Search results for: clinical pathway

Authors: M. Shahana

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Introduction: Leprosy (Hansens) is one of the major health problems in the developing countries. Sixty percent of the world leprosy cases are in India. According to the 2006 census India has about 54% of the total new cases detected globally. The National Leprosy Elimination Programme in 2012 has reported 9.7% of childhood leprosy. There are only few studies related to paediatric leprosy. Aim: To study the epidemiology and various clinical presentations of leprosy in the paediatric age group. Material and Methods: A 4-year prospective study was done in the out-patient department of dermatology in a tertiary care hospital. All the patients were screened for leprosy and children with a confirmed diagnosis of leprosy were taken up for the study. Results: Total of 321 cases of Hansens were recorded during this period out of which 41 were children. The male to female ratio was 2.72:1. A positive family history was found in 18%. Most of them presented with single hypopigmented hypoanesthetic patch. Conclusions: Children presented with more of Borderline tuberculoid type and reactions or deformities were less common.

Keywords: Hansens, hypoaneasthetic patch, leprosy, reactions

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Authors: Junie B. Billones, Maria Constancia O. Carrillo, Voltaire G. Organo, Stephani Joy Y. Macalino, Inno A. Emnacen, Jamie Bernadette A. Sy

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The drug discovery and development process is generally known to be a very lengthy and labor-intensive process. Therefore, in order to be able to deliver prompt and effective responses to cure certain diseases, there is an urgent need to reduce the time and resources needed to design, develop, and optimize potential drugs. Computer-aided drug design (CADD) is able to alleviate this issue by applying computational power in order to streamline the whole drug discovery process, starting from target identification to lead optimization. This drug design approach can be predominantly applied to diseases that cause major public health concerns, such as tuberculosis. Hitherto, there has been no concrete cure for this disease, especially with the continuing emergence of drug resistant strains. In this study, CADD is employed for tuberculosis by first identifying a key enzyme in the mycobacterium’s metabolic pathway that would make a good drug target. One such potential target is the lipoate protein ligase B enzyme (LipB), which is a key enzyme in the M. tuberculosis metabolic pathway involved in the biosynthesis of the lipoic acid cofactor. Its expression is considerably up-regulated in patients with multi-drug resistant tuberculosis (MDR-TB) and it has no known back-up mechanism that can take over its function when inhibited, making it an extremely attractive target. Using cutting-edge computational methods, compounds from AnalytiCon Discovery Natural Derivatives database were screened and docked against the LipB enzyme in order to rank them based on their binding affinities. Compounds which have better binding affinities than LipB’s known inhibitor, decanoic acid, were subjected to in silico toxicity evaluation using the ADMET and TOPKAT protocols. Out of the 31,692 compounds in the database, 112 of these showed better binding energies than decanoic acid. Furthermore, 12 out of the 112 compounds showed highly promising ADMET and TOPKAT properties. Future studies involving in vitro or in vivo bioassays may be done to further confirm the therapeutic efficacy of these 12 compounds, which eventually may then lead to a novel class of anti-tuberculosis drugs.

Keywords: pharmacophore, molecular docking, lipoate protein ligase B (LipB), ADMET, TOPKAT

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Authors: Naridchaya Aberdour, Joanna Kao, Anne Miller, Timothy Shore, Richard Maher, Zhixin Liu

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Background: COVID-19 has and continues to be a strain on healthcare globally, with the number of patients requiring hospitalization exceeding the level of medical support available in many countries. As chest x-rays are the primary respiratory radiological investigation, the Radiological Assessment of Lung Edema (RALE) score was used to quantify the extent of pulmonary infection on baseline imaging. Assessment of RALE score's reproducibility and associations with clinical outcome parameters were then evaluated to determine implications for patient management and prognosis. Methods: A retrospective study was performed with the inclusion of patients testing positive for COVID-19 on nasopharyngeal swab within a single Local Health District in Sydney, Australia and baseline x-ray imaging acquired between January to June 2020. Two independent Radiologists viewed the studies and calculated the RALE scores. Clinical outcome parameters were collected and statistical analysis was performed to assess RALE score reproducibility and possible associations with clinical outcomes. Results: A total of 78 patients met inclusion criteria with the age range of 4 to 91 years old. RALE score concordance between the two independent Radiologists was excellent (interclass correlation coefficient = 0.93, 95% CI = 0.88-0.95, p<0.005). Binomial logistics regression identified a positive correlation with hospital admission (1.87 OR, 95% CI= 1.3-2.6, p<0.005), oxygen requirement (1.48 OR, 95% CI= 1.2-1.8, p<0.005) and invasive ventilation (1.2 OR, 95% CI= 1.0-1.3, p<0.005) for each 1-point increase in RALE score. For each one year increased in age, there was a negative correlation with recovery (0.05 OR, 95% CI= 0.92-1.0, p<0.01). RALE scores above three were positively associated with hospitalization (Youden Index 0.61, sensitivity 0.73, specificity 0.89) and above six were positively associated with ICU admission (Youden Index 0.67, sensitivity 0.91, specificity 0.78). Conclusion: The RALE score can be used as a surrogate to quantify the extent of COVID-19 infection and has an excellent inter-observer agreement. The RALE score could be used to prognosticate and identify patients at high risk of deterioration. Threshold values may also be applied to predict the likelihood of hospital and ICU admission.

Keywords: chest radiography, coronavirus, COVID-19, RALE score

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Authors: Juntip Kanjanasilp, Ratree Sawangjit, Kanokporn Meelap, Kwanchanok Kruthakool

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Depression is a common mental health disorder. Antidepressants are effective pharmacological treatments, but most patients have low medication adherence. This study aims to systematic review and meta-analysis what method increase the antidepressants adherence efficiently and improve clinical outcome. Systematic review of articles of randomized controlled trials obtained by a computerized literature search of The Cochrane, Library, Pubmed, Embase, PsycINFO, CINAHL, Education search, Web of Science and ThaiLIS (28 December 2017). Twenty-three studies were included and assessed the quality of research by ROB 2.0. The results reported that printing media improved in number of people who had medication adherence statistical significantly (p= 0.018), but education, phone call, and program utilization were no different (p=0.172, p=0.127, p=0.659). There was no significant difference in pharmacist’s group, health care team’s group and physician’s group (p=0.329, p=0.070, p=0.040). Times of intervention at 1 month and 6 months improved medication adherence significantly (p= 0.0001, p=0.013). There was significantly improved adherence in single intervention (p=0.027) but no different in multiple interventions (p=0.154). When we analyzed medication adherence with the mean score, no improved adherence was found, not relevant with who gives the intervention and times to intervention. However, the multiple interventions group was statistically significant improved medication adherence (p=0.040). Phone call and the physician’s group were statistically significant improved clinical outcomes in number of improved patients (0.025 and 0.020, respectively). But in the pharmacist’s group and physician’s group were not found difference in the mean score of clinical outcomes (p=0.993, p=0.120, respectively). Times to intervention and number of intervention were not significant difference than usual care. The overall intervention can increase antidepressant adherence, especially the printing media, and the appropriate timing of the intervention is at least 6 months. For effective treatment, the provider should have experience and expert in caring for patients with depressive disorders, such as a psychiatrist. Medical personnel should have knowledge in caring for these patients also.

