Search results for: symptom control in oncology patients
11710 Functional Electrical Stimulator and Neuromuscular Electro Stimulator System Analysis for Foot Drop
Authors: Gül Fatma Türker, Hatice Akman
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Portable muscle stimulators for real-time applications has first introduced by Liberson in 1961. Now these systems has been advanced. In this study, FES (Functional Electrical Stimulator) and NMES (Neuromuscular Electrostimulator) systems are analyzed through their hardware and their quality of life improvements for foot drop patients. FES and NMES systems are used for people whose leg muscles and leg neural connections are healty but not able to walk properly because of their injured central nervous system like spinal cord injuries. These systems are used to stimulate neurons or muscles by getting information from other movements and programming these stimulations to get natural walk and it is accepted as a rehabilitation method for the correction of drop foot. This systems support person to approach natural form of walking. Foot drop is characterized by steppage gait. It is a gait abnormality. This systems helps to person for plantar and dorse reflection movements which are hard to done for foot drop patients.Keywords: FES, foot drop, NMES, stimulator
Procedia PDF Downloads 38611709 The Estimation of Human Vital Signs Complexity
Authors: L. Bikulciene, E. Venskaityte, G. Jarusevicius
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Non-stationary and nonlinear signals generated by living complex systems defy traditional mechanistic approaches, which are based on homeostasis. Previous our studies have shown that the evaluation of the interactions of physiological signals by using special analysis methods is suitable for observation of physiological processes. It is demonstrated the possibility of using deep physiological model, based interpretation of the changes of the human body’s functional states combined with an application of the analytical method based on matrix theory for the physiological signals analysis, which was applied on high risk cardiac patients. It is shown that evaluation of cardiac signals interactions show peculiar for each individual functional changes at the onset of hemodynamic restoration procedure. Therefore we suggest that the alterations of functional state of the body, after patients overcome surgery can be complemented by the data received from the suggested approach of the evaluation of functional variables interactions.Keywords: cardiac diseases, complex systems theory, ECG analysis, matrix analysis
Procedia PDF Downloads 34311708 High-Throughput, Purification-Free, Multiplexed Profiling of Circulating miRNA for Discovery, Validation, and Diagnostics
Authors: J. Hidalgo de Quintana, I. Stoner, M. Tackett, G. Doran, C. Rafferty, A. Windemuth, J. Tytell, D. Pregibon
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We have developed the Multiplexed Circulating microRNA assay that allows the detection of up to 68 microRNA targets per sample. The assay combines particlebased multiplexing, using patented Firefly hydrogel particles, with single step RT-PCR signal. Thus, the Circulating microRNA assay leverages PCR sensitivity while eliminating the need for separate reverse transcription reactions and mitigating amplification biases introduced by target-specific qPCR. Furthermore, the ability to multiplex targets in each well eliminates the need to split valuable samples into multiple reactions. Results from the Circulating microRNA assay are interpreted using Firefly Analysis Workbench, which allows visualization, normalization, and export of experimental data. To aid discovery and validation of biomarkers, we have generated fixed panels for Oncology, Cardiology, Neurology, Immunology, and Liver Toxicology. Here we present the data from several studies investigating circulating and tumor microRNA, showcasing the ability of the technology to sensitively and specifically detect microRNA biomarker signatures from fluid specimens.Keywords: biomarkers, biofluids, miRNA, photolithography, flowcytometry
Procedia PDF Downloads 36811707 Deficient Multisensory Integration with Concomitant Resting-State Connectivity in Adult Attention Deficit/Hyperactivity Disorder (ADHD)
Authors: Marcel Schulze, Behrem Aslan, Silke Lux, Alexandra Philipsen
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Objective: Patients with Attention Deficit/Hyperactivity Disorder (ADHD) often report that they are being flooded by sensory impressions. Studies investigating sensory processing show hypersensitivity for sensory inputs across the senses in children and adults with ADHD. Especially the auditory modality is affected by deficient acoustical inhibition and modulation of signals. While studying unimodal signal-processing is relevant and well-suited in a controlled laboratory environment, everyday life situations occur multimodal. A complex interplay of the senses is necessary to form a unified percept. In order to achieve this, the unimodal sensory modalities are bound together in a process called multisensory integration (MI). In the current study we investigate MI in an adult ADHD sample using the McGurk-effect – a well-known illusion where incongruent speech like phonemes lead in case of successful integration to a new perceived phoneme via late top-down attentional allocation . In ADHD neuronal dysregulation at rest e.g., aberrant within or between network functional connectivity may also account for difficulties in integrating across the senses. Therefore, the current study includes resting-state functional connectivity to investigate a possible relation of deficient network connectivity and the ability of stimulus integration. Method: Twenty-five ADHD patients (6 females, age: 30.08 (SD:9,3) years) and twenty-four healthy controls (9 females; age: 26.88 (SD: 6.3) years) were recruited. MI was examined using the McGurk effect, where - in case of successful MI - incongruent speech-like phonemes between visual and auditory modality are leading to a perception of a new phoneme. Mann-Whitney-U test was applied to assess statistical differences between groups. Echo-planar imaging-resting-state functional MRI was acquired on a 3.0 Tesla Siemens Magnetom MR scanner. A seed-to-voxel analysis was realized using the CONN toolbox. Results: Susceptibility to McGurk was significantly lowered for ADHD patients (ADHDMdn:5.83%, ControlsMdn:44.2%, U= 160.5, p=0.022, r=-0.34). When ADHD patients integrated phonemes, reaction times were significantly longer (ADHDMdn:1260ms, ControlsMdn:582ms, U=41.0, p<.000, r= -0.56). In functional connectivity medio temporal gyrus (seed) was negatively associated with primary auditory cortex, inferior frontal gyrus, precentral gyrus, and fusiform gyrus. Conclusion: MI seems to be deficient for ADHD patients for stimuli that need top-down attentional allocation. This finding is supported by stronger functional connectivity from unimodal sensory areas to polymodal, MI convergence zones for complex stimuli in ADHD patients.Keywords: attention-deficit hyperactivity disorder, audiovisual integration, McGurk-effect, resting-state functional connectivity
Procedia PDF Downloads 12311706 Impact of Out-Of-Pocket Payments on Health Care Finance and Access to Health Care Services: The Case of Health Transformation Program in Turkey
Authors: Bengi Demirci
