Search results for: clinical trial optimization

Authors: Mohamed Wahba

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Objective: To build a comparative arm for product (X) in specific gene mutated advanced gastrointestinal cancer using real world evidence to fulfill HTA requirements in drug evaluation. Methods: Data for product (X) were collected from phase II clinical trial while real world data for (Y) and (Z) were collected from US database. Real-world (RW) cohorts were matched to clinical trial base line characteristics using weighting by odds method. Outcomes included progression-free survival (PFS) and overall survival (OS) rates. Study location and participants: Internationally (product X, n=80) and from USA (Product Y and Z, n=73) Results: Two comparisons were made: trial cohort 1 (X) versus real-world cohort 1 (Z), trial cohort 2 (X) versus real-world cohort 2 (Y). For first line, the median OS was 9.7 months (95% CI 8.6- 11.5) and the median PFS was 5.2 months (95% CI 4.7- not reached) for real-world cohort 1. For second line, the median OS was 10.6 months (95% CI 4.7- 27.3) for real-world cohort 2 and the median PFS was 5.0 months (95% CI 2.1- 29.3). For OS analysis, results were statistically significant but not for PFS analysis. Conclusion: This study provided the clinical comparative outcomes needed for HTA evaluation.

Keywords: real world evidence, pharmacoeconomics, HTA agencies, oncology

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Authors: Matthieu-P. Schapranow

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Recruitment of participants for clinical trials requires the screening of a big number of potential candidates, i.e. the testing for trial-specific inclusion and exclusion criteria, which is a time-consuming and complex task. Today, a significant amount of time is spent on identification of adequate trial participants as their selection may affect the overall study results. We introduce a unique patient eligibility metric, which allows systematic ranking and classification of candidates based on trial-specific filter criteria. Our web application enables real-time analysis of patient data and assessment of candidates using freely definable inclusion and exclusion criteria. As a result, the overall time required for identifying eligible candidates is tremendously reduced whilst additional degrees of freedom for evaluating the relevance of individual candidates are introduced by our contribution.

Keywords: in-memory technology, clinical trials, screening, eligibility metric, data analysis, clustering

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Authors: Tambe Daniel Atem

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Background: Clinical Research is an organized research on human beings intended to provide adequate information on the drug use as a therapeutic agent on its safety and efficacy. The significance of the study is to educate the global health and life science graduates in Clinical Research in depth to perform better as it involves testing drugs on human beings. Objectives: to provide an overall understanding of the scientific approach to the evaluation of new and existing medical interventions and to apply ethical and regulatory principles appropriate to any individual research. Methodology: It is based on – Primary data analysis and Secondary data analysis. Primary data analysis: means the collection of data from journals, the internet, and other online sources. Secondary data analysis: a survey was conducted with a questionnaire to interview the Clinical Research Professionals to understand the need of training to perform clinical trials globally. The questionnaire consisted details of the professionals working with the expertise. It also included the areas of clinical research which needed intense training before entering into hardcore clinical research domain. Results: The Clinical Trials market worldwide worth over USD 26 billion and the industry has employed an estimated 2,10,000 people in the US and over 70,000 in the U.K, and they form one-third of the total research and development staff. There are more than 2,50,000 vacant positions globally with salary variations in the regions for a Clinical Research Coordinator. R&D cost on new drug development is estimated at US$ 70-85 billion. The cost of doing clinical trials for a new drug is US$ 200-250 million. Due to an increase trained Clinical Research Professionals India has emerged as a global hub for clinical research. The Global Clinical Trial outsourcing opportunity in India in the pharmaceutical industry increased to more than $2 billion in 2014 due to increased outsourcing from U.S and Europe to India. Conclusion: Assessment of training need is recommended for newer Clinical Research Professionals and trial sites, especially prior the conduct of larger confirmatory clinical trials.

Keywords: clinical research, clinical trials, clinical research professionals

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Authors: Tuong Thi Van Thuy, Dao Van Toan, Nguyen Duc Phuc

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Mesenchymal stem cells (MSCs) were discovered in the 1970s with their unique properties of differentiation, immunomodulation, multiple secreting, and homing factors to injured organs. MSC-based therapies have emerged as a promising strategy for various diseases such as cancer, tissue regeneration, or immunologic/inflammatory-related diseases. This study evaluated the clinical application of MSCs for cancer therapy in trials registered on Clinical Trial as of July 2022. The results showed 40 clinical trials used MSCs in various cancer conditions. 62% of trials used MSCs for therapeutic purposes to minimize the side effects of cancer treatment. Besides, 38% of trials were focused on using MSCs as a therapeutic agent to treat cancer directly. Most trials (38/40) are ongoing phase I/II, and 2 are entering phase III. 84% of trials used allogeneic MSCs compared with 13% using autologous sources and 3% using both. 25/40 trials showed participants received a single dose of MSCs, while the most times were 12 times in a pancreatic cancer treatment trial. Conclusion: MSC-based therapy for cancer in clinical trials should be applied to (1) minimize the side effects of oncological treatments and (2) directly affect the tumor via selectively delivering anti-cancer payloads to tumor cells. Allogeneic MSCs are a priority selected in clinical cancer therapy.