Keywords: depression, medication adherence, clinical outcomes, systematic review, meta-analysis

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Authors: Rosa L. Figueroa, Christopher A. Flores, Qing Zeng-Treitler

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A regular expression consists of sequence characters which allow describing a text path. Usually, in clinical research, regular expressions are manually created by programmers together with domain experts. Lately, there have been several efforts to investigate how to generate them automatically. This article presents a text classification algorithm based on regexes. The algorithm named REX was designed, and then, implemented as a simplified method to create regexes to classify Spanish text automatically. In order to classify ambiguous cases, such as, when multiple labels are assigned to a testing example, REX includes an information gain method Two sets of data were used to evaluate the algorithm’s effectiveness in clinical text classification tasks. The results indicate that the regular expression based classifier proposed in this work performs statically better regarding accuracy and F-measure than Support Vector Machine and Naïve Bayes for both datasets.

Keywords: information gain, regular expressions, smith-waterman algorithm, text classification

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Authors: Meera Tandan, Mohan Timilsina, Martin Cormican, Akke Vellinga

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Background: In general practice, many infections are treated empirically without microbiological confirmation. Understanding susceptibility of antimicrobials during empirical prescribing can be helpful to reduce inappropriate prescribing. This study aims to apply a prediction model using a decision tree approach to predict the antimicrobial resistance (AMR) of urinary tract infections (UTI) based on non-clinical features of patients over 65 years. Decision tree models are a novel idea to predict the outcome of AMR at an initial stage. Method: Data was extracted from the database of the microbiological laboratory of the University Hospitals Galway on all antimicrobial susceptibility testing (AST) of urine specimens from patients over the age of 65 from January 2011 to December 2014. The primary endpoint was resistance to common antimicrobials (Nitrofurantoin, trimethoprim, ciprofloxacin, co-amoxiclav and amoxicillin) used to treat UTI. A classification and regression tree (CART) model was generated with the outcome ‘resistant infection’. The importance of each predictor (the number of previous samples, age, gender, location (nursing home, hospital, community) and causative agent) on antimicrobial resistance was estimated. Sensitivity, specificity, negative predictive (NPV) and positive predictive (PPV) values were used to evaluate the performance of the model. Seventy-five percent (75%) of the data were used as a training set and validation of the model was performed with the remaining 25% of the dataset. Results: A total of 9805 UTI patients over 65 years had their urine sample submitted for AST at least once over the four years. E.coli, Klebsiella, Proteus species were the most commonly identified pathogens among the UTI patients without catheter whereas Sertia, Staphylococcus aureus; Enterobacter was common with the catheter. The validated CART model shows slight differences in the sensitivity, specificity, PPV and NPV in between the models with and without the causative organisms. The sensitivity, specificity, PPV and NPV for the model with non-clinical predictors was between 74% and 88% depending on the antimicrobial. Conclusion: The CART models developed using non-clinical predictors have good performance when predicting antimicrobial resistance. These models predict which antimicrobial may be the most appropriate based on non-clinical factors. Other CART models, prospective data collection and validation and an increasing number of non-clinical factors will improve model performance. The presented model provides an alternative approach to decision making on antimicrobial prescribing for UTIs in older patients.

Keywords: antimicrobial resistance, urinary tract infection, prediction, decision tree

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Authors: Moshe Wasserblat, Jonathan Mamou, Oren Pereg

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Natural Language Processing (NLP) has made a major leap in the last few years, in practical integration into medical solutions; for example, extracting clinical concepts from medical texts such as medical condition, medication, treatment, and symptoms. However, training and deploying those models in real environments still demands a large amount of annotated data and NLP/Machine Learning (ML) expertise, which makes this process costly and time-consuming. We present a practical and efficient method for clinical concept extraction that does not require costly labeled data nor ML expertise. The method includes three steps: Step 1- the user injects a large in-domain text corpus (e.g., PubMed). Then, the system builds a contextual model containing vector representations of concepts in the corpus, in an unsupervised manner (e.g., Phrase2Vec). Step 2- the user provides a seed set of terms representing a specific medical concept (e.g., for the concept of the symptoms, the user may provide: ‘dry mouth,’ ‘itchy skin,’ and ‘blurred vision’). Then, the system matches the seed set against the contextual model and extracts the most semantically similar terms (e.g., additional symptoms). The result is a complete set of terms related to the medical concept. Step 3 –in production, there is a need to extract medical concepts from the unseen medical text. The system extracts key-phrases from the new text, then matches them against the complete set of terms from step 2, and the most semantically similar will be annotated with the same medical concept category. As an example, the seed symptom concepts would result in the following annotation: “The patient complaints on fatigue [symptom], dry skin [symptom], and Weight loss [symptom], which can be an early sign for Diabetes.” Our evaluations show promising results for extracting concepts from medical corpora. The method allows medical analysts to easily and efficiently build taxonomies (in step 2) representing their domain-specific concepts, and automatically annotate a large number of texts (in step 3) for classification/summarization of medical reports.

Keywords: clinical concepts, concept expansion, medical records annotation, medical records summarization

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Authors: Lancer Scott

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Purpose: High quality clinical disaster medicine requires providers working collaboratively to care for multiple patients in chaotic environments; however, many providers lack adequate training. To address this deficit, we created a competency-based, 5-hour Emergency Preparedness Training (EPT) curriculum using didactics, small-group discussion, and kinetic learning. The goal was to evaluate the effect of a short course on improving provider knowledge, confidence and skills in disaster scenarios. Methods: Diverse groups of medical university students, health care professionals, and community members were enrolled between 2011 and 2014. The course consisted of didactic lectures, small group exercises, and two live, multi-patient mass casualty incident (MCI) scenarios. The outcome measures were based on core competencies and performance objectives developed by a curriculum task force and assessed via trained facilitator observation, pre- and post-testing, and a course evaluation. Results: 708 participants completed were trained between November 2011 and August 2014, including 49.9% physicians, 31.9% medical students, 7.2% nurses, and 11% various other healthcare professions. 100% of participants completed the pre-test and 71.9% completed the post-test, with average correct answers increasing from 39% to 60%. Following didactics, trainees met 73% and 96% of performance objectives for the two small group exercises and 68.5% and 61.1% of performance objectives for the two MCI scenarios. Average trainee self-assessment of both overall knowledge and skill with clinical disasters improved from 33/100 to 74/100 (overall knowledge) and 33/100 to 77/100 (overall skill). The course assessment was completed by 34.3% participants, of whom 91.5% highly recommended the course. Conclusion: A relatively short, intensive EPT course can improve the ability of a diverse group of disaster care providers to respond effectively to mass casualty scenarios.