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Out-of-pocket payments have become one of the common models adopted by health care reforms all over the world, and they have serious implications for not only the financial set-up of the health care systems in question but also for the people involved in terms of their access to the health care services provided. On the one hand, out-of-pocket payments are used in raising resources for the finance of the health care system and in decreasing non-essential health care expenses by having a deterrent role on the patients. On the other hand, out-of-pocket payment model causes regressive distribution effect by putting more burdens on the lower income groups and making them refrain from using health care services. Being a relatively incipient country having adopted the out-of-pocket payment model within the context of its Health Transformation Program which has been ongoing since the early 2000s, Turkey provides a good case for re-evaluating the pros and cons of this model in order not to sacrifice equality in access to health care for raising revenue for health care finance and vice versa. Therefore this study aims at analyzing the impact of out-of-pocket payments on the health finance system itself and on the patients’ access to healthcare services in Turkey where out-of-pocket payment model has been in use for a while. In so doing, data showing the revenue obtained from out-of-pocket payments and their share in health care finance are analyzed. In addition to this, data showing the change in the amount of expenditure made by patients on health care services after the adoption of out-of-pocket payments and the change in the use of various health care services in the meanwhile are examined. It is important for the incipient countries like Turkey to be careful in striking the right balance between the objective of cost efficiency and that of equality in accessing health care services while adopting the out-of-pocket payment model.Keywords: health care access, health care finance, health reform, out-of-pocket payments
Procedia PDF Downloads 37111705 The Superiority of 18F-Sodium Fluoride PET/CT for Detecting Bone Metastases in Comparison with Other Bone Diagnostic Imaging Modalities
Authors: Mojtaba Mirmontazemi, Habibollah Dadgar
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Bone is the most common metastasis site in some advanced malignancies, such as prostate and breast cancer. Bone metastasis generally indicates fewer prognostic factors in these patients. Different radiological and molecular imaging modalities are used for detecting bone lesions. Molecular imaging including computed tomography, magnetic resonance imaging, planar bone scintigraphy, single-photon emission tomography, and positron emission tomography as noninvasive visualization of the biological occurrences has the potential to exact examination, characterization, risk stratification and comprehension of human being diseases. Also, it is potent to straightly visualize targets, specify clearly cellular pathways and provide precision medicine for molecular targeted therapies. These advantages contribute implement personalized treatment for each patient. Currently, NaF PET/CT has significantly replaced standard bone scintigraphy for the detection of bone metastases. On one hand, 68Ga-PSMA PET/CT has gained high attention for accurate staging of primary prostate cancer and restaging after biochemical recurrence. On the other hand, FDG PET/CT is not commonly used in osseous metastases of prostate and breast cancer as well as its usage is limited to staging patients with aggressive primary tumors or localizing the site of disease. In this article, we examine current studies about FDG, NaF, and PSMA PET/CT images in bone metastases diagnostic utility and assess response to treatment in patients with breast and prostate cancer.Keywords: skeletal metastases, fluorodeoxyglucose, sodium fluoride, molecular imaging, precision medicine, prostate cancer (68Ga-PSMA-11)
Procedia PDF Downloads 10811704 Testicular Differential MicroRNA Expression Derived Occupational Risk Factor Assessment in Idiopathic Non-obstructive Azoospermia Cases
Authors: Nisha Sharma, Mili Kaur, Ashutosh Halder, Seema Kaushal, Manoj Kumar, Manish Jain
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Purpose: To investigate microRNAs (miRNA) as an epigenomic etiological factor in idiopathic non-obstructive azoospermia (NOA). In order to achieve the same, an association was seen between occupational exposure to radiation, thermal, and chemical factors and idiopathic cases of non-obstructive azoospermia, and later, testicular differential miRNA expression profiling was done in exposure group NOA cases. Method: It is a prospective study in which 200 apparent idiopathic male factor infertility cases, who have been advised to undergo testicular fine needle aspiration (FNA) evaluation, are recruited. A detailed occupational history was taken to understand the possible type of exposure due to the nature and duration of work. A total of 26 patients were excluded upon XY-FISH and Yq microdeletion tests due to the presence of genetic causes of infertility, 6 hypospermatogeneis (HS), six Sertoli cell-only syndrome (SCOS), and six normospermatogeneis patients testicular FNA samples were used for RNA isolation followed by small RNA sequencing and nCounter miRNA expression analysis. Differential miRNA expression profile of HS and SCOS patients was done. A web-based tool, miRNet, was used to predict the interacting compounds or chemicals using the shortlisted miRNAs with high fold change. The major limitation encountered in this study was the insufficient quantity of testicular FNA sample used for total RNA isolation, which resulted in a low yield and RNA integrity number (RIN) value. Therefore, the number of RNA samples admissible for differential miRNA expression analysis was very small in comparison to the total number of patients recruited. Results: Differential expression analysis revealed 69 down-regulated and 40 up-regulated miRNAs in HS and 66 down-regulated and 33 up-regulated miRNAs in SCOS in comparison to normospermatogenesis controls. The miRNA interaction analysis using the miRNet tool showed that the differential expression profiles of HS and SCOS patients were associated with arsenic trioxide, bisphenol-A, calcium sulphate, lithium, and cadmium. These compounds are reproductive toxins and might be responsible for miRNA-mediated epigenetic deregulation leading to NOA. The association between occupational risk factor exposure and the non-exposure group of NOA patients was not statistically significant, with ꭓ2 (3, N= 178) = 6.70, p= 0.082. The association between individual exposure groups (radiation, thermal, and chemical) and various sub-types of NOA is also not significant, with ꭓ2 (9, N= 178) = 15.06, p= 0.089. Functional analysis of HS and SCOS patients' miRNA profiles revealed some important miR-family members in terms of male fertility. The miR-181 family plays a role in the differentiation of spermatogonia and spermatocytes, as well as the transcriptional regulation of haploid germ cells. The miR-34 family is expressed in spermatocytes and round spermatids and is involved in the regulation of SSCs differentiation. Conclusion: The reproductive toxins might adopt the miRNA-mediated mechanism of disease development in idiopathic cases of NOA. Chemical compound induced; miRNA-mediated epigenetic deregulation can give a future perspective on the etiopathogenesis of the disease.Keywords: microRNA, non-obstructive azoospermia (NOA), occupational exposure, hypospermatogenesis (HS), Sertoli cell only syndrome (SCOS)
Procedia PDF Downloads 8611703 Lentiviral-Based Novel Bicistronic Therapeutic Vaccine against Chronic Hepatitis B Induces Robust Immune Response
Authors: Mohamad F. Jamiluddin, Emeline Sarry, Ana Bejanariu, Cécile Bauche