Keywords: mesenchymal stem cells, MSC-based therapy, cancer condition, cancer treatment, clinical trials

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Authors: Abiola Falilat Ibraheem, Akinyimika Sowunmi, Valerie Otti

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Background: Introduction of innovative cancer clinical trials to Nigeria is a critical step in addressing global inequities of cancer burden. Low health and clinical trial literacy among Nigerian patients have been sighted as a significant barrier to ensuring that patients enrolled in clinical trials are truly informed. Video intervention has been shown to be the most proactive method to improving patient’s clinical trial knowledge. In the US, video interventions have been successful at improving education about cancer clinical trials among minority patients. Thus, this study aimed to apply and adapt video interventions addressing attitudinal barriers peculiar to Nigerian patients. Methods: A hospital-based representative mixed-method study was conducted at the Lagos State University Teaching Hospital (LASUTH) from July to December 2020, comprising of cancer patients aged 18 and above. Patients were randomly selected during every clinic day, of which 63 patients volunteered to participate in this study. We first administered a cancer literacy survey to determine patients’ knowledge about clinical trials. For patients who had prior knowledge, a pre-intervention test was administered, after which a 15-minute video (attitudes and intention to enroll in therapeutic clinical trials (AIET)) to improve patients’ knowledge, perception, and attitudes towards clinical trials was played, and then ended by administering a post-intervention test to the patients. For patients who had no prior knowledge, the AIET video was played for them, followed by the post-intervention test. Results: Out of 63 patients sampled, 43 (68.3%) had breast cancer. On average, patients agreed to understand their cancer diagnosis and treatment very well. 84.1% of patients had never heard about cancer clinical trials, and 85.7% did not know what cancer clinical trials were. There was a strong positive relationship (r=0.916) between the pretest and posttest, which means that the intervention improved patients’ knowledge, perception, and attitudes about cancer clinical trials. In the focus groups, patients recommended adapting the video in Nigerian settings and representing all religions in order to address trust in local clinical trialists. Conclusion: Due to the small size of patients, change in clinical trial knowledge was not statistically significant. However, there is a trend suggesting that culturally adapted video interventions can be used to improve knowledge and perception about cancer clinical trials.

Keywords: clinical trials, culturally targeted intervention, patient education, video intervention

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Authors: Abdoullah Nyassi, Golam Sarwar, Sarra Baldeh, Mamadou S. K. Jallow, Bai Lamin Dondeh, Isaac Osei, Grant A. Mackenzie

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A randomized controlled trial is the "gold standard" for evaluating the efficacy of an intervention. Large-scale, cluster-randomized trials are expensive and difficult to conduct, though. To guarantee the validity and generalizability of findings, high-quality, dependable, and accurate data management systems are necessary. Robust data management systems are crucial for optimizing and validating the quality, accuracy, and dependability of trial data. Regarding the difficulties of data gathering in clinical trials in low-resource areas, there is a scarcity of literature on this subject, which may raise concerns. Effective data management systems and implementation goals should be part of trial procedures. Publicizing the creative clinical data management techniques used in clinical trials should boost public confidence in the study's conclusions and encourage further replication. In the ongoing pneumococcal vaccine schedule study in rural Gambia, this report details the development and deployment of multi-data management systems and methodologies. We implemented six different data management, synchronization, and reporting systems using Microsoft Access, RedCap, SQL, Visual Basic, Ruby, and ASP.NET. Additionally, data synchronization tools were developed to integrate data from these systems into the central server for reporting systems. Clinician, lab, and field data validation systems and methodologies are the main topics of this report. Our process development efforts across all domains were driven by the complexity of research project data collected in real-time data, online reporting, data synchronization, and ways for cleaning and verifying data. Consequently, we effectively used multi-data management systems, demonstrating the value of creative approaches in enhancing the consistency, accuracy, and reporting of trial data in a poor resource setting.

Keywords: data management, data collection, data cleaning, cluster-randomized trial

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Authors: Terentes Printzios Dimitrios, Loanna Gourgouli, Vlachopoulos Charalambos

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

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

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Authors: Syed Auon Raza, Tahir Mahmood, Syed Basit Ali Bukhari

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In power system properly coordinated protection scheme is designed to make sure that only the faulty part of the system will be isolated when abnormal operating condition of the system will reach. The complexity of the system as well as the increased user demand and the deregulated environment enforce the utilities to improve system reliability by using a properly coordinated protection scheme. This paper presents overview of over current relay coordination techniques. Different techniques such as Deterministic Techniques, Meta Heuristic Optimization techniques, Hybrid Optimization Techniques, and Trial and Error Optimization Techniques have been reviewed in terms of method of their implementation, operation modes, nature of distribution system, and finally their advantages as well as the disadvantages.

Keywords: distribution system, relay coordination, optimization, Plug Setting Multiplier (PSM)

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Authors: Milad Yousefi, Moslem Yousefi, Ricarpo Poley, Amer Nordin Darus

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Design optimization of heat exchangers is a very complicated task that has been traditionally carried out based on a trial-and-error procedure. To overcome the difficulties of the conventional design approaches especially when a large number of variables, constraints and objectives are involved, a new method based on a well-stablished evolutionary algorithm, particle swarm optimization (PSO), weighted sum approach and a novel constraint handling strategy is presented in this study. Since, the conventional constraint handling strategies are not effective and easy-to-implement in multi-objective algorithms, a novel feasibility-based ranking strategy is introduced which is both extremely user-friendly and effective. A case study from industry has been investigated to illustrate the performance of the presented approach. The results show that the proposed algorithm can find the near pareto-optimal with higher accuracy when it is compared to conventional non-dominated sorting genetic algorithm II (NSGA-II). Moreover, the difficulties of a trial-and-error process for setting the penalty parameters is solved in this algorithm.

Keywords: Heat exchanger, Multi-objective optimization, Particle swarm optimization, NSGA-II Constraints handling.

