Search results for: sickle disease

Authors: Hassan Nour, Nouh Mounadi, Oussama Abchir, Belaidi Salah, Samir Chtita

Abstract:

Cholinesterase enzymes are biological catalysts essential for the transformation of acetylcholine, which is a neurotransmitter implicated in memory and learning, into acetic acid and choline, altering the neurotransmission process in Alzheimer’s disease patients. Therefore, inhibition of cholinesterase enzymes is a relevant strategy for the symptomatic treatment of Alzheimer’s disease. The current investigation aims to explore potential Cholinesterase (ChE) inhibitors through a comprehensive computational approach. Forty-nine phytoconstituents extracted from Cannabis sativa L were in-silico screened using molecular docking, pharmacokinetic and toxicological analysis to evaluate their possible inhibitory effect towards the cholinesterase enzymes. Two phytoconstituents belonging to cannabinoid derivatives were revealed to be promising candidates for Alzheimer therapy by acting as cholinesterase inhibitors. They have exhibited high binding affinities towards the cholinesterase enzymes and showed their ability to interact with key residues involved in cholinesterase enzymatic activity. In addition, they presented good ADMET profiles allowing them to be promising oral drug candidates. Furthermore, molecular dynamics (MD) simulations were executed to explore their interactions stability under mimetic biological conditions and thus support our findings. To corroborate the docking results, the binding free energy corresponding to the more stable ligand-ChE complexes was re-estimated by applying the MM-PBSA method. MD and MM-PBSA studies affirmed that the ligand-ChE recognition is spontaneous reaction leading to stable complexes. The conducted investigations have led to great findings that would strongly guide the pharmaceutical industries towards the rational development of potent anti-Alzheimer agents.

Keywords: alzheimer’s disease, molecular docking, cannabis sativa l, cholinesterase inhibitors

Procedia PDF Downloads 73

Authors: Seraj Makkawi, Abdulaziz A. Alqarni, Himyan Alghaythee, Suzan Y. Alharbi, Anmar Fatani, Reem Adas, Ahmad R. Abuzinadah

Abstract:

Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease, is a neurodegenerative disease that involves both the upper and lower motor neurons. Familial ALS, including superoxide dismutase 1 (SOD1) mutation, accounts for 5-10% of all cases of ALS. Typically, the symptoms of ALS are purely motor, though coexistent sensory symptoms have been reported in rare cases. In this report, we describe the case of a 47- year-old man who presented with progressive bilateral lower limb weakness and numbness for the last four years. A nerve conduction study (NCS) showed evidence of coexistent axonal sensorimotor polyneuropathy in addition to the typical findings of ALS in needle electromyography. Genetic testing confirmed the diagnosis of familial ALS secondary to the SOD1 genetic mutation. This report highlights that the presence of sensory symptoms should not exclude the possibility of ALS in an appropriate clinical setting.

Keywords: Saudi Arabia, polyneuropathy, SOD1 gene mutation, familial amyotrophic lateral sclerosis, amyotrophic lateral sclerosis

Procedia PDF Downloads 148

Authors: Megha Gupta, Nupur Prakash

Abstract:

Identification of plant diseases has been performed using machine learning and deep learning models on the datasets containing images of healthy and diseased plant leaves. The current study carries out an evaluation of some of the deep learning models based on convolutional neural network (CNN) architectures for identification of plant diseases. For this purpose, the publicly available New Plant Diseases Dataset, an augmented version of PlantVillage dataset, available on Kaggle platform, containing 87,900 images has been used. The dataset contained images of 26 diseases of 14 different plants and images of 12 healthy plants. The CNN models selected for the study presented in this paper are AlexNet, ZFNet, VGGNet (four models), GoogLeNet, and ResNet (three models). The selected models are trained using PyTorch, an open-source machine learning library, on Google Colaboratory. A comparative study has been carried out to analyze the high degree of accuracy achieved using these models. The highest test accuracy and F1-score of 99.59% and 0.996, respectively, were achieved by using GoogLeNet with Mini-batch momentum based gradient descent learning algorithm.

Keywords: comparative analysis, convolutional neural networks, deep learning, plant disease identification

Procedia PDF Downloads 198

Authors: Koteswara Rao Pagolu, Raghava Rao Tamanam

Abstract:

The present study was aimed to find out the prevalence of DD's in Visakhapatnam, one of the north coastal districts of Andhra Pradesh, India during a span of five years. A cross-sectional investigation was held at District early intervention center (DEIC), Visakhapatnam from 2016 to 2020. To identify the pattern and trend of different DD's including seasonal variations, a retrospective analysis of the health center's inpatient database for the past 5 years was done. Male and female children aged 2 months-18 years are included in the study with the prior permission of the concerned medical officer. The screening tool developed by the Ministry of health and family welfare, India, was used for the study. Among 26,423 cases, children with birth defects are 962, 2229 with deficiencies, 7516 with diseases, and 15716 with disabilities were admitted during the study period. From birth defects, congenital deafness occurred in large numbers with 22.66%, and neural tube defect observed in a small number of cases with 0.83% during the period. From the side of deficiencies, severe acute malnutrition has mostly occurred (66.80 %) and a small number of children were affected with goiter (1.70%). Among the diseases, dental carriers (67.97%) are mostly found and these cases were at peak during the years 2016 and 2019. From disabilities, children with vision impairment (20.55%) have mostly approached the center. Over the past 5 years, the admission rate of down's syndrome and congenital deafness cases showed a rising trend up to 2019 and then declined. Hearing impairment, motor delay, and learning disorder showed a steep rise and gradual decline trend, whereas severe anemia, vitamin-D deficiency, otitis media, reactive airway disease, and attention deficit hyperactivity disorder showed a declining trend. However, congenital heart diseases, dental caries, and vision impairment admission rates showed a zigzag pattern over the past 5 years. This center had inadequate diagnostic facilities related to genetic disease management. For advanced confirmation, the cases are referred to a district government hospital or private diagnostic laboratories in the city for genetic tests. Information regarding the overall burden and pattern of admissions in the health center is obtained by the review of DEIC records. Through this study, it is observed that the incidence of birth defects, as well as genetic disease burden, is high in the Visakhapatnam district. Hence there is a need for strengthening of management services for these diseases in this region.