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Introduction: Over 360 million people are chronically infected with hepatitis B virus (HBV), of whom 1 million die each year from HBV-associated liver cirrhosis or hepatocellular carcinoma. Current treatment options for chronic hepatitis B depend on interferon-α (IFNα) or nucleos(t)ide analogs, which control virus replication but rarely eliminate the virus. Treatment with PEG-IFNα leads to a sustained antiviral response in only one third of patients. After withdrawal of the drugs, the rebound of viremia is observed in the majority of patients. Furthermore, the long-term treatment is subsequently associated with the appearance of drug resistant HBV strains that is often the cause of the therapy failure. Among the new therapeutic avenues being developed, therapeutic vaccine aimed at inducing immune responses similar to those found in resolvers is of growing interest. The high prevalence of chronic hepatitis B necessitates the design of better vaccination strategies capable of eliciting broad-spectrum of cell-mediated immunity(CMI) and humoral immune response that can control chronic hepatitis B. Induction of HBV-specific T cells and B cells by therapeutic vaccination may be an innovative strategy to overcome virus persistence. Lentiviral vectors developed and optimized by THERAVECTYS, due to their ability to transduce non-dividing cells, including dendritic cells, and induce CMI response, have demonstrated their effectiveness as vaccination tools. Method: To develop a HBV therapeutic vaccine that can induce a broad but specific immune response, we generated recombinant lentiviral vector carrying IRES(Internal Ribosome Entry Site)-containing bicistronic constructs which allow the coexpression of two vaccine products, namely HBV T- cell epitope vaccine and HBV virus like particle (VLP) vaccine. HBV T-cell epitope vaccine consists of immunodominant cluster of CD4 and CD8 epitopes with spacer in between them and epitopes are derived from HBV surface protein, HBV core, HBV X and polymerase. While HBV VLP vaccine is a HBV core protein based chimeric VLP with surface protein B-cell epitopes displayed. In order to evaluate the immunogenicity, mice were immunized with lentiviral constructs by intramuscular injection. The T cell and antibody immune responses of the two vaccine products were analyzed using IFN-γ ELISpot assay and ELISA respectively to quantify the adaptive response to HBV antigens. Results: Following a single administration in mice, lentiviral construct elicited robust antigen-specific IFN-γ responses to the encoded antigens. The HBV T- cell epitope vaccine demonstrated significantly higher T cell immunogenicity than HBV VLP vaccine. Importantly, we demonstrated by ELISA that antibodies are induced against both HBV surface protein and HBV core protein when mice injected with vaccine construct (p < 0.05). Conclusion: Our results highlight that THERAVECTYS lentiviral vectors may represent a powerful platform for immunization strategy against chronic hepatitis B. Our data suggests the likely importance of Lentiviral vector based novel bicistronic construct for further study, in combination with drugs or as standalone antigens, as a therapeutic lentiviral based HBV vaccines. THERAVECTYS bicistronic HBV vaccine will be further evaluated in animal efficacy studies.Keywords: chronic hepatitis B, lentiviral vectors, therapeutic vaccine, virus-like particle
Procedia PDF Downloads 33211702 Consultation Liasion Psychiatry in a Tertiary Care Hospital
Authors: K. Pankaj, R. K. Chaudhary, B. P. Mishra, S. Kochar
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Introduction: Consultation-Liaison psychiatry is a branch of psychiatry that includes clinical service, teaching and research. A consultation-liaison psychiatrist plays a role in having an expert opinion and linking the patients to other medical professionals and the patient’s bio-psycho-social aspects that may be leading to his/her symptoms. Consultation-Liaison psychiatry has been recognised as 'The guardian of the holistic approach to the patient', underlining its pre-eminent role in the management of patients who are admitted in a tertiary care hospital. Aims/ Objectives: The aim of the study was to analyse the utilization of psychiatric services and reasons for referrals in a tertiary care hospital. Materials and Methods: The study was done in a tertiary care hospital. The study included all the cases referred from different Inpatient wards to the psychiatry department for consultation. The study was conducted on 300 patients over a 3 month period. International classification of diseases 10 was used to diagnose the referred cases. Results: The majority of the referral was from the Medical Intensive care unit (22%) followed by general medical wards (18.66%). Majority of the referral was taken for altered sensorium (24.66%), followed by low mood or unexplained medical symptoms (21%). Majority of the referrals had a diagnosis of alcohol withdrawal syndrome (21%) as per International classification of diseases criteria, followed by unipolar Depression and Anxiety disorder (~ 14%), followed by Schizophrenia (5%) and Polysubstance abuse (2.6%). Conclusions: Our study concludes the importance of utilization of consultation-liaison psychiatric services. Also, the study signifies the need for sensitization of our colleagues regarding psychiatric sign and symptoms from time to time and seek psychiatric consult timely to decrease morbidity.Keywords: consultation-liaison, psychiatry, referral, tertiary care hospital
Procedia PDF Downloads 15111701 The Value of Dynamic Magnetic Resonance Defecography in Assessing the Severity of Defecation Disorders
Authors: Ge Sun, Monika Trzpis, Robbert J. de Haas, Paul M. A. Broens
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Introduction: Dynamic magnetic resonance defecography is frequently used to assess defecation disorders. We aimed to investigate the usefulness of dynamic magnetic resonance defecography for assessing the severity of defecation disorder. Methods: We included patients retrospectively from our tertiary referral hospital who had undergone dynamic magnetic resonance defecography, anorectal manometry, and anal electrical sensitivity tests to assess defecation disorders between 2014 and 2020. The primary outcome was the association between the dynamic magnetic resonance defecography variables and the severity of defecation disorders. We assessed the severity of fecal incontinence and constipation with the Wexner incontinence and Agachan constipation scores. Results: Out of the 32 patients included, 24 completed the defecation questionnaire. During defecation, the M line length at magnetic resonance correlated with the Agachan score (r = 0.45, p = 0.03) and was associated with anal sphincter pressure (r=0.39, p=0.03) just before defecation. During rest and squeezing, the H line length at imaging correlated with the Wexner incontinence score (r=0.49, p=0.01 and r=0.69, p< 0.001, respectively). H line length also correlated positively with the anal electrical sensation threshold during squeezing (r=0.50, p=0.004) and during rest (r= 0.42, p=0.02). Conclusions: The M and H line lengths at dynamic magnetic resonance defecography can be used to assess the severity of constipation and fecal incontinence respectively and reflect anatomic changes of the pelvic floor. However, as these anatomic changes are generally late-stage and irreversible, anal manometry seems a better diagnostic approach to assess early and potentially reversible changes in patients with defecation disorders.Keywords: defecation disorders, dynamic magnetic resonance defecography, anorectal manometry, anal electrical sensitivity tests, H line, M line
Procedia PDF Downloads 10311700 A Single Cell Omics Experiments as Tool for Benchmarking Bioinformatics Oncology Data Analysis Tools
Authors: Maddalena Arigoni, Maria Luisa Ratto, Raffaele A. Calogero, Luca Alessandri