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Authors: Alejandro Rodríguez-Molinero, Carlos Pérez-López, Jorge Hernández-Vara, Àngels Bayes-Rusiñol, Juan Carlos Martínez-Castrillo, David A. Pérez-Martínez

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Background: Monitoring motor symptoms in Parkinson's patients is often a complex and time-consuming task for clinicians, as Hauser's diaries are often poorly completed by patients. Recently, new automatic devices (Parkinson's holter: STAT-ON®) have been developed capable of monitoring patients' motor fluctuations. The MoMoPa-EC clinical trial (NCT04176302) investigates which of the two methods produces better clinical results. In this sub-analysis, the concordance between both methods is analyzed. Methods: In the MoMoPa-EC clinical trial, 164 patients with moderate-severe Parkinson's disease and at least two hours a day of Off will be included. At the time of patient recruitment, all of them completed a seven-day motor fluctuation diary at home (Hauser’s diary) while wearing the Parkinson's holter. In this sub-analysis, 71 patients with complete data for the purpose of this comparison were included. The intraclass correlation coefficient was calculated between the patient diary entries and the Parkinson's holter data in terms of time On, Off, and time with dyskinesias. Results: The intra-class correlation coefficient of both methods was 0.57 (95% CI: 0.3-0.74) for daily time in Off (%), 0.48 (95% CI: 0.14-0.68) for daily time in On (%), and 0.37 (95% CI %: -0.04-0.62) for daily time with dyskinesias (%). Conclusions: Both methods have a moderate agreement with each other. We will have to wait for the results of the MoMoPa-EC project to estimate which of them has the greatest clinical benefits. Acknowledgment: This work is supported by AbbVie S.L.U, the Instituto de Salud Carlos III [DTS17/00195], and the European Fund for Regional Development, 'A way to make Europe'.

Keywords: Parkinson, sensor, motor fluctuations, dyskinesia

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Authors: Simone Huber, Bianca Schnalzer, Baptiste Alcalde, Sten Hanke, Lampros Mpaltadoros, Thanos G. Stavropoulos, Spiros Nikolopoulos, Ioannis Kompatsiaris, Lina Pérez- Breva, Vallivana Rodrigo-Casares, Jaime Fons-Martínez, Jeroen de Bruin

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Developing new medicine and health solutions and improving patient health currently rely on the successful execution of clinical trials, which generate relevant safety and efficacy data. For their success, recruitment and retention of participants are some of the most challenging aspects of protocol adherence. Main barriers include: i) lack of awareness of clinical trials; ii) long distance from the clinical site; iii) the burden on participants, including the duration and number of clinical visits and iv) high dropout rate. Most of these aspects could be addressed with a new paradigm, namely the Remote Decentralized Clinical Trials (RDCTs). Furthermore, the COVID-19 pandemic has highlighted additional advantages and challenges for RDCTs in practice, allowing participants to join trials from home and not depend on site visits, etc. Nevertheless, RDCTs should follow the process and the quality assurance of conventional clinical trials, which involve several processes. For each part of the trial, the Building Blocks, existing software and technologies were assessed through a systematic search. The technology needed to perform RDCTs is widely available and validated but is yet segmented and developed in silos, as different software solutions address different parts of the trial and at various levels. The current paper is analyzing the availability of technology to perform RDCTs, identifying gaps and providing an overview of Basic Building Blocks and functionalities that need to be covered to support the described processes.

Keywords: architectures and frameworks for health informatics systems, clinical trials, information and communications technology, remote decentralized clinical trials, technology availability

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Authors: Paria Baharvand, Mohammad Reza Abbasi, Soha Namazi

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Introduction: Uremic pruritus (UP) is one of the major complaints in hemodialysis patients. The aim of this randomized clinical trial study was the evaluation of the anti-pruritus effect of Melatonin on hemodialysis patients with UP. Methods: This multi-centered double, blinded randomized clinical trial study was conducted on hemodialysis patients with UP that referred to the dialysis department of Imam Khomeini Hospital, Labbafinezhad Hospital and Ghiasi Hospital in Tehran, Iran, in 2018. Forty participants were enrolled and block randomization was performed by using a randomized list and divided into 2 groups of twenty patients. Evaluation of the 12-Item Pruritus Severity Scale (12-PSS), Visual analog scale (VAS), and Calculation of the affected body surface area for pruritus extent (BSA %) was performed every week. The Melatonin group received a 10 mg soft gel capsule, and the placebo group received a soft gel capsule placebo after dinner. For statistical analysis used by SPSS version 21(IRCT20180714040462N1). Results: 38 hemodialysis patients enrolled in this study. The mean age in the placebo group and in the Melatonin group was 55.88 ± 11.70 and 54.52 ± 13.00 years (p> 0.05). Also, 46% of all participants were female. Aspartate transaminase, alanine transaminase and C-reactive protein have significant differences between the two groups (p< 0.05). VAS score reduction in the two groups had a statistically significant (CI 95% = -1.71, P= 0.015(.The results of BSA% showed Melatonin had a significant effect on the decrease of the pruritus extent compared to placebo (CI 95% = -22.82, P= 0.001(. Conclusion: According to the results of this study and the preliminary effects of Melatonin on uremic pruritus, we suggest performing advanced clinical trials studies.

Keywords: Melatonin, Uremic Pruritus, hemodialysis, anti-pruritus

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Authors: Nerella Srinivas

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This study explores the significance of patent protection for artificial intelligence (AI) innovations in the pharmaceutical sector, emphasizing applications in drug discovery, personalized medicine, and clinical trial optimization. The challenges of patenting AI-driven inventions are outlined, focusing on the classification of algorithms as abstract ideas, meeting the non-obviousness standard, and issues around defining inventorship. The methodology includes examining case studies and existing patents, with an emphasis on how companies like Benevolent AI and Insilico Medicine have successfully secured patent rights. Findings demonstrate that a strategic approach to patent protection is essential, with particular attention to showcasing AI’s technical contributions to pharmaceutical advancements. Conclusively, the study underscores the critical role of understanding patent law and innovation strategies in leveraging intellectual property rights in the rapidly advancing field of AI-driven pharmaceuticals.