Keywords: clinical disaster medicine, training, hospital preparedness, surge capacity, education, curriculum, research, performance, training, student, physicians, nurses, health care providers, health care

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Authors: Mequanent Wale Mekonen, Edoardo Otranto, Angela Alibrandi

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Diabetic kidney disease is one of the main microvascular complications caused by diabetes. Several clinical and biochemical variables are reported to be associated with diabetic kidney disease in people with type 2 diabetes. However, their interrelations could distort the effect estimation of these variables for the disease's progression. The objective of the study is to determine how the biochemical and clinical variables in people with type 2 diabetes are interrelated with each other and their effects on kidney disease progression through advanced statistical methods. First, principal component analysis was used to explore how the biochemical and clinical variables intercorrelate with each other, which helped us reduce a set of correlated biochemical variables to a smaller number of uncorrelated variables. Then, ordered logit regression models (cumulative, stage, and adjacent) were employed to assess the effect of biochemical and clinical variables on the order-level response variable (progression of kidney function) by considering the proportionality assumption for more robust effect estimation. This retrospective cross-sectional study retrieved data from a type 2 diabetic cohort in a polyclinic hospital at the University of Messina, Italy. The principal component analysis yielded three uncorrelated components. These are principal component 1, with negative loading of glycosylated haemoglobin, glycemia, and creatinine; principal component 2, with negative loading of total cholesterol and low-density lipoprotein; and principal component 3, with negative loading of high-density lipoprotein and a positive load of triglycerides. The ordered logit models (cumulative, stage, and adjacent) showed that the first component (glycosylated haemoglobin, glycemia, and creatinine) had a significant effect on the progression of kidney disease. For instance, the cumulative odds model indicated that the first principal component (linear combination of glycosylated haemoglobin, glycemia, and creatinine) had a strong and significant effect on the progression of kidney disease, with an effect or odds ratio of 0.423 (P value = 0.000). However, this effect was inconsistent across levels of kidney disease because the first principal component did not meet the proportionality assumption. To address the proportionality problem and provide robust effect estimates, alternative ordered logit models, such as the partial cumulative odds model, the partial adjacent category model, and the partial continuation ratio model, were used. These models suggested that clinical variables such as age, sex, body mass index, medication (metformin), and biochemical variables such as glycosylated haemoglobin, glycemia, and creatinine have a significant effect on the progression of kidney disease.

Keywords: diabetic kidney disease, ordered logit model, principal component analysis, type 2 diabetes

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Authors: Shalinawati Ramli, Khairani Omar, Nurul Azmawati Mohamed, Zarini Ismail, Nur Syahrina Rahim, Nurul Hayati Chamhuri

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Medical doctors’ work to prevent, diagnose, treat diseases, disorders, and injuries as well as prescribing medication. Many people are attracted to this profession because it gives them the opportunity to help others. Doctors’ improve quality of life by providing advice, healing physical ailments and performing complex surgeries. Medicine is a profession in which dedication to the wellbeing of others is of paramount importance. Balancing the requirements of work and personal life can be a struggle as the demand of work as a doctors’ is great. Perception and expectation of medical students regarding the lifestyle of doctors’ is important to ensure that they had made the right career choice. Thus, the aim of this study is to assess the perception of pre-clinical students regarding doctors’ lifestyle. This study is a cross-sectional study involving all third-year pre-clinical medical students at University Sains Islam Malaysia. A total of 81 students participated in this study. Participants were given a set of questionnaire consisting of demographic data, open-ended questions on their perception on doctors’ lifestyle of working environment, salary expectation and family life. Thematic analysis were used to analyse the data. The participants comprised 69% female and their age range was between 20-21 years old. Majority of them were from middle-income families. Majority of the students perceived that the doctors’ lifestyle would be busy (72%). Approximately 30% of them expected that the time schedule will be unpredictable, 21% mentioned that sacrifice is required and 16% perceived it as a tiring job. Other themes emerged were ‘requiring high commitment’ (6%), challenging (7%) and risky (4%). With regards to salary expectation, 48% expected reasonable salary, 33% high salary and 12% described it as 'not worth compared to the workload'. Majority of them perceived that their family life will be restricted (62%) and time management is important (33%). Only 15% mentioned that family members have to sacrifice and spousal understanding is important (7%). About 10% of them perceived that their family will not be affected by their profession. Majority of the medical students perceived a busy doctors’ lifestyle, reasonable salary and restricted family life. However, there was a significant proportion of them who required counselling for better preparation of their future lifestyle.

Keywords: doctors lifestyle, pre-clinical students, perception, understanding

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Authors: Kumar Gular, Viswanathan S., Mastour Saeed Alshahrani, Ravi Shankar Reddy, Jaya Shanker Tedla, Snehil Dixit, Ajay Prasad Gautam, Venkata Nagaraj Kakaraparthi, Devika Rani Sangadala

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Background: Despite trunk control’s significant contribution to improving various functional activity components, the independent effect of trunk performance on quality of life is yet to be estimated in stroke survivors. Ascertaining the correlation between trunk control and self-reported quality of life while evaluating the effect of demographic and clinical characteristics on their relationship will guide concerned healthcare professionals in designing ideal rehabilitation protocols during the late sub-acute stroke stage of recovery. The aims of the present research were to (1) investigate the associations of trunk performance with self-rated quality of life and (2) evaluate if age, body mass index (BMI), and clinical characteristics mediate the relationship between trunk motor performance and perceived quality of life in the sub-acute stroke population. Methods: Trunk motor functions and quality of life among the late sub-acute stroke population aged 57.53 ± 6.42 years were evaluated through the trunk Impairment Scale (TIS) and Stroke specific quality of life (SSQOL) questionnaire, respectively. Pearson correlation coefficients and mediation analysis were performed to elucidate the relationship of trunk motor function with quality of life and determine the mediation impact of demographic and clinical characteristics on their association, respectively. Results: The current study observed significant correlations between trunk motor functions (TIS) and quality of life (SSQOL) with r=0.68 (p<0.001). Age, BMI, and type of stroke were detected as potential mediating factors in the association between trunk performance and quality of life. Conclusion: Validated associations between trunk motor functions and perceived quality of life among the late sub-acute stroke population emphasize the importance of comprehensive evaluation of trunk control. Rehabilitation specialists should focus on appropriate strategies to enhance trunk performance anticipating the potential effects of age, BMI, and type of stroke to improve health-related quality of life in stroke survivors.

Keywords: sub-acute stroke, quality of life, functional independence, trunk control

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Authors: Adila Shaukat, Hussam Al Soub, Muna Al Maslamani, Abdullatif Al Khal

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Background: The aim of this study was to assess clinical presentation and antimicrobial susceptibility of Streptococcus (S.) anginosus group infections in Hamad General Hospital, a tertiary care hospital in the state of Qatar, which is a multinational community. The S. anginosus group is a subgroup of viridans streptococci that consist of 3 different species: S. anginosus, S. constellatus, and S. intermedius. Although a part of the human bacteria flora, they have potential to cause suppurative infections. Method: We studied a total of 101 patients with S. anginosus group infections from January 2006 until March 2012 by reviewing medical records and identification of organisms by VITEK 2 and MALDI-TOF. Results: The most common sites of infection were skin and soft tissue, intra-abdominal, and bacteremia (28.7%, 24.8%, and 22.7%, respectively). Abscess formation was seen in approximately 30% of patients. Streptococcus constellatus was the most common isolated species (40%) followed by S. anginosus(30%) and S. intermedius(7%). In 23% of specimens, the species was unidentified. The most common type of specimen for organism isolation was blood followed by pus and tissue (50%, 22%, and 8%, respectively). Streptococcus constellatus was more frequently associated with abdominal and skin and soft tissue infections than the other 2 species, whereas S. anginosus was isolated more frequently from blood. All isolates were susceptible to penicillin, ceftriaxone, and vancomycin. Susceptibility to erythromycin and clindamycin was also good, reaching 91% and 95%, respectively. Forty percent of patients needed surgical drainage along with antibiotic therapy. Conclusions: Identification of S. anginosus group to species level is helpful in clinical practice because different species exhibit different pathogenic potentials.

