Search results for: neuromuscular disease

Authors: I. Hua Chu, Hsiang-Chi Yu, Hsuan Su

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Purpose: To examine the associations between self-determined motivation and physical activity in patients with coronary heart disease (CHD) in a longitudinal study. Methods: Patients with CHD were recruited for this study. Their motivations for exercise were measured by the Behavioral Regulation in Exercise Questionnaire-2 (BREQ-2). Physical activity was assessed using the 7-day physical activity recall questionnaire. Duration and energy expenditure of moderate to vigorous physical activity (MVPA) were used in data analysis. All outcome measures were assessed at baseline and 12 months follow up. Data were analyzed using Pearson correlation analysis and regression analysis. Results: The results of the 45 participants (mean age 60.24 yr; 90.2% male) revealed that there were significant negative correlations between amotivation at baseline and duration (r=-.295, p=.049) and energy expenditure (r=-.300, p=.045) of MVPA at 12 months. In contrast, there were significant positive correlations between calculated relative autonomy index (RAI) at baseline and duration (r=.377, p=.011) and energy expenditure (r=.382, p=.010) of MVPA at 12 months. There was no significant correlation between other subscales of the BREQ-2 and duration or energy expenditure of MVPA. Regression analyses revealed that RAI was a significant predictor of duration (p=.011) and energy expenditure (p=.010) of MVPA at 12 months follow-up. Conclusions: These results suggest that the relative degree of self-determined motivation could predict long-term MVPA behaviors in CHD patients. Physical activity interventions are recommended to target enhancing one’s identified and intrinsic motivation to increase the likelihood of physical activity participation in this population.

Keywords: self-determined motivation, physical activity, coronary heart disease, relative autonomy index (RAI)

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Authors: Hanane Boutaj, Abdelilah Meddich, Said Wahbi, Zainab El Alaoui-Talibi, Allal Douira, Abdelkarim Filali-Maltouf, Cherkaoui El Modafar

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The present work aims to investigate the effect of arbuscular mycorrhizal fungi (AMF) in improving the olive tree resistance to Verticillium wilt caused by Verticillium dahliae. Inoculated plants with a mycorrhizal autochthonous consortium 'Rhizolive consortium' and pure strain 'Glomus irregulare' were infected after three months with V. dahliae. The improving of olive tree resistance was determined through disease severity, incidence, and defoliation. On the other hand, the defense mechanisms of olive plants were evaluated through lignin content, phenylalanine ammonia lyase (PAL) activity, and polyphenol content. The results revealed that both AMF significantly (p < 0.05) reduced disease development and the rate of defoliation in infected olive plants. Moreover, the contents of lignin were boosted after mycorrhizal inoculation in both the roots and the stems of olive plants, which remained significantly (p < 0.001) higher after the 90th days of V. dahliae inoculation. PAL activity was increased after V. dahliae inoculation in the stems of 'Rhizolive consortium' treatment that were 17 times higher than those in the roots of olive plants. The polyphenol content in the stems was about twice higher than those in the roots. The reduction of disease severity was accompanied by increased levels of lignin content, PAL activity, and polyphenol content, particularly in the stems of olive plants, indicating the strengthening of the olive plant immune system against V. dahliae.

Keywords: olive tree, Mycorrhizal autochthonous consortium, Glomus irregulare, Verticillium dahliae, defense mechanisms

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Authors: Shireen Ibish

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Physical inactivity and unhealthy diets have contributed to a global burden of disease with increased relation to non-communicable diseases, increased risk of colon and breast cancer, high prevalence of depression, reduced quality of life and early death. The World Health Organisation’s facts on Obesity show a tripling in prevalence across the European Region since the 1980s. This has lead to a huge public health burden, being responsible for and 10-13% of deaths (fourth largest cause of global mortality) and 2-8% of health costs in the Region. In the UK alone, the present cost of physical inactivity has been estimated to be £8.2 billion. In 2002 a paper published in the International Journal of Epidemiology on ‘sedentary’ lifestyle, put into figures the increasingly worrying statistics across European countries. “Percentages of sedentary lifestyles across European countries ranged between 43.3% (Sweden) and 87.8% (Portugal)”. This was especially so amongst obese subjects, less- educated people, and smokers. While in the UK’s “50% of adult population in the UK is predicted to be obese by 2050.” Sports and Exercise Medicine, as a specialty, has a lot to offer in targeting this globally increasing epidemic. The worrying figures and the increasing knowledge of combating and preventing this issue have lead to increased awareness amongst the medical profession and more targeted interventions to reduce the burden of disease. “The public health element of the specialty is critical – this is not simply a specialty for the management of elite athletes’ medical conditions – it is central to the promotion of exercise as a means of disease prevention, to enhance well-being and in the management of disease.” WHO advised on creating National policies, encouraging and providing opportunities for greater physical activity, and improve the affordability, availability and accessibility of healthy foods. In the UK various different movements have been established to target this problem. The Motivate2Move, Move Eat Treat and guidelines advising specialties on targeting and encouraging exercise in the population (Sport and Exercise Medicine A Fresh Approach).

Keywords: sedentary lifestyle, obesity, public health burden, medicine

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Authors: Elidrissi Laila, El Rhaoussi Fatima-Zahra, Haddad Fouad, Tahiri Mohamed, Hliwa Wafaa, Bellabah Ahmed, Badre Wafaa

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Introduction: Metabolic Dysfunction Associated with Non-Alcoholic Fatty Liver Disease (MASLD), formerly known as Non-Alcoholic Fatty Liver Disease (NAFLD), is the leading cause of chronic liver disease. The cardiometabolic risk factors associated with MASLD represent common health issues and significant public health challenges. Medical students, being active participants in the healthcare system and a young demographic, are particularly relevant for understanding this entity to prevent its occurrence on a personal and collective level. The objective of our study is to assess the level of knowledge among medical students regarding MASLD, its risk factors, and its long-term consequences. Materials and Methods: We conducted a descriptive cross-sectional study using an anonymous questionnaire distributed through social media over a period of 2 weeks. Medical students from various faculties in Morocco answered 22 questions about MASLD, its etiological factors, diagnosis, complications, and principles of treatment. All responses were analyzed using the Jamovi software. Results: A total of 124 students voluntarily provided complete responses. 59% of our participants were in their 3rd year, with a median age of 21 years. Among the respondents, 27% were overweight, obese, or diabetic. 83% correctly answered more than half of the questions, and 77% believed they knew about MASLD. However, 84% of students were unaware that MASLD is the leading cause of chronic liver disease, and 12% even considered it a rare condition. Regarding etiological factors, overweight and obesity were mentioned in 93% of responses, and type 2 diabetes in 84%. 62% of participants believed that type 1 diabetes could not be implicated in MASLD. For 83 students, MASLD was considered a diagnosis of exclusion, while 41 students believed that a biopsy was mandatory for diagnosis. 12% believed that MASLD did not lead to long-term complications, and 44% were unaware that MASLD could progress to hepatocellular carcinoma. Regarding treatment, 85% included weight loss, and 19% did not consider diabetes management as a therapeutic approach for MASLD. At the end of the questionnaire, 89% of the students expressed a desire to learn more about MASLD and were invited to access an informative sheet through a hyperlink. Conclusion: MASLD represents a significant public health concern due to the prevalence of its risk factors, notably the obesity pandemic, which is widespread among the young population. There is a need for awareness about the seriousness of this emerging and long-underestimated condition among young future physicians.