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The presence of tumor heterogeneity, where distinct cancer cells exhibit diverse morphological and phenotypic profiles, including gene expression, metabolism, and proliferation, poses challenges for molecular prognostic markers and patient classification for targeted therapies. Understanding the causes and progression of cancer requires research efforts aimed at characterizing heterogeneity, which can be facilitated by evolving single-cell sequencing technologies. However, analyzing single-cell data necessitates computational methods that often lack objective validation. Therefore, the establishment of benchmarking datasets is necessary to provide a controlled environment for validating bioinformatics tools in the field of single-cell oncology. Benchmarking bioinformatics tools for single-cell experiments can be costly due to the high expense involved. Therefore, datasets used for benchmarking are typically sourced from publicly available experiments, which often lack a comprehensive cell annotation. This limitation can affect the accuracy and effectiveness of such experiments as benchmarking tools. To address this issue, we introduce omics benchmark experiments designed to evaluate bioinformatics tools to depict the heterogeneity in single-cell tumor experiments. We conducted single-cell RNA sequencing on six lung cancer tumor cell lines that display resistant clones upon treatment of EGFR mutated tumors and are characterized by driver genes, namely ROS1, ALK, HER2, MET, KRAS, and BRAF. These driver genes are associated with downstream networks controlled by EGFR mutations, such as JAK-STAT, PI3K-AKT-mTOR, and MEK-ERK. The experiment also featured an EGFR-mutated cell line. Using 10XGenomics platform with cellplex technology, we analyzed the seven cell lines together with a pseudo-immunological microenvironment consisting of PBMC cells labeled with the Biolegend TotalSeq™-B Human Universal Cocktail (CITEseq). This technology allowed for independent labeling of each cell line and single-cell analysis of the pooled seven cell lines and the pseudo-microenvironment. The data generated from the aforementioned experiments are available as part of an online tool, which allows users to define cell heterogeneity and generates count tables as an output. The tool provides the cell line derivation for each cell and cell annotations for the pseudo-microenvironment based on CITEseq data by an experienced immunologist. Additionally, we created a range of pseudo-tumor tissues using different ratios of the aforementioned cells embedded in matrigel. These tissues were analyzed using 10XGenomics (FFPE samples) and Curio Bioscience (fresh frozen samples) platforms for spatial transcriptomics, further expanding the scope of our benchmark experiments. The benchmark experiments we conducted provide a unique opportunity to evaluate the performance of bioinformatics tools for detecting and characterizing tumor heterogeneity at the single-cell level. Overall, our experiments provide a controlled and standardized environment for assessing the accuracy and robustness of bioinformatics tools for studying tumor heterogeneity at the single-cell level, which can ultimately lead to more precise and effective cancer diagnosis and treatment.Keywords: single cell omics, benchmark, spatial transcriptomics, CITEseq
Procedia PDF Downloads 11611699 A Biomimetic Approach for the Multi-Objective Optimization of Kinetic Façade Design
Authors: Do-Jin Jang, Sung-Ah Kim
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A kinetic façade responds to user requirements and environmental conditions. In designing a kinetic façade, kinetic patterns play a key role in determining its performance. This paper proposes a biomimetic method for the multi-objective optimization for kinetic façade design. The autonomous decentralized control system is combined with flocking algorithm. The flocking agents are autonomously reacting to sensor values and bring about kinetic patterns changing over time. A series of experiments were conducted to verify the potential and limitations of the flocking based decentralized control. As a result, it could show the highest performance balancing multiple objectives such as solar radiation and openness among the comparison group.Keywords: biomimicry, flocking algorithm, autonomous decentralized control, multi-objective optimization
Procedia PDF Downloads 51411698 Non-Adherence to Antidepressant Treatment and Its Predictors among Outpatients with Depressive Disorders
Authors: Selam Mulugeta, Barkot Milkias, Mesfin Araya, Abel Worku, Eyasu Mulugeta
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In Ethiopia, there is inadequate information on non-adherence to antidepressant treatment in patients with depressive disorders. Having awareness of the pattern of adherence is important in future prognosis, quality of life, and functionality in these patients. This hospital-based cross-sectional quantitative study was done on a sample of 216 consecutive outpatients with depressive disorders. Data were collected using questionnaires through in-person and phone call interviews. The 8-item Morisky scale was used to assess the pattern of medication adherence. Other specially developed tools were used to obtain sociodemographic and clinical information from electronic medical records and patient interviews. Data were analyzed using the Statistical Package for the Social Sciences Version - 25. Univariate and multivariable analyses were carried out to assess factors associated with non-adherence. 90% of the participants had a primary diagnosis of major depressive disorder. Based on the 8-item Morisky Medication Adherence Scale, the prevalence of non-adherence was found to be 84.7%. Living distance between 11 to 50 km from the hospital (AOR= 11, 95% CI (29,46.6)), post-secondary level of education (AOR= 8.3, 95% CI (1, 64.4)) and taking multiple medications (AOR= 6.1, 95% CI (1, 34.9)) were found to have significantly increased odds of non-adherence. Non-adherence was significantly associated with factors such as increased living distance from the hospital, relatively higher educational level, and polypharmacy. Proper and patient-centered psychoeducation, addressing the communication gap between patients and doctors, adherence to prescribing guidelines, avoiding polypharmacy unless indicated & working on accessibility of treatment is essential to decrease non-adherence.Keywords: depressive disorders, Ethiopia, medication adherence, Addis Ababa
Procedia PDF Downloads 14711697 Energy Management Method in DC Microgrid Based on the Equivalent Hydrogen Consumption Minimum Strategy
Authors: Ying Han, Weirong Chen, Qi Li
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An energy management method based on equivalent hydrogen consumption minimum strategy is proposed in this paper aiming at the direct-current (DC) microgrid consisting of photovoltaic cells, fuel cells, energy storage devices, converters and DC loads. The rational allocation of fuel cells and battery devices is achieved by adopting equivalent minimum hydrogen consumption strategy with the full use of power generated by photovoltaic cells. Considering the balance of the battery’s state of charge (SOC), the optimal power of the battery under different SOC conditions is obtained and the reference output power of the fuel cell is calculated. And then a droop control method based on time-varying droop coefficient is proposed to realize the automatic charge and discharge control of the battery, balance the system power and maintain the bus voltage. The proposed control strategy is verified by RT-LAB hardware-in-the-loop simulation platform. The simulation results show that the designed control algorithm can realize the rational allocation of DC micro-grid energy and improve the stability of system.Keywords: DC microgrid, equivalent minimum hydrogen consumption strategy, energy management, time-varying droop coefficient, droop control
Procedia PDF Downloads 30111696 Dental Management Particularities of Werner Syndrome: A Report of Two Cases
Authors: Emna Abid, Linda Chebbi, Yosra Mabrouk, Amel Labidi, Lamia Mansour
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Werner syndrome (WS) is a rare genetic disorder inherited in an autosomal recessive pattern characterized by accelerated aging. While extensive research has been conducted on its systemic manifestations, the specific dental implications of WS remain poorly understood. The medical history and the oral health status of two patients diagnosed with WS were detailed. Our findings revealed a high prevalence of dental problems in both patients, including periodontitis, xerostomia, and temporomandibular joint disorders. This article aims to investigate the dental challenges faced by individuals with WS as well as the prosthetic options envisaged through two clinical cases contributing to a deeper understanding of the dental implications of WS and to choose the appropriate prosthetic solution in this population. Future research should focus on larger scale studies and clinical trials to validate these proposed strategies.Keywords: adult progeria, clinical symptoms, oral manifestations, dental care, prosthetic management
