing than previously recognized. In ageing and dementia-related research, disease characterization now involves attempts to understand a much wider range of brain function such as loss of inhibitory control, as against the more common focus on memory and cognition. However, in many studies, the tendency has been to include individuals with clinical anxiety disorders while excluding persons with lower levels of state or trait anxiety. Loss of inhibitory cognitive control can lead to behaviors such as aggression, reduced sensitivity to others, sociopathic thoughts and actions. Anxiety has also been linked to inhibitory control, with research suggesting that people with anxiety are less capable of inhibiting their emotions than the average person. This study investigates the relationship between anxiety and loss of inhibitory control in younger and older adults, using a variety of questionnaires and computers-based tests. Based on the premise that irrespective of classification, anxiety is associated with a wide range of physical, affective, and cognitive responses, this study explores evidence indicative of the potential influence anxiety per se on loss of inhibitory control, in order to contribute to discussion and appropriate consideration of anxiety-related factors in methodological practice.

Keywords: anxiety, ageing, dementia, inhibitory control

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3209 A Principal’s Role in Creating and Sustaining an Inclusive Environment

Authors: Yazmin Pineda Zapata

Abstract:

Leading a complete school and culture transformation can be a daunting task for any administrator. This is especially true when change agents are advocating for inclusive reform in their schools. As leaders embark on this journey, they must ascertain that an inclusive environment is not a place, a classroom, or a resource setting; it is a place of acceptance nurtured by supportive and meaningful learning opportunities where all students can thrive. A qualitative approach, phenomenology, was used to investigate principals’ actions and behaviors that supported inclusive schooling for students with disabilities. Specifically, this study sought to answer the following research question: How do leaders develop and maintain inclusive education? Fourteen K-12 principals purposefully selected from various sources (e.g., School Wide Integrated Framework for Transformation (SWIFT), The Maryland Coalition for Inclusive Education (MCIE), The Arc of Texas Inclusion Works organization, The Association for Persons with Severe Handicaps (TASH), the CAL State Summer Institute in San Marcos, and the PEAK Parent Center and/or other recognitions were interviewed individually using a semi-structured protocol. Upon completion of data collection, all interviews were transcribed and marked using A priori coding to analyze the responses and establish a correlation among Villa and Thousand’s five organizational supports to achieve inclusive educational reform: Vision, Skills, Incentives, Resources, and Action Plan. The findings of this study reveal the insights of principals who met specific criteria and whose schools had been highlighted as exemplary inclusive schools. Results show that by implementing the five organizational supports, principals were able to develop and sustain successful inclusive environments where both teachers and students were motivated, made capable, and supported through the redefinition and restructuring of systems within the school. Various key details of the five variables for change depict essential components within these systems, which include quality professional development, coaching and modeling of co-teaching strategies, collaborative co-planning, teacher leadership, and continuous stakeholder (e.g., teachers, students, support staff, and parents) involvement. The administrators in this study proved the valuable benefits of inclusive education for students with disabilities and their typically developing peers. Together, along with their teaching and school community, school leaders became capable stakeholders that promoted the vision of inclusion, planned a structured approach, and took action to make it a reality.

Keywords: Inclusive education, leaders, principals, shared-decision making, shared leadership, special education, sustainable change

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3208 Mini-Open Repair Using Ring Forceps Show Similar Results to Repair Using Achillon Device in Acute Achilles Tendon Rupture

Authors: Chul Hyun Park

Abstract:

Background:Repair using the Achillon deviceis a representative mini-open repair technique;however, the limitations of this technique includethe need for special instruments and decreasedrepair strength.A modifiedmini-open repair using ring forcepsmight overcome these limitations. Purpose:This study was performed to compare the Achillon device with ring forceps in mini-open repairsof acute Achilles tendon rupture. Study Design:This was a retrospective cohort study, and the level of evidence was3. Methods:Fifty patients (41 men and 9 women), withacute Achilles tendon rupture on one foot, were consecutively treated using mini-open repair techniques. The first 20 patients were treated using the Achillon device (Achillon group) and the subsequent 30 patients were treated using a ring forceps (Forcep group). Clinical, functional, and isokinetic results,and postoperative complications were compared between the two groups at the last follow-up. Clinical evaluations wereperformed using the American Orthopedic Foot and Ankle Society (AOFAS) score, Achilles tendon Total Rupture Score (ATRS), length of incision, and operation time. Functional evaluationsincludedactive range of motion (ROM) of the ankle joint, maximum calf circumference (MCC), hopping test, and single limb heel-rise (SLHR) test. Isokinetic evaluations were performed using the isokinetic test for ankle plantar flexion. Results:The AOFAS score (p=0.669), ATRS (p=0.753), and length of incision (p=0.305) were not significantly different between the groups. Operative times in the Achillon group were significantly shorter than that in the Forcep group (p<0.001).The maximum height of SLHR (p=0.023) and number of SLHRs (p=0.045) in the Forcep group were significantly greater than that in the Achillon group. No significant differences in the mean peak torques for plantar flexion at angular speeds of 30°/s (p=0.219) and 120°/s (p=0.656) were detected between the groups. There was no significant difference in the occurrence of postoperative complications between the groups (p=0.093). Conclusion:The ring forceps technique is comparable with the Achillon technique with respect to clinical, functional, and isokinetic results and the postoperative complications. Given that no special instrument is required, the ring forceps technique could be a better option for acute Achilles tendon rupture repair.