Keywords: artificial intelligence, pharmaceutical industry, patent protection, drug discovery, personalized medicine, clinical trials, intellectual property, non-obviousness

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Authors: Moon Jung Kim, Guil Rhim

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The clinical sensitivity of the “VEUPLEXTM TBI assay”, a clinical trial medical device, in mild traumatic brain injury was 28.6% (95% CI, 19.7%-37.5%), and the clinical specificity was 94.0% (95% CI, 89.3%). -98.7%). In addition, when the results analyzed by marker were put together, the sensitivity was higher when interpreting the two tests together than the two tests, UCHL1 and GFAP alone. Additionally, when sensitivity and specificity were analyzed based on CT results for the mild traumatic brain injury patient group, the clinical sensitivity for 2 CT-positive cases was 50.0% (95% CI: 1.3%-98.7%), and 19 CT-negative cases. The clinical specificity for cases was 68.4% (95% CI: 43.5% - 87.4%). Since the low clinical sensitivity for the two CT-positive cases was not statistically significant due to the small number of samples analyzed, it was judged necessary to secure and analyze more samples in the future. Regarding the clinical specificity analysis results for 19 CT-negative cases, there were a large number of patients who were actually clinically diagnosed with mild traumatic brain injury but actually received a CT-negative result, and about 31.6% of them showed abnormal results on VEUPLEXTM TBI assay. Although traumatic brain injury could not be detected in 31.6% of the CT scans, the possibility of actually suffering a mild brain injury could not be ruled out, so it was judged that this could be confirmed through follow-up observation of the patient. In addition, among patients with mild traumatic brain injury, CT examinations were not performed in many cases because the symptoms were very mild, but among these patients, about 25% or more showed abnormal results in the VEUPLEXTM TBI assay. In fact, no damage is observed with the naked eye immediately after traumatic brain injury, and traumatic brain injury is not observed even on CT. But in some cases, brain hemorrhage may occur (delayed cerebral hemorrhage) after a certain period of time, so the patients who did show abnormal results on VEUPLEXTM TBI assay should be followed up for the delayed cerebral hemorrhage. In conclusion, it was judged that it was difficult to judge mild traumatic brain injury with the VEUPLEXTM TBI assay only through clinical findings without CT results, that is, based on the GCS value. Even in the case of CT, it does not detect all mild traumatic brain injury, so it is difficult to necessarily judge that there is no traumatic brain injury, even if there is no evidence of traumatic brain injury in CT. And in the long term, more patients should be included to evaluate the usefulness of the VEUPLEXTM TBI assay in the detection of microscopic traumatic brain injuries without using CT.

Keywords: brain injury, traumatic brain injury, GFAP, UCHL1

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Authors: Maryam Shayani Rad, Seyed Ahmad Mohajeri, Mohsen Mouhebati, Seyed Danial Mousavi

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High blood pressure is one of the most important and serious health-threatening because of no symptoms in most people, which can lead to sudden heart attack, heart failure, and stroke. Nowadays, herbal medicine is one of the best and safest strategies for treatment that have no adverse effects. Apium graveolens (celery) can be used as an alternative treatment for many health conditions such as hypertension. Natural compounds reduce blood pressure via different mechanisms in which Apium graveolens extract provides potent calcium channel blocking properties. A randomized, double-blind, placebo-controlled, cross-over clinical trial was done to evaluate the efficacy of formulated Apium graveolens extract with a maximum yield of 3-n-butylphthalide to reduce systolic and diastolic blood pressure in patients with hypertension. 54 hypertensive patients in the range of 20-68 years old were randomly assigned to the treatment group (26 cases) and the placebo control group (26 cases) and were crossed over after washout duration. The treatment group received at least 2 grams of formulated powder in hard capsules orally, before each meal, 2 times daily. The control group received 2 grams of placebo in hard capsules orally, exactly as the same as shape, time, and doses of treatment group. Treatment was administrated in 12 weeks with 4 weeks washout period at the middle of the study, meaning 4 weeks drug consumption for the treatment group, 4 weeks washout and 4 weeks placebo consumption, and vice versa for the placebo control group. The clinical assessment was done 4 times, including at the beginning and ending of the drug and placebo consumption period by 24-hour ambulatory blood pressure monitoring (ABPM) holter, which measured blood pressure every 15 minutes continuously. There was a statistically significant decrease in both systolic blood pressure (SBP) and diastolic blood pressure (DBP) at the end of drug duration compared to baseline. The changes after 4 weeks on average was about 12.34 mm Hg for the SBP (P < 0.005) and 7.83 mm Hg for the DBP (P < 0.005). The results from this clinical trial study showed this Apium graveolens extract formulation in the mentioned dosage had a significant effect on blood pressure-lowering for hypertensive patients.

Keywords: Apium graveolens extract, clinical trial, cross-over, hypertension

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Authors: R. Botrugno, S Basyuni, G. Nugent, I. Jenkyn, A. Ferro, H. Bennett, C. Hjalmarsson, J. Chu, V. Santhanam

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This trainee led randomised controlled trial (RCT) aims to assess various outcomes for resorbable versus non-resorbable sutures for traumatic lacerations to the face. Within this trial of resorbable versus non-resorbable sutures for traumatic lacerations of the face (TORNFace), patient recruitment was facilitated by trainees who were employed at an NHS University Teaching Hospital in the United Kingdom. The trainees received appropriate training prior to recruiting patients for the trial. This included the completion of a national research e-learning module and face-to-face training that was provided locally. The locally delivered training provided an understanding of the eligibility criteria for the trial and the consent process. Existing trainee skills were utilised involving clinical photography to record baseline data and delivering the intervention based on the treatment arm selected. Eligible patients who required primary closure of traumatic lacerations of the face were randomised into one of two treatment arms. These comprised of resorbable (vicryl rapide) or non-resorbable sutures (ethilon). Primarily the cosmetic outcome was assessed. Secondary outcomes included: complications rates, health care economics, and patient-reported outcomes. Remote follow-up of recruited patients utilised photographs of the facial laceration which had received the intervention. These took place at 1 week, 3 months and 6 months post-intervention. This study aims to demonstrate an example of trainee-led research within the specialty of oral and maxillofacial surgery. The available data for the randomised controlled trial will also be presented.