Keywords: child health screening, developmental delays, district early intervention center, genetic disease management, infrastructural facility, Visakhapatnam district

Procedia PDF Downloads 213

Authors: Swati Gautam, Salman Akhtar, S. P. Jaiswar, Amita Jain

Abstract:

Background: FGTB is now a major global health problem mostly in developing countries including India. In humans, Mycobacterium Tuberculosis (M.tb) is a causating agent of infection. High index of suspicion is required for early diagnosis due to asymptomatic presentation of FGTB disease. In macrophages Toll Like Receptor-2 (TLR-2) is one which mediated host’s immune response to M.tb. The expression of TLR-2 on macrophages is important to determine the fate of innate immune responses to M.tb. TLR-2 have two work. First its high expression on macrophages worsen the outer of infection and another side, it maintains M.tb to its dormant stage avoids activation of M.tb from latent phase. Single Nucleotide Polymorphism (SNP) of TLR-2 gene plays an important role in susceptibility to TB among different populations and subsequently, in the development of infertility. Methodology: This Case-Control study was done in the Department of Obs and Gynae and Department of Microbiology at King George’s Medical University, U.P, Lucknow, India. Total 300 subjects (150 Cases and 150 Controls) were enrolled in the study. All subjects were enrolled only after fulfilling the given inclusion and exclusion criteria. Inclusion criteria: Age 20-35 years, menstrual-irregularities, positive on Acid-Fast Bacilli (AFB), TB-PCR, (LJ/MGIT) culture in Endometrial Aspiration (EA). Exclusion criteria: Koch’s active, on ATT, PCOS, and Endometriosis fibroid women, positive on Gonococal and Chlamydia. Blood samples were collected in EDTA tubes from cases and healthy control women (HCW) and genomic DNA extraction was carried out by salting-out method. Genotyping of TLR2 genetic variants (Arg753Gln and Arg677Trp) were performed by using single amplification refractory mutation system (ARMS) PCR technique. PCR products were analyzed by electrophoresis on 1.2% agarose gel and visualized by gel-doc. Statistical analysis of the data was performed using the SPSS 16.3 software and computing odds ratio (OR) with 95% CI. Linkage Disequiliribium (LD) analysis was done by SNP stats online software. Results: In TLR-2 (Arg753Gln) polymorphism significant risk of FGTB observed with GG homozygous mutant genotype (OR=13, CI=0.71-237.7, p=0.05), AG heterozygous mutant genotype (OR=13.7, CI=0.76-248.06, p=0.03) however, G allele (OR=1.09, CI=0.78-1.52, p=0.67) individually was not associated with FGTB. In TLR-2 (Arg677Trp) polymorphism a significant risk of FGTB observed with TT homozygous mutant genotype (OR= 0.020, CI=0.001-0.341, p < 0.001), CT heterozygous mutant genotype (OR=0.53, CI=0.33-0.86, p=0.014) and T allele (OR=0.463, CI=0.32-0.66, p < 0.001). TT mutant genotype was only found in FGTB cases and frequency of CT heterozygous more in control group as compared to FGTB group. So, CT genotype worked as protective mutation for FGTB susceptibility group. In haplotype analysis of TLR-2 genetic variants, four possible combinations, i.e. (G-T, A-C, G-C, and A-T) were obtained. The frequency of haplotype A-C was significantly higher in FGTB cases (0.32). Control group did not show A-C haplotype and only found in FGTB cases. Conclusion: In conclusion, study showed a significant association with both genetic variants of TLR-2 of FGTB disease. Moreover, the presence of specific associated genotype/alleles suggest the possibility of disease severity and clinical approach aimed to prevent extensive damage by disease and also helpful for early detection of disease.

Keywords: ARMS, EDTA, FGTB, TLR

Procedia PDF Downloads 306

Authors: Cassey Younghans

Abstract:

Background: Current health care trends demonstrate that there is an increasing number of patients being hospitalized with complex comorbidities. These complex needs require advanced therapies, and treatment goals often focus on doing everything possible to prolong life rather than focusing on the individual patient’s quality of life which is the goal of palliative care efforts. Patients benefit from palliative care in the early stages of the illness rather than after the disease progressed or the state of acuity has advanced. The clinical problem identified was that palliative care was not being implemented early enough in the disease process with patients who had complex medical conditions and who would benefit from the philosophy and skills of palliative care professionals. Purpose: The purpose of this quality improvement study was to increase the number of palliative care screenings and consults completed on adults after being admitted to one Non-ICU and Non-COVID hospital unit. Methods: A retrospective chart review assessing for possible missed opportunities to introduce palliation was performed for patients with six primary diagnoses, including heart failure, liver failure, end stage renal disease, chronic obstructive pulmonary disease, cerebrovascular accident, and cancer in a population of adults over the ago of 19 on one medical-surgical unit over a three-month period prior to the intervention. An educational session with the nurses on the benefits of palliative care was conducted by the researcher, and a screening tool was implemented. The expected outcome was to have an increase in early palliative care consultation with patients with complex comorbid conditions and a decrease in missed opportunities for the implementation of palliative care. Another retrospective chart review was completed following completion of the three month piloting of the tool. Results: During the retrospective chart review, 46 patients were admitted to the medical-surgical floor with the primary diagnoses identified in the inclusion criteria. Six patients had palliative care consults completed during that time. Twenty-two palliative care screening tools were completed during the intervention period. Of those, 15 of the patients scored a 7 or higher, suggesting that a palliative care consultation was warranted. The final retrospective chart review identified that 4 palliative consults were implemented during that time of the 31 patients who were admitted over the three month time frame. Conclusion: Educating nurses and implementing a palliative care screening upon admission can be of great value in providing early identification of patients who might benefit from palliative care. Recommendations – It is recommended that this screening tool should be used to help identify the patents of whom would benefit from a palliative care consult, and nurses would be able to initiated a palliative care consultation themselves.

