Search results for: Sami Naouali
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 70

Search results for: Sami Naouali

10 In Silico Analysis of Deleterious nsSNPs (Missense) of Dihydrolipoamide Branched-Chain Transacylase E2 Gene Associated with Maple Syrup Urine Disease Type II

Authors: Zainab S. Ahmed, Mohammed S. Ali, Nadia A. Elshiekh, Sami Adam Ibrahim, Ghada M. El-Tayeb, Ahmed H. Elsadig, Rihab A. Omer, Sofia B. Mohamed

Abstract:

Maple syrup urine (MSUD) is an autosomal recessive disease that causes a deficiency in the enzyme branched-chain alpha-keto acid (BCKA) dehydrogenase. The development of disease has been associated with SNPs in the DBT gene. Despite that, the computational analysis of SNPs in coding and noncoding and their functional impacts on protein level still remains unknown. Hence, in this study, we carried out a comprehensive in silico analysis of missense that was predicted to have a harmful influence on DBT structure and function. In this study, eight different in silico prediction algorithms; SIFT, PROVEAN, MutPred, SNP&GO, PhD-SNP, PANTHER, I-Mutant 2.0 and MUpo were used for screening nsSNPs in DBT including. Additionally, to understand the effect of mutations in the strength of the interactions that bind protein together the ELASPIC servers were used. Finally, the 3D structure of DBT was formed using Mutation3D and Chimera servers respectively. Our result showed that a total of 15 nsSNPs confirmed by 4 software (R301C, R376H, W84R, S268F, W84C, F276C, H452R, R178H, I355T, V191G, M444T, T174A, I200T, R113H, and R178C) were found damaging and can lead to a shift in DBT gene structure. Moreover, we found 7 nsSNPs located on the 2-oxoacid_dh catalytic domain, 5 nsSNPs on the E_3 binding domain and 3 nsSNPs on the Biotin Domain. So these nsSNPs may alter the putative structure of DBT’s domain. Furthermore, we detected all these nsSNPs are on the core residues of the protein and have the ability to change the stability of the protein. Additionally, we found W84R, S268F, and M444T have high significance, and they affected Leucine, Isoleucine, and Valine, which reduces or disrupt the function of BCKD complex, E2-subunit which the DBT gene encodes. In conclusion, based on our extensive in-silico analysis, we report 15 nsSNPs that have possible association with protein deteriorating and disease-causing abilities. These candidate SNPs can aid in future studies on Maple Syrup Urine Disease type II base in the genetic level.

Keywords: DBT gene, ELASPIC, in silico analysis, UCSF chimer

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9 Physical Inactivity and Junk Food Consumption Consequent Obesity among University Girls: A Cross Sectional Study Unveils the Mayhem

Authors: Shahid Mahmood, Ghulam Mueen-Ud-Din, Farah Naz Akbar, Yousaf Quddoos, Syeda Mahvish Zahra, Wajiha Saeed, Tayyaba Sami Ullah

Abstract:

Obesity is an epidemic across the globe that affects all the segments of the population. Physical inactivity, passionate consumption of junk food, inadequate water intake and an unhealthy lifestyle are evident among university girls that are ruining their health gravely especially fat accumulation. The study was carried out to investigate the potential etiological factors of obesity development in university girls. The cross sectional study was carried out after approval of the Departmental Review Committee for Ethics (DRCE) as the par Declaration of Helsinki at Institute of Food Science and Nutrition (IFSN), University of Sargodha, Sargodha-Pakistan and Department of Food Science and Home Economics, G. C. Women University, Faisalabad-Pakistan. 400 girls were selected randomly from different departments of both universities. Nutritional status of the volunteers was assessed through approved protocols for demographics, anthropometrics, body composition, energetics, vital signs, clinical signs and symptoms, medical/family history, and dietary intake assessment (FFQ), water intake and physical activity level. The obesity was determined on body fat (%). Alarming and unheeded etiological factors for the development of obesity in girls were explored by the study. About 93 % girls had a sedentary level of physical activity, zealous consumption of junk food (5.31±1.23 servings), drank little water (1.09±0.26 L/day) that consequent high heaps of fat (35.06±3.02 %), measly body water (52.38±3.4 %), poor bone mass (05.14±0.31 Kg), and high BMI (26.68±1.14 Kg/m²) in 34% girls. The malnutrition also depicted by poor vital signs i.e. low body temperature (97.11±0.93 °F), slightly higher blood pressure (124.19±4.08 / 85.25±2.97 mmHg), rapid pulse rate (99.2 ± 6.85 beats/min), reduced blood O₂ saturation (96.53±0.96 %), scanty peak expiratory flow rate (297 ± 15.7 L /min). The outcomes of the research articulated that physical inactivity; extreme intakes of junk food, insufficient water consumption are etiological factors for obesity development among girls which are usually overlooked in Pakistan.