Keywords: laceration, suture, trauma, trial

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Authors: Mostafa Solati

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Objectives: Considering the gap of information regarding the optimal antimicrobial efficacy of metronidazole for application in the implant screw hole, this study aimed to compare the antimicrobial efficacy of 0.75% metronidazole and 2% chlorhexidine (CHX) gel applied in the implant screw hole. Materials and Methods: This randomized controlled clinical trial evaluated 60 implants (20 patients, each requiring three implants) in three groups (n=20). In group 1, 0.75% metronidazole gel was applied to the implant screw hole. In group 2, 2% CHX gel was applied, and in group 3, no material was used. Microbial samples were collected from the screw holes after three months, and the microbial colonies were counted. Data were analyzed using ANOVA. Results: The number of bacteria in the control group was significantly higher than that in 0.75% metronidazole gel and 2% CHX groups (P<0.05). The CHX group caused the maximum reduction in colony count with no significant difference from the metronidazole group (P>0.05). Conclusion: The application of 0.75% metronidazole gel and 2% CHX can effectively decrease the colony count in the implant screw hole and can probably play a role in the preservation of peri-implant tissue health.

Keywords: dental implant, metronidazole, CHX, screw hole

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Authors: Neda Jamalimoghadam, Naval Heydari, Maliheh Abootalebi, Maryam Kasraeian, M. Emamghoreishi , Akbarzadeh Marzieh

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Background: The aim was to investigate the effect of aromatherapy using Citrus aurantium blossom essential oil on premenstrual syndrome in university students. Methods: In this double-blind clinical trial was controlled on 62 students from March 2016 to February 2017. The intervention with 0.5% of C. Aurantium blossom essential oil and control was inhalation of odorless sweet almond oil in the luteal phase of the menstrual cycle. The screening questionnaire (PSST) for PMSwas filled out before and also one and two months after the intervention. Results: Mean score of overall symptoms of PMS between the Bitter orange and control groups In the first (p < 0.003) and second months (p < 0.001) of the intervention was significant. Besides, decreased the mean score of psychological symptoms in the intervention group (p < 0.001), but on physical symptoms and social function were not significant (p > 0.05). Conclusion: The aromatherapy with Citrus aurantium blossom improved the symptoms of premenstrual syndrome.

Keywords: aromatherapy, Citrus Aurantium, premenstrual syndrome, oil, students

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Authors: Hussain Syed Asad, Richard Kwok Kit Yuen, Gongsheng Huang

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Real-time optimization has been considered an effective approach for improving energy efficient operation of heating, ventilation, and air-conditioning (HVAC) systems. In model-based real-time optimization, model mismatches cannot be avoided. When model mismatches are significant, the performance of the real-time optimization will be impaired and hence the expected energy saving will be reduced. In this paper, the model mismatches for chiller plant on real-time optimization are considered. In the real-time optimization of the chiller plant, simplified semi-physical or grey box model of chiller is always used, which should be identified using available operation data. To overcome the model mismatches associated with the chiller model, hybrid Genetic Algorithms (HGAs) method is used for online real-time training of the chiller model. HGAs combines Genetic Algorithms (GAs) method (for global search) and traditional optimization method (i.e. faster and more efficient for local search) to avoid conventional hit and trial process of GAs. The identification of model parameters is synthesized as an optimization problem; and the objective function is the Least Square Error between the output from the model and the actual output from the chiller plant. A case study is used to illustrate the implementation of the proposed method. It has been shown that the proposed approach is able to provide reliability in decision making, enhance the robustness of the real-time optimization strategy and improve on energy performance.

Keywords: energy performance, hybrid adaptive modeling, hybrid genetic algorithms, real-time optimization, heating, ventilation, and air-conditioning

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Authors: Fasanmi Samuel Sunday

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This study investigated the influence of gender and personality traits on emotional distress among awaiting trial inmates in Nigeria. Participants were three hundred and twenty (320) awaiting trial inmates, drawn from three main correctional centres in Northeast Nigeria, namely: Gashua Correctional Centre, Postiskum Correctional Centre, and Bauchi Correctional Centre. Expo facto research design was adopted. Questionnaires such as the Big Five Inventory and the Perceived Emotional Distress Inventory (PEDI) were used to measure the variables of the study. Three hypotheses were tested. Logistic regression was used for data analysis. Results of the analysis indicated that conscientiousness significantly predicted emotional distress among awaiting trial inmates. However, most of the identified personality traits did not significantly predict emotional distress among awaiting trial inmates. There was no significant gender difference in emotional distress among awaiting-trial inmates. The implications of the study were discussed.

Keywords: personality traits, emotional distress, awaiting-trial inmates, gender

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Authors: Ifeoma C. Afiaenyi, Elizabeth K. Ngwu, Rufina N. B. Ayogu