Keywords: MASLD, medical students, obesity, diabetes

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Authors: Huimin Zhao, Xiaoquan Liu, Haochen Liu

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The major challenge facing Alzheimer's Disease (AD) drug development is how to effectively improve cognitive function in clinical practice. Growing evidence indicates that stimulating hippocampal neurogenesis is a strategy for restoring cognition in animal models of AD. The mitogen-activated protein kinase (MAPK) pathway is a crucial factor in neurogenesis, which is negatively regulated by Dual-specificity phosphatase 16 (DUSP16). Transcriptome analysis of post-mortem brain tissue revealed up-regulation of DUSP16 expression in AD patients. Additionally, DUSP16 was involved in regulating the proliferation and neural differentiation of neural progenitor cells (NPCs). Nevertheless, whether the effect of DUSP16 on ameliorating cognitive disorders by influencing NPCs differentiation in AD mice remains unclear. Our study demonstrates an association between DUSP16 SNPs and clinical progression in individuals with mild cognitive impairment (MCI). Besides, we found that increased DUSP16 expression in both 3×Tg and SAMP8 models of AD led to NPC differentiation impairments. By silencing DUSP16, cognitive benefits, the induction of AHN and synaptic plasticity, were observed in AD mice. Furthermore, we found that DUSP16 is involved in the process of NPC differentiation by regulating c-Jun N-terminal kinase (JNK) phosphorylation. Moreover, the increased DUSP16 may be regulated by the ETS transcription factor (ELK1), which binds to the promoter region of DUSP16. Loss of ELK1 resulted in decreased DUSP16 mRNA and protein levels. Our data uncover a potential regulatory role for DUSP16 in adult hippocampal neurogenesis and provide a possibility to find the target of AD intervention.

Keywords: alzheimer's disease, cognitive function, DUSP16, hippocampal neurogenesis

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Authors: Yan Lu, Song Hong, Janakiraman Udaiyappan, Aarti Nagayach, Quoc-Viet A. Duong, Masao Morita, Shun Saito, Yuichi Kobayashi, Yuhai, Zhao, Hongying Peng, Nicholas B. Pham, Walter J Lukiw, Christopher A. Vuong, Nicolas G. Bazan

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Aims: Neurodegeneration and behavior dysfunction occurs in patients with Alzheimer's Disease (AD), and as the disease progresses many patients develop cognitive impairment. 5XFAD mouse model of AD is widely used to study AD pathogenesis and treatment. This study aimed to investigate the effect of maresin like 1 (MaR-L1) treatment in AD pathology using 5XFAD mice. Methods: We tested 12-month-old male 5XFAD mice and wild type control mice treated with MaR-L1 in a battery of behavioral tasks. We performed open field test, beam walking test, clasping test, inverted grid test, acetone test, marble burring test, elevated plus maze test, cross maze test and novel object recognition test. We also studied neuronal loss, amyloid β burden, and inflammation in the brains of 5XFAD mice using immunohistology and Western blotting. Results: MaR-L1 treatment to the 5XFAD mice showed improved cognitive function of 5XFAD mice. MaR-L1 showed decreased anxiety behavior in open field test and marble burring test, increased muscular strength in the beam walking test, clasping test and inverted grid test. Cognitive function was improved in MaR-L1 treated 5XFAD mice in the novel object recognition test. MaR-L1 prevented neuronal loss and aberrant inflammation. Conclusion: Our finding suggests that behavioral abnormalities were normalized by the administration of MaR-L1 and the neuroprotective role of MaR-L1 in the AD. It also indicates that MaR-L1 treatment is able to prevent and or ameliorate neuronal loss and aberrant inflammation. Further experiments to validate the results are warranted using other AD models in the future.

Keywords: Alzheimer's disease, motor and cognitive behavior, 5XFAD mice, Maresin Like 1, microglial cell, astrocyte, neurodegeneration, inflammation, resolution of inflammation

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

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

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

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Authors: Sina Mahdavi

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Background and Objective: Multiple sclerosis (MS) is the most common inflammatory autoimmune disease of the central nervous system (CNS) that affects the myelination process in the CNS. Complex interactions of various "environmental or infectious" factors may act as triggers in autoimmunity and disease progression. The association between viral infections, especially Epstein-Barr virus (EBV) and MS, is one potential cause that is not well understood. In this study, we aim to summarize the available data on EBV infection in MS disease progression. Materials and Methods: For this study, the keywords "Multiple sclerosis," "Epstein-Barr virus," and "central nervous system" in the databases PubMed, Google Scholar, Sid, and MagIran between 2016 and 2022 were searched, and 14 articles were chosen, studied, and analyzed. Results: Demyelinated lesions isolated from MS patients contain EBNAs from EBV proteins. The EBNA1 domain contains a pentapeptide fragment identical to B-crystallin, a heat shock peptide, that is increased in peripheral B cells in response to B-crystallin infection, resulting in myelin-directed autoimmunity mediated by proinflammatory T cells. EBNA2, which is involved in the regulation of viral transcription, may enhance transcription from MS risk loci. A 7-fold increase in the risk of MS has been observed in EBV infection with HLA-DR15 synergy. Conclusion: EBV infection along with a variety of specific genetic risk alleles, cause inflammatory cascades in the CNS by infected B cells. There is a high expression of EBV during the course of MS, which indicates the relationship between EBV and MS, that this virus can play a role in the development of MS by creating an inflammatory state. Therefore, measures to modulate the expression of EBV may be effective in reducing inflammatory processes in demyelinated areas of MS patients.