Keywords: palliative care, screening, early, palliative care consult

Procedia PDF Downloads 152

Authors: Jessica A. Hellings, Piyushkumar Jani

Abstract:

Background: Systemic autoimmune disorders are increasingly implicated in neuropsychiatric illness, especially in the setting of treatment resistance in individuals of all ages. Gluten allergy in fullest extent results in celiac disease, affecting multiple organs including central nervous system (CNS). Clinicians often lack awareness of the association between neuropsychiatric illness and gluten allergy, partly since many such research studies are published in immunology and gastroenterology journals. Methods: Following a Pubmed literature search and online searches on celiac disease websites, 40 articles are critically reviewed in detail. This work reviews celiac disease, gluten intolerance and current evidence of their relationship to neuropsychiatric and systemic illnesses. The review also covers current work-up and diagnosis, as well as dietary interventions, gluten restriction outcomes, and future research directions. Results: Gluten allergy in susceptible individuals damages the small intestine, producing a leaky gut and malabsorption state, as well as allowing antibodies into the bloodstream, which attack major organs. Lack of amino acid precursors for neurotransmitter synthesis together with antibody-associated brain changes and hypoperfusion may result in neuropsychiatric illness. This is well documented; however, studies in neuropsychiatry are often small. In the large CATIE trial, subjects with schizophrenia had significantly increased antibodies to tissue transglutaminase (TTG), and antigliadin antibodies, both significantly greater gluten antibodies than in control subjects. On later follow up, TTG-6 antibodies were identified in these subjects’ brains but not in their intestines. Significant evidence mostly from small studies also exists for gluten allergy and celiac-related depression, anxiety disorders, attention-deficit/hyperactivity disorder, autism spectrum disorders, ataxia, and epilepsy. Dietary restriction of gluten resulted in remission in several published cases, including for treatment-resistant schizophrenia. Conclusions: Ongoing and larger studies are needed of the diagnosis and treatment efficacy of the gluten-free diet in neuropsychiatric illness. Clinicians should ask about the patient history of anemia, hypothyroidism, irritable bowel syndrome and family history of benefit from the gluten-free diet, not limited to but especially in cases of treatment resistance. Obtaining gluten antibodies by a simple blood test, and referral for gastrointestinal work-up in positive cases should be considered.

Keywords: celiac, gluten, neuropsychiatric, translational

Procedia PDF Downloads 161

Authors: Anton Bahtiar, Lukas Tjandra Leksana, Fransiscus D. Suyatna

Abstract:

Hypercholesterolemia is one of the major risk factors that can trigger the development of cardiovascular disease, especially coronary heart disease. One of the traditional drugs used for hypercholesterolemia is a combination of herbs celery (Apium graveolens) and garlic (Allium sativum). This study aimed to investigate the effects of the extract on lipid profile in hypercholesterolemic subjects. Subjects consisted of patients with traditional medicine clinic in Jakarta. Each subject received treatment capsules containing herbal extract and placebo capsules. On the 44 subjects, the lipid profile was examined blood levels of total cholesterol, HDL, LDL, and triglycerides. Paired two-tailed t-test was used for the difference between lipid profile of the therapy group and the placebo group. The changes in the lipid profile between the treatment groups and the placebo group for total cholesterol, HDL, LDL, and triglycerides was 14,82 ± 6,946;1.45 ± 2,945;6,98 ± 8,105;2,48 ± 6,504 mg/dL. The herbal extract decrease blood cholesterol and LDL levels significantly (P <0.05).

Keywords: Allium sativum, Apium graveolens, hypercholesterolemia, cholesterol, HDL, LDL

Procedia PDF Downloads 332

Authors: Wan Aminah Hasbullah

Abstract:

The knowledge of medicine in Malay society stemmed out from the need to remedy disease process. Such knowledge came from observations by looking at the signs on the plants which signify it uses, the doctrine of signature, and also observing what kind of animal and its parts that can be used to treat the disease. Prayers (jampi and doa’) play a very important role in the therapeutic processes addressing the ethereal part of the body. In Malay medicine, prayers were said in the heart of the Malay bomoh (medicine man) when they are first approaching the diseased person, seeking the help of Allah in accurately directing his mind into making the right diagnosis and subsequently the right choice of treatment. In the making of medicine, similar rituals were religiously followed, starting from gathering the materia medica to the final concoction of the medicine. Thus, all the materia medica and the prayers in Malay medicine were gathered and documented in the medical manuscript known as MSS 2999 Kitab Tibb. For this study, a collection of vegetative materia medica which is specialized for the women illness from this manuscript will be gathered and analysed. A medical and cultural interpretation will be highlighted to see the relationship between efficacy in traditional Malay medicine as practiced in the past and the recent practice of the modern medicine.

Keywords: vegetative, materia medica, woman illness, Malay medical manuscript

Procedia PDF Downloads 252

Authors: Szu-Yi Chang, Jiin-Ru Rong

Abstract:

This paper discussed a case involving a young female patient with schizophrenia. The patient's condition was deteriorating, and she was becoming increasingly reliant on her family to take care of her, and as her father did not understand the illness well and was afraid that others will learn about the presence of a mentally ill individual in their family, he and the patient's mother were thus unable to cope with the patient's deteriorating condition, which in turn caused her to suffer from a lack of self-confidence and low self-esteem. The patient received nursing care from July 26th to October 25th, 2017, during which counseling, family visits, and phone interviews were carried out, and her condition was monitored. By referring to the practical ability indicators for community psychiatric mental health nursing that were developed by the psychiatric mental health nurses' association of the Republic of China, defining categories such as 'self-construction,' 'self-management,' 'disease management,' and 'family nursing,' and incorporating indicators for empowerment and various skills into the steps and strategies used for nursing care, we will able to help the patient to construct her own identity, raise her self-esteem, improve her ability to independently perform activities of daily living, strengthen her disease management ability, and gradually build up her life management skills. The patient's family was also encouraged to communicate more among themselves, so as to align them with the nursing care objectives of improving the patient's ability to adapt to community life and her disease. The results indicated that the patient was able to maintain her mental stability within her community. By implementing effective self-management and maintaining a routine life, the patient was able to continue her active participation in community work and rehabilitation activities. Improvements were also achieved with respect to family role issues by establishing mutual understanding among the patient's family members and gaining their support. It is recommended that mental health nurses can leverage their community mental health nursing skills and the related strategies to promote adaptation to community life among mental life patients.

