Search results for: Alaa E. Abdallah

Authors: Alaa Abdellatif, Gabrièle Breda

Abstract:

Background. Advanced therapy medicinal products (ATMPs) are innovative therapies that mainly target orphan diseases and high unmet medical needs. ATMP includes gene therapy medicinal products (GTMP), somatic cell therapy medicinal products (CTMP), and tissue-engineered therapies (TEP). Since legislation opened the way in 2007, 25 ATMPs have been approved in the EU, which is about the same amount as the U.S. Food and Drug Administration. However, not all of the ATMPs that have been approved have successfully reached the market and retained their approval. Objectives. We aim to understand all the factors limiting the market access to very promising therapies in a systemic approach, to be able to overcome these problems, in the future, with scientific, regulatory and commercial innovations. Further to recent reviews that focus either on specific countries, products, or dimensions, we will address all the challenges faced by ATMP development today. Methodology. We used mixed methods and a multi-level approach for data collection. First, we performed an updated academic literature review on ATMP development and their scientific and market access challenges (papers published between 2018 and April 2023). Second, we analyzed industry feedback from cell and gene therapy webinars and white papers published by providers and pharmaceutical industries. Finally, we established a comparative analysis of the regulatory guidelines published by EMA and the FDA for ATMP approval. Results: The main challenges in bringing these therapies to market are the high development costs. Developing ATMPs is expensive due to the need for specialized manufacturing processes. Furthermore, the regulatory pathways for ATMPs are often complex and can vary between countries, making it challenging to obtain approval and ensure compliance with different regulations. As a result of the high costs associated with ATMPs, challenges in obtaining reimbursement from healthcare payers lead to limited patient access to these treatments. ATMPs are often developed for orphan diseases, which means that the patient population is limited for clinical trials which can make it challenging to demonstrate their safety and efficacy. In addition, the complex manufacturing processes required for ATMPs can make it challenging to scale up production to meet demand, which can limit their availability and increase costs. Finally, ATMPs face safety and efficacy challenges: dangerous adverse events of these therapies like toxicity related to the use of viral vectors or cell therapy, starting material and donor-related aspects. Conclusion. As a result of our mixed method analysis, we found that ATMPs face a number of challenges in their development, regulatory approval, and commercialization and that addressing these challenges requires collaboration between industry, regulators, healthcare providers, and patient groups. This first analysis will help us to address, for each challenge, proper and innovative solution(s) in order to increase the number of ATMPs approved and reach the patients

Keywords: advanced therapy medicinal products (ATMPs), product development, market access, innovation

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Authors: Alaa Fezai, Anuj Sharma, Wolfgang Mueller-Hirsch, André Zimmermann

Abstract:

Viscoelastic materials have been widely used in the automotive industry over the last few decades with different functionalities. Besides their main application as a simple and efficient surface damping treatment, they may ensure optimal operating conditions for on-board electronics as thermal interface or sealing layers. The dynamic behavior of viscoelastic materials is generally dependent on many environmental factors, the most important being temperature and strain rate or frequency. Prior to the reliability analysis of systems including viscoelastic layers, it is, therefore, crucial to accurately predict the dynamic and lifetime behavior of these materials. This includes the identification of the dynamic material parameters under critical temperature and frequency conditions along with a precise damage localization and identification methodology. The goal of this work is twofold. The first part aims at applying an inverse viscoelastic material-characterization approach for a wide frequency range and under different temperature conditions. For this sake, dynamic measurements are carried on a single lap joint specimen using an electrodynamic shaker and an environmental chamber. The specimen consists of aluminum beams assembled to adapter plates through a viscoelastic adhesive layer. The experimental setup is reproduced in finite element (FE) simulations, and frequency response functions (FRF) are calculated. The parameters of both the generalized Maxwell model and the fractional derivatives model are identified through an optimization algorithm minimizing the difference between the simulated and the measured FRFs. The second goal of the current work is to guarantee an on-line detection of the damage, i.e., delamination in the viscoelastic bonding of the described specimen during frequency monitored end-of-life testing. For this purpose, an inverse technique, which determines the damage location and size based on the modal frequency shift and on the change of the mode shapes, is presented. This includes a preliminary FE model-based study correlating the delamination location and size to the change in the modal parameters and a subsequent experimental validation achieved through dynamic measurements of specimen with different, pre-generated crack scenarios and comparing it to the virgin specimen. The main advantage of the inverse characterization approach presented in the first part resides in the ability of adequately identifying the material damping and stiffness behavior of soft viscoelastic materials over a wide frequency range and under critical temperature conditions. Classic forward characterization techniques such as dynamic mechanical analysis are usually linked to limitations under critical temperature and frequency conditions due to the material behavior of soft viscoelastic materials. Furthermore, the inverse damage detection described in the second part guarantees an accurate prediction of not only the damage size but also its location using a simple test setup and outlines; therefore, the significance of inverse numerical-experimental approaches in predicting the dynamic behavior of soft bonding layers applied in automotive electronics.