Keywords: achilles tendon, acute rupture, repair, mini-open

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3207 Unlocking the Puzzle of Borrowing Adult Data for Designing Hybrid Pediatric Clinical Trials

Authors: Rajesh Kumar G

Abstract:

A challenging aspect of any clinical trial is to carefully plan the study design to meet the study objective in optimum way and to validate the assumptions made during protocol designing. And when it is a pediatric study, there is the added challenge of stringent guidelines and difficulty in recruiting the necessary subjects. Unlike adult trials, there is not much historical data available for pediatrics, which is required to validate assumptions for planning pediatric trials. Typically, pediatric studies are initiated as soon as approval is obtained for a drug to be marketed for adults, so with the adult study historical information and with the available pediatric pilot study data or simulated pediatric data, the pediatric study can be well planned. Generalizing the historical adult study for new pediatric study is a tedious task; however, it is possible by integrating various statistical techniques and utilizing the advantage of hybrid study design, which will help to achieve the study objective in a smoother way even with the presence of many constraints. This research paper will explain how well the hybrid study design can be planned along with integrated technique (SEV) to plan the pediatric study; In brief the SEV technique (Simulation, Estimation (using borrowed adult data and applying Bayesian methods)) incorporates the use of simulating the planned study data and getting the desired estimates to Validate the assumptions.This method of validation can be used to improve the accuracy of data analysis, ensuring that results are as valid and reliable as possible, which allow us to make informed decisions well ahead of study initiation. With professional precision, this technique based on the collected data allows to gain insight into best practices when using data from historical study and simulated data alike.

Keywords: adaptive design, simulation, borrowing data, bayesian model

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3206 Development of a Diagnostic Device to Predict Clinically Significant Inflammation Associated with Cardiac Surgery

Authors: Mohamed Majrashi, Patricia Connolly, Terry Gourlay

Abstract:

Cardiopulmonary bypass is known to cause inflammatory response during open heart surgery. It includes the initiation of different cascades such as coagulation, complement system and cytokines. Although the immune system is body’s key defense mechanism against external assault, when overexpressed, it can be injurious to the patient, particularly in a cohort of patients in which there is a heightened and uncontrolled response. The inflammatory response develops in these patients to an exaggerated level resulting in an autoimmune injury and may lead to poor postoperative outcomes (systemic inflammatory response syndrome and multi-organs failure). Previous studies by this group have suggested a correlation between the level of IL6 measured in patient’s blood before surgery and after polymeric activation and the observed inflammatory response during surgery. Based upon these findings, the present work is aimed at using this response to develop a test which can be used prior to the open heart surgery to identify the high-risk patients before their operation. The work will be accomplished via three main clinical phases including some pilot in-vitro studies, device development and clinical investigation. Current findings from studies using animal blood, employing DEHP and DEHP plasticized PVC materials as the activator, support the earlier results in patient samples. Having established this relationship, ongoing work will focus on developing an activated lateral flow strip technology as a screening device for heightened inflammatory propensity.

Keywords: cardiopulmonary bypass, cytokines, inflammatory response, overexpression

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3205 An Approach for Association Rules Ranking