Keywords: community psychiatric mental health nursing, family nursing, schizophrenia, self-management

Procedia PDF Downloads 278

Authors: Baburao Ganpat Apte, Gajodhar

Abstract:

Introduction: diopathic Parkinson’s disease (PD) is the most common neurodegenerative disorder. Early PD may present a diagnostic challenge with broad differential diagnoses that are not associated with striatal dopamine deficiency. This test was performed by using special type of radioactive precursor which was made available through our logistics. 131I-TOPA L-6-[131I] Iodo-3,4-Trihydroxyphenylalnine (131I -TOPA) is a positron emission tomography (PET) agent that measures the uptake of dopamine precursors for assessment of presynaptic dopaminergic integrity and has been shown to accurately reflect the sign of nervous mind going in patients suffers from monoaminergic disturbances in PD. Both qualitative and quantitative analyses of the scans were performed. Therefore, the early clinical diagnosis alone may be accurate and this reinforces the importance of functional imaging targeting the patholigically of the disease process. The patient’s medical records were then assessed for length of follow-up, response to levotopa, clinical course of sickness, and usually though of symptoms at time of 131I -TOPA PET. A respective analysis was carried out for all patients that gone through 131I -TOPA PET brain scan for motor symptoms suspicious for PD between 2000 - 2006. The eventual diagnosis by the referring neurologist, movement therapist, physiotherapist, was used as the accurate measurements in standard for further analysis. In this study, our goal to illustrate our local experience to determine the accuracy of 131I -TOPA PET for diagnosis of PD. We studied a total of 48 patients. Of the 25 scans, it found that one was a false negative, 40 were true positives, and 7 were true negatives. The resultant values are Sensitivity 90.4% (95% CI: 100%-71.3%), Specificity 100% (92% CI: 100%-58.0%), PPV 100% (91% CI 100%-75.7%), and NPV 80.5% (95% CI: 92.5%-48.5%). Result: Twenty-three patients were found in the initial query, and 1 were excluded (2 uncertain diagnosis, 2 inadequate follow-up). Twenty-eight patients (28 scans) remained with 15 males (62%) and 8 females (30%). All the patients had a clinical follow-up of at least 3 years, however the median length of follow-up was 5.5 years (range: 2-8 years). The median age at scan time was 51.2 years (range: 35-75)

Keywords: 18F-TOPA, petct, parkinson’s disease, cardiac

Procedia PDF Downloads 27

Authors: Fernanda Miranda da Cruz

Abstract:

This paper aims to systematize, descriptively and analytically, the relations between language, body and material world explored in a specific empirical context: everyday co-presence interactions between children diagnosed with Autistic Spectrum Disease ASD and various interlocutors. We will work based on 20 hours of an audiovisual corpus in Brazilian Portuguese language. This analysis focuses on 1) the analysis of daily interactions that have the presence/participation of subjects with a diagnosis of ASD based on an embodied interaction perspective; 2) the study of the status and role of gestures, body and material world in the construction and constitution of human interaction and its relation with linguistic-cognitive processes and Autistic Spectrum Disorders; 3) to highlight questions related to the field of videoanalysis, such as: procedures for recording interactions in complex environments (involving many participants, use of objects and body movement); the construction of audiovisual corpora for linguistic-interaction research; the invitation to a visual analytical mentality of human social interactions involving not only the verbal aspects that constitute it, but also the physical space, the body and the material world.

Keywords: autism spectrum disease, multimodality, social interaction, non-verbal interactions

Procedia PDF Downloads 114

Authors: Radhe Tado, Ashish B. Deoghare, K. M. Pandey

Abstract:

The aim of this study is to estimate the effect of blood flow through the coronary artery in human heart so as to assess the coronary artery disease.Velocity, wall shear stress (WSS), strain rate and wall pressure distribution are some of the important hemodynamic parameters that are non-invasively assessed with computational fluid dynamics (CFD). These parameters are used to identify the mechanical factors responsible for the plaque progression and/or rupture in left coronary arteries (LCA) in coronary arteries.The initial step for CFD simulations was the construction of a geometrical model of the LCA. Patient specific artery model is constructed using computed tomography (CT) scan data with the help of MIMICS Research 19.0. For CFD analysis ANSYS FLUENT-14.5 is used.Hemodynamic parameters were quantified and flow patterns were visualized both in the absence and presence of coronary plaques. The wall pressure continuously decreased towards distal segments and showed pressure drops in stenotic segments. Areas of high WSS and high flow velocities were found adjacent to plaques deposition.

Keywords: angiography, computational fluid dynamics (CFD), time-average wall shear stress (TAWSS), wall pressure, wall shear stress (WSS)

Procedia PDF Downloads 183

Authors: Hassan Nour, Nouh Mounadi, Oussama Abchir, Belaidi Salah, Samir Chtita

Abstract:

Cholinesterase enzymes are biological catalysts essential for the transformation of acetylcholine, which is a neurotransmitter implicated in memory and learning, into acetic acid and choline, altering the neurotransmission process in Alzheimer’s disease patients. Therefore, inhibition of cholinesterase enzymes is a relevant strategy for the symptomatic treatment of Alzheimer’s disease. The current investigation aims to explore potential cholinesterase (ChE) inhibitors through a comprehensive computational approach. Forty-nine phytoconstituents extracted from Cannabis sativa L. were in-silico screened using molecular docking and pharmacokinetic and toxicological analysis to evaluate their possible inhibitory effect on the cholinesterase enzymes. Two phytoconstituents belonging to cannabinoid derivatives were revealed to be promising candidates for Alzheimer's therapy by acting as cholinesterase inhibitors. They have exhibited high binding affinities towards the cholinesterase enzymes and showed their ability to interact with key residues involved in cholinesterase enzymatic activity. In addition, they presented good ADMET profiles allowing them to be promising oral drug candidates. Furthermore, molecular dynamics (MD) simulations were executed to explore their interaction stability under mimetic biological conditions and thus support our findings. To corroborate the docking results, the binding free energy corresponding to the more stable ligand-ChE complexes was re-estimated by applying the MM-PBSA method. MD and MM-PBSA studies affirmed that the ligand-ChE recognition is a spontaneous reaction leading to stable complexes. The conducted investigations have led to great findings that would strongly guide the pharmaceutical industries toward the rational development of potent anti-Alzheimer agents.

Keywords: Alzheimer’s disease, molecular docking, Cannabis sativa L., cholinesterase inhibitors, molecular dynamics, ADMET, MM-PBSA

Procedia PDF Downloads 83

Authors: Naznine Anwar, Kim Cornish, Izelle Labuschagne, Nellie Georgiou-Karistianis

Abstract:

Falls and subsequent injuries are common features in symptomatic Huntington’s disease (symp-HD) individuals. As part of daily walking, navigating around obstacles may incur a greater risk of falls in symp-HD. We designed obstacle-crossing experiment to examine adaptive gait dynamics and to identify underlying spatiotemporal gait characteristics that could increase the risk of falling in symp-HD. This experiment involved navigating around one or two ground-based obstacles under two conditions (walking while navigating around one obstacle, and walking while navigating around two obstacles). A total of 32 participants were included, 16 symp-HD and 16 healthy controls with age and sex matched. We used a GAITRite electronic walkway to examine the spatiotemporal gait characteristics and inter-trail gait variability when participants walked at their preferable speed. A minimum of six trials were completed which were performed for baseline free walk and also for each and every condition during navigating around the obstacles. For analysis, we separated all walking steps into three phases as approach steps, navigating steps and recovery steps. The mean and inter-trail variability (within participant standard deviation) for each step gait variable was calculated across the six trails. We found symp-HD individuals significantly decreased their gait velocity and step length and increased step duration variability during the navigating steps and recovery steps compared with approach steps. In contrast, HC individuals showed less difference in gait velocity, step time and step length variability from baseline in both respective conditions as well as all three approaches. These findings indicate that increasing spatiotemporal gait variability may be a possible compensatory strategy that is adopted by symp-HD individuals to effectively navigate obstacles during walking. Such findings may offer benefit to clinicians in the development of strategies for HD individuals to improve functional outcomes in the home and hospital based rehabilitation program.