Keywords: multiple sclerosis, Epstein-Barr virus, central nervous system, EBNAs

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Authors: Raphael M. Ritti-Dias, Marilia A. Correia, Wagner J. R. Domingues, Aline C. Palmeira, Paulo Longano, Nelson Wolosker, Lauro C. Vianna, Gabriel G. Cucato

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Patients with peripheral arterial disease (PAD) have a high prevalence of hypertension, which contributes to a high risk of acute cardiovascular events and cardiovascular mortality. Strategies to reduce cardiovascular risk of these patients are needed. Meta-analysis studies have shown that isometric handgrip training promotes reductions in clinical blood pressure in normotensive, pre-hypertensive and hypertensive individuals. However, the effect of this exercise training on other cardiovascular function indicators in PAD patients remains unknown. Thus, the aim of this study was to analyze the effects of isometric handgrip training on blood pressure in patients with PAD. In this clinical trial, 28 patients were randomly allocated into two groups: isometric handgrip training (HG) and control (CG). The HG conducted the unilateral handgrip training three days per week (four sets of two minutes, with 30% of maximum voluntary contraction with an interval of four minutes between sets). CG was encouraged to increase their physical activity levels. At baseline and after eight weeks blood pressure and heart rate were obtained. ANOVA two-way for repeated measures with the group (GH and GC) and time (pre- and post-intervention) as factors was performed. After 8 weeks of training there were no significant changes in systolic blood pressure (HG pre 141 ± 24.0 mmHg vs. HG post 142 ± 22.0 mmHg; CG pre 140 ± 22.1 mmHg vs. CG post 146 ± 16.2 mmHg; P=0.18), diastolic blood pressure (HG pre 74 ± 10.4 mmHg vs. HG post 74 ± 11.9 mmHg; CG pre 72 ± 6.9 mmHg vs. CG post 74 ± 8.0 mmHg; P=0.22) and heart rate (HG pre 61 ± 10.5 bpm vs. HG post 62 ± 8.0 bpm; CG pre 64 ± 11.8 bpm vs. CG post 65 ± 13.6 bpm; P=0.81). In conclusion, our preliminary data indicate that isometric handgrip training did not modify blood pressure and heart rate in patients with PAD.

Keywords: blood pressure, exercise, isometric, peripheral artery disease

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Authors: Anneke Van Biljon

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Background: Exercise is a primary form of preventing and improving cardiometabolic disease risk factors; however specific exercise variables and their associated health benefits in children are inconclusive. A preliminary study revealed that different exercise variables may improve particular cardiometabolic health benefits. Objectives: This study further investigated the specific cardiometabolic health benefits associated with three isocaloric exercise interventions set at different intensities. Methods: Hundred-and-twenty (n = 120) participants between the ages of 10 – 14 years old were assigned to four different study groups 1. High intensity interval training (HIIT) at > 80% MHR 2. Moderate intensity continuous training (MICT) at 65% – 70% MHR 3. Alternative intensities (ALT) of HIIT and MICT 4. Control group. Exercise interventions were designed to generate isocaloric workloads of ~154.77 kcal per session, three times per week for five weeks. The one-way ANOVA test established comparisons between group means. Post hoc tests were calculated to determine specific group differences. Results: Although, all exercise groups improved cardiometabolic health, the MICT group showed greater improvements in fasting glucose (-9.30%), whereas cardiorespiratory fitness increased most by 31.33% (p = 0.000) within the HIIT group. Finally, ALT group recorded overall superior and additional cardiometabolic health benefits compared with both MICT and HIIT groups. Conclusion: The findings of this study indicate that superior benefits may be elicited when combining and alternating MICT and HIIT. These results provide specific exercise recommendations for achieving optimal and substantial cardiometabolic health benefits in children which will contribute towards achieving the health-related Sustainable Development Goals for 2030.

Keywords: cardiometabolic disease risk factors, exercise, pediatrics, interventions

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Authors: Ankita Shukla, Tiratha Raj Singh

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Colorectal cancer (CRC) imposes serious mortality burden worldwide and it has been increasing for past consecutive years. Continuous efforts have been made so far to diagnose the disease condition and to identify the root cause for it. In this study, we performed the pathway level as well as the differential gene expression studies for CRC. We analyzed the gene expression profile GSE24514 from Gene Expression Omnibus (GEO) along with the gene pathways involved in the CRC. This analysis helps us to understand the behavior of the genes that have shown differential expression through their targeted pathways. Pathway analysis for the targeted genes covers the wider area which therefore decreases the possibility to miss the significant ones. This will prove to be beneficial to expose the ones that have not been given attention so far. Through this analysis, we attempt to understand the various neighboring genes that have close relationship to the targeted one and thus proved to be significantly controlling the CRC. It is anticipated that the identified hub and neighboring genes will provide new directions to look at the pathway level differently and will be crucial for the regulatory processes of the disease.

Keywords: mismatch repair, microsatellite instability, carcinogenesis, morbidity

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Authors: Cornelia-Eugenia Munteanu

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The goal of this paper is to present the diagnostic contribution that the screening instrument, Mini-Mental State Examination-2: Expanded Version (MMSE-2:EV), brings in detecting the cognitive impairment or in monitoring the progress of degenerative disorders. The diagnostic signification is underlined by the interpretation of the MMSE-2:EV scores, resulted from the test application to patients with mild and major neurocognitive disorders. The original MMSE is one of the most widely used screening tools for detecting the cognitive impairment, in clinical settings, but also in the field of neurocognitive research. Now, the practitioners and researchers are turning their attention to the MMSE-2. To enhance its clinical utility, the new instrument was enriched and reorganized in three versions (MMSE-2:BV, MMSE-2:SV and MMSE-2:EV), each with two forms: blue and red. The MMSE-2 was adapted and used successfully in Romania since 2013. The cases were selected from current practice, in order to cover vast and significant neurocognitive pathology: mild cognitive impairment, Alzheimer’s disease, vascular dementia, mixed dementia, Parkinson’s disease, conversion of the mild cognitive impairment into Alzheimer’s disease. The MMSE-2:EV version was used: it was applied one month after the initial assessment, three months after the first reevaluation and then every six months, alternating the blue and red forms. Correlated with age and educational level, the raw scores were converted in T scores and then, with the mean and the standard deviation, the z scores were calculated. The differences of raw scores between the evaluations were analyzed from the point of view of statistic signification, in order to establish the progression in time of the disease. The results indicated that the psycho-diagnostic approach for the evaluation of the cognitive impairment with MMSE-2:EV is safe and the application interval is optimal. The alternation of the forms prevents the learning phenomenon. The diagnostic accuracy and efficient therapeutic conduct derive from the usage of the national test norms. In clinical settings with a large flux of patients, the application of the MMSE-2:EV is a safe and fast psycho-diagnostic solution. The clinicians can draw objective decisions and for the patients: it doesn’t take too much time and energy, it doesn’t bother them and it doesn’t force them to travel frequently.