Authors: Rihab Idoudi, Karim Saheb Ettabaa, Basel Solaiman, Kamel Hamrouni

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Medical association rules induction is used to discover useful correlations between pertinent concepts from large medical databases. Nevertheless, ARs algorithms produce huge amount of delivered rules and do not guarantee the usefulness and interestingness of the generated knowledge. To overcome this drawback, we propose an ontology based interestingness measure for ARs ranking. According to domain expert, the goal of the use of ARs is to discover implicit relationships between items of different categories such as ‘clinical features and disorders’, ‘clinical features and radiological observations’, etc. That’s to say, the itemsets which are composed of ‘similar’ items are uninteresting. Therefore, the dissimilarity between the rule’s items can be used to judge the interestingness of association rules; the more different are the items, the more interesting the rule is. In this paper, we design a distinct approach for ranking semantically interesting association rules involving the use of an ontology knowledge mining approach. The basic idea is to organize the ontology’s concepts into a hierarchical structure of conceptual clusters of targeted subjects, where each cluster encapsulates ‘similar’ concepts suggesting a specific category of the domain knowledge. The interestingness of association rules is, then, defined as the dissimilarity between corresponding clusters. That is to say, the further are the clusters of the items in the AR, the more interesting the rule is. We apply the method in our domain of interest – mammographic domain- using an existing mammographic ontology called Mammo with the goal of deriving interesting rules from past experiences, to discover implicit relationships between concepts modeling the domain.

Keywords: association rule, conceptual clusters, interestingness measures, ontology knowledge mining, ranking

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3204 The Improvement of Disease-Modifying Osteoarthritis Drugs Model Uptake and Retention within Two Cartilage Models

Authors: Polina Prokopovich

Abstract:

Disease-modifying osteoarthritis drugs (DMOADs) are a new therapeutic class for OA, preventing or inhibiting OA development. Unfortunately, none of the DMOADs have been clinically approved due to their poor therapeutic effects in clinical trials. The joint environment has played a role in the poor clinical performance of these drugs by limiting the amount of drug effectively delivered as well as the time that the drug spends within the joint space. The current study aims to enhance the cartilage uptake and retention time of the DMOADs-model (licofelone), which showed a significant therapeutic effect against OA progression and is currently in phase III. Licofelone will be covalently conjugated to the hydrolysable, cytocompatible, and cationic poly beta-amino ester polymers (PBAE). The cationic polymers (A16 and A87) can be electrostatically attached to the negatively charged cartilage component (glycosaminoglycan), which will increase the drug penetration through the cartilage and extend the drug time within the cartilage. In the cartilage uptake and retention time studies, an increase of 18 to 37 times of the total conjugated licofelone to A87 and A16 was observed when compared to the free licofelone. Furthermore, the conjugated licofelone to A87 was detectable within the cartilage at 120 minutes, while the free licofelone was not detectable after 60 minutes. Additionally, the A87-licofelone conjugate showed no effect on the chondrocyte viability. In conclusion, the cationic A87 and A16 polymers increased the percentage of licofelone within the cartilage, which could potentially enhance the therapeutic effect and pharmacokinetic performance of licofelone or other DMOADs clinically.

Keywords: PBAE, cartilage., osteoarthritis, injectable biomaterials, drug delivery

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3203 Top Skills That Build Cultures at Organizations

Authors: Priyanka Botny Srinath, Alessandro Suglia, Mel McKendrick

Abstract:

Background: Organizational cultural studies integrate sociology and anthropology, portraying man as a creator of symbols, languages, beliefs, and ideologies -essentially, a creator and manager of meaning. In our research, we leverage analytical measures to discern whether an organization embodies a singular culture or a myriad of subcultures. Fast-forward to 2023, our research thesis focuses on digitally measuring culture, coining it as the "Work Culture Quotient." This entails conceptually mapping common experiential patterns to provide executives insights into the digital organization journey, aiding in understanding their current position and identifying future steps. Objectives: Finding the new age skills that help in defining the culture; understand the implications of post-COVID effects; derive a digital framework for measuring skillsets. Method: We conducted two comprehensive Delphi studies to distill essential insights. Delphi 1: Through a thematic analysis of interviews with 20 high-level leaders representing companies across diverse regions -India, Japan, the US, Canada, Morocco, and Uganda- we identified 20 key skills critical for cultivating a robust organizational culture. The skills are -influence, self-confidence, optimism, empathy, leadership, collaboration and cooperation, developing others, commitment, innovativeness, leveraging diversity, change management, team capabilities, self-control, digital communication, emotional awareness, team bonding, communication, problem solving, adaptability, and trustworthiness. Delphi 2: Subject matter experts were asked to complete a questionnaire derived from the thematic analysis in stage 1 to formalise themes and draw consensus amongst experts on the most important workplace skills. Results: The thematic analysis resulted in 20 workplace employee skills being identified. These skills were all included in the Delphi round 2 questionnaire. From the outputs, we analysed the data using R Studio for arriving at agreement and consensus, we also used sum of squares method to compare various agreements to extract various themes with a threshold of 80% agreements. This yielded three themes at over 80% agreement (leadership, collaboration and cooperation, communication) and three further themes at over 60% agreement (commitment, empathy, trustworthiness). From this, we selected five questionnaires to be included in the primary data collection phase, and these will be paired with the digital footprints to provide a workplace culture quotient. Implications: The findings from these studies bear profound implications for decision-makers, revolutionizing their comprehension of organizational culture. Tackling the challenge of mapping the digital organization journey involves innovative methodologies that probe not only external landscapes but also internal cultural dynamics. This holistic approach furnishes decision-makers with a nuanced understanding of their organizational culture and visualizes pivotal skills for employee growth. This clarity enables informed choices resonating with the organization's unique cultural fabric. Anticipated outcomes transcend mere individual cultural measurements, aligning with organizational goals to unveil a comprehensive view of culture, exposing artifacts and depth. Armed with this profound understanding, decision-makers gain tangible evidence for informed decision-making, strategically leveraging cultural strengths to cultivate an environment conducive to growth, innovation, and enduring success, ultimately leading to measurable outcomes.