Keywords: Huntington’s disease, gait variables, navigating around obstacle, basal ganglia dysfunction

Procedia PDF Downloads 443

Authors: Dimas Tri Anantyo, Zsa-Zsa Ayu Laksmi, Adhie Nur Radityo, Arsita Eka Rini, Gatot Irawan Sarosa

Abstract:

A six-point-two-magnitude earthquake rocked Mamuju District, West Sulawesi Province, Indonesia, on 15 January 2021, causing significant health issues for the affected community, particularly among vulnerable populations such as neonates and children. The aim of this study is to examine and describe the diseases diagnosed in the pediatric population in Mamuju 14 days after the earthquake. This study uses a prospective observational study of the pediatric population presenting at West Sulawesi Regional Hospital, Mamuju Regional Public Hospital, and Bhayangkara Hospital for the period of 14 days after the earthquake. Demographic and clinical information were recorded. One hundred and fifty-three children were admitted to the health center. Children younger than six years old were the highest proportion (78%). Out of 153 children, 82 of them were male (54%). The most frequently diagnosed disease during the first and second weeks after the earthquake was respiratory problems, followed by gastrointestinal problems that showed an increase in incidence in the second week. This study found that age has a correlation with frequent disease in children after an earthquake. Respiratory and gastrointestinal problems were found to be the most common diseases among the pediatric population in Mamuju after the earthquake.

Keywords: health outcomes, pediatric population, earthquake, Mamuju

Procedia PDF Downloads 90

Authors: Ida Shafinaz Mohamed Kamil, Mohd Dahlan Abdul Malek

Abstract:

Today, the whole world is facing a catastrophe called the novel coronavirus disease known as COVID-19. As of October 2021, it has been reported that more than 248 million cases and 5 million deaths have been recorded worldwide. In Malaysia, 2,466,663 cases were reported, with 28,876 deaths recorded on 30 October 2021. Unfortunately, the world is not only facing the COVID-19 pandemic but the COVID-19 infodemic as well, where fake news about COVID-19 disease is spreading faster and more widely than from the virus itself. The spread of fake news is amplified through various social media platforms, which is causing concern among the community. The uncertainty in understanding what fake news really is has caused difficulties and challenges in providing a solution to the hazards that it creates. This article discusses what constitutes fake news and examines the current legal framework put in place to combat fake news in Malaysia. Employing a doctrinal research methodology, this article thoroughly analyzes the relevant legal provisions under the Communications and Multimedia Act 1998, the Penal Code and the Emergency (Essential Powers) Ordinance (No.2) 2021, which came into force on 12 March 2021 as well as related case laws, for offenses and punishments with regards to fake news. The findings from the analysis indicate that there is still room for improvement in regulating fake news, in particular concerning COVID-19.

Keywords: fake news, legal pespective, covid 19, pendemic

Procedia PDF Downloads 85

Authors: Marek Kuźniewski, Magdalena B. Kaziuk , Danuta Fedak, Paulina Dumnicka, Ewa Stępień, Beata Kuśnierz-Cabala, Władysław Sułowicz

Abstract:

Background: The high prevalence of cardiovascular morbidity and mortality among patients with chronic kidney disease (CKD) is observed especially in those undergoing dialysis. Osteoprotegerin (OPG) and its ligands, receptor activator of nuclear factor kappa-B ligand (RANKL) and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) have been associated with cardiovascular complications. Our aim was to study their role as cardiovascular risk factors in stage 5 CKD patients. Methods: OPG, RANKL and TRAIL concentrations were measured in 69 hemodialyzed CKD patients and 35 healthy volunteers. In CKD patients, cardiovascular dysfunction was assessed with aortic pulse wave velocity (AoPWV), carotid artery intima-media thickness (CCA-IMT), coronary artery calcium score (CaSc) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) serum concentration. Cardiovascular and overall mortality data were collected during a 7-years follow-up. Results: OPG plasma concentrations were higher in CKD patients comparing to controls. Total soluble RANKL was lower and OPG/RANKL ratio higher in patients. Soluble TRAIL concentrations did not differ between the groups and OPG/TRAIL ratio was higher in CKD patients. OPG and OPG/TRAIL positively predicted long-term mortality (all-cause and cardiovascular) in CKD patients. OPG positively correlated with AoPWV, CCA-IMT and NT-proBNP whereas OPG/TRAIL with AoPWV and NT-proBNP. Described relationships were independent of classical and non-classical cardiovascular risk factors, with exception of age. Conclusions: Our study confirmed the role of OPG as a biomarker of cardiovascular dysfunction and a predictor of mortality in stage 5 CKD. OPG/TRAIL ratio can be proposed as a predictor of cardiovascular dysfunction and mortality.

Keywords: osteoprotegerin, tumor necrosis factor-related apoptosis-inducing ligand, receptor activator of nuclear factor kappa-B ligand, hemodialysis, chronic kidney disease, cardiovascular disease

Procedia PDF Downloads 334

Authors: Parastoo Motallebi, Vahid Niknam, Hassan Ebrahimzadeh, Majid Hashemi

Abstract:

Wheat, the most strategically important worldwide crop, is widely grown in various countries. Based on international wheat production statistics (FAOSTAT database), the total production of wheat in 2012 was 13.8 in Iran. Fusarium culmorum is one of the principal causative agents of Fusarium crown rot (FCR), an overwhelming disease of wheat and barley which is in the early stages causing yield losses, stand reductions and rotting of root and lower stem tissues. In this study inoculation of two wheat seedlings of the susceptible cultivar Falat and the partially field-resistant cultivar Pishtaz were carried out in greenhouse conditions and root samples were taken for 6 days. The activity of peroxidase (POX) and polyphenoloxidase (PPO) enzymes were analyzed to identify possible relations between resistance and enzymatic activities. Although the POX and PPO activities in both geno types increased, this significant increase was more dominant in Pishtaz. The results showed an earlier elevation in the activity of these defense related enzymes in semi-resistant cv. Pishtaz after inoculation, suggested that the activities of POX and PPO in wheat geno types play an important role in the induction of resistance to this disease.

