Search results for: clinical experimentation

Authors: M. A. Sohaly, M. A. Elfouly

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Parkinson's disease (PD) is a heterogeneous movement disorder that often appears in the elderly. PD is induced by a loss of dopamine secretion. Some drugs increase the secretion of dopamine. In this paper, we will simply study the stability of PD models as a nonlinear delay differential equation. After a period of taking drugs, these act as positive feedback and increase the tremors of patients, and then, the differential equation has positive coefficients and the system is unstable under these conditions. We will present a set of suggested modifications to make the system more compatible with the biodynamic system. When giving a set of numerical examples, this research paper is concerned with the mathematical analysis, and no clinical data have been used.

Keywords: Parkinson's disease, stability, simulation, two delay differential equation

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Authors: Nayera E. Hassan, Sahar A. El-Masry, Rokia El-Banna, Mohamed S. El Hussieny

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There are several different modalities for treatment of obesity. Common intervention methods for obesity include low-calorie diet, exercise. Also acupuncture has shown good therapeutic results in the treatment of obesity. A recent clinical observation showed that laser acupuncture could reduce body weight and body mass index in obese persons. So, the aim of this research is focused on body composition changes as related to type of intervention, before and after intentional weight loss in overweight and obesity. 76 subjects were included in the study analysis. The present study recommended that every obese female must do lipid profile and fasting blood sugar analysis before weight-loss intervention to take the decision of which method should be used.

Keywords: obesity, weight-loss, body composition, modalities

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Authors: Denis Jordan, Daniel Golkowski, Mathias Lukas, Katharina Merz, Caroline Mlynarcik, Max Maurer, Valentin Riedl, Stefan Foerster, Eberhard F. Kochs, Andreas Bender, Ruediger Ilg

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Introduction: So far, clinical assessments that rely on behavioral responses to differentiate coma states or even predict outcome in coma patients are unreliable, e.g. because of some patients’ motor disabilities. The present study was aimed to provide prognosis in coma patients using markers from electroencephalogram (EEG), blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) and [18F]-fluorodeoxyglucose (FDG) positron emission tomography (PET). Unsuperwised principal component analysis (PCA) was used for multimodal integration of markers. Methods: Approved by the local ethics committee of the Technical University of Munich (Germany) 20 patients (aged 18-89) with severe brain damage were acquired through intensive care units at the Klinikum rechts der Isar in Munich and at the Therapiezentrum Burgau (Germany). At the day of EEG/fMRI/PET measurement (date I) patients (<3.5 month in coma) were grouped in the minimal conscious state (MCS) or vegetative state (VS) on the basis of their clinical presentation (coma recovery scale-revised, CRS-R). Follow-up assessment (date II) was also based on CRS-R in a period of 8 to 24 month after date I. At date I, 63 channel EEG (Brain Products, Gilching, Germany) was recorded outside the scanner, and subsequently simultaneous FDG-PET/fMRI was acquired on an integrated Siemens Biograph mMR 3T scanner (Siemens Healthineers, Erlangen Germany). Power spectral densities, permutation entropy (PE) and symbolic transfer entropy (STE) were calculated in/between frontal, temporal, parietal and occipital EEG channels. PE and STE are based on symbolic time series analysis and were already introduced as robust markers separating wakefulness from unconsciousness in EEG during general anesthesia. While PE quantifies the regularity structure of the neighboring order of signal values (a surrogate of cortical information processing), STE reflects information transfer between two signals (a surrogate of directed connectivity in cortical networks). fMRI was carried out using SPM12 (Wellcome Trust Center for Neuroimaging, University of London, UK). Functional images were realigned, segmented, normalized and smoothed. PET was acquired for 45 minutes in list-mode. For absolute quantification of brain’s glucose consumption rate in FDG-PET, kinetic modelling was performed with Patlak’s plot method. BOLD signal intensity in fMRI and glucose uptake in PET was calculated in 8 distinct cortical areas. PCA was performed over all markers from EEG/fMRI/PET. Prognosis (persistent VS and deceased patients vs. recovery to MCS/awake from date I to date II) was evaluated using the area under the curve (AUC) including bootstrap confidence intervals (CI, *: p<0.05). Results: Prognosis was reliably indicated by the first component of PCA (AUC=0.99*, CI=0.92-1.00) showing a higher AUC when compared to the best single markers (EEG: AUC<0.96*, fMRI: AUC<0.86*, PET: AUC<0.60). CRS-R did not show prediction (AUC=0.51, CI=0.29-0.78). Conclusion: In a multimodal analysis of EEG/fMRI/PET in coma patients, PCA lead to a reliable prognosis. The impact of this result is evident, as clinical estimates of prognosis are inapt at time and could be supported by quantitative biomarkers from EEG, fMRI and PET. Due to the small sample size, further investigations are required, in particular allowing superwised learning instead of the basic approach of unsuperwised PCA.

Keywords: coma states and prognosis, electroencephalogram, entropy, functional magnetic resonance imaging, machine learning, positron emission tomography, principal component analysis

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Authors: Nancy Wilson

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In utero, fetal drug exposure is prevalent amongst birthing facilities. Assessment tools for neonatal abstinence syndrome (NAS) are often cumbersome and ill-fitting, harboring immense subjectivity. This paradox often leads the clinical assessor to be hypervigilant when assessing the newborn for subtle symptoms of NAS, often mistaken for normal newborn behaviors. As a quality improvement initiative, this project led to a more adaptable NAS tool termed eat, sleep, console (ESC). This function-based NAS assessment scores the infant based on the ability to accomplish three basic newborn necessities- to sleep, to eat, and to be consoled. Literature supports that ESC methodology improves patient and family outcomes while providing more cost-effective care.

Keywords: neonatal abstinence syndrome, neonatal opioid withdrawal, maternal substance abuse, pregnancy, and addiction, Finnegan neonatal abstinence syndrome tool, eat, sleep, console

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Authors: Mary Rose Eunice S. Gundayao, Manolo M. Fernandez

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Metachromatic leukodystrophy (MLD) is a rare lysosomal storage disorder with an autosomal recessive inheritance pattern. Lysosomal storage disorders are often severe, follow a progressively neurodegenerative path, and may result in multi-organ failure, potentially leading to death within 5 to 6 years in cases of early-onset forms. There are limited data regarding cases of MLD in Filipino children. This is the case of a 2-year-old Filipino girl who presented with progressive neurological deterioration and was diagnosed with metachromatic leukodystrophy by molecular genetic testing. This case report aims to present this patient’s clinical history, neurological findings, diagnosis and novel genetic mutations causing MLD. A concise review of updated literature on MLD will be discussed.