Keywords: leadership, cooperation, collaboration, teamwork, work culture

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3202 Response of Newzealand Rabbits to Drinking Water Treated with PolyDADMAC

Authors: Amna Beshir Medani Ahmed, Samia Mohammed Ali El Badwi, Ahmed El Amin Mohammed

Abstract:

This work has been managed to yield toxicity information on water treatment agents in the Sudan namely polyDADMAC, using New Zealand rabbits at multiple daily oral doses for a period of 10 weeks. Thirty-three heads of New Zealand rabbits were divided into 11 groups, each of three. Group 1 animals were the undosed controls. Test groups of either species were given polyDADMAC at similar dose rates of 0.5, 2.5, 4.5, 10, 15, 20, 25, 50, 100 and 150 mg/kg body weight respectively for groups 2,3,4,5,6,7,8,9,10 and 11. Clinical signs were closely observed with postmortem and histopathological examinations. Chemical investigations included enzymatic concentrations of ALP, GOT, CK, GPT and LDH together with hematological changes in Hb, PCV, RBCs and WBCs. Mortalities occurred to variable degrees irrespective of the dose level. On polyDADMAC challenge, the test species showed clinical signs of dullness, loss of weight, anorexia, diarrhea, difficulty in respiration, hind limb paralysis and recumbency. Notably oral dosing with polyDADMAC caused lung emphysema, hepatic and renal dysfunctions, irregularity in enzymatic activities and serum metabolites, sloughing of intestinal epithelium, decreased electrolytes in serum, and splenic haemosiderosis. On evaluation of the above results, polyDADMAC was considered toxic to New Zealand rabbits at all dose rates tried. Practical implications of the results were highlighted and suggestions for future work were put forward.

Keywords: polydiallyldiethylaluminiumchloride (polyDADMAC), nubian goats, toxicity of drinking water, treatment of drinking water using chemicals

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3201 Predictive Analysis of Chest X-rays Using NLP and Large Language Models with the Indiana University Dataset and Random Forest Classifier

Authors: Azita Ramezani, Ghazal Mashhadiagha, Bahareh Sanabakhsh

Abstract:

This study researches the combination of Random. Forest classifiers with large language models (LLMs) and natural language processing (NLP) to improve diagnostic accuracy in chest X-ray analysis using the Indiana University dataset. Utilizing advanced NLP techniques, the research preprocesses textual data from radiological reports to extract key features, which are then merged with image-derived data. This improved dataset is analyzed with Random Forest classifiers to predict specific clinical results, focusing on the identification of health issues and the estimation of case urgency. The findings reveal that the combination of NLP, LLMs, and machine learning not only increases diagnostic precision but also reliability, especially in quickly identifying critical conditions. Achieving an accuracy of 99.35%, the model shows significant advancements over conventional diagnostic techniques. The results emphasize the large potential of machine learning in medical imaging, suggesting that these technologies could greatly enhance clinician judgment and patient outcomes by offering quicker and more precise diagnostic approximations.

Keywords: natural language processing (NLP), large language models (LLMs), random forest classifier, chest x-ray analysis, medical imaging, diagnostic accuracy, indiana university dataset, machine learning in healthcare, predictive modeling, clinical decision support systems

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3200 Disseminated Tuberculosis: Experience from Tuberculosis Directly Observed Treatment Short Course Center at a Tertiary Care Teaching Hospital in the Philippines

Authors: Jamie R. Chua, Christina Irene D. Mejia, Regina P. Berba

Abstract:

Disseminated tuberculosis is an infectious disease caused by Mycobacterium tuberculosis involving two or more non-contiguous sites identified through bacteriologic confirmation or clinical diagnosis. Over the five year period included in the study, the UP-PGH TB DOTS clinic had total of 3,967 referrals, and the prevalence of disseminated tuberculosis is 1% (68/3967). The mean age was 33.9 years (range 19-64 years) with a male: female ratio of 1:1. 67% (52 patients) had no predisposing comorbid illness or immune disorder. The most common presenting symptoms were abdominal pain (19%), back pain (13%), abdominal enlargement (11%) and mass (10.2%). Anemia, leukocytosis, hypoalbuminemia, and high-normal serum calcium were common biochemical and hematologic findings. Around 36% (25) of patients were diagnosed clinically with disseminated tuberculosis despite lacking bacteriologic evidence of multi-organ involvement. The lungs (86%) is still the most commonly involved site, followed by intestinal (22%), vertebral/Pott’s (27%), and pelvic/genital (19%). The mean time from presentation to initiation of therapy was 22 days (SD 32.7). Only 18 patients (29.3%) were properly recorded to have been referred to local TB DOTs facilities. Of the 68 patients, only 16% (11 patients) continued follow-up at PGH, and all had documented treatment completion. Treatment outcomes of the remaining were unknown. Due to the variety of involved sites, a high index of suspicion is required. Knowledge on clinical features, common radiographic findings, and histopathologic characteristics of disseminated TB is important as bacteriologic evidence of infection is not always apparent.

Keywords: disseminated tuberculosis, Mycobacterium tuberculosis, miliary tuberculosis, tuberculosis

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3199 Clinical Features of Acute Aortic Dissection Patients Initially Diagnosed with ST-Segment Elevation Myocardial Infarction

Authors: Min Jee Lee, Young Sun Park, Shin Ahn, Chang Hwan Sohn, Dong Woo Seo, Jae Ho Lee, Yoon Seon Lee, Kyung Soo Lim, Won Young Kim

Abstract:

Background: Acute myocardial infarction (AMI) concomitant with acute aortic syndrome (AAS) is rare but prompt recognition of concomitant AAS is crucial, especially in patients with ST-segment elevation myocardial infarction (STEMI) because misdiagnosis with early thrombolytic or anticoagulant treatment may result in catastrophic consequences. Objectives: This study investigated the clinical features of patients of STEMI concomitant with AAS that may lead to the diagnostic clue. Method: Between 1 January 2010 and 31 December 2014, 22 patients who were the initial diagnosis of acute coronary syndrome (AMI and unstable angina) and AAS (aortic dissection, intramural hematoma and ruptured thoracic aneurysm) in our emergency department were reviewed. Among these, we excluded 10 patients who were transferred from other hospital and 4 patients with non-STEMI, leaving a total of 8 patients of STEMI concomitant with AAS for analysis. Result: The mean age of study patients was 57.5±16.31 years and five patients were Standford type A and three patients were type B aortic dissection. Six patients had ST-segment elevation in anterior leads and two patients had in inferior leads. Most of the patients had acute onset, severe chest pain but no patients had dissecting nature chest pain. Serum troponin I was elevated in three patients but all patients had D-dimer elevation. Aortic regurgitation or regional wall motion abnormality was founded in four patients. However, widened mediastinum was seen in all study patients. Conclusion: When patients with STEMI have elevated D-dimer and widened mediastinum, concomitant AAS may have to be suspected.

Keywords: aortic dissection, myocardial infarction, ST-segment, d-dimer

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3198 The Anti-Globalization Movement, Brexit, Outsourcing and the Current State of Globalization

Authors: Alexis Naranjo

Abstract:

In the current global stage, a new sense and mix feelings against the globalization has started to take shape thanks to events such as Brexit and the 2016 US election. The perceptions towards the globalization have started to focus in a resistance movement called the 'anti-globalization movement'. This paper examines the current global stage vs. leadership decisions in a time when market integrations are not longer seeing as an opportunity for an economic growth buster. The biggest economy in the world the United States of America has started to face a new beginning of something called 'anti-globalization', in the current global stage starting with the United Kingdom to the United States a new strategy to help local economies has started to emerge. A new nationalist movement has started to focus on their local economies which now represents a direct threat to the globalization, trade agreements, wages and free markets. Business leaders of multinationals now in our days face a new dilemma, how to address the feeling that globalization and outsourcing destroy and take away jobs from local economies. The initial perception of the literature and data rebels that companies in Western countries like the US sees many risks associate with outsourcing, however, saving cost associated with outsourcing is greater than the firm’s local reputation. Starting with India as a good example of a supplier of IT developers, analysts and call centers we can start saying that India is an industrialized nation which has not yet secured its spot and title. India has emerged as a powerhouse in the outsource industry, which makes India hold the number one spot in the world to outsource IT services. Thanks to the globalization of economies and markets around the globe that new ideas to increase productivity at a lower cost has been existing for years and has started to offer new ideas and options to businesses in different industries. The economic growth of the information technology (IT) industry in India is an example of the power of the globalization which in the case of India has been tremendous and significant especially in the economic arena. This research paper concentrates in understand the behavior of business leaders: First, how multinational’s leaders will face the new challenges and what actions help them to lead in turbulent times. Second, if outsourcing or withdraw from a market is an option what are the consequences and how you communicate and negotiate from the business leader perspective. Finally, is the perception of leaders focusing on financial results or they have a different goal? To answer these questions, this study focuses on the most recent data available to outline and present the findings of the reason why outsourcing is and option and second, how and why those decisions are made. This research also explores the perception of the phenomenon of outsourcing in many ways and explores how the globalization has contributed to its own questioning.