Keywords: Defense responses, Fusarium culmorum, Wheat

Procedia PDF Downloads 539

Authors: Sadra Abbasi

Abstract:

The complex connection between psychological stress and the onset of different diseases has been an ongoing issue in the mental health field for a long time. Multiple studies have demonstrated that long-term stress can greatly heighten the likelihood of developing health issues like heart disease, cancer, arthritis, and severe depression. Recent research in cognitive science has provided insight into the intricate processes involved in posttraumatic stress disorder (PTSD), suggesting that distinct memory systems are accountable for both vivid reliving and normal autobiographical memories of traumatic incidents, as proposed by dual representation theory. This theory has important consequences for our comprehension of the neural mechanisms involved in fear and behavior related to threats, highlighting the amygdala-hippocampus-medial prefrontal cortex circuit as a crucial component in this process. This particular circuit, extensively researched in behavioral neuroscience, is essential for regulating the body's reactions to stress and trauma. This review will examine how incorporating a modern neuroscience viewpoint into an integrative case formulation offers a current way to comprehend the intricate connections among psychological stress, trauma, and disease.

Keywords: social, cognitive, stress, neuroscience, behavior, PTSD

Procedia PDF Downloads 36

Authors: Devendra Gupta, S. P. Ambesh, P. K Singh

Abstract:

Introduction: Minimally invasive coronary artery bypass grafting (MICABG) is a less invasive method of performing surgical revascularization. Minimally invasive direct coronary artery bypass (MIDCAB) provides many anesthetic challenges including one lung ventilation (OLV), managing myocardial ischemia, and pain. We present an early and midterm result of the use of this technique with OLV. Method: We enrolled 62 patients for analysis operated between 2008 and 2012. Patients were anesthetized and left endobronchial tube was placed. During the procedure left lung was isolated and one lung ventilation was maintained through right lung. Operation was performed utilizing off pump technique of coronary artery bypass grafting through a minimal invasive incision. Left internal mammary artery graft was done for single vessel disease and radial artery was utilized for other grafts if required. Postoperative ventilation was done with single lumen endotracheal tube. Median follow-up is 2.5 years (6 months to 4 years). Results: Median age was 58.5 years (41-77) and all were male. Single vessel disease was present in 36, double vessel in 24 and triple vessel disease in 2 patients. All the patients had normal left ventricular size and function. In 2 cases difficulty were encounter in placement of endobronchial tube. In 1 case cuff of endobronchial tube was ruptured during intubation. High airway pressure was developed on OLV in 1 case and surgery was accomplished with two lung anesthesia with low tidal volume. Mean postoperative ventilation time was 14.4 hour (11-22). There was no perioperative and 30 day mortality. Conversion to median sternotomy to complete the operation was done in 3.23% (2 out of 62 patients). One patient had acute myocardial infarction postoperatively and there were no deaths during follow-up. Conclusion: MICABG is a safe and effective method of revascularization with OLV in low risk candidates for coronary artery bypass grafting.

Keywords: MIDCABG, one lung ventilation, coronary artery bypass grafting, endobronchial tube

Procedia PDF Downloads 425

Authors: Ajit Kumar Yadav, Priyanka Yadav, F. Ram

Abstract:

In present study is an effort to analyse the burden of diseases in the state. Disability Adjusted Life Years (DALY) is estimated non-communicable diseases. Multi-rounds (52nd, 60th and 71st round) of the National Sample Surveys (NSSO), conducted in 1995-96, 2004 and 2014 respectively, and Million Deaths Study (MDS) of 2001-03, 2006 and 2013-14 datasets are used. Descriptive and multivariate analyses are carried out to identify the determinants of different types of self-reported morbidity and DALY. The prevalence was higher for population aged 60 and above, among females, illiterates, and rich across the time period and for all the selected morbidities. The results were found to be significant at P<0.001. The estimation of DALY revealed that, the burden of communicable diseases was higher during infancy, noticeably among males than females in 2002. However, females aged 1-5 years were more vulnerable to report communicable diseases than the corresponding males. The age distribution of DALY indicates that individuals aged below 5 years and above 60 year were more susceptible to ill health. The growing incidence of non-communicable diseases especially among the older generations put additional burden on the health system in the state. The state has to grapple with the unsettled preventable infectious diseases in one hand and growing non-communicable in other hand.

Keywords: disease burden, non-communicable, communicable, India and region

Procedia PDF Downloads 251

Authors: Andi Aliah Hidayani, Asmi Citra Malina A. R. Tassakka, Andi Parenrengi

Abstract:

Vanname Shrimp is one of the high yielding varieties that are more resistant to virus attacks. However, now this shrimp more death due to virus attack such as white spot disease caused by white spot syndrome virus (WSSV). Various efforts have done to prevent the disease, like immunostimulatory, probiotics, and vaccine. White spot syndrome virus (WSSV) envelope protein VP19 gene is important because of its involvement in the system infection of shrimp. This study aimed to isolate and characterize an envelope protein VP19 – encoding gene of WSSV using WSSV infected Vanname Shrimp sample from some areas in South Sulawesi (Pangkep, Barru and Pinrang). The genomic of DNA were isolated from shrimp muscle using DTAB-CTAB method. Isolation of gene encoding envelope protein VP19 WSSV ws successfully performed with the results of the length of DNA fragment was 387 bp. The results of homology analysis using BLASTn homology suggested that these isolates genes from Barru, Pangkep and Pinrang have closest relationship with isolates from Mexican.