Keywords: abscess, bacterial infection, bacteremia, Streptococcus anginosus

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Authors: Madhavi-Priya Singh, Liam Lowe, Farouk Arnaout, Ludmilla Pillay, Giordan Perez, Luke Mischker, Steve Costa

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An Emergency Department consultant identified the failure of medical students to complete the task of clerking a patient in its entirety. As six medical students on our first clinical placement, we recognised our own failure and endeavoured to examine why this failure was consistent among all medical students that had been given this task, despite our best motivations as adult learner. Our aim is to understand and investigate the elements which impeded our ability to learn and perform as medical students in the clinical environment, with reference to the prescribed task. We also aim to generate a discussion around the delivery of medical education with potential solutions to these barriers. Six medical students gathered together to have a comprehensive reflective discussion to identify possible factors leading to the failure of the task. First, we thoroughly analysed the delivery of the instructions with reference to the literature to identify potential flaws. We then examined personal, social, ethical, and cultural factors which may have impacted our ability to complete the task in its entirety. Through collation of our shared experiences, with support from discussion in the field of medical education and ethics, we identified two major areas that impacted our ability to complete the set task. First, we experienced an ethical conflict where we believed the inconvenience and potential harm inflicted on patients did not justify the positive impact the patient interaction would have on our medical learning. Second, we identified a lack of confidence stemming from multiple factors, including the conflict between preclinical and clinical learning, perceptions of perfectionism in the culture of medicine, and the influence of upward social comparison. After discussions, we found that the various factors we identified exacerbated the fears and doubts we already had about our own abilities and that of the medical education system. This doubt led us to avoid completing certain aspects of the tasks that were prescribed and further reinforced our vulnerability and perceived incompetence. Exploration of philosophical theories identified the importance of the role of doubt in education. We propose the need for further discussion around incorporating both pedagogic and andragogic teaching styles in clinical medical education and the acceptance of doubt as a driver of our learning. Doubt will continue to permeate our thoughts and actions no matter what. The moral or psychological distress that arises from this is the key motivating factor for our avoidance of tasks. If we accept this doubt and education embraces this doubt, it will no longer linger in the shadows as a negative and restrictive emotion but fuel a brighter dialogue and positive learning experience, ultimately assisting us in achieving our full potential.

Keywords: medical education, clinical education, andragogy, pedagogy

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Authors: Eashwar V. Somasundaram, Raoul R. Wadhwa, Jacob G. Scott

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The use of radiomics in measuring geometric properties of tumor images such as size, surface area, and volume has been invaluable in assessing cancer diagnosis, treatment, and prognosis. In addition to analyzing geometric properties, radiomics would benefit from measuring topological properties using persistent homology. Intuitively, features uncovered by persistent homology may correlate to tumor structural features. One example is necrotic cavities (corresponding to 2D topological features), which are markers of very aggressive tumors. We develop a data pipeline in R that clusters tumors images based on persistent homology is used to identify meaningful clinical distinctions between tumors and possibly new relationships not captured by established clinical categorizations. A preliminary analysis was performed on 16 Magnetic Resonance Imaging (MRI) breast tissue segments downloaded from the 'Investigation of Serial Studies to Predict Your Therapeutic Response with Imaging and Molecular Analysis' (I-SPY TRIAL or ISPY1) collection in The Cancer Imaging Archive. Each segment represents a patient’s breast tumor prior to treatment. The ISPY1 dataset also provided the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) status data. A persistent homology matrix up to 2-dimensional features was calculated for each of the MRI segmentation. Wasserstein distances were then calculated between all pairwise tumor image persistent homology matrices to create a distance matrix for each feature dimension. Since Wasserstein distances were calculated for 0, 1, and 2-dimensional features, three hierarchal clusters were constructed. The adjusted Rand Index was used to see how well the clusters corresponded to the ER/PR/HER2 status of the tumors. Triple-negative cancers (negative status for all three receptors) significantly clustered together in the 2-dimensional features dendrogram (Adjusted Rand Index of .35, p = .031). It is known that having a triple-negative breast tumor is associated with aggressive tumor growth and poor prognosis when compared to non-triple negative breast tumors. The aggressive tumor growth associated with triple-negative tumors may have a unique structure in an MRI segmentation, which persistent homology is able to identify. This preliminary analysis shows promising results in the use of persistent homology on tumor imaging to assess the severity of breast tumors. The next step is to apply this pipeline to other tumor segment images from The Cancer Imaging Archive at different sites such as the lung, kidney, and brain. In addition, whether other clinical parameters, such as overall survival, tumor stage, and tumor genotype data are captured well in persistent homology clusters will be assessed. If analyzing tumor MRI segments using persistent homology consistently identifies clinical relationships, this could enable clinicians to use persistent homology data as a noninvasive way to inform clinical decision making in oncology.

Keywords: cancer biology, oncology, persistent homology, radiomics, topological data analysis, tumor imaging

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Authors: Omneya M. Helmy, Mona T. Kashef

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Aminoglycosides are used in treating a wide range of infections caused by both Gram-negative and Gram positive bacteria. The presence of 16S rRNA methyl transferases (16S-RMTase) is among the newly discovered resistance mechanisms that confer high resistance to clinically useful aminoglycosides. Cephalosporins are the most commonly used antimicrobials in Egypt; therefore, this study was conducted to determine the isolation frequency of 16S rRNA methyl transferases among third generation cephalosporin-resistant clinical isolates in Egypt. One hundred and twenty three cephalosporin resistant Gram-negative clinical isolates were screened for aminoglycoside resistance by the Kirby Bauer disk diffusion method and tested for possible production of 16S-RMTase. PCR testing and sequencing were used to confirm the presence of 16S-RMTase and the associated antimicrobial resistance determinants, as well as the genetic region surrounding the armA gene. Out of 123 isolates, 66 (53.66%) were resistant to at least one aminoglycoside antibiotic. Only one Escherichia coli isolate (E9ECMO) which was totally resistant to all tested aminoglycosides, was confirmed to have the armA gene in association with blaTEM-1, blaCTX-M-15, blaCTX-M-14 and aac(6)-Ib genes. The armA gene was found to be carried on a large A/C plasmid. Genetic mapping of the armA surrounding region revealed, for the first time, the association of armA with aac(6)-Ib on the same transposon. In Conclusion, the isolation frequency of 16S-RMTase was low among the tested cephalosporin-resistant clinical samples. However, a novel composite transposon has been detected conferring high-level aminoglycosides resistance.