Procedia PDF Downloads 5011695 Barriers to Health Promotion Advice Delivered by Paramedics and Emergency Department Nurses – Promoted Study
Authors: B. Schofield, F. Gul, S. McClean, R. Hoskins, R. Terry, U. Rolfe, A. Gibson, S. Voss, J. Benger
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Aim: The aim of this study is to determine whether and how health promotion activities are undertaken by paramedics and emergency department nurses and investigate ways of overcoming potential barriers. Background: Paramedics and emergency department nurses are uniquely placed to reach millions of people and could use these contacts as positive opportunities to help people improve their health by identifying people with risk factors and provide information, brief interventions, and signposting to locally provided services. These interventions can be carried out when the opportunity arises, typically take no more than a few minutes, have a low financial cost and can be a highly efficient method of health promotion. Methodology: Three NHS Emergency Departments and four Ambulance Trusts in England were recruited to the study. A link to an online survey was distributed to paramedics and emergency department nurses at participating sites. Staff were invited to participate in virtual semi-structured interviews. Patients seen, treated, and discharged at the participating sites were invited to virtual semistructured interviews. Findings: A total of 331 survey responses were received, 21 virtual semi-structured staff interviews and 11 patient interviews were completed. Staff reported lack of time to prioritise, lack of knowledge, resources, and confidence as barriers. Receptiveness of patients guided their decision to undertake health promotion activities. They reported a desire to learn how to undertake health promotion conversations. Emergency department nurses felt more supported than paramedics by their organisations to undertake health promotion activities. Patients were not aware of health promotion activities and reported fear and lack of privacy as barriers. Conclusions: These results will guide the development of an intervention to support the provision of health promotion by staff in urgent and emergency care settings. The components of the intervention will be mapped to a framework which will consider the needs of staff working within these settings, patients they treat, and organisational issues and practices related to the implementation of such an intervention.Keywords: emergency service, hospital, nursing, allied health personnel, emergency medical services, health promotion
Procedia PDF Downloads 6011694 A Multicenter Assessment on Psychological Well-Being Status among Medical Residents in the United Arab Emirates
Authors: Mahera Abdulrahman
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Objective: Healthcare transformation from traditional to modern in the country recently prompted the need to address career choices, accreditation perception and satisfaction among medical residents. However, a concerted nationwide study to understand and address burnout in the medical residency program has not been conducted in the UAE and the region. Methods: A nationwide, multicenter, cross-sectional study was designed to evaluate professional burnout and depression among medical residents in order to address the gap. Results: Our results indicate that 75.5% (216/286) of UAE medical residents had moderate to high emotional exhaustion, 84% (249/298) had high depersonalization, and 74% (216/291) had a low sense of personal accomplishment. In aggregate, 70% (212/302) of medical residents were considered to be experiencing at least one symptom of burnout based on a high emotional exhaustion score or a high depersonalization score. Depression ranging from 6-22%, depending on the specialty was also striking given the fact the Arab culture lays high emphasis on family bonding. Interestingly 83% (40/48) of medical residents who had high scores for depression also reported burnout. Conclusion: Our data indicate that burnout and depression among medical residents is epidemic. There is an immediate need to address burnout through effective interventions at both the individual and institutional levels. It is imperative to reconfigure the approach to medical training for the well-being of the next generation of physicians in the Arab world.Keywords: mental health, Gulf, Arab, residency training, burnout, depression
Procedia PDF Downloads 29411693 Hybrid Multipath Congestion Control
Authors: Akshit Singhal, Xuan Wang, Zhijun Wang, Hao Che, Hong Jiang
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Multiple Path Transmission Control Protocols (MPTCPs) allow flows to explore path diversity to improve the throughput, reliability and network resource utilization. However, the existing solutions may discourage users to adopt the solutions in the face of multipath scenario where different paths are charged based on different pricing structures, e.g., WiFi vs cellular connections, widely available for mobile phones. In this paper, we propose a Hybrid MPTCP (H-MPTCP) with a built-in mechanism to incentivize users to use multiple paths with different pricing structures. In the meantime, H-MPTCP preserves the nice properties enjoyed by the state-of-the-art MPTCP solutions. Extensive real Linux implementation results verify that H-MPTCP can indeed achieve the design objectives.Keywords: network, TCP, WiFi, cellular, congestion control
Procedia PDF Downloads 71211692 Mass Media and Tobacco in Bangladesh: An Investigation on the Role of Mass Media in the Light of Tobacco Control
Authors: Tahsina Sadeque Kapil Ahmed
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Context: The tobacco epidemic is one of the biggest public health threats the world has ever faced. Tobacco use is a widespread phenomenon in Bangladesh, and that causes numerous deaths and disabilities in a year. The studies conducted elsewhere have strengthened the evidence that mass media campaigns conducted in the context of comprehensive tobacco control programs can promote quitting and reduce smoking, as well as smokeless tobacco prevalence. Awareness building campaigns in mass-media against tobacco use should be prioritized more, and this paper will be an initiative towards enhancing mass-media’s role in controlling tobacco in Bangladesh. Objective: the main objective of this study is to investigate the role of mass-media in controlling tobacco in Bangladesh. Methods: This is a qualitative study and both primary, as well as secondary data were used where information gathered through the Key Informant Interviews (KIIs) and media contents. The employees of media houses (five national papers, two online news portals and six TV channels) were selected as study respondent. Media Content Analysis is used through the broad range of ‘texts’ from transcripts of interviews and discussions along with the materials like reports, footages, advertisements, talk-shows, articles etc. Results: The study result documented several opinions of discussants where Mass media was found to play a strong role in support of the amended tobacco control law and its implication that could be created public support against tobacco farming, exposing to companies’ tactics and other tobacco control activities. The study results also revealed that in controlling tobacco supply and demand effectively, media has been assisting the government and anti-tobacco activities productively. Majority of the Key Informants opined spontaneously on tobacco control program publicity, organizational interference, and influence of other activities on media. They also emphasized role of media for activities of anti-tobacco organizations, awareness building actions, popularization of tobacco control law and its amendment. Conclusion and Recommendation: The study shows evidence that mass media coverage of tobacco control issues is influencing the context of comprehensive tobacco control programs. To reduce tobacco consumption, along with strict enforcement efforts, media should be used to assist with the implementation of the tobacco control law. A sustained nationwide campaign to educate the masses against the dangers of smoking and smokeless tobacco is needed, and media can play an important role in creating further awareness about the dangers associated with tobacco consumption.Keywords: Bangladesh media, mass media, role of media, tobacco control