Keywords: metachromatic leukodystrophy, ARSA gene, peripheral neuropathy, case report, demyelinating disease

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Authors: Rachel S. E. Lim, Winnie L. C. Tan

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Visual literacy is about making meaning through the interaction of images, words, and sounds. Graphic communication students typically develop visual literacy through critique and production of studio-based projects for their portfolios. However, the abrupt switch to online learning during the COVID-19 pandemic has made it necessary to consider new strategies of visualization and planning to scaffold teaching and learning. This study, therefore, investigated how MIRO, a cloud-based visual collaboration platform, could be used to develop the visual literacy confidence of 30 diploma in graphic communication students attending a graphic design course at a Singapore arts institution. Due to COVID-19, the course was taught fully online throughout a 16-week semester. Guided by Kolb’s Experiential Learning Cycle, the two lecturers developed students’ engagement with visual literacy concepts through different activities that facilitated concrete experiences, reflective observation, abstract conceptualization, and active experimentation. Throughout the semester, students create, collaborate, and centralize communication in MIRO with infinite canvas, smart frameworks, a robust set of widgets (i.e., sticky notes, freeform pen, shapes, arrows, smart drawing, emoticons, etc.), and powerful platform capabilities that enable asynchronous and synchronous feedback and interaction. Students then drew upon these multimodal experiences to brainstorm, research, and develop their motion design project. A survey was used to examine students’ perceptions of engagement (E), confidence (C), learning strategies (LS). Using multiple regression, it¬ was found that the use of MIRO helped students develop confidence (C) with visual literacy, which predicted performance score (PS) that was measured against their application of visual literacy to the creation of their motion design project. While students’ learning strategies (LS) with MIRO did not directly predict confidence (C) or performance score (PS), it fostered positive perceptions of engagement (E) which in turn predicted confidence (C). Content analysis of students’ open-ended survey responses about their learning strategies (LS) showed that MIRO provides organization and structure in documenting learning progress, in tandem with establishing standards and expectations as a preparatory ground for generating feedback. With the clarity and sequence of the mentioned conditions set in place, these prerequisites then lead to the next level of personal action for self-reflection, self-directed learning, and time management. The study results show that the affordances of MIRO can develop visual literacy and make up for the potential pitfalls of student isolation, communication, and engagement during online learning. The context of how MIRO could be used by lecturers to orientate students for learning in visual literacy and studio-based projects for future development are discussed.

Keywords: design education, graphic communication, online learning, visual literacy

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Authors: Rajish Shil, Amal Alduhoori, Vipin Thomachan, Jamal Teir, Radhakrishnan Renganathan

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Background: Antiphospholipid antibody syndrome (APS) has a broad spectrum of thrombotic and non-thrombotic clinical manifestations. We present a case of APS presenting with seizure, stroke, and atrial mass. Case Description: A 38-year-old male presented with headache of 10 days duration and tonic-clonic seizure. The neurological examination was normal. Magnetic resonance imaging of brain showed small acute right cerebellar infarct. Magnetic resonance angiography of brain and neck showed a focal narrowing in the origin of the internal carotid artery bilaterally. Electroencephalogram was normal. He was started on aspirin, atorvastatin, and carbamazepine. Transthoracic and trans-esophageal echocardiography showed a pedunculated and lobular atrial mass, measuring 1 X 1.5 cm, which was freely mobile across mitral valve opening across the left ventricular inflow. Autoimmune screening showed positive Antiphospholipid antibodies in high titer (Cardiolipin IgG > 120 units/ml, B2 glycoprotein IgG 90 units/mL). Anti-nuclear antibody was negative. Erythrocyte sedimentation rate and C-reactive protein levels were normal. Platelet count was low (111 x 109/L). The patient underwent successful surgical removal of the mass, which looked like a thrombotic clot, and Histopathological analysis confirmed it as a fibrinous clot, with no evidence of tumor cells. The patient was started on full anticoagulation treatment and was followed up regularly in the clinic, where our patient did not have any further complications from the disease. Discussion: Our patient was diagnosed to have APS based on the features of high positive anticardiolipin antibody IgG and B2 glycoprotein IgG levels, Stroke, thrombocytopenia, and abnormal echo findings. Thrombotic vegetation can mimic an atrial myxoma on echo. Conclusion: APS can present with neurological and cardiac manifestations, and therefore a high index of suspicion is necessary for a diagnosis of the disease as it can affect both short and long term treatment plans and prognosis. Therefore, in patients presenting with neurological symptoms like seizures, weakness and radiological diagnosis of stroke in a young patient, where atrial masses could be thought to be the cause of stroke, they should be screened for any concomitant findings of thrombocytopenia and/or activated partial thromboplastin time prolongation, which should raise the suspicion of vasculitis, specifically APS to be the primary cause of the clinical presentation.

Keywords: antiphospholipid syndrome, seizures, atrial mass, stroke

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Authors: O. B. Iskender, K. V. Ling, V. Dubanchet, L. Simonini

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This paper discusses the recent advances and future prospects of spacecraft position and attitude control using Model Predictive Control (MPC). First, the challenges of the space missions are summarized, in particular, taking into account the errors, uncertainties, and constraints imposed by the mission, spacecraft and, onboard processing capabilities. The summary of space mission errors and uncertainties provided in categories; initial condition errors, unmodeled disturbances, sensor, and actuator errors. These previous constraints are classified into two categories: physical and geometric constraints. Last, real-time implementation capability is discussed regarding the required computation time and the impact of sensor and actuator errors based on the Hardware-In-The-Loop (HIL) experiments. The rationales behind the scenarios’ are also presented in the scope of space applications as formation flying, attitude control, rendezvous and docking, rover steering, and precision landing. The objectives of these missions are explained, and the generic constrained MPC problem formulations are summarized. Three key design elements used in MPC design: the prediction model, the constraints formulation and the objective cost function are discussed. The prediction models can be linear time invariant or time varying depending on the geometry of the orbit, whether it is circular or elliptic. The constraints can be given as linear inequalities for input or output constraints, which can be written in the same form. Moreover, the recent convexification techniques for the non-convex geometrical constraints (i.e., plume impingement, Field-of-View (FOV)) are presented in detail. Next, different objectives are provided in a mathematical framework and explained accordingly. Thirdly, because MPC implementation relies on finding in real-time the solution to constrained optimization problems, computational aspects are also examined. In particular, high-speed implementation capabilities and HIL challenges are presented towards representative space avionics. This covers an analysis of future space processors as well as the requirements of sensors and actuators on the HIL experiments outputs. The HIL tests are investigated for kinematic and dynamic tests where robotic arms and floating robots are used respectively. Eventually, the proposed algorithms and experimental setups are introduced and compared with the authors' previous work and future plans. The paper concludes with a conjecture that MPC paradigm is a promising framework at the crossroads of space applications while could be further advanced based on the challenges mentioned throughout the paper and the unaddressed gap.