Keywords: informed consent, junk food, obesity, physical inactivity

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8 Application of Lattice Boltzmann Method to Different Boundary Conditions in a Two Dimensional Enclosure

Authors: Jean Yves Trepanier, Sami Ammar, Sagnik Banik

Abstract:

Lattice Boltzmann Method has been advantageous in simulating complex boundary conditions and solving for fluid flow parameters by streaming and collision processes. This paper includes the study of three different test cases in a confined domain using the method of the Lattice Boltzmann model. 1. An SRT (Single Relaxation Time) approach in the Lattice Boltzmann model is used to simulate Lid Driven Cavity flow for different Reynolds Number (100, 400 and 1000) with a domain aspect ratio of 1, i.e., square cavity. A moment-based boundary condition is used for more accurate results. 2. A Thermal Lattice BGK (Bhatnagar-Gross-Krook) Model is developed for the Rayleigh Benard convection for both test cases - Horizontal and Vertical Temperature difference, considered separately for a Boussinesq incompressible fluid. The Rayleigh number is varied for both the test cases (10^3 ≤ Ra ≤ 10^6) keeping the Prandtl number at 0.71. A stability criteria with a precise forcing scheme is used for a greater level of accuracy. 3. The phase change problem governed by the heat-conduction equation is studied using the enthalpy based Lattice Boltzmann Model with a single iteration for each time step, thus reducing the computational time. A double distribution function approach with D2Q9 (density) model and D2Q5 (temperature) model are used for two different test cases-the conduction dominated melting and the convection dominated melting. The solidification process is also simulated using the enthalpy based method with a single distribution function using the D2Q5 model to provide a better understanding of the heat transport phenomenon. The domain for the test cases has an aspect ratio of 2 with some exceptions for a square cavity. An approximate velocity scale is chosen to ensure that the simulations are within the incompressible regime. Different parameters like velocities, temperature, Nusselt number, etc. are calculated for a comparative study with the existing works of literature. The simulated results demonstrate excellent agreement with the existing benchmark solution within an error limit of ± 0.05 implicates the viability of this method for complex fluid flow problems.

Keywords: BGK, Nusselt, Prandtl, Rayleigh, SRT

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7 The Effect of Nanotechnology Structured Water on Lower Urinary Tract Symptoms in Men with Benign Prostatic Hyperplasia: A Double-Blinded Randomized Study

Authors: Ali Kamal M. Sami, Safa Almukhtar, Alaa Al-Krush, Ismael Hama-Amin Akha Weas, Ruqaya Ahmed Alqais

Abstract:

Introduction and Objectives Lower urinary tract symptoms (LUTS) are common among men with benign prostatic hyperplasia (BPH). The combination of 5 alpha-reductase inhibitors and alpha-blockers has been used as a conservative treatment of male LUTS secondary to BPH. Nanotechnology structured water magnalife is a type of water that is produced by modulators and specific frequency and energy fields that transform ordinary water into this Nanowater. In this study, we evaluated the use of Nano-water with the conservative treatment and to see if it improves the outcome and gives better results in those patients with LUTS/BPH. Material and methods For a period of 3 months, 200 men with International Prostate Symptom Score (IPSS)≥13, maximum flow rate (Qmax)≤ 15ml/s, and prostate volume > 30 and <80 ccs were randomly divided into two groups. Group A 100 men were given Nano-water with the (tamsulosindutasteride) and group B 100 men were given ordinary bottled water with the (tamsulosindutasteride). The water bottles were unlabeled and were given in a daily dose of 20ml/kg body weight. Dutasteride 0.5mg and tamsulosin 0.4 mg daily doses. Both groups were evaluated for the IPSS, Qmax, Residual Urine (RU), International Index of Erectile Function–Erectile Function (IIEF-EF) domain at the beginning (baseline data), and at the end of the 3 months. Results Of the 200 men with LUTS who were included in this study, 193 men were followed, and 7 men dropped out of the study for different reasons. In group A which included 97 men with LUTS, IPSS decreased by 16.82 (from 20.47 to 6.65) (P<0.00001) and Qmax increased by 5.73 ml/s (from 11.71 to 17.44) (P<0.00001) and RU <50 ml in 88% of patients (P<0.00001) and IIEF-EF increased to 26.65 (from 16.85) (P<0.00001). While in group B, 96 men with LUTS, IPSS decreased by 8.74(from 19.59 to 10.85)(P<0.00001) and Qmax increased by 4.67 ml/s(from 10.74 to 15.41)(P<0.00001), RU<50 ml in 75% of patients (P<0.00001), and IIEF-EF increased to 21(from 15.87)(P<0.00001). Group A had better results than group B. IPSS in group A decreased to 6.65 vs 10.85 in group B(P<0.00001), also Qmax increased to 17.44 in group A vs 15.41 in group B(P<0.00001), group A had RU <50 ml in 88% of patients vs 75% of patients in group B(P<0.00001).Group A had better IIEF-EF which increased to 26.65 vs 21 in group B(P<0.00001). While the differences between the baseline data of both groups were statistically not significant. Conclusion The use of nanotechnology structured water magnalife gives a better result in terms of LUTS and scores in patients with BPH. This combination is showing improvements in IPSS and even in erectile function in those men after 3 months.