Keywords: MMSE-2, dementia, cognitive impairment, neuropsychology

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Authors: Deepanjali Gurav, Kun Qian

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In-vitro metabolic diagnosis relies on designed materials-based analytical platforms for detection of selected metabolites in biological samples, which has a key role in disease detection and therapeutic evaluation in clinics. However, the basic challenge deals with developing a simple approach for metabolic analysis in bio-samples with high sample complexity and low molecular abundance. In this work, we report a designer plasmonic nanoshells based platform for direct detection of small metabolites in clinical samples for in-vitro metabolic diagnostics. We first synthesized a series of plasmonic core-shell particles with tunable nanoshell structures. The optimized plasmonic nanoshells as new matrices allowed fast, multiplex, sensitive, and selective LDI MS (Laser desorption/ionization mass spectrometry) detection of small metabolites in 0.5 μL of bio-fluids without enrichment or purification. Furthermore, coupling with isotopic quantification of selected metabolites, we demonstrated the use of these plasmonic nanoshells for disease detection and therapeutic evaluation in clinics. For disease detection, we identified patients with postoperative brain infection through glucose quantitation and daily monitoring by cerebrospinal fluid (CSF) analysis. For therapeutic evaluation, we investigated drug distribution in blood and CSF systems and validated the function and permeability of blood-brain/CSF-barriers, during therapeutic treatment of patients with cerebral edema for pharmacokinetic study. Our work sheds light on the design of materials for high-performance metabolic analysis and precision diagnostics in real cases.

Keywords: plasmonic nanoparticles, metabolites, fingerprinting, mass spectrometry, in-vitro diagnostics

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Authors: Shaine Mehta, Neelam Parmar, Patrick White, Mark Ashworth

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Patients with a history of substance have a high prevalence of comorbidities, including asthma and chronic obstructive pulmonary disease (COPD). Mortality rates are higher than that of the general population and the link to respiratory disease is reported. Randomised controlled trials (RCTs) support opioid substitution therapy as an effective means for harm reduction. However, whilst a high proportion of patients receiving opioid substitution therapy are smokers, to the author’s best knowledge there have been no studies of respiratory disease and smoking intensity in these patients. A cross sectional prevalence study was conducted using an anonymised patient-level database in primary care, Lambeth DataNet (LDN). We included patients aged 18 years and over who had records of ever having been prescribed methadone in primary care. Patients under 18 years old or prescribed buprenorphine (because of uncertainty about the prescribing indication) were excluded. Demographic, smoking, alcohol and asthma and COPD coding data were extracted. Differences between methadone and non-methadone users were explored with multivariable analysis. LDN contained data on 321, 395 patients ≥ 18 years; 676 (0.16%) had a record of methadone prescription. Patients prescribed methadone were more likely to be male (70.7% vs. 50.4%), older (48.9yrs vs. 41.5yrs) and less likely to be from an ethnic minority group (South Asian 2.1% vs. 7.8%; Black African 8.9% vs. 21.4%). Almost all those prescribed methadone were smokers or ex-smokers (97.3% vs. 40.9%); more were non-alcohol drinkers (41.3% vs. 24.3%). We found a high prevalence of COPD (12.4% vs 1.4%) and asthma (14.2% vs 4.4%). Smoking intensity data shows a high prevalence of ≥ 20 cigarettes per day (21.5% vs. 13.1%). Risk of COPD, adjusted for age, gender, ethnicity and deprivation, was raised in smokers: odds ratio 14.81 (95%CI 11.26, 19.47), and in the methadone group: OR 7.51 (95%CI: 5.78, 9.77). Furthermore, after adjustment for smoking intensity (number of cigarettes/day), the risk was raised in methadone group: OR 4.77 (95%CI: 3.13, 7.28). High burden of respiratory disease compounded by the high rates of smoking is a public health concern. This supports an integrated approach to health in patients treated for opiate dependence, with access to smoking cessation support. Further work may evaluate the current structure and commissioning of substance misuse services, including smoking cessation. Regression modelling highlights that methadone as a ‘risk factor’ was independently associated with COPD prevalence, even after adjustment for smoking intensity. This merits further exploration, as the association may be related to unexplored aspects of smoking (such as the number of years smoked) or may be related to other related exposures, such as smoking heroin or crack cocaine.

Keywords: methadone, respiratory disease, smoking cessation, substance misuse

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Authors: Netasha Shaikh, Bryony Wood, Demitra Tsivos, Michael Knight, Risto Kauppinen, Elizabeth Coulthard

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Background: Effective treatment of dementia will require early diagnosis, before significant brain damage has accumulated. Memory loss is an early symptom of Alzheimer’s disease (AD). The hippocampus, a brain area critical for memory, degenerates early in the course of AD. The hippocampus comprises several subfields. In contrast to healthy aging where CA3 and dentate gyrus are the hippocampal subfields with most prominent atrophy, in AD the CA1 and subiculum are thought to be affected early. Conventional clinical structural neuroimaging is not sufficiently sensitive to identify preferential atrophy in individual subfields. Here, we will explore the sensitivity of new magnetic resonance imaging (MRI) sequences designed to interrogate medial temporal regions as an early marker of Alzheimer’s. As it is likely a combination of tests may predict early Alzheimer’s disease (AD) better than any single test, we look at the potential efficacy of such imaging alone and in combination with standard and novel cognitive tasks of hippocampal dependent memory. Methods: 20 patients with mild cognitive impairment (MCI), 20 with mild-moderate AD and 20 age-matched healthy elderly controls (HC) are being recruited to undergo 3T MRI (with sequences designed to allow volumetric analysis of hippocampal subfields) and a battery of cognitive tasks (including Paired Associative Learning from CANTAB, Hopkins Verbal Learning Test and a novel hippocampal-dependent abstract word memory task). AD participants and healthy controls are being tested just once whereas patients with MCI will be tested twice a year apart. We will compare subfield size between groups and correlate subfield size with cognitive performance on our tasks. In the MCI group, we will explore the relationship between subfield volume, cognitive test performance and deterioration in clinical condition over a year. Results: Preliminary data (currently on 16 participants: 2 AD; 4 MCI; 9 HC) have revealed subfield size differences between subject groups. Patients with AD perform with less accuracy on tasks of hippocampal-dependent memory, and MCI patient performance and reaction times also differ from healthy controls. With further testing, we hope to delineate how subfield-specific atrophy corresponds with changes in cognitive function, and characterise how this progresses over the time course of the disease. Conclusion: Novel sequences on a MRI scanner such as those in route in clinical use can be used to delineate hippocampal subfields in patients with and without dementia. Preliminary data suggest that such subfield analysis, perhaps in combination with cognitive tasks, may be an early marker of AD.