Keywords: convex optimization, model predictive control, rendezvous and docking, spacecraft autonomy

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Authors: Rajendra Kanojia

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Femoral components with inbuilt rotation require thicker flexion resection of the lateral femoral condyle and could potential risk to damage the popliteus tendon especially in the smaller Asian knees. We prospectively evaluated 10 patients with bilateral varus osteoarthritis knee to size the cuts and their location in relation to the popliteus tendon. Two different types of implant were used on either side, one side requires resection in 3° external rotation (group A) and other side femoral component with inbuilt external roation (group B). We had popliteus tendon injury in 3 knees all from group B. Risk of damaging the popliteus tendon was found higher in group B.

Keywords: popliteaus tendon injury, TKA, orthopaedic surgery, biomechanics and clinical applications

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Authors: Neha Bhattacharyya, Soumendra Singh, Amrita Banerjee, Ria Ghosh, Oindrila Sinha, Nairit Das, Rajkumar Gayen, Somya Subhra Pal, Sahely Ganguly, Tanmoy Dasgupta, Tanusree Dasgupta, Pulak Mondal, Aniruddha Adhikari, Sharmila Sarkar, Debasish Bhattacharyya, Asim Kumar Mallick, Om Prakash Singh, Samir Kumar Pal

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Background: We aim to develop an integrated device comprised of single-probe EEG and CCD-based motion sensors for a more objective measure of Attention-deficit Hyperactivity Disorder (ADHD). While the integrated device (MAHD) relies on the EEG signal (spectral density of beta wave) for the assessment of attention during a given structured task (painting three segments of a circle using three different colors, namely red, green and blue), the CCD sensor depicts movement pattern of the subjects engaged in a continuous performance task (CPT). A statistical analysis of the attention and movement patterns was performed, and the accuracy of the completed tasks was analysed using indigenously developed software. The device with the embedded software, called MAHD, is intended to improve certainty with criterion E (i.e. whether symptoms are better explained by another condition). Methods: We have used the EEG signal from a single-channel dry sensor placed on the frontal lobe of the head of the subjects (3-5 years old pre-schoolers). During the painting of three segments of a circle using three distinct colors (red, green, and blue), absolute power for delta and beta EEG waves from the subjects are found to be correlated with relaxation and attention/cognitive load conditions. While the relaxation condition of the subject hints at hyperactivity, a more direct CCD-based motion sensor is used to track the physical movement of the subject engaged in a continuous performance task (CPT) i.e., separation of the various colored balls from one table to another. We have used our indigenously developed software for the statistical analysis to derive a scale for the objective assessment of ADHD. We have also compared our scale with clinical ADHD evaluation. Results: In a limited clinical trial with preliminary statistical analysis, we have found a significant correlation between the objective assessment of the ADHD subjects with that of the clinician’s conventional evaluation. Conclusion: MAHD, the integrated device, is supposed to be an auxiliary tool to improve the accuracy of ADHD diagnosis by supporting greater criterion E certainty.

Keywords: ADHD, CPT, EEG signal, motion sensor, psychometric test

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Authors: J. Luché-Thayer, C. Perronne, C. Meseko

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We reviewed how certain institutional policies and practices, as well as questionable research, are creating obstacles to care and informed consent for Lyme and relapsing fever Borreliosis patients. The interference is denying access to treatments that meet the internationally accepted standards as set by the Institute of Medicine. This obstruction to care contributes to significant human suffering, disability and negative economic effect across many nations and in many regions of the world. We note how evidence based medicine emphasizes the importance of clinical experience and patient-centered care and how these patients benefit significantly when their rights to choose among treatment options are upheld.  

Keywords: conflicts of interest, obstacles to healthcare accessibility, patient-centered care, the right to informed consent

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Authors: Lucie Mrackova, Helena Kisvetrova

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Spirituality is an integral part of human life. In a secular environment, spiritual needs are often overlooked, especially in acute nursing care. Spiritual needs assessment for patients (SNAP), which also exists in the Czech version (SNAP-CZ), can be used for objective evaluation. The aim of this study was to measure the psychometric properties of SNAP-CZ and to find correlations between SNAP-CZ and sociodemographic and clinical variables. A cross-sectional study with tools assessing spiritual needs (SNAP-CZ), anxiety (Beck Anxiety Inventory; BAI), depression (Beck Depression Inventory; BDI), pain (Visual Analogue Scale; VAS), self-sufficiency (Barthel Index; BI); cognitive function (Montreal Cognitive Test; MoCa) and selected socio-demographic data was performed. The psychometric properties of SNAP-CZ were tested using factor analysis, reliability and validity tests, and correlations between the questionnaire and sociodemographic data and clinical variables. Internal consistency was established with Cronbach’s alfa for the overall score, respective domains, and individual items. Reliability was assessed by test-retest by Interclass correlation coefficient (ICC). Data for correlation analysis were processed according to Pearson's correlation coefficient. The study included 172 trauma patients (the mean age = 40.6 ± 12.1 years) who experienced polytrauma or severe monotrauma. There were a total of 106 (61.6%) male subjects, 140 (81.4%) respondents identified themselves as non-believers. The full-scale Cronbach's alpha was 0.907. The test-retest showed the reliability of the individual domains in the range of 0.924 to 0.960 ICC. Factor analysis resulted in a three-factor solution (psychosocial needs (alfa = 0.788), spiritual needs (alfa = 0.886) and religious needs (alfa = 0.841)). Correlation analysis using Pearson's correlation coefficient showed that the domain of psychosocial needs significantly correlated only with gender (r = 0.178, p = 0.020). Males had a statistically significant lower average value in this domain (mean = 12.5) compared to females (mean = 13.8). The domain of spiritual needs significantly correlated with gender (r = 0.199, p = 0.009), social status (r = 0.156, p = 0.043), faith (r = -0.250, p = 0.001), anxiety (r = 0.194, p = 0.011) and depression (r = 0.155, p = 0.044). The domain of religious needs significantly correlated with age (r = 0,208, p = 0,007), education (r = -0,161, p = 0,035), faith (r = -0,575, p < 0,0001) and depression (r = 0,179, p = 0,019). Overall, the whole SNAP scale significantly correlated with gender (r = 0.219, p = 0.004), social status (r = 0.175, p = 0.023), faith (r = -0.334, p <0.0001), anxiety (r = 0.177, p = 0.022) and depression (r = 0.173, p = 0.025). The results of this study corroborate the reliability of the SNAP-CZ and support its future use in the nursing care of trauma patients in a secular society. Acknowledgment: The study was supported by grant nr. IGA_FZV_2020_003.