Keywords: anti-globalization, globalization, leadership, outsourcing

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3197 Endotracheal Intubation Self-Confidence: Report of a Realistic Simulation Training

Authors: Cleto J. Sauer Jr., Rita C. Sauer, Chaider G. Andrade, Doris F. Rabelo

Abstract:

Introduction: Endotracheal Intubation (ETI) is a procedure for clinical management of patients with severe clinical presentation of COVID-19 disease. Realistic simulation (RS) is an active learning methodology utilized for clinical skill's improvement. To improve ETI skills of public health network's physicians from Recôncavo da Bahia region in Brazil, during COVID-19 outbreak, RS training was planned and carried out. Training scenario included the Nasco Lifeform realistic simulator, and three actions were simulated: ETI procedure, sedative drugs management, and bougie guide utilization. Training intervention occurred between May and June 2020, as an interinstitutional cooperation between the Health's Department of Bahia State and the Federal University from Recôncavo da Bahia. Objective: The main objective is to report the effects on participants' self-confidence perception for ETI procedure after RS based training. Methods: This is a descriptive study, with secondary data extracted from questionnaires applied throughout RS training. Priority workplace, time from last intubation, and knowledge about bougie were reported on a preparticipation questionnaire. Additionally, participants completed pre- and post-training qualitative self-assessment (10-point Likert scale) regarding self-confidence perception in performing each of simulated actions. Distribution analysis for qualitative data was performed with Wilcoxon Signed Rank Test, and self-confidence increase analysis in frequency contingency tables with Fisher's Exact Test. Results: 36 physicians participated of training, 25 (69%) from primary care setting, 25 (69%) performed ETI over a year ago, and only 4 (11%) had previous knowledge about the bougie guide utilization. There was an increase in self-confidence medians for all three simulated actions. Medians (variation) for self-confidence before and after training, for each simulated action were as follows: ETI [5 (1-9) vs. 8 (6-10) (p < 0.0001)]; Sedative drug management [5 (1-9) vs. 8 (4-10) (p < 0.0001)]; Bougie guide utilization [2.5 (1-7) vs. 8 (4-10) (p < 0.0001)]. Among those who performed ETI over a year ago (n = 25), an increase in self-confidence greater than 3 points for ETI was reported by 23 vs. 2 physicians (p = 0.0002), and by 21 vs. 4 (p = 0.03) for sedative drugs management. Conclusions: RS training contributed to self-confidence increase in performing ETI. Among participants who performed ETI over a year, there was a significant association between RS training and increase of more than 3 points in self-confidence, both for ETI and sedative drug management. Training with RS methodology is suitable for ETI confidence enhancement during COVID-19 outbreak.

Keywords: confidence, COVID-19, endotracheal intubation, realistic simulation

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3196 Study of Circulatory MiR-122 and MiR-130a Expression among Chronic Hepatitis C Egyptian Patients

Authors: Hend K. Moosa, Eman A. Rashwan, Ezzat M. Hassan, Amany A. Ghazy, Amel G. Sheredy

Abstract:

The stability of microRNA (miR) in the circulation can show a great progress toward the discovery of non-invasive diagnostic and prognostic biomarkers in many diseases. In the present study, circulatory miR-122 and miR-130a were analysed in chronic hepatitis C Egyptian patients in predicting the clinical outcome of interferon treatment. In addition, their expression levels were correlated to viral RNA levels, necro-inflammatory markers (AST, ALT) and to each other. This study was conducted on 51 subjects where 36 were chronic HCV patients in which they were divided into naive and interferon treated HCV patients (responders and non-responders) and 15 matched healthy controls. Serum quantification of miR-122 and miR-130a were performed by quantitative Real-time Polymerase Chain Reaction (qRT-PCR). The results showed a significant upregulation of miR-122 in non-responder patients (P=0.049). By receiver operating characteristic analysis curve, miR-122 revealed 65% sensitivity and 92.3% specificity in predicting non-responsiveness of patients to IFN treatment, while miR-130a showed a sensitivity of 100% and specificity of 53.85%. Remarkably, there was a significant positive correlation between miR-122 and miR-130a in naive HCV patients (r=0.714, p=0.003). However, there was no significant correlation between serum miR-122, miR-130a expression levels and necro-inflammatory markers (AST, ALT). To conclude, miR-122 and miR-130a have a significant association with viral RNA levels and accordingly, they may have a synergistic power in promoting viral replication. Interestingly, miR-122 and miR-130a have a predictive power in predicting clinical outcome of IFN treatment which can be further studied in currently used drugs in order to reduce the socio-economic burden of potentially non-responders.