Keywords: aminoglcosides, armA gene, β lactmases, 16S rRNA methyl transferases

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Authors: Mona T. Kashef, Omneya M. Helmy

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Multidrug resistant (MDR) bacteria have become a significant public health threat. The prevalence rates, of Gram negative MDR bacteria, are in continuous increase. However, few data are available about these resistant strains. Since, third generation cephalosporins are one of the most commonly used antimicrobials, we set out to investigate the prevalence, different mechanisms and clonal relatedness of multidrug resistance among third generation resistant Gram negative clinical isolates. A total of 114 Gram negative clinical isolates, previously characterized as being resistant to at least one of 3rd generation cephalosporins, were included in this study. Each isolate was tested, using Kirby Bauer disk diffusion method, against its assigned categories of antimicrobials. The role of efflux pump in resistance development was tested by the efflux pump inhibitor-based microplate assay using chloropromazine as an inhibitor. Detecting different aminoglycosides, β-lactams and quinolones resistance genes was done using polymerase chain reaction. The genetic diversity of MDR isolates was investigated using Random Amplification of Polymorphic DNA technique. MDR phenotype was detected in 101 isolates (89%). Efflux pump mediated resistance was detected in 49/101 isolates. Aminoglycosides resistance genes; armA and aac(6)-Ib were detected in one and 53 isolates, respectively. The aac(6)-Ib-cr allele, that also confers resistance to floroquinolones, was detected in 28/53 isolates. β-lactam resistance genes; blaTEM, blaSHV, blaCTX-M group 1 and group 9 were detected in 52, 29, 61 and 35 isolates, respectively. Quinolone resistance genes; qnrA, qnrB and qnrS were detectable in 2, 14, 8 isolates respectively, while qepA was not detectable at all. High diversity was observed among tested MDR isolates. MDR is common among 3rd generation cephalosporins resistant Gram negative bacteria, in Egypt. In most cases, resistance was caused by different mechanisms. Therefore, new treatment strategies should be implemented.

Keywords: gram negative, multidrug resistance, RAPD typing, resistance genes

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Authors: I. Ling Tsai, Shu Fen Wu, Chen-Fuh Lam, Chia Yu Chen, Shu Jiuan Chen, Yen Lin Liu

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Purpose: Following the conduction of the National Health Insurance (NHI) system in Taiwan since 1995, the demand for anesthesia services continues to increase in the operating rooms and other medical units. It has been well recognized that increased work stress not only affects the clinical performance of the medical staff, long-term work load may also result in occupational burnout. Our study aimed to determine the influence of working environment, work stress and job satisfaction on the occupational burnout in nurse anesthetists. The ultimate goal of this research project is to develop a strategy in establishing a friendly, less stressful workplace for the nurse anesthetists to enhance their job satisfaction, thereby reducing occupational burnout and increasing the career life for nurse anesthetists. Methods: This was a cross-sectional, descriptive study performed in a metropolitan teaching hospital in southern Taiwan between May 2017 to July 2017. A structured self-administered questionnaire, modified from the Practice Environment Scale of the Nursing Work Index (PES-NWI), Occupational Stress Indicator 2 (OSI-2) and Maslach Burnout Inventory (MBI) manual was collected from the nurse anesthetists. The relationships between two numeric datasets were analyzed by the Pearson correlation test (SPSS 20.0). Results: A total of 66 completed questionnaires were collected from 75 nurses (response rate 88%). The average scores for the working environment, job satisfaction, and work stress were 69.6%, 61.5%, and 63.9%, respectively. The three perspectives used to assess the occupational burnout, namely emotional exhaustion, depersonalization and sense of personal accomplishment were 26.3, 13.0 and 24.5, suggesting the presence of moderate to high degrees of burnout in our nurse anesthetists. The presence of occupational burnout was closely correlated with the unsatisfactory working environment (r=-0.385, P=0.001) and reduced job satisfaction (r=-0.430, P=0.000). Junior nurse anesthetists (<1-year clinical experience) reported having higher satisfaction in working environment than the seniors (5 to 10-year clinical experience) (P=0.02). Although the average scores for work stress, job satisfaction, and occupational burnout were lower in junior nurses, the differences were not statistically different. The linear regression model, the working environment was the independent factor that predicted occupational burnout in nurse anesthetists up to 19.8%. Conclusions: High occupational burnout is more likely to develop in senior nurse anesthetists who experienced the dissatisfied working environment, work stress and lower job satisfaction. In addition to the regulation of clinical duties, the increased workload in the supervision of the junior nurse anesthetists may result in emotional stress and burnout in senior nurse anesthetists. Therefore, appropriate adjustment of clinical and teaching loading in the senior nurse anesthetists could be helpful to improve the occupational burnout and enhance the retention rate.

Keywords: nurse anesthetists, working environment, work stress, job satisfaction, occupational burnout

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Authors: Avantika Verma

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In industrialized nations, corneal lacerations are one of the most common reason for hospitalization. This study was designed to study visual and clinical outcome in patients presenting with full thickness corneal lacerations in Indian population and to ascertain the impact of various preoperative and operative factors influencing prognosis after repair of corneal lacerations. Males in third decade with injuries at work with metallic objects were common. Lens damage, hyphema, vitreous hemorrhage, retinal detachment and endophthalmitis were seen. All the patients underwent primary repair within first 24 hours of presentation. At 3 months, 74.3% had a good visual outcome. About 5.7% of patients had no perception of light.In conclusion, various demographic and preoperative factors like age, time of presentation, vision at presentation, length of corneal wound, involvement of visual axis, associated ocular features like hyphaema, lenticular changes, vitreous haemorrhage and retinal detachment are significant prognostic indicators for final visual outcome.

Keywords: corneal laceration, corneal wound repair, injury, visual outcome

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Authors: Claude Takenga, Rolf-Dietrich Berndt, Erling Si, Markus Diem, Guohui Qiao, Melanie Gau, Michael Brandstoetter, Martin Kampel, Michael Dworzak

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In patients with acute lymphoblastic leukaemia (ALL), treatment response is increasingly evaluated with minimal residual disease (MRD) analyses. Flow Cytometry (FCM) is a fast and sensitive method to detect MRD. However, the interpretation of these multi-parametric data requires intensive operator training and experience. This paper presents a pipeline-software, as a ready-to-use FCM-based MRD-assessment tool for the daily clinical practice for patients with ALL. The new tool increases accuracy in assessment of FCM-MRD in samples which are difficult to analyse by conventional operator-based gating since computer-aided analysis potentially has a superior resolution due to utilization of the whole multi-parametric FCM-data space at once instead of step-wise, two-dimensional plot-based visualization. The system developed as a telemedical network reduces the work-load and lab-costs, staff-time needed for training, continuous quality control, operator-based data interpretation. It allows dissemination of automated FCM-MRD analysis to medical centres which have no established expertise for the benefit of an even larger community of diseased children worldwide. We established a telemedical network system for analysis and clinical follow-up and treatment monitoring of Leukaemia. The system is scalable and adapted to link several centres and laboratories worldwide.