Keywords: acute nursing care, assessment of spiritual needs, patient, psychometric validation, spirituality

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Authors: Virany Diana, Martono Tri Utomo, Risa Etika

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Background: Shock is one severe condition that can be a major cause of morbidity and mortality in the Neonatal Intensive Care Unit. Preterm infants are very susceptible to shock caused by many complications such as asphyxia, patent ductus arteriosus, intra ventricle haemorrhage, necrotizing enterocolitis, persistent pulmonal hypertension of the newborn, and septicaemia. Limited hemodynamic monitoring for early detection of shock causes delayed intervention and comprises the outcomes. Clinical parameters still used in neonatal shock detection, such as Capillary Refill Time, heart rate, cold extremity, and urine production. Blood pressure is most frequently used to evaluate preterm's circulation, but hypotension indicates uncompensated shock. Near-infrared spectroscopy (NIRS) is known as a noninvasive tool for monitoring and detecting the state of inadequate tissue perfusion. Muscle oxygen saturation shows decreased cardiac output earlier than systemic parameters of tissue oxygenation when cerebral regional oxygen saturation is still stabilized by autoregulation. However, to our best knowledge, until now, no study has analyzed the decrease of muscle oxygen regional saturation (mRSO₂) and the ratio of muscle and cerebral oxygen regional saturation (mRSO₂/cRSO₂) by NIRS in preterm with shock. Purpose: The purpose of this study is to analyze the decrease of mRSO₂ and ratio of muscle to cerebral oxygen regional saturation (mRSO₂/cRSO₂) by NIRS in preterm with shock. Patients and Methods: This cross-sectional study was conducted on preterm infants with 28-34 weeks gestational age, admitted to the NICU of Dr. Soetomo Hospital from November to January 2022. Patients were classified into two groups: shock and non-shock. The diagnosis of shock is based on clinical criteria (tachycardia, prolonged CRT, cold extremity, decreased urine production, and MAP Blood Pressure less than GA in weeks). Measurement of mRSO₂ and cRSO₂ by NIRS was performed by the doctor in charge when the patient came to NICU. Results: We enrolled 40 preterm infants. The initial conventional hemodynamic parameter as the basic diagnosis of shock showed significant differences in all variables. Preterm with shock had higher mean HR (186.45±1.5), lower MAP (29.8±2.1), and lower SBP (45.1±4.28) than non-shock children, and most had a prolonged CRT. The patients’ outcome was not a significant difference between shock and non-shock patients. The mean mRSO₂ in the shock and non-shock groups were 33,65 ± 11,32 vs. 69,15 ± 3,96 (p=0.001), and the mean ratio mRSO₂/cRSO₂ 0,45 ± 0,12 vs. 0,84 ± 0,43 (p=0,001), were significantly different. The mean cRSO₂ in the shock and non-shock groups were 71,60 ± 4,90 vs. 81,85 ± 7,85 (p 0.082), not significantly different. Conclusion: The decrease of mRSO₂ and ratio of mRSO₂/cRSO₂ can differentiate between shock and non-shock in the preterm infant when cRSO₂ is still normal.

Keywords: preterm infant, regional muscle oxygen saturation, regional cerebral oxygen saturation, NIRS, shock

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Authors: Melikulov A. A., Toshpulotov Sh. G., Akhmedova M. F., Beshimov A. S., Rakhimov M. K. Zokirov N. K.

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Postinfarction ventricular septal defect (PVSD) is a rare but life-threatening complication of acute myocardial infarction. Currently, an alternative direction of minimally invasive treatment of postinfarction ventricular septal defect (PVSD) is being developed - transcatheter closure of the defect using an occluder, but surgical closure of the defect remains the <> correction of post-infarction VSD. Our article presents a case of successful surgical treatment of a patient with a large post-infarction rupture of the interventricular septum (IVS) and post-infarction LV aneurysm under cardiopulmonary bypass and parallel perfusion.

Keywords: echocardiography, myocardial infarction, ventricular septal defect, parallel perfusion

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Authors: Tan Hui Ying Renee, Stella Rizalina Sasha, Farah Safdar Husain