Keywords: vanname, shrimp, WSSV, viral protein 19

Procedia PDF Downloads 535

Authors: Alan Ruiz-Padilla, Brando Villalobos-Villalobos, Yeniley Ruiz-Noa, Claudia Mendoza-Macías, Claudia Palafox-Sánchez, Miguel Marín-Rosales, Álvaro Cruz, Rubén Rangel-Salazar

Abstract:

Introduction: In patients with rheumatoid arthritis, resistance or poor response to disease modifying antirheumatic drugs (DMARD) may be a reflection of the increase in g-P. The expression of g-P may be important in mediating the effluence of DMARD from the cell. In addition, P-glycoprotein is involved in the transport of cytokines, IL-1, IL-2 and IL-4, from normal lymphocytes activated to the surrounding extracellular matrix, thus influencing the activity of RA. The involvement of P-glycoprotein in the transmembrane transport of cytokines can serve as a modulator of the efficacy of DMARD. It was shown that a number of lymphocytes with glycoprotein P activity is increased in patients with RA; therefore, P-glycoprotein expression could be related to the activity of RA and could be a predictor of poor response to therapy. Objective: To evaluate in RA patients, if the G2677T/A MDR1 polymorphisms is associated with differences in the rate of therapeutic response to disease-modifying antirheumatic agents in patients with rheumatoid arthritis. Material and Methods: A prospective cohort study was conducted. Fifty seven patients with RA were included. They had an active disease according to DAS-28 (score >3.2). We excluded patients receiving biological agents. All the patients were followed during 6 months in order to identify the rate of therapeutic response according to the American College of Rheumatology (ACR) criteria. At the baseline peripheral blood samples were taken in order to identify the G2677T/A MDR1 polymorphisms using PCR- Specific allele. The fragment was identified by electrophoresis in polyacrylamide gels stained with ethidium bromide. For statistical analysis, the genotypic and allelic frequencies of MDR1 gene polymorphism between responders and non-responders were determined. Chi-square tests as well as, relative risks with 95% confidence intervals (95%CI) were computed to identify differences in the risk for achieving therapeutic response. Results: RA patients had a mean age of 47.33 ± 12.52 years, 87.7% were women with a mean for DAS-28 score of 6.45 ± 1.12. At the 6 months, the rate of therapeutic response was 68.7 %. The observed genotype frequencies were: for G/G 40%, T/T 32%, A/A 19%, G/T 7% and for A/A genotype 2%. Patients with G allele developed at 6 months of treatment, higher rate for therapeutic response assessed by ACR20 compared to patients with others alleles (p=0.039). Conclusions: Patients with G allele of the - G2677T/A MDR1 polymorphisms had a higher rate of therapeutic response at 6 months with DMARD. These preliminary data support the requirement for a deep evaluation of these and other genotypes as factors that may influence the therapeutic response in RA.

Keywords: pharmacogenetics, MDR1, P-glycoprotein, therapeutic response, rheumatoid arthritis

Procedia PDF Downloads 208

Authors: Maarja Karbus, Elsbet Lippmaa, Kadri Kööp, Mare Tupits

Abstract:

Aim: The aim is to describe the experiences and needs of mothers of children with cancer in coping with the child's illness. Background: Cancer affects different life areas. Especially if it is a child, in this case the whole family is involved. Loved ones are mentally affected, there are limitations, and life changes need to be made to make the whole treatment regimen and recovery as comfortable as possible. Also, the whole process is expensive and time consuming. The research is part of a larger project that covers the experiences and needs of parents of children with chronic illness and coping strategies related to the child's illness. Design: Qualitative, empirical, descriptive research. Method: Semi-structured interviews were used to collect data and inductive content analysis was used to analyze the data. The interviews were conducted in the autumn of 2020, 5 respondents participated in the research. Results and Conclusions: The research revealed that the mothers' experiences of coping with a child's disease included health-related experiences, material aspects, changes in lifestyle, support systems and contact with professionals. Regarding the organizational and material aspects of life, the subjects presented experiences with economic problems, adaptation of changes in lifestyle, access to information and changes in the treatment process. With regard to health, the respondents identified experiences with the mother's physical and mental health and experiences with the health of an ill child. The experience of different support systems was related to the support of family, friends, acquaintances, various organizations and specialists. Experiences with specialist support included experiences with family relationships and positive and negatiive experiences with staff. The mothers' needs in dealing with the child's disease included the mother's emotional needs, the support of other family members, and the need for various support systems and services. The needs of coping with the child were the need for understanding, support, confidence, the need to be strong and courageous, the need to ignore one's own needs, and the need for personal time and rest. The needs of other family members included the needs of an ill child and the need to pay attention to other children in the family. The needs of different supporters and services were related to different helpers and different services.

Keywords: cancer, mother, coping, child, need, experience, illness

Procedia PDF Downloads 150

Authors: Jane E. Hill

Abstract:

Many variables led to the changes in the insanity defense since the Wild Beast Standard of 1723 until the Federal Insanity Defense Reform Act of 1984. The insanity defense is used in criminal trials and argued that the defendant is ‘not guilty by reason of insanity’ because the individual was unable to distinguish right from wrong during the time they were breaking the law. The issue that surrounds whether or not to use the insanity defense in the criminal court depends on the mental state of the defendant at the time the criminal act was committed. This leads us to the question of did the defendant know right from wrong when they broke the law? In 1723, The Wild Beast Test stated that to be exempted from punishment the individual is totally deprived of their understanding and memory and doth not know what they are doing. The Wild Beast Test became the standard in England for over seventy-five years. In 1800, James Hadfield attempted to assassinate King George III. He only made the attempt because he was having delusional beliefs. The jury and the judge gave a verdict of not guilty. However, to legal confine him; the Criminal Lunatics Act was enacted. Individuals that were deemed as ‘criminal lunatics’ and were given a verdict of not guilty would be taken into custody and not be freed into society. In 1843, the M'Naghten test required that the individual did not know the quality or the wrongfulness of the offense at the time they committed the criminal act(s). Daniel M'Naghten was acquitted on grounds of insanity. The M'Naghten Test is still a modern concept of the insanity defense used in many courts today. The Irresistible Impulse Test was enacted in the United States in 1887. The Irresistible Impulse Test suggested that offenders that could not control their behavior while they were committing a criminal act were not deterrable by the criminal sanctions in place; therefore no purpose would be served by convicting the offender. Due to the criticisms of the latter two contentions, the federal District of Columbia Court of Appeals ruled in 1954 to adopt the ‘product test’ by Sir Isaac Ray for insanity. The Durham Rule also known as the ‘product test’, stated an individual is not criminally responsible if the unlawful act was the product of mental disease or defect. Therefore, the two questions that need to be asked and answered are (1) did the individual have a mental disease or defect at the time they broke the law? and (2) was the criminal act the product of their disease or defect? The Durham courts failed to clearly define ‘mental disease’ or ‘product.’ Therefore, trial courts had difficulty defining the meaning of the terms and the controversy continued until 1972 when the Durham rule was overturned in most places. Therefore, the American Law Institute combined the M'Naghten test with the irresistible impulse test and The United States Congress adopted an insanity test for the federal courts in 1984.