Keywords: hepatitis C, microRNA, miR-122, miR-130a

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3195 Phenotype and Psychometric Characterization of Phelan-Mcdermid Syndrome Patients

Authors: C. Bel, J. Nevado, F. Ciceri, M. Ropacki, T. Hoffmann, P. Lapunzina, C. Buesa

Abstract:

Background: The Phelan-McDermid syndrome (PMS) is a genetic disorder caused by the deletion of the terminal region of chromosome 22 or mutation of the SHANK3 gene. Shank3 disruption in mice leads to dysfunction of synaptic transmission, which can be restored by epigenetic regulation with both Lysine Specific Demethylase 1 (LSD1) inhibitors. PMS subjects result in a variable degree of intellectual disability, delay or absence of speech, autistic spectrum disorders symptoms, low muscle tone, motor delays and epilepsy. Vafidemstat is an LSD1 inhibitor in Phase II clinical development with a well-established and favorable safety profile, and data supporting the restoration of memory and cognition defects as well as reduction of agitation and aggression in several animal models and clinical studies. Therefore, vafidemstat has the potential to become a first-in-class precision medicine approach to treat PMS patients. Aims: The goal of this research is to perform an observational trial to psychometrically characterize individuals carrying deletions in SHANK3 and build a foundation for subsequent precision psychiatry clinical trials with vafidemstat. Methodology: This study is characterizing the clinical profile of 20 to 40 subjects, > 16-year-old, with genotypically confirmed PMS diagnosis. Subjects will complete a battery of neuropsychological scales, including the Repetitive Behavior Questionnaire (RBQ), Vineland Adaptive Behavior Scales, Escala de Observación para el Diagnostico del Autismo (Autism Diagnostic Observational Scale) (ADOS)-2, the Battelle Developmental Inventory and the Behavior Problems Inventory (BPI). Results: By March 2021, 19 patients have been enrolled. Unsupervised hierarchical clustering of the results obtained so far identifies 3 groups of patients, characterized by different profiles of cognitive and behavioral scores. The first cluster is characterized by low Battelle age, high ADOS and low Vineland, RBQ and BPI scores. Low Vineland, RBQ and BPI scores are also detected in the second cluster, which in contrast has high Battelle age and low ADOS scores. The third cluster is somewhat in the middle for the Battelle, Vineland and ADOS scores while displaying the highest levels of aggression (high BPI) and repeated behaviors (high RBQ). In line with the observation that female patients are generally affected by milder forms of autistic symptoms, no male patients are present in the second cluster. Dividing the results by gender highlights that male patients in the third cluster are characterized by a higher frequency of aggression, whereas female patients from the same cluster display a tendency toward higher repetitive behavior. Finally, statistically significant differences in deletion sizes are detected comparing the three clusters (also after correcting for gender), and deletion size appears to be positively correlated with ADOS and negatively correlated with Vineland A and C scores. No correlation is detected between deletion size and the BPI and RBQ scores. Conclusions: Precision medicine may open a new way to understand and treat Central Nervous System disorders. Epigenetic dysregulation has been proposed to be an important mechanism in the pathogenesis of schizophrenia and autism. Vafidemstat holds exciting therapeutic potential in PMS, and this study will provide data regarding the optimal endpoints for a future clinical study to explore vafidemstat ability to treat shank3-associated psychiatric disorders.

Keywords: autism, epigenetics, LSD1, personalized medicine

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3194 Analysing Perceptions of Online Games-Based Learning: Case Study of the University of Northampton

Authors: Alison Power

Abstract:

Games-based learning aims to enhance students’ engagement with and enjoyment of learning opportunities using games-related principles to create a fun yet productive learning environment. Motivating students to learn in an online setting can be particularly challenging, so a cross-Faculty synchronous online session provided students with the opportunity to engage with ‘GAMING’: an interactive, flexible and scalable e-resource for students to work synchronously in groups to complete a series of e-tivities designed to enhance their skills of leadership, collaboration and negotiation. Findings from a post-session online survey found the majority of students had a positive learning experience, finding 'GAMING' to be an innovative and engaging e-resource which motivated their group to learn.