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Introduction: Menopause Hormone Therapy (MHT) is an effective drug indicated for the treatment of menopausal symptoms and as replacement therapy in women who undergo premature menopause. In 2020, less than 8.8% of perimenopausal Singaporean women are on hormonal therapy, as compared to the Western population, where up to 50% may be on MHT. Factors associated with MHT utilization have been studied from patient characteristics, but the impact of locally prescribing physicians resulting in low MHT utilization has yet to be evaluated. The aim of the study is to determine the level of knowledge physicians in the Obstetrics and Gynaecology specialty have and their attitudes toward MHT. We believe that knowledge of MHT is lacking and that negative attitudes towards MHT may influence its use and undermine the benefits MHT may have for women. This paper is a part of a larger study on Singaporean physicians’ knowledge and attitudes towards MHT. Methods: This is a cross-sectional study intended to assess the knowledge and attitudes of physicians toward Menopausal Hormone Therapy. An anonymous questionnaire was disseminated via institutional internal circulations to optimize reach to physicians who may prescribe MHT, particularly in the fields of Gynaecology, Family Medicine and Endocrinology. Responses were completed voluntarily. Physicians had the option for each question to declare that they were ‘unsure’ or that the question was ‘beyond their expertise’. 21 knowledge questions tested factual recall on indications, contraindications, and risks of MHT. The remaining 6 questions were clinical scenarios crafted with the intention of testing specific principles related to the use of MHT. These questions received face validation from experts in the field. 198 responses were collected, 79 of which were from physicians in the Obstetrics and Gynaecology specialty. The data will be statistically analyzed to investigate areas that can be improved to increase the overall benefits of MHT for the Singaporean population. Results: Preliminary results show that the prevailing factors that limit Singaporean gynecologists and obstetricians from prescribing MHT are a lack of knowledge of MHT and a lack of confidence in prescribing MHT. Risks and indications of MHT were not well known by many physicians, with the majority of the questions having more than 25% incorrect and ‘unsure’ as their reply. The clinical scenario questions revealed significant shortcomings in knowledge on how to navigate real-life challenges in MHT use, with 2 of 6 questions with more than 50% incorrect or ‘beyond their expertise’ as their reply. The portion of the questionnaire that investigated the attitudes of physicians showed that though a large majority believed MHT to be an effective drug, only 40.5% were confident in prescribing it. Conclusion: Physicians in the Obstetrics and Gynaecology specialty lack knowledge and confidence in MHT. Therefore, it is imperative to formulate solutions on both the individual and institutional levels to fill these gaps and ensure that MHT is used appropriately and prescribed to the patients who need it.

Keywords: menopause, menopause hormone therapy, physician factors, obstetrics and gynecology, menopausal symptoms, Singapore

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Authors: Markus Bredel, Sindhu Nair, Hoa Q. Trummell, Rajani Rajbhandari, Christopher D. Willey, Lewis Z. Shi, Zhuo Zhang, William J. Placzek, James A. Bonner

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Purpose: EGFR-targeted monoclonal antibodies (mAbs) provide clinical benefit in some patients with H&N squamous cell carcinoma (HNSCC), but others progress with minimal response. Missense mutations in the EGFR ectodomain (ECD) can be acquired under mAb therapy by mimicking the effect of large deletions on receptor untethering and activation. Little is known about the contribution of EGFR ECD mutations to EGFR activation and anti-EGFR response in HNSCC. Methods: We selected patient-derived HNSCC cells (UM-SCC-1) for resistance to mAb Cetuximab (CTX) by repeated, stepwise exposure to mimic what may occur clinically and identified two concurrent EGFR ECD mutations (UM-SCC-1R). We examined the competence of the mutants to bind EGF ligand or CTX. We assessed the potential impact of the mutations through visual analysis of space-filling models of the native sidechains in the original structures vs. their respective side-chain mutations. We performed CRISPR in combination with site-directed mutagenesis to test for the effect of the mutants on ligand-independent EGFR activation and sorting. We determined the effects on receptor internalization, endocytosis, downstream signaling, and radiation sensitivity. Results: UM-SCC-1R cells carried two non-synonymous missense mutations (G33S and N56K) mapping to domain I in or near the EGF binding pocket of the EGFR ECD. Structural modeling predicted that these mutants restrict the adoption of a tethered, inactive EGFR conformation while not permitting association of EGFR with the EGF ligand or CTX. Binding studies confirmed that the mutant, untethered receptor displayed a reduced affinity for both EGF and CTX but demonstrated sustained activation and presence at the cell surface with diminished internalization and sorting for endosomal degradation. Single and double-mutant models demonstrated that the G33S mutant is dominant over the N56K mutant in its effect on EGFR activation and EGF binding. CTX-resistant UM-SCC-1R cells demonstrated cross-resistance to mAb Panitumuab but, paradoxically, remained sensitive to the reversible receptor tyrosine kinase inhibitor Erlotinib. Conclusions: HNSCC cells can select for EGFR ECD mutations under EGFR mAb exposure that converge to trap the receptor in an open, constitutively activated state. These mutants impede the receptor’s competence to bind mAbs and EGF ligand and alter its endosomal trafficking, possibly explaining certain cases of clinical mAb and radiation resistance.

Keywords: head and neck cancer, EGFR mutation, resistance, cetuximab

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Authors: Vivek Bhat, Rohini Kelkar, Sanjay Biswas

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Introduction: Cancer patients are at increased risk of bacterial infections. This may due to the disease process itself, the effect of chemotherapeutic drugs or invasive procedures such as catheterization. A wide variety of bacteria including some emerging pathogens are increasingly being reported from these patients. The incidence of multidrug-resistant organisms particularly in the Gram negative group is also increasing, with higher resistance rates seen to cephalosporins, β-lactam/β-lactam inhibitor combinations, and the carbapenems. This study documents the bacteriological spectrum of infections and their resistance patterns in cancer patients. Methods: This study includes all bacterial isolates recovered from infections cancer patients over a period of 18 months. Samples included Blood cultures, Pus/wound swabs, urine, tissue biopsies, body fluids, catheter tips and respiratory specimens such as sputum and bronchoalveolar lavage (BAL). All samples were processed in the microbiology laboratory as per standard laboratory protocols. Organisms were identified to species level and antimicrobial susceptibility testing was performed manually by the disc diffusion technique or in the Vitek-2 (Biomereux, France) instrument. Interpretations were as per Clinical laboratory Standards Institute (CLSI) guidelines. Results: A total of 1150 bacterial isolates were cultured from 884 test samples during the study period. Of these 227 were Gram-positive and 923 were Gram-negative organisms. Staphylococcus aureus (99 isolates) was the commonest Gram-positive isolate followed by Enterococcus (79) and Gr A Streptococcus (30). Among the Gram negatives, E. coli (304), Pseudomonas aeruginosa (201) and Klebsiella pneumoniae (190) were the most common. Of the Staphylococcus aureus isolates 27.2% were methicillin resistant. Only 5.06% enterococci were vancomycin resistant. High rates of resistance to cefotaxime and ciprofloxacin were seen amongst E. coli (84.8% & 83.55%) and Klebsiella pneumoniae (71 & 62.1%) respectively. Resistance to carbapenems (meropenem) was high at 70% in Acinetobacter spp.; however all isolates were sensitive to colistin. Among the aminoglycosides, amikacin retained good efficacy against Escherichia coli (82.9%) and Pseudomonas aeruginosa (78.1%). Occasional isolates of emerging pathogens such as Chryseobacterium indologens, Roseomonas, and Achromobacter xyloxidans were also recovered. Conclusion: The common infections in cancer patients include respiratory, wound, tract infections and sepsis. The commonest isolates include Staphylococcus aureus, Enterococci, Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa. There is a high level of resistance to the commonly used antibiotics among Gram-negative organisms.