Keywords: Alzheimer's disease, dementia, memory, cognition, hippocampus

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Authors: Aneena Suresh, C. S. Sidharth

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Drug related problems (DRPs) are common in chronic kidney disease (CKD) patients and end stage patients undergoing hemodialysis. To treat the co-morbid conditions of the patients, more complex therapeutic regimen is required, and it leads to development of DRPs. So, this calls for frequent monitoring of the patients. Due to the busy work schedules, physicians are unable to deliver optimal care to these patients. Addition of a clinical pharmacist in the team will improve the standard of care offered to CKD patients by minimizing DRPs. In India, the role of clinical pharmacists in the improving the health outcomes in CKD patients is poorly recognized. Therefore, this study is conducted to put an insight on the role of clinical pharmacist in improving Drug Related Problems in patients with chronic kidney disease, thereby helping them to achieve desired therapeutic outcomes in the patients. A prospective interventional study was conducted for a year in a 620 bedded tertiary care hospital in India. Data was collected using an unstructured questionnaire, medication charts, etc. DRPs were categorized using Hepler and Strand classification. Relationships between the age, weight, GFR, average no of medication taken, average no of comorbidities, and average length of hospital days with the DRPs were identified using Mann Whitney U test. The study population primarily constituted of patients above the age of 50 years with a mean age of 59.91±13.59. Our study showed that 25% of the population presented with DRPs. On an average, CKD patients are prescribed at least 8 medications for the treatment in our study. This explains the high incidence of drug interactions in patients suffering from CKD (45.65%). The least common DRPs in our study were found to be sub therapeutic dose (2%) and adverse drug reactions (2%). Out of this, 60 % of the DRPs were addressed successfully. In our study, there is an association between the DRPs with the average number of medications prescribed, the average number of comorbidities, and the length of the hospital days with p value of 0.022, 0.004, and 0.000, respectively. In the current study, 86% of the proposed interventions were accepted, and 41 % were implemented by the physician, and only 14% were rejected. Hence, it is evident that clinical pharmacist interventions will contribute significantly to diminish the DRPs in CKD patients, thereby decreasing the economic burden of healthcare costs and improving patient’s quality of life.

Keywords: chronic kidney disease, clinical pharmacist, drug related problem, intervention

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Authors: Mohammed Bnebaghdad, Feriel Betouche, Malika Semmani

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Image processing become more sophisticated over time due to technological advances, especially artificial intelligence (AI) technology. Currently, AI image processing is used in many areas, including surveillance, industry, science, and medicine. AI in medical image processing can help doctors diagnose diseases faster, with minimal mistakes, and with less effort. Among these diseases is malaria, which remains a major public health challenge in many parts of the world. It affects millions of people every year, particularly in tropical and subtropical regions. Early detection of malaria is essential to prevent serious complications and reduce the burden of the disease. In this paper, we propose and implement a scheme based on AI image processing to enhance malaria disease diagnosis through automated analysis of blood smear images. The scheme is based on the convolutional neural network (CNN) method. So, we have developed a model that classifies infected and uninfected single red cells using images available on Kaggle, as well as real blood smear images obtained from the Central Laboratory of Medical Biology EHS Laadi Flici (formerly El Kettar) in Algeria. The real images were segmented into individual cells using the watershed algorithm in order to match the images from the Kaagle dataset. The model was trained and tested, achieving an accuracy of 99% and 97% accuracy for new real images. This validates that the model performs well with new real images, although with slightly lower accuracy. Additionally, the model has been embedded in a Raspberry Pi4, and a graphical user interface (GUI) was developed to visualize the malaria diagnostic results and facilitate user interaction.

Keywords: medical image processing, malaria parasite, classification, CNN, artificial intelligence

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Authors: Parisa Mansour

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Introduction: Early diagnosis of coronavirus disease (COVID-19) is extremely important to isolate and treat patients in time, thus preventing the spread of the disease, improving prognosis and reducing mortality. High-resolution computed tomography (HRCT) chest imaging and artificial intelligence (AI)-based analysis of HRCT chest images can play a central role in the treatment of patients with COVID-19. Objective: To investigate different chest HRCT findings in different stages of COVID-19 pneumonia and to evaluate the potential role of artificial intelligence in the quantitative assessment of lung parenchymal involvement in COVID-19 pneumonia. Materials and Methods: This retrospective observational study was conducted between May 1, 2020 and August 13, 2020. The study included 2169 patients with COVID-19 who underwent chest HRCT. HRCT images showed the presence and distribution of lesions such as: ground glass opacity (GGO), compaction, and any special patterns such as septal thickening, inverted halo, mark, etc. HRCT findings of the breast at different stages of the disease (early: andlt) 5 days, intermediate: 6-10 days and late stage: >10 days). A CT severity score (CTSS) was calculated based on the extent of lung involvement on HRCT, which was then correlated with clinical disease severity. Use of artificial intelligence; Analysis of CT pneumonia and quot; An algorithm was used to quantify the extent of pulmonary involvement by calculating the percentage of pulmonary opacity (PO) and gross opacity (PHO). Depending on the type of variables, statistically significant tests such as chi-square, analysis of variance (ANOVA) and post hoc tests were applied when appropriate. Results: Radiological findings were observed in HRCT chest in 1438 patients. A typical pattern of COVID-19 pneumonia, i.e., bilateral peripheral GGO with or without consolidation, was observed in 846 patients. About 294 asymptomatic patients were radiologically positive. Chest HRCT in the early stages of the disease mostly showed GGO. The late stage was indicated by such features as retinal enlargement, thickening and the presence of fibrous bands. Approximately 91.3% of cases with a CTSS = 7 were asymptomatic or clinically mild, while 81.2% of cases with a score = 15 were clinically severe. Mean PO and PHO (30.1 ± 28.0 and 8.4 ± 10.4, respectively) were significantly higher in the clinically severe categories. Conclusion: Because COVID-19 pneumonia progresses rapidly, radiologists and physicians should become familiar with typical TC chest findings to treat patients early, ultimately improving prognosis and reducing mortality. Artificial intelligence can be a valuable tool in treating patients with COVID-19.

Keywords: chest, HRCT, covid-19, artificial intelligence, chest HRCT

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Authors: Z. Nurzaireena, K. Azalea, T. Azirawaty, S. Jameela, G. Muralitharan