Keywords: data security, flow cytometry, leukaemia, telematics platform, telemedicine

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Authors: Francisco Dos Santos, Diogo Fonseca-Pereira, Sílvia Arroz-Madeira, Henrique Veiga-Fernandes

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Haematopoiesis is a developmental process that generates all blood cell lineages in health and disease. This relies on quiescent haematopoietic stem cells (HSCs) that are able to differentiate, self renew and expand upon physiological demand. HSCs have great interest in regenerative medicine, including haematological malignancies, immunodeficiencies and metabolic disorders. However, the limited yield from existing HSC sources drives the global need for reliable techniques to expand harvested HSCs at high quality and sufficient quantities. With the extensive use of cord blood progenitors for clinical applications, there is a demand for a safe and efficient expansion protocol that is able to overcome the limitations of the cord blood as a source of HSC. StemCell2MAXTM developed a technology that enhances the survival, proliferation and transplantation efficiency of HSC, leading the way to a more widespread use of HSC for research and clinical purposes. StemCell2MAXTM MIX is a solution that improves HSC expansion up to 20x, while preserving stemness, when compared to state-of-the-art. In a recent study by a leading cord blood bank, StemCell2MAX MIX was shown to support a selective 100-fold expansion of CD34+ Hematopoietic Stem and Progenitor Cells (when compared to a 10-fold expansion of Total Nucleated Cells), while maintaining their multipotent differentiative potential as assessed by CFU assays. The technology developed by StemCell2MAXTM opens new horizons for the usage of expanded hematopoietic progenitors for both research purposes (including quality and functional assays in Cord Blood Banks) and clinical applications.

Keywords: cord blood, expansion, hematopoietic stem cell, transplantation

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Authors: Armin Khaghani Boroujeni, Leila Dehghani, Parham Talebi Boroujeni, Sahar Rostamian, Ali Asilian

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Background: Hair loss is a common complaint observed in both genders. Androgenetic alopecia is known pattern for hair loss. To assess new regenerative strategies (PRP, A-SC-BT, conditioned media, exosome-based treatments) compared to conventional therapies for hair loss or hair regeneration, an updated review was undertaken. To address this issue, we carried out this systematic review to comprehensively evaluate the efficacy of cell-based therapies on hair loss. Methods: The available online databases, including ISI Web of Science, Scopus, and PubMed, were searched systematically up to February 2022. The quality assessment of included studies was done using the Cochrane Collaboration's tool. Results: As a result, a total of 90 studies involving 2345 participants were included in the present study. The enrolled studies were conducted between 2010 and 2022. The subjects’ mean age ranged from 19 to 55.11 years old. Approaches using platelet rich plasma (PRP) provide a beneficial impact on hair regrowth. However, other cell-based therapies, including stem cell transplant, stem cell-derived conditioned medium, and stem cell-derived exosomes, revealed conflicting evidence. Conclusion: However, cell-based therapies for hair loss are still in their infancy, and more robust clinical studies are needed to better evaluate their mechanisms of action, efficacy, safety, benefits, and limitations. In this review, we provide the resources to the latest clinical studies and a more detailed description of the latest clinical studies concerning cell-based therapies in hair loss.

Keywords: cell-based therapy, exosome, hair restoration, systematic review

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Authors: Amber Elyse Corrigan, Alexander Smith, Anna Pennington, Ben Carter, Jonathan Hewitt

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Background and Purpose: Morbidity secondary to stroke is highly heterogeneous, but it is important to both patients and clinicians in post-stroke management and adjustment to life after stroke. The consideration of post-stroke morbidity clinically and from the patient perspective has been poorly measured. The patient-reported outcome measures (PROs) in morbidity assessment help improve this knowledge gap. The primary aim of this study was to consider the association between PRO outcomes and stroke predictors. Methods: A multicenter prospective cohort study assessed 549 stroke patients at 19 hospital sites across England and Wales during 2019. Following a stroke event, demographic, clinical, and PRO measures were collected. Prevalence of morbidity within PRO measures was calculated with associated 95% confidence intervals. Predictors of domain outcome were calculated using a multilevel generalized linear model. Associated P -values and 95% confidence intervals are reported. Results: Data were collected from 549 participants, 317 men (57.7%) and 232 women (42.3%) with ages ranging from 25 to 97 (mean 72.7). PRO morbidity was high post-stroke; 93.2% of the cohort report post-stroke PRO morbidity. Previous stroke, diabetes, and gender are associated with worse patient-reported outcomes across both the physical and cognitive domains. Conclusions: This large-scale multicenter cohort study illustrates the high proportion of morbidity in PRO measures. Further, we demonstrate key predictors of adverse outcomes (Diabetes, previous stroke, and gender) congruence with clinical predictors. The PRO has been demonstrated to be an informative and useful stroke when considering patient-reported outcomes and has wider implications for considerations of PROs in clinical management. Future longitudinal follow-up with PROs is needed to consider association of long-term morbidity.

Keywords: morbidity, patient-reported outcome, PRO, stroke

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Authors: Terentes Printzios Dimitrios, Loanna Gourgouli, Vlachopoulos Charalambos

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Aims: Atrial fibrillation (AF) remains one of the major causes of stroke, heart failure, sudden death and cardiovascular morbidity. Ablation techniques are becoming more appealing after the latest results of randomized trials showing the overall clinical benefit. On the other hand, imaging techniques and the frontier application of 3D printing are emerging as a valuable ally for cardiac procedures. However, no randomized trial has directly assessed the impact of preprocedural imaging and especially 3D printing guidance for AF ablation. The present study is designed to investigate for the first time the effect of 3D printing of the heart on the safety and effectiveness of the ablation procedure. Methods and design: The 3D-GALA trial is a randomized, open-label, controlled, multicentre clinical trial of 2 parallel groups designed to enroll a total of 100 patients undergoing ablation using cryo-balloon for paroxysmal and persistent AF. Patients will be randomized with a patient allocation ratio of 1: 1 to preprocedural MRI scan of the heart and 3D printing of left atrium and pulmonary veins and cryoablation versus standard cryoablation without imaging. Patients will be followed up to 6 months after the index procedure. The primary outcome measure is the reduction of radiation dose and contrast amount during pulmonary veins isolation. Secondary endpoints will include the percentage of atrial fibrillation relapse at 24h-Holter electrocardiogram monitoring at 6 months after initial treatment. Discussion: To our knowledge, the 3D-GALA trial will be the first study to provide evidence about the clinical impact of preprocedural imaging and 3D printing before cryoablation.

Keywords: atrial fibrillation, cardiac MRI, cryoablation, 3-d printing

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Authors: Hend Almaseb

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​The motivational model proposed by Self-Determination Theory provided an explanation for clients’ motivation for therapy. Among a sample of 78 inpatient residents in the Addiction Treatment Center, this study examined the relationship between three types of motivation (Autonomous, Controlled, and Amotivation) and each of the following variables: Age, Marital Status, Educational Level of Participant, and Number of Years of Addiction. In addition, the study investigated whether or not the participants are motivated to receive therapy. The results showed 1) a significant relationship between Controlled Motivation and the following variables: Age, Marital Status, and Number of Years of Addiction; 2) a significant relationship between Autonomous Motivation and Number of Years of Addiction; and a significant relationship between Educational Level and Amotivation. The results also illustrated that the participants of this study were not motivated to seek therapy.