Keywords: bacteria, resistance, infection, cancer

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Authors: L. K. Akila

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Art activities can fund as a clinical support tool (CST) between interventions in Art Therapy to direct the client back towards better outcome goals. In the present study, during free art sessions, researcher examined the possibilities of motivating the adolescent group to involve in art making process by reflecting upon art intervention administered. Results show that adolescents’ reflecting upon their art works generated during the intervention; could change their perceptions and cognitions to improve their positive approach by restructuring their art expressions. Consequently, such reflections triggered and improved their emotions, feelings and ideas, and produced secure attachment between family, peers and teachers. By the end of interference, transformations experienced were effective more upon depression, self-image, and self-efficacy, and to a certain extent on aggressive patterns represented.

Keywords: adolescent, adolescent psychology, aggression, art, art therapy, cognition, depression, emotion, self-image

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Authors: Catherine Bernard

Abstract:

The maldistribution of clinicians within countries is well documented. It is a common theme throughout the world that rural areas often struggle to recruit and retain health workers resulting in inadequate healthcare for many. This paper will concentrate on the responsibilities that medical schools may have in addressing this shortage of rural health workers. Recommendations are made with regards to targeted rural student admissions, rurally-based medical schools, rural clinical rotations and a curriculum orientated towards rural health issues. The evidence gathered suggests that individual factors are positive in encouraging health workers to practice in rural locations. However, there is strength in numbers, and combining all the recommendations will likely result in a synergistic effect, thereby increasing numbers of rural health workers and achieving accessible healthcare for those living in rural populations.

Keywords: medical education, medical education design, public health, rural health

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Authors: A. Elsariti, T. Evans

Abstract:

An understanding of the interaction between acoustic waves and cancellous bone is needed in order to realize the full clinical potential of ultrasonic bone measurements. Scattering is likely to be of central importance but has received little attention to date. Few theoretical approaches have been described to explain scattering of ultrasound from bone. In this study, a scattering model based on velocity and density fluctuations in a binary mixture (marrow fat and cortical matrix) was used to estimate the ultrasonic attenuation in cancellous bone as a function of volume fraction. Predicted attenuation and backscatter coefficient were obtained for a range of porosities and scatterer size. At 600 kHZ and for different scatterer size the effect of velocity and density fluctuations in the predicted attenuation was approximately 60% higher than velocity fluctuations.

Keywords: ultrasound scattering, sound speed, density fluctuations, attenuation coefficient

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Authors: Girum Tedla Assefa

Abstract:

Background: Granulomatous mycosis fungoides is an extremely rare type of cutaneous T-cell lymphoma (<55 cases reported worldwide). Case report: A 36-year-old female presented with soft tissue atrophy of right lower limb (dermis + hypodermis) of 22 years and plaques over trunk of 3 years duration. Histological examination of a biopsy taken from the atrophied tissue showed a granulomatous reaction with epidermotropic atypical lymphocytes. However, in other areas there were only findings of conventional MF without granuloma. Conclusion: The diagnosis of a granulomatous mycosis fungoides depends exclusively on the histological demonstration of granulomas. Distinct clinical characteristics are not present. This case highlights the importance of thorough investigation of lipoatrophic skin changes in the adult to exclude underlying causes, including MF.

Keywords: cutaneous lymphoma, granulomatous skin lymphoma, mycoses fungoides, skin atrophy

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Authors: Shreya Saxena, Felix Miller-Molloy, Phillipa Bowen, Greg Fellows, Elizabeth Bowen

Abstract:

Background: Complex fluid balance abnormalities are well-established post-neurosurgery and traumatic brain injury (TBI). The triple-phase response requires fluid management strategies reactive to urine output and sodium homeostasis as patients shift between Diabetes Insipidus (DI) and Syndrome of Inappropriate ADH (SIADH). It was observed, at a tertiary paediatric center, a relatively high prevalence of the above complications within a cohort of paediatric post-neurosurgical and TBI patients. An audit of the clinical practice against set institutional guidelines was undertaken and analyzed to understand why this was occurring. Based on those results, new guidelines were developed with structured educational packages for the specialist teams involved. This was then reaudited, and the findings were compared. Methods: Two independent audits were conducted across two time periods, pre and post guideline change. Primary data was collected retrospectively, including both qualitative and quantitative data sets from the CQUIN neurosurgical database and electronic medical records. All paediatric patients post posterior fossa (PFT) or supratentorial surgery or with a TBI were included. A literature review of evidence-based practice, initial audit data, and stakeholder feedback was used to develop new clinical guidelines and nursing standard operation procedures. Compliance against these newly developed guidelines was re-assessed and a thematic, trend-based analysis of the two sets of results was conducted. Results: Audit-1 January2017-June2018, n=80; Audit-2 January2020-June2021, n=30 (reduced operative capacity due to COVID-19 pandemic). Overall, improvements in the monitoring of both fluid balance and electrolyte trends were demonstrated; 51% vs. 77% and 78% vs. 94%, respectively. The number of clear fluid management plans documented postoperatively also increased (odds ratio of 4), leading to earlier recognition and management of evolving fluid-balance abnormalities. The local paediatric endocrine team was involved in the care of all complex cases and notified sooner for those considered to be developing DI or SIADH (14% to 35%). However, significant Na fluctuations (>12mmol in 24 hours) remained similar – 5 vs six patients – found to be due to complex pituitary hypothalamic pathology – and the recommended adaptive fluid management strategy was still not always used. Qualitative data regarding useability and understanding of fluid-balance abnormalities and the revised guidelines were obtained from health professionals via surveys and discussion in the specialist teams providing care. The feedback highlighted the new guidelines provided a more consistent approach to the post-operative care of these patients and was a better platform for communication amongst the different specialist teams involved. The potential limitation to our study would be the small sample size on which to conduct formal analyses; however, this reflects the population that we were investigating, which we cannot control. Conclusion: The revised clinical guidelines, based on audited data, evidence-based literature review and stakeholder consultations, have demonstrated an improvement in understanding of the neuro-endocrine complications that are possible, as well as increased compliance to post-operative monitoring of fluid balance and electrolytes in this cohort of patients. Emphasis has been placed on preventative rather than treatment of DI and SIADH. Consequently, this has positively impacted patient safety for the center and highlighted the importance of educational awareness and multi-disciplinary team working.