Procedia PDF Downloads 21211691 A Possible Connection Between Taste Change and Zinc Deficiency after Bariatric Surgery: A Literature Review
Authors: Boshra Mozaffar, Iskandar Idris
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Taste change is a common complication after Bariatric surgery (BS). However, the cause of this is still not clear. Since zinc is important fortaste perception, zinc deficiency, which is common after BS, may play an important role for taste change after BS. In this review, we aimto collate evidence relating to taste change and zinc deficiencyin relation to BS; effects of zinc replacement on taste perception in general and thereafter discuss the possible role of zinc deficiency to induce taste change after BS. A literature search was conducted, using four electronic bibliographical databases—EMBASE, PubMed, AMED and MEDLINE. We identified all available and relevant articles published before 30th February 2021.In total, 33 studies were included. The total number of participants analysed was N= 3264. We showed that taste change is a frequent complication after BS, especially after Roux-en-Y gastric bypass RYGBP comparing to other types of procedures. Patients' taste sensitivity differs among studies, but the most important decline in taste preference was observed for sweet food. Twelve studies investigating zinc deficiency following BS showed a significant decrease in zinc levels at six months after surgery. Supplementation with 45–50 mg of zinc sulphate was effective in improving taste, except in cancer patients, who showed no improvement in taste following zinc supplementation. Zinc deficiency appears to be associated with taste change after BS. Supplementation with much higher levels of zinc, at 45–50 mg, was effective in taste change treatment for many cases of taste disorder. The currently recommended levels of zinc replacements currently prescribed to patients following BS were not effective for avoiding zinc deficiency after BS—and thus not effective for averting taste change. It is therefore suggested that taste change following BS is closely related to zinc deficiency induced by the surgery.Keywords: taste change, taste disorder, bariatric surgery, zinc, zinc sulphate or Zn, deficiency, supplementation, and micro-nutrient deficiencies
Procedia PDF Downloads 18811690 Improvement plan for Integrity of Intensive Care Unit Patients Withdrawn from Life-Sustaining Medical Care
Authors: Shang-Sin Shiu, Shu-I Chin, Hsiu-Ju Chen, Ru-Yu Lien
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The Hospice and Palliative Care Act has undergone three revisions, making it less challenging for terminal patients to withdraw life support systems. However, the adequacy of care before withdraw is a crucial factor in end-of-life medical treatment. The author observed that intensive care unit (ICU) nursing staff often rely on simple flowcharts or word of mouth, leading to inadequate preparation and failure to meet patient needs before withdraw. This results in confusion or hesitation among those executing the process. Therefore, there is a motivation to improve the withdraw of patient care processes, establish standardized procedures, ensure the accuracy of removal execution, enhance end-of-life care self-efficacy for nursing staff, and improve the overall quality of care. The investigation identified key issues: the lack of applicable guidelines for ICU care for withdraw from life-sustaining, insufficient education and training on withdraw and end-of-life care, scattered locations of withdraw-related tools, and inadequate self-efficacy in withdraw from life-sustaining care. Solutions proposed include revising withdraw care processes and guidelines, integrating tools and locations, conducting educational courses, and forming support groups. After the project implementation, the accuracy of removal cognition improved from 78% to 96.5%, self-efficacy in end-of-life care after removal increased from 54.7% to 93.1%, and the correctness of care behavior progressed from 27.7% to 97.8%. It is recommended to regularly conduct courses on removing life support system care and grief consolation to enhance the quality of end-of-life care.Keywords: the intensive care unit (ICU) patients, nursing staff, withdraw life support systems, self-efficacy
Procedia PDF Downloads 5011689 The Uniting Control Lyapunov Functions in Permanent Magnet Synchronous Linear Motor
Authors: Yi-Fei Yang, Nai-Bao He, Shao-Bang Xing
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This study investigates the permanent magnet synchronous linear motor (PMSLM) chaotic motion under the specific physical parameters, the stability and the security of motor-driven system will be unavoidably influenced. Therefore, it is really necessary to investigate the methods of controlling or suppressing chaos in PMSLM. Firstly, we derive a chaotic model of PMSLM in the closed-loop system. Secondly, in order to realize the local asymptotic stabilization of the mechanical subsystem and the global stabilization of the motor-driven system including electrical subsystem, we propose an improved uniting control lyapunov functions by introducing backstepping approach. Finally, an illustrated example is also given to show the electiveness of the obtained results.Keywords: linear motor, lyapunov functions, chao control, hybrid controller
Procedia PDF Downloads 33511688 Laser Corneoplastique™: A Refractive Surgery for Corneal Scars
Authors: Arun C. Gulani, Aaishwariya A. Gulani, Amanda Southall
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Background: Laser Corneoplastique™ as a least interventional, visually promising technique for patients with vision disability from corneal scars of varied causes has been retrospectively reviewed and proves to cause a paradigm shift in mindset and approach towards corneal scars as a Refractive surgery aiming for emmetropic, unaided vision of 20;/20 in most cases. Three decades of work on this technique has been compiled in this 15-year study. Subject and Methods: The objective of this study was to determine the success of Laser Corneoplastique™ surgery as a treatment of corneal scar cases. A survey of corneal scar cases caused by various medical histories that had undergone Laser Corneoplastique™ surgery over the past twenty years by a single surgeon Arun C. Gulani, M.D. were retrospectively reviewed. The details of each of the cases were retrieved from their medical records and analyzed. Each patient had been examined thoroughly at their preoperative appointments for stability of refraction and vision, depth of scar, pachymetry, topography, pattern of the scar and uncorrected and best corrected vision potential, which were all taken into account in the patients' treatment plans. Results: 64 eyes of 53 patients were investigated for scar etiology, keratometry, visual acuity, and complications. There were 25 different etiologies seen, with the most common being a Herpetic scar. The average visual acuity post-op was, on average, 20/23.55 (±7.05). Laser parameters used were depth and pulses. Overall, the mean Laser ablation depth was 30.67 (±19.05), ranging from 2 to 73 µm. Number of Laser pulses averaged 191.85 (±112.02). Conclusion: Refractive Laser Corneoplastique™ surgery, when practiced as an art, can address all levels of ametropia while reversing complex corneas and scars from refractive surgery complications back to 20/20 vision.Keywords: corneal scar, refractive surgery, corneal transplant, laser corneoplastique