Keywords: insanity defense, psychology law, The Federal Insanity Defense Reform Act of 1984, The Wild Beast Standard in 1723

Procedia PDF Downloads 143

Authors: Marina G. Galitskaya, Svetlana G. Makarova, Andrey P. Fisenko.

Abstract:

Children on medication-induced immunosuppression are at high risk of developing severe course infectious diseases. Therefore, preventive vaccination is especially important for these children. However, due to the immunosuppressive effects of treatment for the underlying disease, the effectiveness of vaccination may decrease below the protective level. In a multidisciplinary children's medical center, post-vaccination immunity was studied in 79 children aged 4-17 years. The children were divided into 2 groups: Group 1 (38 children) with kidney pathology (Nephrotic Syndrome) and Group 2 (41 children) with inflammatory bowel diseases (Ulcerative Colitis, Crohn's Disease). Both groups of children were vaccinated according to the national vaccination calendar and received immunosuppressive therapy (prednisolone, methotrexate, cyclosporine, and other drugs) for at least 1 year. Using the enzyme-linked immunosorbent assay method, specific IgG antibodies to vaccine-preventable infections were determined: measles, rubella, mumps, diphtheria, pertussis, tetanus, and hepatitis B. The study showed the percentage of children with positive IgG values for vaccine-preventable infections. The highest percentage of children had protective antibody levels to measles (84.2% in children with nephrotic syndrome and 92.6% in those with inflammatory bowel disease) and rubella (71% and 80.4%, respectively). The lowest percentage of children with protective antibodies was for hepatitis B (5.2% and 29.2% respectively). Antibodies to mumps, diphtheria, pertussis, and tetanus were found not in all children (from 39,4% to 82,9%). The remaining percentage of children did not have detectable IgG antibodies to vaccine-preventable infections. Not all children, despite the previous vaccination, preserved antibodies to vaccine-controlled infections and remained unprotected by specific IgG antibodies. The issue of a booster vaccine dose should be considered in children without contraindications to vaccination. Children receiving long-term immunosuppressive therapy require an individual vaccination approach, including a specific definition of the performed vaccination.

Keywords: immunosuppressive therapy, inflammatory bowel diseases, nephrotic syndrome, post-vaccination immunity, specific antibodies, vaccine-preventable infections.

Procedia PDF Downloads 33

Authors: A. E. Elkorany, Eman Elsrgawy

Abstract:

Eighty six isolates of Phytophthora infestans dating back to 2006 were recovered from potato tubers that were on sale in Alexandria markets, Egypt. The isolates were characterized for mating type and colony morphology. Both A1 and A2 mating types were detected in the isolate collection, however, the A2 constituted 5.8% of the total isolates made while the A1 mating type isolates constituted 91.9%. The self-fertile phenotype was also detected but at a lower percentage of 2.3% of the total isolates. This indicated that Mexico, the probable origin of the disease, is no longer the only place where A2 mating type ever exists. The lumpy phenotype was the only trait observed linked to the A2 mating type isolates on rye A agar medium. The self-fertile isolates, however, exhibited colonies of a waxy appearance with little aerial hyphae and the culture were backed full with oospores. The A1 mating colonies were of smooth white abundant aerial hyphae. The metalaxyl resistant isolates were also detected among the analyzed isolates and constituted 4.6% of the total (86) isolates investigated. The appearance of the A2 mating type outside Mexico and the variation revealed in the population of Phytophthora infestans investigated supported the hypothesis of a second worldwide migration of the fungus from its origin which could constitute a threat to potato cultivation around the world.

Keywords: Phytophthora infestans, potato, Egypt, fungus

Procedia PDF Downloads 384

Authors: M. S. Deshpande, Snehal D. Bomble

Abstract:

Tuberculosis (TB) is a deadly contagious disease that is caused by a bacterium called Mycobacterium tuberculosis. More than sixty years ago, the introduction of the first anti-TB drugs for the treatment of TB (streptomycin (STR), p-aminosalcylic acid (PAS), isoniazid (INH), and then later ethambutol (EMB) and rifampicin (RIF)) gave optimism to the medical community, and it was believed that the disease would be completely eradicated soon. Worldwide, the number of TB cases has continued to increase, but the incidence rate has decreased since 2003. Recently, highly drug-resistant forms of TB have emerged worldwide. The prolonged use of classical drugs developed a growing resistance and these drugs have gradually become less effective and incapable to meet the challenges, especially those of multi drug resistant (MDR)-TB, extensively drug resistant (XDR)-TB, and HIV-TB co-infections. There is an unmet medical need to discover newer synthetic molecules and new generation of potent drugs for the treatment of tuberculosis which will shorten the time of treatment, be potent and safe while effective facing resistant strains and non-replicative, latent forms, reduce adverse side effect and not interfere in the antiretroviral therapy. This paper attempts to bring out the review of anti-TB drugs, and presents a novel method of synthesizing new anti-tuberculosis drugs and potential compounds to overcome the bacterial resistance and combat the re-emergence of tuberculosis.

Keywords: tuberculosis, mycobacterium, multi-drug resistant (MDR)-TB, extensively drug resistant (XDR)-TB

Procedia PDF Downloads 380

Authors: Daniel C. Bonzo

Abstract:

Practical considerations lead to the use of unit of analysis within subjects, e.g., bleeding episodes or treatment-related adverse events, in rare disease settings. This is coupled with data augmentation techniques such as extrapolation to enlarge the subject base. In general, one can think about extrapolation of data as extending information and conclusions from one estimand to another estimand. This approach induces hierarchichal clustered data with varying cluster sizes. Extrapolation of clinical trial data is being accepted increasingly by regulatory agencies as a means of generating data in diverse situations during drug development process. Under certain circumstances, data can be extrapolated to a different population, a different but related indication, and different but similar product. We consider here the problem of estimation (point and interval) using a mixed-models approach under an extrapolation. It is proposed that estimators (point and interval) be constructed using weighting schemes for the clusters, e.g., equally weighted and with weights proportional to cluster size. Simulated data generated under varying scenarios are then used to evaluate the performance of this approach. In conclusion, the evaluation result showed that the approach is a useful means for improving statistical inference in rare disease settings and thus aids not only signal detection but risk-benefit evaluation as well.

Keywords: clustered data, estimand, extrapolation, mixed model

Procedia PDF Downloads 136