Keywords: collaboration, games-based learning, groupwork, synchronous online learning, teamwork

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3193 Effects of Sacubitril and Valsartan on Gut Microbiome

Authors: Wei-Ju Huang, Hung-Pin Hsu

Abstract:

[Background] In congestive heart failure (CHF), it has always been the principle of clinical treatment to control the water retention mechanism in the body to prevent excessive fluid retention. Early control of sympathetic nerves, Renin-Angiotensin-Aldosterone system (RAA system, RAAS), or strengthening of Atrial Natriuretic Peptide (ANP) was the point. In RAA system, related hormones, such as angiotensin, or enzymes in the pathway, such as ACE-I, can be used with corresponding inhibitors to reduce water content.[Aim] In recent years, clinical studies have pointed out that if different mechanisms are combined, the control effect seems to be better. For example, recent studies showed that ENTRESTO, a combination of Sacubitril and Valsartan, is a good new drug for CHF. Sacubitril is a prodrug. After activation, it can inhibit neprilysin and act as a neprilysin inhibitor (ARNI) to reduce the breakdown of natriuretic peptides(ANP). Valsartan is a kind of angiotensin receptor blocker (ARB), both of which are used to treat heart failure at the same time, have excellent curative effects.[Materials and Methods] Considering the side effects of this drug, coughing and a few cases of diarrhea were observed. However, the effect of this drug on the patient's intestinal tract has not been confirmed. On the other hand, studies have pointed out that ANP supplement can improve the CHF and increase the inhibitory effect on cancer cells. Therefore, the purpose of this study is to use a special microbial detection method to prove that whether oral drugs have an effect on microorganisms.The experimental method uses Nissui Compact Dry to observe the situation in different types of microorganisms. After the drug is dissolved in water, it is implanted in a petri dish, and the presence of different microorganisms is detected through different antibody reactions to confirm whether the drug has some toxicology in the gut.[Results and Discussion]From the above experimental results, it can be known that among the effects of Sacubitril and Valsartan on the basic microbial flora of the human body, low doses had no significant effect on Escherichia coli or intestinal bacteria. If Sacubitril or Valsartan with a high concentration of 3mg/ml is used alone or under the stimulation of a high concentration of the two drugs, it has a significant inhibitory effect on Escherichia coli. However, in terms of the effect on intestinal bacteria, high concentration of Sacubitril has a more significant inhibitory effect on intestinal bacteria, while high concentration of Valsartan has a less significant inhibitory effect on intestinal bacteria. The inhibitory effect of the combination of the two drugs on intestinal bacteria is also less significant.[Conclusion]The results of this study can be used as a further reference for the possible side effects of the clinical use of Sacubitril and Valsartan on the intestinal tract of patients,

Keywords: sacubitril, valsartan, entresto, congestive heart failure (CHF)

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3192 Co-payment Strategies for Chronic Medications: A Qualitative and Comparative Analysis at European Level

Authors: Pedro M. Abreu, Bruno R. Mendes

Abstract:

The management of pharmacotherapy and the process of dispensing medicines is becoming critical in clinical pharmacy due to the increase of incidence and prevalence of chronic diseases, the complexity and customization of therapeutic regimens, the introduction of innovative and more expensive medicines, the unbalanced relation between expenditure and revenue as well as due to the lack of rationalization associated with medication use. For these reasons, co-payments emerged in Europe in the 70s and have been applied over the past few years in healthcare. Co-payments lead to a rationing and rationalization of user’s access under healthcare services and products, and simultaneously, to a qualification and improvement of the services and products for the end-user. This analysis, under hospital practices particularly and co-payment strategies in general, was carried out on all the European regions and identified four reference countries, that apply repeatedly this tool and with different approaches. The structure, content and adaptation of European co-payments were analyzed through 7 qualitative attributes and 19 performance indicators, and the results expressed in a scorecard, allowing to conclude that the German models (total score of 68,2% and 63,6% in both elected co-payments) can collect more compliance and effectiveness, the English models (total score of 50%) can be more accessible, and the French models (total score of 50%) can be more adequate to the socio-economic and legal framework. Other European models did not show the same quality and/or performance, so were not taken as a standard in the future design of co-payments strategies. In this sense, we can see in the co-payments a strategy not only to moderate the consumption of healthcare products and services, but especially to improve them, as well as a strategy to increment the value that the end-user assigns to these services and products, such as medicines.

Keywords: clinical pharmacy, co-payments, healthcare, medicines

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