Keywords: addiction, clinical social work, motivation, self-determination

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Authors: Junaid Mahmood Alam, Sana Anwar, Sarah Sughra Asghar

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Chronic hepatitis or Hepatitis C viral (HCV) infection has been identified as one of the factors that could elicit autoimmune disease resulting in the development of auto-antibodies. Furthermore, HCV is implicated in contravening of forbearance to antigens, therefore, inciting auto-reactivity. In this regard, several near and past studies noted the prevalence of thyroid dysfunction and production of anti-thyroid antibodies (ATAb) such as anti-thyroid peroxidase (AntiTPO) and anti-thyroglobulin (AntiTG) in patients with HCV. Likewise, one of the etiologies of augmentation of thyroid disease is basically interferon therapy for HCV infections, for which a number of autoimmune diseases have been noted including Grave’s disease, Hishimoto thyroiditis. A prospectively case-control study was therefore carried out at department of clinical biochemistry lab services and chemical pathology in collaboration with department of clinical microbiology, at Liaquat National Hospital and Medical College, Karachi Pakistan for the period January 2015 to December 2017. Two control groups were inducted for comparison purpose, control group 1 = without HCV infection and with thyroid disorders (n = 20), control group 2 = with HCV infection and without thyroid disorders (n = 20), whereas HCV infected were n = 40 where more than half were noted to be positive for either of HCV IgG and Ag. In HCV group, patients with existing sub-clinical hypothyroidism and clinical hyperthyroidism were less than 5%. Analysis showed the presence of AntiTG in 12 HCV patients (30%), AntiTPO in 15 (37.5%) and both AntiTG and antiTPO in 10 patients (25%). Only 3 patients were found with the history of anti-thyroid auto-antibodies (7.5%) and one with parents and relatives with auto-immune disorders (2.5%). Patients that remained untreated were 12 (30%), under treatment 18 (45%) and with complete-course of treatment 10 (25%). As per review of the literature, meta-analysis of evident data and cross-sectional studies of selective cohorts (as studied in presented research), thyroid connection is designated as one of the most recurrent endocrine ailment associated with chronic HCV infection. Moreover, it also represents an extrahepatic disease in the continuum of HCV syndrome. In conclusion, HCV patients were more likely to encompass thyroid disorders especially related to development of either of ATAb or both antiTG and AntiTPO.

Keywords: Hepatitis C viral (HCV) infection, anti-thyroid antibodies, anti-thyroid peroxidase antibodies, anti-thyroglobulin antibodies

Procedia PDF Downloads 157

Authors: Jiajia Peng, Danni Cheng, Jianqing Qiu, Yufang Rao, Minzi Mao, Ke Qiu, Junhong Li, Fei Chen, Feng Liu, Jun Liu, Xiaosong Mu, Wenxin Yu, Wei Zhang, Wei Xu, Yu Zhao, Jianjun Ren

Abstract:

Background: Currently, primary B-cell non-Hodgkin lymphoma (B-NHL) and T/NK-cell non-Hodgkin lymphoma (NKT-NHL) originated from the nasal cavity (NC), nasopharynx (NP) and nasal sinus (NS) distinguished unclearly in the clinic. Objective: We sought to compare the clinical and survival differences of B-NHL and NKT-NHL that occurred in NC, NP, and NS, respectively. Methods: Retrospective data of patients diagnosed with nasal cavity lymphoma (NCL), nasopharyngeal lymphoma (NPL), and nasal sinus lymphoma (NSL) between 1975 and 2017 from the Surveillance, Epidemiology, and End Results (SEER) database were collected. We identified the B/NKT-NHL patients based on the histological type and performed univariate, multivariate, and Kaplan-Meier analyses to investigate the survival rates. Results: Of the identified 3,101 B-NHL and 738 NKT-NHL patients, those with B-NHL in NP were the majority (43%) and had better cancer-specific survival than those in NC and NS from 2010 to 2017 (5-year-CSS, NC vs. NP vs. NS: 81% vs. 83% vs. 82%). In contrast, most of the NKT-NHL originated from NC (68%) and had the highest CSS rate in the recent seven years (2010-2017, 5-year-CSS: 63%). Additionally, the survival outcomes of patients with NKT-NHL-NP (HR: 1.34, 95% CI: 0.62-2.89, P=0.460) who had received surgery were much worse than those of patients with NKT-NHL-NC (HR: 1.07, 95% CI: 0.75-1.52, P=0.710) and NKT-NHL-NS (HR: 1.11, 95% CI: 0.59-2.07, P=0.740). NKT-NHL-NS patients who had radiation performed (HR: 0.38, 95% CI: 0.19-0.73, P=0.004) showed the highest survival rates, while chemotherapy performed (HR: 1.01, 95% CI: 0.43-2.37, P=0.980) presented opposite results. Conclusions: Although B-NHL and NKT-NHL originating from NC, NP and NS had similar anatomical locations, their clinical characteristics, treatment therapies, and prognoses were different in this study. Our findings may suggest that B-NHL and NKT-NHL in NC, NP, and NS should be treated as different diseases in the clinic.

Keywords: nasopharyngeal lymphoma, nasal cavity lymphoma, nasal sinus lymphoma, B-cell non-Hodgkin lymphoma, T/NK-cell non-Hodgkin lymphoma

Procedia PDF Downloads 184

Authors: S. Shafiee Ardestani, A. Najafi, N. Valizadeh, E. Payani, H. Karimian

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Objectives: Treatment of mild traumatic brain injury in emergency ward patients with any type of traumatic intracranial hemorrhage is flexible. The aim of this study is to assess the clinical outcomes of mild traumatic brain injury patients who had acute traumatic intracranial hemorrhage on initial emergency ward neuroimaging. Materials-Methods: From March 2011 to November 2012 in a retrospective cohort study we enrolled emergency ward patients with mild traumatic brain injury with Glasgow Coma Scale (GCS) scores of 14 or 15 and who had stable vital signs. Patients who had any type of intracranial hemorrhage on first head CT and repeat head CT within 24 hours were included. Patients with initial GCS < 14, injury > 24 hours old, pregnancy, concomitant non-minor injuries, and coagulopathy were excluded. Primary endpoints were neurosurgical procedures and/or death and for discharged patients, return to the emergency ward during one week. Results: Among 755 patients who were referred to the emergency ward and underwent two head CTs during first 24 hours, 302 (40%) were included. The median interval between CT scans was 6 hours (ranging 4 to 8 hours). Consequently, 135 (45%) patients had subarachnoid hemorrhage, 124 (41%) patients had subdural hemorrhage, 15 (5%) patients had epidural hemorrhage, 28 (9%) patients had cerebral contusions, and 54 (18%) patients had intra-parenchymal hemorrhage. Six of 302 patients died within 15 days of injury. 200 patients (66%) have been discharged from the emergency ward, 25 (12%) of whom returned to the emergency ward after one week. Conclusion: Discharge of the head trauma patients after a repeat head CT and brief period of observation in the emergency ward lead to early discharge of mild traumatic brain injury patients with traumatic ICH without adverse events.