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Diabetes has crept into the rural areas of Nigeria, causing devastating effects on its sufferers; most of them could not afford diabetic medications. Moringa oleifera has been used extensively in animal models to demonstrate its antilipidaemic and haematinic qualities; however, there is a scarcity of data on the effect of graded levels of Moringa oleifera leaves on the lipid profile and hematological parameters in human diabetic subjects. The study determined the effect of Moringa oleifera leaves on the lipid profile and hematological parameters of type 2 diabetic subjects in Ukehe, a rural Nigerian community. Twenty-four adult male and female diabetic subjects were purposively selected for the study. These subjects were shared into four groups of six subjects each. The diets used in the study were isocaloric. A control group (diabetics, group 1) was fed diets without Moringa oleifera leaves. Experimental groups 2, 3 and 4 received 20g, 40g and 60g of Moringa oleifera leaves daily, respectively, in addition to the diets. The subjects' lipid profile and hematological parameters were measured prior to the feeding trial and at the end of the feeding trial. The feeding trial lasted for fourteen days. The data obtained were analyzed using the computer program Statistical Product for Service Solution (SPSS) for windows version 21. A Paired-samples t-test was used to compare the means of values collected before and after the feeding trial within the groups and significance was accepted at p < 0.05. There was a non-significant (p > 0.05) decrease in the mean total cholesterol of the subjects in groups 1, 2 and 3 after the feeding trial. There was a non-significant (p > 0.05) decrease in the mean triglyceride levels of the subjects in group 1 after the feeding trial. Groups 1 and 3 subjects had a non-significant (p > 0.05) decrease in their mean low-density lipoprotein (LDL) cholesterol after the feeding trial. Groups 1, 2 and 4 had a significant (p < 0.05) increase in their mean high-density lipoprotein (HDL) cholesterol after the feeding trial. A significant (p < 0.05) decrease in the mean hemoglobin level was observed only in group 4 subjects. Similarly, there was a significant (p < 0.05) decrease in the mean packed cell volume of group 4 subjects. It was only in group 4 that a significant (p < 0.05) decrease in the mean white blood cells of the subjects was also observed. The changes observed in the parameters assessed were not dose-dependent. Therefore, a similar study of longer duration and more samples is imperative to authenticate these results.

Keywords: anemia, diabetic subjects, lipid profile, moringa oleifera

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Authors: Muhammad Fatahillah Akbar

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Criminal Procedural Law is established to protect the society from the abuse of authority. To achieve that purpose, the criminal procedural law shall be established in accordance with the laws of human right and the protection of the society. One of the mechanisms to protect human rights and to ensure the compliance of authorities in criminal procedural law is pre-trial mechanism. In many countries, there are various mechanisms of pre-trial. In the recent cases in Indonesia, pre-trial has been an interesting issue. The issue is also addressed by the Constitutional Court Decision Number 21/PUU-XII/2014 which enhance the competence of pre-trial which includes the suspect determination and the legality of seizure and search. Before that decision, some pre-trial decisions have made landmark decision by enhancing the competence of pre-trial, such as the suspect determination case in Budi Gunawan Case and legality of the investigation in Hadi Purnomo Case. These pre-trial cases occurred because the society needs protection even though it is not provided by written legislations, in this matter, The Indonesian Criminal Procedural Code (KUHAP). For instance, a person can be a suspect for unlimited time because the Criminal Procedural Code does not regulate the limit of investigation, so the suspect enactment shall be able to be challenged to protect human rights. Before the Constitutional Court Decision Suspect Determination cannot be challenged so that the society is not fully protected. The Constitutional Court Decision has provided more protections. Nowadays, investigators shall be more careful in conducting the investigation. However, those decisions, including the Constitutional Court Decision are not sufficient for society to be protected by abuse of authority. For example, on 7 March 2017, a single judge, in a Pre-Trial, at the Surabaya District Court, decided that the investigation was unlawful and shall be terminated. This is not regulated according to the Code and also any decisions in pre-trial. It can be seen that the reform of pre-trial is necessary. Hence, this paper aims to examine how pre-trial shall be developed in the future to provide wide access for society to have social justice in criminal justice system. The question will be answered by normative, historical, and comparative approaches. Firstly, the paper will examine the history of pre-trial in Indonesia and also landmark decisions on pre-trial. Then, the lessons learned from other countries regarding to the pre-trial mechanism will be elaborated to show how pre-trial shall be developed and what the competences of a pre-trial are. The focus of all discussions shall be on how the society is protected and provided access to legally complain to the authority. At the end of the paper, the recommendation to reform the pre-trial mechanism will be suggested.

Keywords: pre-trial, criminal procedural law, society

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Authors: Ayon Mukherjee

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Covariate-adjusted response-adaptive (CARA) designs use the available responses to skew the treatment allocation in a clinical trial in towards treatment found at an interim stage to be best for a given patient's covariate profile. Extensive research has been done on various aspects of CARA designs with the patient responses assumed to follow a parametric model. However, ranges of application for such designs are limited in real-life clinical trials where the responses infrequently fit a certain parametric form. On the other hand, robust estimates for the covariate-adjusted treatment effects are obtained from the parametric assumption. To balance these two requirements, designs are developed which are free from distributional assumptions about the survival responses, relying only on the assumption of proportional hazards for the two treatment arms. The proposed designs are developed by deriving two types of optimum allocation designs, and also by using a distribution function to link the past allocation, covariate and response histories to the present allocation. The optimal designs are based on biased coin procedures, with a bias towards the better treatment arm. These are the doubly-adaptive biased coin design (DBCD) and the efficient randomized adaptive design (ERADE). The treatment allocation proportions for these designs converge to the expected target values, which are functions of the Cox regression coefficients that are estimated sequentially. These expected target values are derived based on constrained optimization problems and are updated as information accrues with sequential arrival of patients. The design based on the link function is derived using the distribution function of a probit model whose parameters are adjusted based on the covariate profile of the incoming patient. To apply such designs, the treatment allocation probabilities are sequentially modified based on the treatment allocation history, response history, previous patients’ covariates and also the covariates of the incoming patient. Given these information, an expression is obtained for the conditional probability of a patient allocation to a treatment arm. Based on simulation studies, it is found that the ERADE is preferable to the DBCD when the main aim is to minimize the variance of the observed allocation proportion and to maximize the power of the Wald test for a treatment difference. However, the former procedure being discrete tends to be slower in converging towards the expected target allocation proportion. The link function based design achieves the highest skewness of patient allocation to the best treatment arm and thus ethically is the best design. Other comparative merits of the proposed designs have been highlighted and their preferred areas of application are discussed. It is concluded that the proposed CARA designs can be considered as suitable alternatives to the traditional balanced randomization designs in survival trials in terms of the power of the Wald test, provided that response data are available during the recruitment phase of the trial to enable adaptations to the designs. Moreover, the proposed designs enable more patients to get treated with the better treatment during the trial thus making the designs more ethically attractive to the patients. An existing clinical trial has been redesigned using these methods.