Procedia PDF Downloads 18711687 Backstepping Controller for a Variable Wind Speed Energy Conversion System Based on a DFIG
Authors: Sara Mensou, Ahmed Essadki, Issam Minka, Tamou Nasser, Badr Bououlid Idrissi
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In this paper we present a contribution for the modeling and control of wind energy conversion system based on a Doubly Fed Induction Generator (DFIG). Since the wind speed is random the system has to produce an optimal electrical power to the Network and ensures important strength and stability. In this work, the Backstepping controller is used to control the generator via two converter witch placed a DC bus capacitor and connected to the grid by a Filter R-L, in order to optimize capture wind energy. All is simulated and presented under MATLAB/Simulink Software to show performance and robustness of the proposed controller.Keywords: wind turbine, doubly fed induction generator, MPPT control, backstepping controller, power converter
Procedia PDF Downloads 18811686 Bank Internal Controls and Credit Risk in Europe: A Quantitative Measurement Approach
Authors: Ellis Kofi Akwaa-Sekyi, Jordi Moreno Gené
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Managerial actions which negatively profile banks and impair corporate reputation are addressed through effective internal control systems. Disregard for acceptable standards and procedures for granting credit have affected bank loan portfolios and could be cited for the crises in some European countries. The study intends to determine the effectiveness of internal control systems, investigate whether perceived agency problems exist on the part of board members and to establish the relationship between internal controls and credit risk among listed banks in the European Union. Drawing theoretical support from the behavioural compliance and agency theories, about seventeen internal control variables (drawn from the revised COSO framework), bank-specific, country, stock market and macro-economic variables will be involved in the study. A purely quantitative approach will be employed to model internal control variables covering the control environment, risk management, control activities, information and communication and monitoring. Panel data from 2005-2014 on listed banks from 28 European Union countries will be used for the study. Hypotheses will be tested and the Generalized Least Squares (GLS) regression will be run to establish the relationship between dependent and independent variables. The Hausman test will be used to select whether random or fixed effect model will be used. It is expected that listed banks will have sound internal control systems but their effectiveness cannot be confirmed. A perceived agency problem on the part of the board of directors is expected to be confirmed. The study expects significant effect of internal controls on credit risk. The study will uncover another perspective of internal controls as not only an operational risk issue but credit risk too. Banks will be cautious that observing effective internal control systems is an ethical and socially responsible act since the collapse (crisis) of financial institutions as a result of excessive default is a major contagion. This study deviates from the usual primary data approach to measuring internal control variables and rather models internal control variables in a quantitative approach for the panel data. Thus a grey area in approaching the revised COSO framework for internal controls is opened for further research. Most bank failures and crises could be averted if effective internal control systems are religiously adhered to.Keywords: agency theory, credit risk, internal controls, revised COSO framework
Procedia PDF Downloads 31511685 Challenges of Management of Acute Pancreatitis in Low Resource Setting
Authors: Md. Shakhawat Hossain, Jimma Hossain, Md. Naushad Ali
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Acute pancreatitis is a dangerous medical emergency in the practice of gastroenterology. Management of acute pancreatitis needs multidisciplinary approach with support starts from emergency to ICU. So, there is a chance of mismanagement in every steps, especially in low resource settings. Other factors such as patient’s financial condition, education, social custom, transport facility, referral system from periphery may also challenge the current guidelines for management. The present study is intended to determine the clinico-pathological profile, severity assessment and challenges of management of acute pancreatitis in a government laid tertiary care hospital to image the real scenario of management in a low resource place. A total 100 patients of acute pancreatitis were studied in this prospective study, held in the Department of Gastroenterology, Rangpur medical college hospital, Bangladesh from July 2017 to July 2018 within one year. Regarding severity, 85 % of the patients were mild, whereas 13 were moderately severe, and 2 had severe acute pancreatitis according to the revised Atlanta criteria. The most common etiologies of acute pancreatitis in our study were gall stone (15%) and biliary sludge (15%), whereas 54% were idiopathic. The most common challenges we faced were delay in hospital admission (59%) and delay in hospital diagnosis (20%). Others are non-adherence of patient party, and lack of investigation facility, physician’s poor knowledge about current guidelines. We were able to give early aggressive fluid to only 18% of patients as per current guideline. Conclusion: Management of acute pancreatitis as per guideline is challenging when optimum facility is lacking. So, modified guidelines for assessment and management of acute pancreatitis should be prepared for low resource setting.Keywords: acute pancreatitis, challenges of management, severity, prognosis
Procedia PDF Downloads 12811684 A System Dynamics Model for Analyzing Customer Satisfaction in Healthcare Systems
Authors: Mahdi Bastan, Ali Mohammad Ahmadvand, Fatemeh Soltani Khamsehpour
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Health organizations’ sustainable development has nowadays become highly affected by customers’ satisfaction due to significant changes made in the business environment of the healthcare system and emerging of Competitiveness paradigm. In case we look at the hospitals and other health organizations as service providers concerning profit issues, the satisfaction of employees as interior customers, and patients as exterior customers would be of significant importance in health business success. Furthermore, satisfaction rate could be considered in performance assessment of healthcare organizations as a perceived quality measure. Several researches have been carried out in identification of effective factors on patients’ satisfaction in health organizations. However, considering a systemic view, the complex causal relations among many components of healthcare system would be an issue that its acquisition and sustainability requires an understanding of the dynamic complexity, an appropriate cognition of different components, and effective relationships among them resulting ultimately in identifying the generative structure of patients’ satisfaction. Hence, the presenting paper applies system dynamics approaches coherently and methodologically to represent the systemic structure of customers’ satisfaction of a health system involving the constituent components and interactions among them. Then, the results of different policies taken on the system are simulated via developing mathematical models, identifying leverage points, and using scenario making technique and then, the best solutions are presented to improve customers’ satisfaction of the services. The presenting approach supports taking advantage of decision support systems. Additionally, relying on understanding of system behavior Dynamics, the effective policies for improving the health system would be recognized.Keywords: customer satisfaction, healthcare, scenario, simulation, system dynamics