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The aim of this study is the review of the management practices of sickle cell disease patients during pregnancy, as well as the maternal and neonatal outcome at Ampang Hospital, Selangor. The study consisted of a review of pregnant patients with sickle cell disease under follow up at the Hematology Clinic, Ampang Hospital over the last seven years to assess their management and maternal-fetal outcome. The results of the review show that Ampang Hospital is considered the public hematology centre for sickle cell disease and had successfully managed three pregnancies throughout the last seven years. Patients’ presentations, managements and maternal-fetal outcome were compared and reviewed for academic improvements. All three patients were seen very early in their pregnancy and had been given a regime of folic acid, antibiotics and thrombo-prophylactic drugs. Close monitoring of maternal and fetal well being was done by the hematologists and obstetricians. Among the patients, there were multiple admissions during the pregnancy for either a painful sickle cell bone crisis, haemolysis following an infection and anemia requiring phenotype- matched blood and exchange transfusions. Broad spectrum antibiotics coverage during and infection, hydration, pain management and venous-thrombolism prophylaxis were mandatory. The pregnancies managed to reach near term in the third trimester but all required emergency caesarean section for obstetric indications. All pregnancies resulted in live births with good fetal outcome. During post partum all were nursed closely in the high dependency units for further complications and were discharged well. Post partum follow up and contraception counseling was comprehensively given for future pregnancies. Sickle cell disease is uncommonly seen in the East, especially in the South East Asian region, yet more cases are seen in the current decade due to improved medical expertise and advance medical laboratory technologies. Pregnancy itself is a risk factor for sickle cell patients as increased thrombosis event and risk of infections can lead to multiple crisis, haemolysis, anemia and vaso-occlusive complications including eclampsia, cerebrovasular accidents and acute bone pain. Patients mostly require multiple blood product transfusions thus phenotype-matched blood is required to reduce the risk of alloimmunozation. Emphasizing the risks and complications in preconception counseling and establishing an ultimate pregnancy plan would probably reduce the risk of morbidity and mortality to the mother and unborn child. Early management for risk of infection, thromboembolic events and adequate hydration is mandatory. A holistic approach involving multidisciplinary team care between the hematologist, obstetricians, anesthetist, neonatologist and close nursing care for both mother and baby would ensure the best outcome. In conclusion, sickle cell disease by itself is a high risk medical condition and pregnancy would further amplify the risk. Thus, close monitoring with combine multidisciplinary care, counseling and educating the patients are crucial in achieving the safe outcome.

Keywords: anaemia, haemoglobinopathies, pregnancy, sickle cell disease

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Authors: Ana Munguia, Gerardo Ortiz, Guadalupe Gonzalez, Fiacro Jimenez

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Parkinson's disease (PD) is a neurodegenerative disorder that causes motor and cognitive symptoms. The first-choice treatment for these patients is pharmacological, but this generates several side effects. Because of that new treatments were introduced such as Repetitive Transcranial Magnetic Stimulation (rTMS) in order to improve the life quality of the patients. Several studies suggest significant changes in motor symptoms. However, there is a great diversity in the number of pulses, amplitude, frequency and stimulation targets, which results in inconsistent data. In addition, these studies do not have an analysis of the neuropsychological effects of the treatment. The main purpose of this study is to evaluate the impact of rTMS on the cognitive performance of 6 patients with H&Y III and IV (45-65 years, 3 men and 3 women). An initial neuropsychological and neurological evaluation was performed. Patients were randomized into two groups; in the first phase one received rTMS in the supplementary motor area, the other group in the dorsolateral prefrontal cortex contralateral to the most affected hemibody. In the second phase, each group received the stimulation in the area that he had not been stimulated previously. Reassessments were carried out at the beginning, at the end of each phase and a follow-up was carried out 6 months after the conclusion of the stimulation. In these preliminary results, it is reported that there's no statistically significant difference before and after receiving rTMS in the neuropsychological test scores of the patients, which suggests that the cognitive performance of patients is not detrimental. There are even tendencies towards an improvement in executive functioning after the treatment. What added to motor improvement, showed positive effects in the activities of the patients' daily life. In a later and more detailed analysis, will be evaluated the effects in each of the patients separately in relation to the functionality of the patients in their daily lives.

Keywords: Parkinson's disease, rTMS, cognitive, treatment

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Authors: Frederick Huie, Lauren Fusfeld, William Burchenal, Scott Howell, Alyssa McVey, Thomas F. Goss

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Alzheimer’s Disease (AD) is a degenerative brain disease characterized by memory loss and cognitive decline that presents a substantial economic burden for patients and health insurers in the US. This study evaluates the payer budget impact of the DISCERN™ test in the diagnosis and management of patients with symptoms of dementia evaluated for AD. DISCERN™ comprises three assays that assess critical factors related to AD that regulate memory, formation of synaptic connections among neurons, and levels of amyloid plaques and neurofibrillary tangles in the brain and can provide a quicker, more accurate diagnosis than tests in the current diagnostic pathway (CDP). An Excel-based model with a three-year horizon was developed to assess the budget impact of DISCERN™ compared with CDP in a Medicare Advantage plan with 1M beneficiaries. Model parameters were identified through a literature review and were verified through consultation with clinicians experienced in diagnosis and management of AD. The model assesses direct medical costs/savings for patients based on the following categories: •Diagnosis: costs of diagnosis using DISCERN™ and CDP. •False Negative (FN) diagnosis: incremental cost of care avoidable with a correct AD diagnosis and appropriately directed medication. •True Positive (TP) diagnosis: AD medication costs; cost from a later TP diagnosis with the CDP versus DISCERN™ in the year of diagnosis, and savings from the delay in AD progression due to appropriate AD medication in patients who are correctly diagnosed after a FN diagnosis.•False Positive (FP) diagnosis: cost of AD medication for patients who do not have AD. A one-way sensitivity analysis was conducted to assess the effect of varying key clinical and cost parameters ±10%. An additional scenario analysis was developed to evaluate the impact of individual inputs. In the base scenario, DISCERN™ is estimated to decrease costs by $4.75M over three years, equating to approximately $63.11 saved per test per year for a cohort followed over three years. While the diagnosis cost is higher with DISCERN™ than with CDP modalities, this cost is offset by the higher overall costs associated with CDP due to the longer time needed to receive a TP diagnosis and the larger number of patients who receive a FN diagnosis and progress more rapidly than if they had received appropriate AD medication. The sensitivity analysis shows that the three parameters with the greatest impact on savings are: reduced sensitivity of DISCERN™, improved sensitivity of the CDP, and a reduction in the percentage of disease progression that is avoided with appropriate AD medication. A scenario analysis in which DISCERN™ reduces the utilization for patients of computed tomography from 21% in the base case to 16%, magnetic resonance imaging from 37% to 27% and cerebrospinal fluid biomarker testing, positive emission tomography, electroencephalograms, and polysomnography testing from 4%, 5%, 10%, and 8%, respectively, in the base case to 0%, results in an overall three-year net savings of $14.5M. DISCERN™ improves the rate of accurate, definitive diagnosis of AD earlier in the disease and may generate savings for Medicare Advantage plans.

Keywords: Alzheimer’s disease, budget, dementia, diagnosis.