Keywords: censored response, Cox regression, efficiency, ethics, optimal allocation, power, variability

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Authors: Ghazal Zahed, Leila Tabatabaee, Amirhossein Hosseini, Somaye Fatahi

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Functional retentive overflow incontinence (Retentive FI) is the most common cause of fecal soiling in children. Affected patients may have more problems with their parents and peer group, self-esteem issues, and more psychiatric comorbidities than the general population. Therapeutic interventions for Retentive FI and related problems and comorbid conditions are needed at the same time. Based on the clinical experiences, patients with retentive FI and comorbid psychiatric disorders, were accelerated in their treatment of fecal incontinence when they were being treated with Risperidone for their psychiatric comorbidities, therefore this study was conducted to evaluate the effect of Risperidone in the treatment of Retentive FI in children and adolescents. In this double-blind randomized clinical trial, 136 patients aged 4-18 years eligible for the study were randomly divided into two groups receiving Risperidone and placebo. About half of these patients had newly diagnosed psychiatric disorders and were drug naïve, this was considered in their division. In addition to polyethylene glycol, all the participants received family counseling and education for withholding behaviors and related behavioral interventions, and nonpharmacological interventions for psychiatric comorbidities. A significant correlation was observed between the duration of treatment with risperidone and the presence of psychiatric comorbidities (P <0.001) for diurnal fecal incontinence. Based on our findings in this study, Risperidone, used commonly for psychiatric disorders in children and adolescents, may be useful in the treatment of retentive fecal incontinence in the presence of psychiatric comorbidities, and along with other interventions.

Keywords: Retentive Fecal Incontinence, Risperidone, Treatment, Pediatric, Encopresis, Atypical Antipsychotics, Fecal Soiling

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Authors: Senait Belay Adugna, Mirutse Giday, Tsegahun Manyazewal

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Background: The emergence and resurgence of zoonotic diseases have continued to be a major threat to global health and the economy. Developing countries are particularly vulnerable due to agricultural expansions and the domestication of animals by humans. Scientifically sound clinical trials are important to find better ways to prevent, diagnose, and treat zoonotic diseases, while there is a lack of evidence to inform the clinical trials’ capacity and practice in countries highly affected by the diseases. This study aimed to investigate researchers’ perceptions and experiences in conducting clinical trials on zoonotic diseases in Ethiopia. Methods: This study employed a descriptive, qualitative study design. It included major academic and research institutions in Ethiopia that had active engagements in veterinary and public health research. It included the National Veterinary Institute, the National Animal Health Diagnostic and Investigation Center, the College of Veterinary Medicine at Addis Ababa University, the Ethiopian Public Health Institute, the Armauer Hansen Research Institute, and the College of Health Sciences at Addis Ababa University. In-depth interviews were conducted with 14 senior researcher investigators in the institutions who hold a proven exhibit primarily leading research activities or research units. Data were collected from October 2019 to April 2020. Data analysis was undertaken using open code 4.03 for qualitative data analysis. Results: Five major themes, with 18 sub-themes, emerged from the in-depth interview in connection. These were: challenges in the prevention, control, and treatment of zoonotic diseases; One Health approach to mitigate zoonotic diseases; personal and institutional experiences in conducting clinical trials on zoonotic diseases; barriers in conducting clinical trials towards zoonotic diseases; and strategies that promote conducting clinical trials on zoonotic diseases. Conducting clinical trials on zoonotic diseases in Ethiopia is hampered by a lack of clearly articulated ethics and regulatory frameworks, trial experts, financial resources, and good governance. Conclusions: In Ethiopia, conducting clinical trials on zoonotic diseases deserves due attention. Strengthening institutional and human resources capacity is a precondition to harnessing effective implementation of clinical trials on zoonotic diseases in the country. In Ethiopia, where skilled human resource is scarce, the One Health approach has the potential to form multidisciplinary teams to systematically improve clinical trials capacity and outcomes in the country.

Keywords: Ethiopia, clinical triak, zoonoses, disease

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Authors: Mitat Uysal

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A new met heuristic optimization algorithm called as Migrating Birds Optimization is used for curve fitting by rational cubic Bezier Curves. This requires solving a complicated multivariate optimization problem. In this study, the solution of this optimization problem is achieved by Migrating Birds Optimization algorithm that is a powerful met heuristic nature-inspired algorithm well appropriate for optimization. The results of this study show that the proposed method performs very well and being able to fit the data points to cubic Bezier Curves with a high degree of accuracy.

Keywords: algorithms, Bezier curves, heuristic optimization, migrating birds optimization

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Authors: Omar Bouhassoun, Cristian Garrido, César Hueso

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The radiation shielding design is an optimization problem with multiple -constrained- objective functions (radiation dose, weight, price, etc.) that depend on several parameters (material, thickness, position, etc.). The classical approach for shielding design consists of a brute force trial-and-error process subject to previous designer experience. Therefore, the result is an empirical solution but not optimal, which can degrade the overall performance of the shielding. In order to automate the shielding design procedure, the IDOM Shielding Optimization Tool (ISOT) has been developed. This software combines optimization algorithms with the capabilities to read/write input files, run calculations, as well as parse output files for different radiation transport codes. In the first stage, the software was established to adjust the input files for two well-known Monte Carlo codes (MCNP and Serpent) and optimize the result (weight, volume, price, dose rate) using multi-objective genetic algorithms. Nevertheless, its modular implementation easily allows the inclusion of more radiation transport codes and optimization algorithms. The work related to the development of ISOT and its verification on a simple 3D multi-layer shielding problem using both MCNP and Serpent will be presented. ISOT looks very promising for achieving an optimal solution to complex shielding problems.