Keywords: post-operative, fluid-balance management, neuro-endocrine complications, paediatric

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Authors: Sara Assi, Berthe Hayar, Claudio Pisano, Nadine Darwiche, Walid Saad

Abstract:

Nanomedicine, the application of nanotechnology to medicine, is an emerging discipline that has gained significant attention in recent years. Current breakthroughs in nanomedicine have paved the way to develop effective drug delivery systems that can be used to target cancer. The use of nanotechnology provides effective drug delivery, enhanced stability, bioavailability, and permeability, thereby minimizing drug dosage and toxicity. As such, the use of nanoparticle (NP) formulations in drug delivery has been applied in various cancer models and have shown to improve the ability of drugs to reach specific targeted sites in a controlled manner. Cancer is one of the major causes of death worldwide; in particular, colorectal cancer (CRC) is the third most common type of cancer diagnosed amongst men and women and the second leading cause of cancer related deaths, highlighting the need for novel therapies. Retinoids, consisting of natural and synthetic derivatives, are a class of chemical compounds that have shown promise in preclinical and clinical cancer settings. However, retinoids are limited by their toxicity and resistance to treatment. To overcome this resistance, various synthetic retinoids have been developed, including the adamantyl retinoid ST1926, which is a potent anti-cancer agent. However, due to its limited bioavailability, the development of ST1926 has been restricted in phase I clinical trials. We have previously investigated the preclinical efficacy of ST1926 in CRC models. ST1926 displayed potent inhibitory and apoptotic effects in CRC cell lines by inducing early DNA damage and apoptosis. ST1926 significantly reduced the tumor doubling time and tumor burden in a xenograft CRC model. Therefore, we developed ST1926-NPs and assessed their efficacy in CRC models. ST1926-NPs were produced using Flash NanoPrecipitation with the amphiphilic diblock copolymer polystyrene-b-ethylene oxide and cholesterol as a co-stabilizer. ST1926 was formulated into NPs with a drug to polymer mass ratio of 1:2, providing a stable formulation for one week. The contin ST1926-NP diameter was 100 nm, with a polydispersity index of 0.245. Using the MTT cell viability assay, ST1926-NP exhibited potent anti-growth activities as naked ST1926 in HCT116 cells, at pharmacologically achievable concentrations. Future studies will be performed to study the anti-tumor activities and mechanism of action of ST1926-NPs in a xenograft mouse model and to detect the compound and its glucuroconjugated form in the plasma of mice. Ultimately, our studies will support the use of ST1926-NP formulations in enhancing the stability and bioavailability of ST1926 in CRC.

Keywords: nanoparticles, drug delivery, colorectal cancer, retinoids

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Authors: Muhammad Zeeshan

Abstract:

This case study is about a 54 years man named Mr. U, referred to Capital Hospital, Islamabad, with the presenting complaints of Generalized Anxiety Disorder (GAD). Contrary to his complaints, the client reported psychological symptoms such as restlessness, low mood and fear of darkness and fear from closed places from the last 30 days. He also had a fear of death and his existence in the grave. His sleep was also disturbed due to excessive urination due to diabetes. He was also suffering from semantic symptoms such as headache, numbness of feet and pain in the chest and blockage of the nose. A complete history was taken and informal assessment (clinical interview and MSE) and formal testing (BAI) was applied that showed the clear diagnosis of Generalized Anxiety Disorder. CBT, relaxation techniques, prayer chart and behavioural techniques were applied for the treatment purposes.

Keywords: generalized anxiety disorder, presenting complaints, formal and informal assessment, diagnosis

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Authors: Ferreira R., Rocha K.

Abstract:

Ozone therapy is indicated for improving skin aesthetics, bio-stimulating and ergogenic effect. This paper aims to carry out a case report that demonstrates the positive results of ozone therapy in buttock augmentation. The application showed positive results for skin bio stimulating, neocollagenesis, adipogenesis, and ergogenic muscle effect in the reported case, demonstrating to be a viable clinical technique. Buttock augmentation with ozone therapy is a promising aesthetic therapeutic modality with fast and safe results as an aesthetic therapeutic option for buttock augmentation.

Keywords: bio-stimulating effect, ozone therapy, muscular ergogenic, buttock augmentation

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Authors: Hakim Derradji, Abdelkader Yahi, Abdelmalek Sabrou, Nacer Tabet

Abstract:

Introduction: Cystic lesions located in the sellar and suprasellar region cause a diagnostic and therapeutic problem, given their location and their impact on neighboring structures. The patient's symptomatology varies from a simple headache to serious visual and endocrine disorders, involving the functional prognosis, sometimes even the vital prognosis. Surgery in this region remains a therapeutic challenge, and several surgical techniques have been described and used. Material and Methods: We treated 15 patients during the period from 2015 to 2022, whose clinical, biological, radiological, and therapeutic characteristics will be presented in detail in this work, and in whom the surgical technique differs from one case to another. Conclusion: We will discuss in this work the different techniques used to treat these lesions and the different objectives to be achieved for each case, as well as the complications and our conduct to be taken per and post-operative.