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Authors: Destin Kurniawati

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Asthma is one of the deadly diseases in the world. According to the World Health Organization in 2012, 300 million people suffer from asthma of different races and classes. An estimated 250,000 people die because of asthma annually.As well as more than 57% of children and 51% of adults with asthma. There two risk factors for asthma. That risk factors are the host and environmental. One of the environmental factors that can bring asthma is allergens. When an allergen enters the body, the allergen binds to IgE and cause cell granulat- issued several mediators such as histamine, leukotrienes, bradykinin or something like that. This will cause localized edema effect on bronchial walls of small, thick mucous secretions in the bronchioles, and bronchial smooth muscle spasm. Then there will be inflammation of the airways. Methodology this research is by literature. Therefore, to anticipate and cope with asthma is to control environmental factors that serve to minimize allergens and controlling one's intake in the form of antioxidant-rich foods. Foods rich in antioxidants serve to improve lung function and decrease symptoms of the disease of the respiratory tract.

Keywords: asthma, deadly disease, allergen, environmental and food control

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Authors: Marwan Jarrah, Nadia Nugrush, Sukainah Ali, Areej Allawzi

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This research article investigates how illnesses (different types and severity) are expressed in Arabic discourse with a particular focus on input coming from Colloquial Jordanian Arabic (CJA). Drawing on a corpus of naturally occurring conversations, this article offers evidence that illnesses are predominantly expressed through two different sets of expressive strategies, namely direct expressive strategies (DES) and indirect expressive strategies (IES). The latter are exclusively used when cancer and mental health disorders are targeted. IES include the substitution of the name of the illness with some religious expressions (e.g., ʔallah ʔijdʒi:rna ‘May Allah keeps us safe’) or certain terms especially when cancer is meant (e.g., haðˤa:k ʔil-maraðˤ ‘that disease’). On the other hand, DES are used in conjunction with other illnesses (e.g., heart, kidneys, diabetes, etc.), regardless of their severity. DES include specific formulas that remarkably mention the name of the inflicted organ (e.g., [with-SOMEONE the ORGAN] as in ʕinduh ʔil-qalb ‘lit. with-him the heart’ meaning ‘He has a heart disease). We discuss the effects of religious beliefs and local norms and values in determining the use of these strategies.

Keywords: Illnesses, pragmatics, expressive strategies, religion

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Authors: Khalda Amr, Noha Eltaweel, Sherif Ismail, Hala Raslan

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Introduction: Osteoarthritis is the most common form of arthritis that involves the wearing away of the cartilage that caps the bones in the joints. While rheumatoid arthritis is an autoimmune disease in which the immune system attacks the joints, beginning with the lining of joints. In this study, we aimed to study the top deregulated miRNAs that might be the cause of pathogenesis in both diseases. Methods: Eight cases were recruited in this study: 4 rheumatoid arthritis (RA), 2 osteoarthritis (OA) patients, as well as 2 healthy controls. Total RNA was isolated from plasma to be subjected to miRNA profiling by NGS. Sequencing libraries were constructed and generated using the NEBNextR UltraTM small RNA Sample Prep Kit for Illumina R (NEB, USA), according to the manufacturer’s instructions. The quality of samples were checked using fastqc and multiQC. Results were compared RA vs Controls and OA vs. Controls. Target gene prediction and functional annotation of the deregulated miRNAs were done using Mienturnet. The top deregulated miRNAs in each disease were selected for further validation using qRT-PCR. Results: The average number of sequencing reads per sample exceeded 2.2 million, of which approximately 57% were mapped to the human reference genome. The top DEMs in RA vs controls were miR-6724-5p, miR-1469, miR-194-3p (up), miR-1468-5p, miR-486-3p (down). In comparison, the top DEMs in OA vs controls were miR-1908-3p, miR-122b-3p, miR-3960 (up), miR-1468-5p, miR-15b-3p (down). The functional enrichment of the selected top deregulated miRNAs revealed the highly enriched KEGG pathways and GO terms. Six of the deregulated miRNAs (miR-15b, -128, -194, -328, -542 and -3180) had multiple target genes in the RA pathway, so they are more likely to affect the RA pathogenesis. Conclusion: Six of our studied deregulated miRNAs (miR-15b, -128, -194, -328, -542 and -3180) might be highly involved in the disease pathogenesis. Further functional studies are crucial to assess their functions and actual target genes.

Keywords: next generation sequencing, mirnas, rheumatoid arthritis, osteoarthritis

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Authors: Eun Kyung Kim, Kyehan Rhee

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Viscoelastic wall properties of the arterial plaques change as the disease progresses, and estimation of wall viscoelasticity can provide a valuable assessment tool for plaque rupture prediction. Cross section of the stenotic coronary artery was modeled based on the IVUS image, and the finite element analysis was performed to get wall deformation under pulsatile pressure. The effects of viscoelastic parameters of the plaque on luminal diameter variations were explored. The result showed that decrease of viscous effect reduced the phase angle between the pressure and displacement waveforms, and phase angle was dependent on the viscoelastic properties of the wall. Because viscous effect of tissue components could be identified using the phase angle difference, wall deformation waveform analysis may be applied to predict plaque wall composition change and vascular wall disease progression.

Keywords: atherosclerotic plaque, diameter variation, finite element method, viscoelasticity

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Authors: Stephen L. Roberts

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This article offers a critical analysis of the rise of syndromic surveillance systems for the advanced detection of pandemic threats within contemporary global health security frameworks. The article traces the iterative evolution and ascendancy of three such novel syndromic surveillance systems for the strengthening of health security initiatives over the past two decades: 1) The Program for Monitoring Emerging Diseases (ProMED-mail); 2) The Global Public Health Intelligence Network (GPHIN); and 3) HealthMap. This article demonstrates how each newly introduced syndromic surveillance system has become increasingly oriented towards the integration of digital algorithms into core surveillance capacities to continually harness and forecast upon infinitely generating sets of digital, open-source data, potentially indicative of forthcoming pandemic threats. This article argues that the increased centrality of the algorithm within these next-generation syndromic surveillance systems produces a new and distinct form of infectious disease surveillance for the governing of emergent pathogenic contingencies. Conceptually, the article also shows how the rise of this algorithmic mode of infectious disease surveillance produces divergences in the governmental rationalities of global health security, leading to the rise of an algorithmic governmentality within contemporary contexts of Big Data and these surveillance systems. Empirically, this article demonstrates how this new form of algorithmic infectious disease surveillance has been rapidly integrated into diplomatic, legal, and political frameworks to strengthen the practice of global health security – producing subtle, yet distinct shifts in the outbreak notification and reporting transparency of states, increasingly scrutinized by the algorithmic gaze of syndromic surveillance.