Keywords: optimization, shielding, nuclear, genetic algorithm

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Authors: Claire Williams

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Randomised controlled Trials (RCTs) of efficacy are still perceived as the gold standard for the generation of evidence, and whilst advances in data collection methods are well developed, this progress has not been matched for the reporting of adverse events (AEs). Assessment and reporting of AEs in clinical trials are fraught with human error and inefficiency and are extremely time and resource intensive. Recent research conducted into the quality of reporting of AEs during clinical trials concluded it is substandard and reporting is inconsistent. Investigators commonly send reports to sponsors who are incorrectly categorised and lacking in critical information, which can complicate the detection of valid safety signals. In our presentation, we will describe an electronic data capture system, which has been designed to support clinical trial processes by reducing the resource burden on investigators, improving overall trial efficiencies, and making trials safer for patients. This proprietary technology was developed using expertise proven in the delivery of the world’s first prospective, phase 3b real-world trial, ‘The Salford Lung Study, ’ which enabled robust safety monitoring and reporting processes to be accomplished by the remote monitoring of patients’ EHRs. This technology enables safety alerts that are pre-defined by the protocol to be detected from the data extracted directly from the patients EHR. Based on study-specific criteria, which are created from the standard definition of a serious adverse event (SAE) and the safety profile of the medicinal product, the system alerts the investigator or study team to the safety alert. Each safety alert will require a clinical review by the investigator or delegate; examples of the types of alerts include hospital admission, death, hepatotoxicity, neutropenia, and acute renal failure. This is achieved in near real-time; safety alerts can be reviewed along with any additional information available to determine whether they meet the protocol-defined criteria for reporting or withdrawal. This active surveillance technology helps reduce the resource burden of the more traditional methods of AE detection for the investigators and study teams and can help eliminate reporting bias. Integration of multiple healthcare data sources enables much more complete and accurate safety data to be collected as part of a trial and can also provide an opportunity to evaluate a drug’s safety profile long-term, in post-trial follow-up. By utilising this robust and proven method for safety monitoring and reporting, a much higher risk of patient cohorts can be enrolled into trials, thus promoting inclusivity and diversity. Broadening eligibility criteria and adopting more inclusive recruitment practices in the later stages of drug development will increase the ability to understand the medicinal products risk-benefit profile across the patient population that is likely to use the product in clinical practice. Furthermore, this ground-breaking approach to AE detection not only provides sponsors with better-quality safety data for their products, but it reduces the resource burden on the investigator and study teams. With the data taken directly from the source, trial costs are reduced, with minimal data validation required and near real-time reporting enables safety concerns and signals to be detected more quickly than in a traditional RCT.

Keywords: more comprehensive and accurate safety data, near real-time safety alerts, reduced resource burden, safer trials

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Authors: Ibraheem Husain, Abul Kalam Najmi, Karishma Chester

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First-in-human (FIH) studies are a critical step in clinical development of any molecule that has shown therapeutic promise in preclinical evaluations, since preclinical research and safety studies into clinical development is a crucial step for successful development of monoclonal antibodies for guidance in pharmaceutical industry for the treatment of human diseases. Therefore, comparison between USFDA and nine pharmacologically guided approaches (PGA) (simple allometry, maximum life span potential, brain weight, rule of exponent (ROE), two species methods and one species methods) were made to determine maximum recommended starting dose (MRSD) for first in human clinical trials using four drugs namely Denosumab, Bevacizumab, Anakinra and Omalizumab. In our study, the predicted pharmacokinetic (pk) parameters and the estimated first-in-human dose of antibodies were compared with the observed human values. The study indicated that the clearance and volume of distribution of antibodies can be predicted with reasonable accuracy in human and a good estimate of first human dose can be obtained from the predicted human clearance and volume of distribution. A pictorial method evaluation chart was also developed based on fold errors for simultaneous evaluation of various methods.

Keywords: clinical pharmacology (CPH), clinical research (CRE), clinical trials (CTR), maximum recommended starting dose (MRSD), clearance and volume of distribution

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Authors: Yong Cang

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RJV001 is a subcutaneous injection containing mutated recombinant Collagenase H (ColH), leading to disruption of collagen matrix in adipose tissue and programmed cell death of adipocytes. Here we reported our clinical investigation of the safety, tolerance and pharmacodynamics of localized RJV001 injection into healthy human abdominal fat tissues (NCT04821648, Arizona Research Center). Investigate the safety, tolerance and clinical pharmacodynamics of subcutaneous RJV001 in humans. In the dose-escalating study, 18 subjects completed the study, 100% female, 78% white, with a mean age of 42[±9.9]. All three tested dose (0.05, 0.075 and 0.15 mg/injection), up to 30 injections, were safe and well-tolerated. Bruising and tenderness to palpation, mild to moderate, were the most frequent local skin reactions but nearly all resolved within 30 days. Additionally, physician-monitored ultrasound measurement showed that a reduction in abdominal fat tissue thickness was consistently observed in Cohort C (0.075, 0.15 mg/injection, 30injections), with a mean reduction of 7.37 [± 2.020] mm. Based on this clinical study, RJV001 has been advanced to phase II clinical studies. In the dose-escalating study, subcutaneously administered RJV001 was safe and well-tolerated in healthy adults up to 0.15 mg/injection, 30 injections. Fat reduction and adipocytolysis were observed by ultrasound measurements and histological analysis for exploratory purposes.

Keywords: fat reduction, mutant collagenase, clinical trial, subcutaneous injection

Procedia PDF Downloads 106