Keywords: clinical outcomes, emergency ward, mild traumatic intracranial hemorrhage, Glasgow Coma Scale (GCS)

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Authors: Benjamin J. Kuo, Silvia D. Vaca, Joao Ricardo Nickenig Vissoci, Catherine A. Staton, Linda Xu, Michael Muhumuza, Hussein Ssenyonjo, John Mukasa, Joel Kiryabwire, Lydia Nanjula, Christine Muhumuza, Henry E. Rice, Gerald A. Grant, Michael M. Haglund

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Background: Traumatic Brain Injury (TBI) is disproportionally concentrated in low- and middle-income countries (LMICs), with the odds of dying from TBI in Uganda more than 4 times higher than in high income countries (HICs). The disparities in the injury incidence and outcome between LMICs and resource-rich settings have led to increased health outcomes research for TBIs and their associated risk factors in LMICs. While there have been increasing TBI studies in LMICs over the last decade, there is still a need for more robust prospective registries. In Uganda, a trauma registry implemented in 2004 at the Mulago National Referral Hospital (MNRH) showed that RTI is the major contributor (60%) of overall mortality in the casualty department. While the prior registry provides information on injury incidence and burden, it’s limited in scope and doesn’t follow patients longitudinally throughout their hospital stay nor does it focus specifically on TBIs. And although these retrospective analyses are helpful for benchmarking TBI outcomes, they make it hard to identify specific quality improvement initiatives. The relationship among epidemiology, patient risk factors, clinical care, and TBI outcomes are still relatively unknown at MNRH. Objective: The objectives of this study are to describe the processes of care and determine risk factors predictive of poor outcomes for TBI patients presenting to a single tertiary hospital in Uganda. Methods: Prospective data were collected for 563 TBI patients presenting to a tertiary hospital in Kampala from 1 June – 30 November 2016. Research Electronic Data Capture (REDCap) was used to systematically collect variables spanning 8 categories. Univariate and multivariate analysis were conducted to determine significant predictors of mortality. Results: 563 TBI patients were enrolled from 1 June – 30 November 2016. 102 patients (18%) received surgery, 29 patients (5.1%) intended for surgery failed to receive it, and 251 patients (45%) received non-operative management. Overall mortality was 9.6%, which ranged from 4.7% for mild and moderate TBI to 55% for severe TBI patients with GCS 3-5. Within each TBI severity category, mortality differed by management pathway. Variables predictive of mortality were TBI severity, more than one intracranial bleed, failure to receive surgery, high dependency unit admission, ventilator support outside of surgery, and hospital arrival delayed by more than 4 hours. Conclusions: The overall mortality rate of 9.6% in Uganda for TBI is high, and likely underestimates the true TBI mortality. Furthermore, the wide-ranging mortality (3-82%), high ICU fatality, and negative impact of care delays suggest shortcomings with the current triaging practices. Lack of surgical intervention when needed was highly predictive of mortality in TBI patients. Further research into the determinants of surgical interventions, quality of step-up care, and prolonged care delays are needed to better understand the complex interplay of variables that affect patient outcome. These insights guide the development of future interventions and resource allocation to improve patient outcomes.

Keywords: care continuum, global neurosurgery, Kampala Uganda, LMIC, Mulago, prospective registry, traumatic brain injury

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Authors: Masoumeh Khailghi Sikaroudi, Mohsen Masoodi, Fazad Shidfar, Meghdad Sedaghat

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Background: The hypertonicity of internal anal sphincter resting pressure is one of the main reasons for chronic anal fissures. The aim of this study is to assess the effect of oral administration of L-arginine on anal fissure symptom improvement by relaxation of the internal anal sphincter. Method: Seventy-six chronic anal fissure patients (age: 18-65 years) took part in this randomized, double-blind, placebo-controlled trial study from February 2019 to October 2020 at Rasoul-e-Akram Hospital, Tehran, Iran. Participants were allocated into treatment (L-arginine) or placebo groups. They took a 1000 mg capsule three times a day for one month and were followed up at the end of the first and third months after receiving the intervention. Clinical symptoms, anal sphincter resting pressure, and quality of life (QoL) were completed at baseline and the end of the study. Result: The analysis of data was shown significant improvement in bleeding, fissure size, and pain within each group; however, this effect was more seen in the arginine group compared to the control group at the end of the study (P-values<0.001). Following that, a significant increase in QoL was seen just in patients who were treated with arginine (P-value=0.006). Also, the comparison of anal pressures to baseline and between groups at the end of the study showed a significant reduction in sphincter pressure in treated patients (P-value<0.001, =0.049; respectively). Conclusion: Oral administration of 3000 mg L-arginine can heal chronic anal fissures by reducing anal internal sphincter pressure with fewer side effects. However, a long-term study with more follow-up is recommended.

Keywords: L-arginine, anal fissure, sphincter pressure, clinical symptoms, quality of life

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Authors: K. Thiel, P. Patrikainen, C. Nagy, D. Fitzpatrick, E.-M. Aro, P. Kallio

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Photosynthetic cyanobacteria have been recognized as potential future biotechnological hosts for the direct conversion of CO₂ into chemicals of interest using sunlight as the solar energy source. However, in order to develop commercially viable systems, the flux of electrons from the photosynthetic light reactions towards specified target chemicals must be significantly improved. The objective of the study was to investigate whether the autotrophic production efficiency of specified end-metabolites can be improved in engineered cyanobacterial cells by rescuing excited electrons that are normally lost to molecular oxygen due to the cyanobacterial flavodiiron protein Flv1/3. Natively Flv1/3 dissipates excess electrons in the photosynthetic electron transfer chain by directing them to molecular oxygen in Mehler-like reaction to protect photosystem I. To evaluate the effect of flavodiiron inactivation on autotrophic production efficiency in the cyanobacterial host Synechocystis sp. PCC 6803 (Synechocystis), sucrose was selected as the quantitative reporter and a representative of a potential end-product of interest. The concept is based on the native property of Synechocystis to produce sucrose as an intracellular osmoprotectant when exposed to high external ion concentrations, in combination with the introduction of a heterologous sucrose permease (CscB from Escherichia coli), which transports the sucrose out from the cell. In addition, cell growth, photosynthetic gas fluxes using membrane inlet mass spectrometry and endogenous storage compounds were analysed to illustrate the consequent effects of flv deletion on pathway flux distributions. The results indicate that a significant proportion of the electrons can be lost to molecular oxygen via Flv1/3 even when the cells are grown under high CO₂ and that the inactivation of flavodiiron activity can enhance the photosynthetic electron flux towards optionally available sinks. The flux distribution is dependent on the light conditions and the genetic context of the Δflv mutants, and favors the production of either sucrose or one of the two storage compounds, glycogen or polyhydroxybutyrate. As a conclusion, elimination of the native Flv1/3 reaction and concomitant introduction of an engineered product pathway as an alternative sink for excited electrons could enhance the photosynthetic electron flux towards the target endproduct without compromising the fitness of the host.

Keywords: cyanobacterial engineering, flavodiiron proteins, redirecting electron flux, sucrose

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