Procedia PDF Downloads 41311683 A Systematic Review and Meta-Analysis in Slow Gait Speed and Its Association with Worse Postoperative Outcomes in Cardiac Surgery
Authors: Vignesh Ratnaraj, Jaewon Chang
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Background: Frailty is associated with poorer outcomes in cardiac surgery, but the heterogeneity in frailty assessment tools makes it difficult to ascertain its true impact in cardiac surgery. Slow gait speed is a simple, validated, and reliable marker of frailty. We performed a systematic review and meta-analysis to examine the effect of slow gait speed on postoperative cardiac surgical patients. Methods: PubMED, MEDLINE, and EMBASE databases were searched from January 2000 to August 2021 for studies comparing slow gait speed and “normal” gait speed. The primary outcome was in-hospital mortality. Secondary outcomes were composite mortality and major morbidity, AKI, stroke, deep sternal wound infection, prolonged ventilation, discharge to a healthcare facility, and ICU length of stay. Results: There were seven eligible studies with 36,697 patients. Slow gait speed was associated with an increased likelihood of in-hospital mortality (risk ratio [RR]: 2.32; 95% confidence interval [CI]: 1.87–2.87). Additionally, they were more likely to suffer from composite mortality and major morbidity (RR: 1.52; 95% CI: 1.38–1.66), AKI (RR: 2.81; 95% CI: 1.44–5.49), deep sternal wound infection (RR: 1.77; 95% CI: 1.59–1.98), prolonged ventilation >24 h (RR: 1.97; 95% CI: 1.48–2.63), reoperation (RR: 1.38; 95% CI: 1.05–1.82), institutional discharge (RR: 2.08; 95% CI: 1.61–2.69), and longer ICU length of stay (MD: 21.69; 95% CI: 17.32–26.05). Conclusion: Slow gait speed is associated with poorer outcomes in cardiac surgery. Frail patients are twofold more likely to die during hospital admission than non-frail counterparts and are at an increased risk of developing various perioperative complications.Keywords: cardiac surgery, gait speed, recovery, frailty
Procedia PDF Downloads 7111682 Comparative Study of Active Release Technique and Myofascial Release Technique in Patients with Upper Trapezius Spasm
Authors: Harihara Prakash Ramanathan, Daksha Mishra, Ankita Dhaduk
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Relevance: This qualitative study will educate the clinician in putting into practice the advanced method of movement science in restoring the function. Purpose: The purpose of this study is to compare the effectiveness of Active Release Technique and myofascial release technique on range of motion, neck function and pain in patients with upper trapezius spasm. Methods/Analysis: The study was approved by the institutional Human Research and Ethics committee. This study included sixty patients of age group between 20 to 55 years with upper trapezius spasm. Patients were randomly divided into two groups receiving Active Release Technique (Group A) and Myofascial Release Technique (Group B). The patients were treated for 1 week and three outcome measures ROM, pain and functional level were measured using Goniometer, Visual analog scale(VAS), Neck disability Index Questionnaire(NDI) respectively. Paired Sample 't' test was used to compare the differences of pre and post intervention values of Cervical Range of motion, Neck disability Index, Visual analog scale of Group A and Group B. Independent't' test was used to compare the differences between two groups in terms of improvement in cervical range of motion, decrease in visual analogue scale(VAS), decrease in Neck disability index score. Results: Both the groups showed statistically significant improvements in cervical ROM, reduction in pain and in NDI scores. However, mean change in Cervical flexion, cervical extension, right side flexion, left side flexion, right side rotation, left side rotation, pain, neck disability level showed statistically significant improvement (P < 0. 05)) in the patients who received Active Release Technique as compared to Myofascial release technique. Discussion and conclusions: In present study, the average improvement immediately post intervention is significantly greater as compared to before treatment but there is even more improvement after seven sessions as compared to single session. Hence, this proves that several sessions of Manual techniques are necessary to produce clinically relevant results. Active release technique help to reduce the pain threshold by removing adhesion and promote normal tissue extensibility. The act of tensioning and compressing the affected tissue both with digital contact and through the active movement performed by the patient can be a plausible mechanism for tissue healing in this study. This study concluded that both Active Release Technique (ART) and Myofascial release technique (MFR) are equally effective in managing upper trapezius muscle spasm, but more improvement can be achieved by Active Release Technique (ART). Impact and Implications: Active Release Technique can be adopted as mainstay of treatment approach in treating trapezius spasm for faster relief and improving the functional status.Keywords: trapezius spasm, myofascial release, active release technique, pain
Procedia PDF Downloads 27211681 The Second Generation of Tyrosine Kinase Inhibitor Afatinib Controls Inflammation by Regulating NLRP3 Inflammasome Activation
Authors: Shujun Xie, Shirong Zhang, Shenglin Ma
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Background: Chronic inflammation might lead to many malignancies, and inadequate resolution could play a crucial role in tumor invasion, progression, and metastases. A randomised, double-blind, placebo-controlled trial shows that IL-1β inhibition with canakinumab could reduce incident lung cancer and lung cancer mortality in patients with atherosclerosis. The process and secretion of proinflammatory cytokine IL-1β are controlled by the inflammasome. Here we showed the correlation of the innate immune system and afatinib, a tyrosine kinase inhibitor targeting epidermal growth factor receptor (EGFR) in non-small cell lung cancer. Methods: Murine Bone marrow derived macrophages (BMDMs), peritoneal macrophages (PMs) and THP-1 were used to check the effect of afatinib on the activation of NLRP3 inflammasome. The assembly of NLRP3 inflammasome was check by co-immunoprecipitation of NLRP3 and apoptosis-associated speck-like protein containing CARD (ASC), disuccinimidyl suberate (DSS)-cross link of ASC. Lipopolysaccharide (LPS)-induced sepsis and Alum-induced peritonitis were conducted to confirm that afatinib could inhibit the activation of NLRP3 in vivo. Peripheral blood mononuclear cells (PBMCs) from non-small cell lung cancer (NSCLC) patients before or after taking afatinib were used to check that afatinib inhibits inflammation in NSCLC therapy. Results: Our data showed that afatinib could inhibit the secretion of IL-1β in a dose-dependent manner in macrophage. Moreover, afatinib could inhibit the maturation of IL-1β and caspase-1 without affecting the precursors of IL-1β and caspase-1. Next, we found that afatinib could block the assembly of NLRP3 inflammasome and the ASC speck by blocking the interaction of the sensor protein NLRP3 and the adaptor protein ASC. We also found that afatinib was able to alleviate the LPS-induced sepsis in vivo. Conclusion: Our study found that afatinib could inhibit the activation of NLRP3 inflammasome in macrophage, providing new evidence that afatinib could target the innate immune system to control chronic inflammation. These investigations will provide significant experimental evidence in afatinib as therapeutic drug for non-small cell lung cancer or other tumors and NLRP3-related diseases and will explore new targets for afatinib.Keywords: inflammasome, afatinib, inflammation, tyrosine kinase inhibitor
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