Keywords: cystic lesions, adenomas, sellar and suprasellar region, neuroendoscopy

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Authors: John T. Leman, James Gibson, Peter J. Bonitatibus

Abstract:

There have been no potential clinically translatable developments of intravenous CT contrast materials over decades, and iodinated contrast agents (ICA) remain the only FDA-approved media for CT. Small molecule ICA used to highlight vascular anatomy have weak CT signals in large-to-obese patients due to their rapid redistribution from plasma into interstitial fluid, thereby diluting their intravascular concentration, and because of a mismatch of iodine’s K-edge and the high kVp settings needed to image this patient population. The use of ICA is also contraindicated in a growing population of renally impaired patients who are hypersensitive to these contrast agents; a transformative intravenous contrast agent with improved capabilities is urgently needed. Tantalum oxide nanoparticles (TaO NPs) with zwitterionic siloxane polymer coatings have high potential as clinically translatable general-purpose CT contrast agents because of (1) substantially improved imaging efficacy compared to ICA in swine/phantoms emulating medium-sized and larger adult abdomens and superior thoracic vascular contrast enhancement of thoracic arteries and veins in rabbit, (2) promising biological safety profiles showing near-complete renal clearance and low tissue retention at 3x anticipated clinical dose (ACD), and (3) clinically acceptable physiochemical parameters as concentrated bulk solutions(250-300 mgTa/mL). Here, we review requirements for general-purpose intravenous CT contrast agents in terms of patient safety, X-ray attenuating properties and contrast-producing capabilities, and physicochemical and pharmacokinetic properties. We report the current status of a TaO NP-based contrast agent, including chemical process technology developments and results of newly defined scaled-up processes for NP synthesis and purification, yielding reproducible formulations with appropriate size and concentration specifications. We discuss recent results of recent pre-clinical in vitro immunology, non-GLP high dose tolerability in rats (10x ACD), non-GLP long-term biodistribution in rats at 3x ACD, and non-GLP repeat dose in rats at ACD. We also include a discussion of NP characterization, in particular size-stability testing results under accelerated conditions (37C), and insights into TaO NP purity, surface structure, and bonding of the zwitterionic siloxane polymer coating by multinuclear (1H, 13C, 29Si) and multidimensional (2D) solution NMR spectroscopy.

Keywords: nanoparticle, imaging, diagnostic, process technology, nanoparticle characterization

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Authors: Sukryool Kang, James McConnaughey, Robin Doroshow, Raj Shekhar

Abstract:

Still’s murmur, a vibratory heart murmur, is the most common normal innocent murmur of childhood. Many children with this murmur are unnecessarily referred for cardiology consultation and testing, which exacts a high cost financially and emotionally on the patients and their parents. Pediatricians to date are not successful at distinguishing Still’s murmur from murmurs of true heart disease. In this paper, we present a new algorithmic approach to distinguish Still’s murmur from pathological murmurs in children. We propose two distinct features, spectral width and signal power, which describe the sharpness of the spectrum and the signal intensity of the murmur, respectively. Seventy pediatric heart sound recordings of 41 Still’s and 29 pathological murmurs were used to develop and evaluate our algorithm that achieved a true positive rate of 97% and false positive rate of 0%. This approach would meet clinical standards in recognizing Still’s murmur.

Keywords: AR modeling, auscultation, heart murmurs, Still's murmur

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Authors: Dorota Witkowska, Paweł Gosek, Lukasz Swiecicki, Wojciech Jernajczyk, Bruce J. West, Miroslaw Latka

Abstract:

In clinical practice, the selection of an antidepressant often degrades to lengthy trial-and-error. In this work we employ a normalized wavelet power of alpha waves as a biomarker of antidepressant treatment response. This novel EEG metric takes into account both non-stationarity and intersubject variability of alpha waves. We recorded resting, 19-channel EEG (closed eyes) in 22 inpatients suffering from unipolar (UD, n=10) or bipolar (BD, n=12) depression. The EEG measurement was done at the end of the short washout period which followed previously unsuccessful pharmacotherapy. The normalized alpha wavelet power of 11 responders was markedly different than that of 11 nonresponders at several, mostly temporoparietal sites. Using the prediction of treatment response based on the normalized alpha wavelet power, we achieved 81.8% sensitivity and 81.8% specificity for channel T4.

Keywords: alpha waves, antidepressant, treatment outcome, wavelet

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Authors: Ruth Green, Samantha Milton, Rinal Desai

Abstract:

Background/Aims: Eye pain/swelling/redness is a common presentation to Barnet General Hospital (a district general hospital), pediatric emergency department, and is managed by both the pediatric and emergency teams. The management of each child differs dramatically depending on the healthcare professional who reviews them. There also appears to be confusion in diagnosis between periorbital cellulitis, pre-septal cellulitis, and orbital cellulitis. Pre septal cellulitis refers to an inflammation of the eyelids and soft tissue anterior to the orbital septum. In contrast, orbital cellulitis is a serious, rapidly progressive infection of soft tissues located posterior to the orbital septum. Pre-septal cellulitis is more prevalent and less serious than orbital cellulitis, although it may be part of a continuous spectrum if untreated. Pre-septal cellulitis should there be diagnosed and treated urgently to prevent spread to the septum. For the purpose of the audit, the term periorbital cellulitis has been used as an umbrella term for all spectrums of this infection. The audit aimed to look at, how as a whole, the department is diagnosing and managing orbital and pre-septal cellulitis. Gold Standard: Patients of the same age and diagnosis should be treated with the same medication, advice, and follow-up. Method: Data was collected retrospectively from pediatric patients ( < 18years) who attended the emergency department from June 2019 to February 2020 who had been coded as pre-septal cellulitis, periorbital cellulitis, orbital cellulitis, or eye pain/swelling/redness. Demographics, signs and symptoms, management, and follow-up were recorded for all patients with any of the diagnoses of pre-septal, periorbital, or orbital cellulitis. A Microsoft Excel spreadsheet was used to record the anonymised data. Results: There were vast discrepancies in the diagnosis, management, and follow-up of patients with periorbital cellulitis. Conclusion/Discussion: The audit concluded there is no uniform approach to managing periorbital cellulitis in Barnet General Hospital Paediatric Emergency Department. Healthcare professionals misdiagnosed conjunctivitis as periorbital cellulitis, and adequate steps did not appear to be documented on excluding red flag signs and symptoms of patients presenting. There was no consistency in follow-up, with some patients having timely phone reviews or clinical reviews for mild symptoms. Advice given by the staff was appropriate, and patients did return when symptoms got worse and were treated accordingly. Plan: Given the inconsistency, a gold standard care pathway or local easily accessible clinical guideline can be developed to help with the diagnosis and management of periorbital cellulitis. Along with this, a teaching session can be carried out for the staff of the pediatric team and emergency department to disseminate the teaching. Following the introduction of a guideline and teaching sessions, patients notes can be re-reviewed to check improvement in patient care.

Keywords: periorbital cellulitis, preseptal cellulitis, orbital cellulitis, erythematous eyelid

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