Keywords: damage detection, dynamic characterization, inverse approaches, vibration testing, viscoelastic layers

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Authors: Nervana Elbakary, Sami Ouanes, Sadaf Riaz, Oraib Abdallah, Islam Mahran, Noriya Al-Khuzaei, Yassin Eltorki

Abstract:

Major Depressive Disorder (MDD) requires therapeutic interventions during the initial month after being diagnosed for better disease outcomes. International guidelines recommend a duration of 4–12 weeks for an initial antidepressant (IAD) trial at an optimized dose to get a response. If depressive symptoms persist after this duration, guidelines recommend switching, augmenting, or combining strategies as the next step. Most patients with MDD in the mental health setting have been labeled incorrectly as treatment-resistant where in fact they have not been subjected to an adequate trial of guideline-recommended therapy. Premature discontinuation of IAD due to ineffectiveness can cause unfavorable consequences. Avoiding irrational practices such as subtherapeutic doses of IAD, premature switching between the ADs, and refraining from unjustified polypharmacy can help the disease to go into a remission phase We aimed to determine the prevalence and the patterns of strategies applied after an IAD was changed because of a suboptimal response as a primary outcome. Secondary outcomes included the median survival time on IAD before any change; and the predictors that were associated with IAD change. This was a retrospective cross- sectional study conducted in Mental Health Services in Qatar. A dataset between January 1, 2018, and December 31, 2019, was extracted from the electronic health records. Inclusion and exclusion criteria were defined and applied. The sample size was calculated to be at least 379 patients. Descriptive statistics were reported as frequencies and percentages, in addition, to mean and standard deviation. The median time of IAD to any change strategy was calculated using survival analysis. Associated predictors were examined using two unadjusted and adjusted cox regression models. A total of 487 patients met the inclusion criteria of the study. The average age for participants was 39.1 ± 12.3 years. Patients with first experience MDD episode 255 (52%) constituted a major part of our sample comparing to the relapse group 206(42%). About 431 (88%) of the patients had an occurrence of IAD change to any strategy before end of the study. Almost half of the sample (212 (49%); 95% CI [44–53%]) had their IAD changed less than or equal to 30 days. Switching was consistently more common than combination or augmentation at any timepoint. The median time to IAD change was 43 days with 95% CI [33.2–52.7]. Five independent variables (age, bothersome side effects, un-optimization of the dose before any change, comorbid anxiety, first onset episode) were significantly associated with the likelihood of IAD change in the unadjusted analysis. The factors statistically associated with higher hazard of IAD change in the adjusted analysis were: younger age, un-optimization of the IAD dose before any change, and comorbid anxiety. Because almost half of the patients in this study changed their IAD as early as within the first month, efforts to avoid treatment failure are needed to ensure patient-treatment targets are met. The findings of this study can have direct clinical guidance for health care professionals since an optimized, evidence-based use of AD medication can improve the clinical outcomes of patients with MDD; and also, to identify high-risk factors that could worsen the survival time on IAD such as young age and comorbid anxiety

Keywords: initial antidepressant, dose optimization, major depressive disorder, comorbid anxiety, combination, augmentation, switching, premature discontinuation

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Authors: Essam Gooda, Chadi Abdallah, Hamdi Seif, Safaa Baydoun, Rouya Hdeib, Hilal Obeid

Abstract:

Floods are common natural disaster occurring in semi-arid regions in Lebanon. This results in damage to human life and deterioration of environment. Despite their destructive nature and their immense impact on the socio-economy of the region, flash floods have not received adequate attention from policy and decision makers. This is mainly because of poor understanding of the processes involved and measures needed to manage the problem. The current understanding of flash floods remains at the level of general concepts; most policy makers have yet to recognize that flash floods are distinctly different from normal riverine floods in term of causes, propagation, intensity, impacts, predictability, and management. Flash floods are generally not investigated as a separate class of event but are rather reported as part of the overall seasonal flood situation. As a result, Lebanon generally lacks policies, strategies, and plans relating specifically to flash floods. Main objective of this research is to improve flash flood prediction by providing new knowledge and better understanding of the hydrological processes governing flash floods in the East Catchments of El Assi River. This includes developing rainstorm time distribution curves that are unique for this type of study region; analyzing, investigating, and developing a relationship between arid watershed characteristics (including urbanization) and nearby villages flow flood frequency in Ras Baalbeck and Fekha. This paper discusses different levels of integration approach¬es between GIS and hydrological models (HEC-HMS & HEC-RAS) and presents a case study, in which all the tasks of creating model input, editing data, running the model, and displaying output results. The study area corresponds to the East Basin (Ras Baalbeck & Fakeha), comprising nearly 350 km2 and situated in the Bekaa Valley of Lebanon. The case study presented in this paper has a database which is derived from Lebanese Army topographic maps for this region. Using ArcMap to digitizing the contour lines, streams & other features from the topographic maps. The digital elevation model grid (DEM) is derived for the study area. The next steps in this research are to incorporate rainfall time series data from Arseal, Fekha and Deir El Ahmar stations to build a hydrologic data model within a GIS environment and to combine ArcGIS/ArcMap, HEC-HMS & HEC-RAS models, in order to produce a spatial-temporal model for floodplain analysis at a regional scale. In this study, HEC-HMS and SCS methods were chosen to build the hydrologic model of the watershed. The model then calibrated using flood event that occurred between 7th & 9th of May 2014 which considered exceptionally extreme because of the length of time the flows lasted (15 hours) and the fact that it covered both the watershed of Aarsal and Ras Baalbeck. The strongest reported flood in recent times lasted for only 7 hours covering only one watershed. The calibrated hydrologic model is then used to build the hydraulic model & assessing of flood hazards maps for the region. HEC-RAS Model is used in this issue & field trips were done for the catchments in order to calibrated both Hydrologic and Hydraulic models. The presented models are a kind of flexible procedures for an ungaged watershed. For some storm events it delivers good results, while for others, no parameter vectors can be found. In order to have a general methodology based on these ideas, further calibration and compromising of results on the dependence of many flood events parameters and catchment properties is required.

Keywords: flood risk management, flash flood, semi arid region, El Assi River, hazard maps

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