Keywords: algorithms, global health, pandemic, surveillance

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Authors: Vincent A. Adzika, Franklin N. Glozah, Collins S. K. Ahorlu

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Background: Sickle Cell Disease (SCD) is of major public-health concern globally, with majority of patients living in Africa. Despite its relevance, there is a dearth of research to determine the socio-demographic distribution and psychosocial impact of SCD in Africa. The objective of this study therefore was to examine the socio-demographic distribution and psychosocial consequences of SCD among patients in Ghana and to assess their quality of life and coping mechanisms. Methods: A cross-sectional research design was used, involving the completion of questionnaires on socio-demographic characteristics, quality of life of individuals, anxiety and depression. Participants were 387 male and female patients attending a sickle cell clinic in a public hospital. Results: Results showed no gender and marital status differences in anxiety and depression. However, there were age and level of education variances in depression but not in anxiety. In terms of quality of life, patients were more satisfied by the presence of love, friends, relatives as well as home, community and neighbourhood environment. While pains of varied nature and severity were the major reasons for attending hospital in SCD condition, going to the hospital as well as having Faith in God was the frequently reported mechanisms for coping with an unbearable SCD attacks. Multiple regression analysis showed that some socio-demographic and quality of life indicators had strong associations with anxiety and/or depression. Conclusion: It is recommended that a multi-dimensional intervention strategy incorporating psychosocial dimensions should be considered in the treatment and management of SCD.

Keywords: anxiety, depression, sickle cell disease, socio-demographic quality of life, characteristics, Ghana

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Authors: Joanna Maj

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Body machine interfaces (BMIs) afford users a non-invasive way coordinate movement. Vibrotactile stimulation has been incorporated into BMIs to allow feedback in real-time and guide movement control to benefit patients with cognitive deficits, such as stroke survivors. To advance research in this area, we examined vibrational discrimination thresholds at four body locations to determine suitable application sites for future multi-channel BMIs using vibration cues to guide movement planning and control. Twelve healthy adults had a pair of small vibrators (tactors) affixed to the skin at each location: forearm, shoulders, torso, and knee. A "standard" stimulus (186 Hz; 750 ms) and "probe" stimuli (11 levels ranging from 100 Hz to 235 Hz; 750 ms) were delivered. Probe and test stimulus pairs could occur sequentially or simultaneously (timing). Participants verbally indicated which stimulus felt more intense. Stimulus order was counterbalanced across tactors and body locations. Probabilities that probe stimuli felt more intense than the standard stimulus were computed and fit with a cumulative Gaussian function; the discrimination threshold was defined as one standard deviation of the underlying distribution. Threshold magnitudes depended on stimulus timing and location. Discrimination thresholds were better for stimuli applied sequentially vs. simultaneously at the torso as well as the knee. Thresholds were small (better) and relatively insensitive to timing differences for vibrations applied at the shoulder. BMI applications requiring multiple channels of simultaneous vibrotactile stimulation should therefore consider the shoulder as a deployment site for a vibrotactile BMI interface.

Keywords: electromyography, electromyogram, neuromuscular disorders, biomedical instrumentation, controls engineering

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Authors: Sabrina Azzi, Michal Iglewski, Véronique Nabelsi

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Diagnosis error problem is frequent and one of the most important safety problems today. One of the main objectives of our work is to propose an ontological representation that takes into account the diagnostic criteria in order to improve the diagnostic. We choose pneumonia disease since it is one of the frequent diseases affected by diagnosis errors and have harmful effects on patients. To achieve our aim, we use a semi-automated method to integrate diverse knowledge sources that include publically available pneumonia disease guidelines from international repositories, biomedical ontologies and electronic health records. We follow the principles of the Open Biomedical Ontologies (OBO) Foundry. The resulting ontology covers symptoms and signs, all the types of pneumonia, antecedents, pathogens, and diagnostic testing. The first evaluation results show that most of the terms are covered by the ontology. This work is still in progress and represents a first and major step toward a development of a diagnosis decision support system for pneumonia.

Keywords: Clinical decision support system, Diagnostic errors, Ontology, Pneumonia

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Authors: Amirah Azzeri, Fatiha H. Shabaruddin, Scott A. McDonald, Rosmawati Mohamed, Maznah Dahlui

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Objective: A scaled-up treatment cascade with direct-acting antiviral (DAA) therapy is necessary to achieve global WHO targets for hepatitis C virus (HCV) elimination in Malaysia. Recently, limited access to Sofosbuvir/Daclatasvir (SOF/DAC) is available through compulsory licensing, with future access to Sofosbuvir/Velpatasvir (SOF/VEL) expected through voluntary licensing due to recent agreements. SOF/VEL has superior clinical outcomes, particularly for cirrhotic stages, but has higher drug acquisition costs compared to SOF/DAC. It has been proposed that a stratified treatment cascade might be the most cost-efficient approach for Malaysia whereby all HCV patients are treated with SOF/DAC except for patients with cirrhosis who are treated with SOF/VEL. This study aimed to conduct a five-year budget impact analysis from the provider perspective of the proposed stratified treatment cascade for HCV treatment in Malaysia. Method: A disease progression model that was developed based on model-predicted HCV epidemiology data in Malaysia was used for the analysis, where all HCV patients in scenario A were treated with SOF/DAC for all disease stages while in scenario B, SOF/DAC was used only for non-cirrhotic patients and SOF/VEL was used for the cirrhotic patients. The model projections estimated the annual numbers of patients in care and the numbers of patients to be initiated on DAA treatment nationally. Healthcare costs associated with DAA therapy and disease stage monitoring was included to estimate the downstream cost implications. For scenario B, the estimated treatment uptake of SOF/VEL for cirrhotic patients were 25%, 50%, 75%, 100% and 100% for 2018, 2019, 2020, 2021 and 2022 respectively. Healthcare costs were estimated based on standard clinical pathways for DAA treatment described in recent guidelines. All costs were reported in US dollars (conversion rate US$1=RM4.09, the price year 2018). Scenario analysis was conducted for 5% and 10% reduction of SOF/VEL acquisition cost anticipated from the competitive market pricing of generic DAA in Malaysia. Results: The stratified treatment cascade with SOF/VEL in Scenario B was found to be cost-saving compared to Scenario A. A substantial portion of the cost reduction was due to the costs associated with DAA therapy which resulted in USD 40 thousand (year 1) to USD 443 thousand (year 5) savings annually, with cumulative savings of USD 1.1 million after 5 years. Cost reductions for disease stage monitoring were seen in year three onwards which resulted in cumulative savings of USD 1.1 thousand. Scenario analysis estimated cumulative savings of USD 1.24 to USD 1.35 million when the acquisition cost of SOF/VEL was reduced. Conclusion: A stratified treatment cascade with SOF/VEL was expected to be cost-saving and can results in a budget impact reduction in overall healthcare expenditure in Malaysia compared to treatment with SOF/DAC. The better clinical efficacy with SOF/VEL is expected to halt patients’ HCV disease progression and may reduce downstream costs of treating advanced disease stages. The findings of this analysis may be useful to inform healthcare policies for HCV treatment in Malaysia.

Keywords: Malaysia, direct acting antiviral, compulsory licensing, voluntary licensing

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