Keywords: nano water, lower urinary tract symptoms, benign prostatic hypertrophy, erectile dysfunction

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6 Imputation of Incomplete Large-Scale Monitoring Count Data via Penalized Estimation

Authors: Mohamed Dakki, Genevieve Robin, Marie Suet, Abdeljebbar Qninba, Mohamed A. El Agbani, Asmâa Ouassou, Rhimou El Hamoumi, Hichem Azafzaf, Sami Rebah, Claudia Feltrup-Azafzaf, Nafouel Hamouda, Wed a.L. Ibrahim, Hosni H. Asran, Amr A. Elhady, Haitham Ibrahim, Khaled Etayeb, Essam Bouras, Almokhtar Saied, Ashrof Glidan, Bakar M. Habib, Mohamed S. Sayoud, Nadjiba Bendjedda, Laura Dami, Clemence Deschamps, Elie Gaget, Jean-Yves Mondain-Monval, Pierre Defos Du Rau

Abstract:

In biodiversity monitoring, large datasets are becoming more and more widely available and are increasingly used globally to estimate species trends and con- servation status. These large-scale datasets challenge existing statistical analysis methods, many of which are not adapted to their size, incompleteness and heterogeneity. The development of scalable methods to impute missing data in incomplete large-scale monitoring datasets is crucial to balance sampling in time or space and thus better inform conservation policies. We developed a new method based on penalized Poisson models to impute and analyse incomplete monitoring data in a large-scale framework. The method al- lows parameterization of (a) space and time factors, (b) the main effects of predic- tor covariates, as well as (c) space–time interactions. It also benefits from robust statistical and computational capability in large-scale settings. The method was tested extensively on both simulated and real-life waterbird data, with the findings revealing that it outperforms six existing methods in terms of missing data imputation errors. Applying the method to 16 waterbird species, we estimated their long-term trends for the first time at the entire North African scale, a region where monitoring data suffer from many gaps in space and time series. This new approach opens promising perspectives to increase the accuracy of species-abundance trend estimations. We made it freely available in the r package ‘lori’ (https://CRAN.R-project.org/package=lori) and recommend its use for large- scale count data, particularly in citizen science monitoring programmes.

Keywords: biodiversity monitoring, high-dimensional statistics, incomplete count data, missing data imputation, waterbird trends in North-Africa

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5 Robust Electrical Segmentation for Zone Coherency Delimitation Base on Multiplex Graph Community Detection

Authors: Noureddine Henka, Sami Tazi, Mohamad Assaad

Abstract:

The electrical grid is a highly intricate system designed to transfer electricity from production areas to consumption areas. The Transmission System Operator (TSO) is responsible for ensuring the efficient distribution of electricity and maintaining the grid's safety and quality. However, due to the increasing integration of intermittent renewable energy sources, there is a growing level of uncertainty, which requires a faster responsive approach. A potential solution involves the use of electrical segmentation, which involves creating coherence zones where electrical disturbances mainly remain within the zone. Indeed, by means of coherent electrical zones, it becomes possible to focus solely on the sub-zone, reducing the range of possibilities and aiding in managing uncertainty. It allows faster execution of operational processes and easier learning for supervised machine learning algorithms. Electrical segmentation can be applied to various applications, such as electrical control, minimizing electrical loss, and ensuring voltage stability. Since the electrical grid can be modeled as a graph, where the vertices represent electrical buses and the edges represent electrical lines, identifying coherent electrical zones can be seen as a clustering task on graphs, generally called community detection. Nevertheless, a critical criterion for the zones is their ability to remain resilient to the electrical evolution of the grid over time. This evolution is due to the constant changes in electricity generation and consumption, which are reflected in graph structure variations as well as line flow changes. One approach to creating a resilient segmentation is to design robust zones under various circumstances. This issue can be represented through a multiplex graph, where each layer represents a specific situation that may arise on the grid. Consequently, resilient segmentation can be achieved by conducting community detection on this multiplex graph. The multiplex graph is composed of multiple graphs, and all the layers share the same set of vertices. Our proposal involves a model that utilizes a unified representation to compute a flattening of all layers. This unified situation can be penalized to obtain (K) connected components representing the robust electrical segmentation clusters. We compare our robust segmentation to the segmentation based on a single reference situation. The robust segmentation proves its relevance by producing clusters with high intra-electrical perturbation and low variance of electrical perturbation. We saw through the experiences when robust electrical segmentation has a benefit and in which context.

Keywords: community detection, electrical segmentation, multiplex graph, power grid

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4 An Exploration of the Emergency Staff’s Perceptions and Experiences of Teamwork and the Skills Required in the Emergency Department in Saudi Arabia

Authors: Sami Alanazi

Abstract:

Teamwork practices have been recognized as a significant strategy to improve patient safety, quality of care, and staff and patient satisfaction in healthcare settings, particularly within the emergency department (ED). The EDs depend heavily on teams of interdisciplinary healthcare staff to carry out their operational goals and core business of providing care to the serious illness and injured. The ED is also recognized as a high-risk area in relation to service demand and the potential for human error. Few studies have considered the perceptions and experiences of the ED staff (physicians, nurses, allied health professionals, and administration staff) about the practice of teamwork, especially in Saudi Arabia (SA), and no studies have been conducted to explore the practices of teamwork in the EDs. Aim: To explore the practices of teamwork from the perspectives and experiences of staff (physicians, nurses, allied health professionals, and administration staff) when interacting with each other in the admission areas in the ED of a public hospital in the Northern Border region of SA. Method: A qualitative case study design was utilized, drawing on two methods for the data collection, comprising of semi-structured interviews (n=22) with physicians (6), nurses (10), allied health professionals (3), and administrative members (3) working in the ED of a hospital in the Northern Border region of SA. The second method is non-participant direct observation. All data were analyzed using thematic analysis. Findings: The main themes that emerged from the analysis were as follows: the meaningful of teamwork, reasons of teamwork, the ED environmental factors, the organizational factors, the value of communication, leadership, teamwork skills in the ED, team members' behaviors, multicultural teamwork, and patients and families behaviors theme. Discussion: Working in the ED environment played a major role in affecting work performance as well as team dynamics. However, Communication, time management, fast-paced performance, multitasking, motivation, leadership, and stress management were highlighted by the participants as fundamental skills that have a major impact on team members and patients in the ED. It was found that the behaviors of the team members impacted the team dynamics as well as ED health services. Behaviors such as disputes among team members, conflict, cooperation, uncooperative members, neglect, and emotions of the members. Besides that, the behaviors of the patients and their accompanies had a direct impact on the team and the quality of the services. In addition, the differences in the cultures have separated the team members and created undesirable gaps such the gender segregation, national origin discrimination, and similarity and different in interests. Conclusion: Effective teamwork, in the context of the emergency department, was recognized as an essential element to obtain the quality of care as well as improve staff satisfaction.

Keywords: teamwork, barrier, facilitator, emergencydepartment

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3 Generic Early Warning Signals for Program Student Withdrawals: A Complexity Perspective Based on Critical Transitions and Fractals

Authors: Sami Houry

Abstract:

Complex systems exhibit universal characteristics as they near a tipping point. Among them are common generic early warning signals which precede critical transitions. These signals include: critical slowing down in which the rate of recovery from perturbations decreases over time; an increase in the variance of the state variable; an increase in the skewness of the state variable; an increase in the autocorrelations of the state variable; flickering between different states; and an increase in spatial correlations over time. The presence of the signals has management implications, as the identification of the signals near the tipping point could allow management to identify intervention points. Despite the applications of the generic early warning signals in various scientific fields, such as fisheries, ecology and finance, a review of literature did not identify any applications that address the program student withdrawal problem at the undergraduate distance universities. This area could benefit from the application of generic early warning signals as the program withdrawal rate amongst distance students is higher than the program withdrawal rate at face-to-face conventional universities. This research specifically assessed the generic early warning signals through an intensive case study of undergraduate program student withdrawal at a Canadian distance university. The university is non-cohort based due to its system of continuous course enrollment where students can enroll in a course at the beginning of every month. The assessment of the signals was achieved through the comparison of the incidences of generic early warning signals among students who withdrew or simply became inactive in their undergraduate program of study, the true positives, to the incidences of the generic early warning signals among graduates, the false positives. This was achieved through significance testing. Research findings showed support for the signal pertaining to the rise in flickering which is represented in the increase in the student’s non-pass rates prior to withdrawing from a program; moderate support for the signals of critical slowing down as reflected in the increase in the time a student spends in a course; and moderate support for the signals on increase in autocorrelation and increase in variance in the grade variable. The findings did not support the signal on the increase in skewness of the grade variable. The research also proposes a new signal based on the fractal-like characteristic of student behavior. The research also sought to extend knowledge by investigating whether the emergence of a program withdrawal status is self-similar or fractal-like at multiple levels of observation, specifically the program level and the course level. In other words, whether the act of withdrawal at the program level is also present at the course level. The findings moderately supported self-similarity as a potential signal. Overall, the assessment of the signals suggests that the signals, with the exception with the increase of skewness, could be utilized as a predictive management tool and potentially add one more tool, the fractal-like characteristic of withdrawal, as an additional signal in addressing the student program withdrawal problem.

Keywords: critical transitions, fractals, generic early warning signals, program student withdrawal

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2 Photobleaching Kinetics and Epithelial Distribution of Hexylaminoleuilinate Induced PpIX in Rat Bladder Cancer

Authors: Sami El Khatib, Agnès Leroux, Jean-Louis Merlin, François Guillemin, Marie-Ange D’Hallewin

Abstract:

Photodynamic therapy (PDT) is a treatment modality based on the cytotoxic effect occurring on the target tissues by interaction of a photosensitizer with light in the presence of oxygen. One of the major advances in PDT can be attributed to the use of topical aminolevulinic (ALA) to induce Protoporphyrin IX (PpIX) for the treatment of early stage cancers as well as diagnosis. ALA is a precursor of the heme synthesis pathway. Locally delivered to the target tissue ALA overcomes the negative feedback exerted by heme and promotes the transient formation of PpIX in situ to reach critical effective levels in cells and tissue. Whereas early steps of the heme pathway occur in the cytosol, PpIX synthesis is shown to be held in the mitochondrial membranes and PpIX fluorescence is expected to accumulate in close vicinity of the initial building site and to progressively diffuse to the neighboring cytoplasmic compartment or other lipophylic organelles. PpIX is known to be highly reactive and will be degraded when irradiated with light. PpIX photobleaching is believed to be governed by a singlet oxygen mediated mechanism in the presence of oxidized amino acids and proteins. PpIX photobleaching and subsequent spectral phototransformation were described widely in tumor cells incubated in vitro with ALA solution, or ex vivo in human and porcine mucosa superfused with hexylaminolevulinate (hALA). PpIX photobleaching was also studied in vivo, using animal models such as normal or tumor mice skin and orthotopic rat bladder model. Hexyl aminolevulinate a more potent lipophilic derivative of ALA was proposed as an adjunct to standard cystoscopy in the fluorescence diagnosis of bladder cancer and other malignancies. We have previously reported the effectiveness of hALA mediated PDT of rat bladder cancer. Although normal and tumor bladder epithelium exhibit similar fluorescence intensities after intravesical instillation of two hALA concentrations (8 and 16 mM), the therapeutic response at 8mM and 20J/cm2 was completely different from the one observed at 16mM irradiated with the same light dose. Where the tumor is destroyed, leaving the underlying submucosa and muscle intact after an 8 mM instillation, 16mM sensitization and subsequent illumination results in the complete destruction of the underlying bladder wall but leaves the tumor undamaged. The object of the current study is to try to unravel the underlying mechanism for this apparent contradiction. PpIX extraction showed identical amounts of photosensitizer in tumor bearing bladders at both concentrations. Photobleaching experiments revealed mono-exponential decay curves in both situations but with a two times faster decay constant in case of 16mM bladders. Fluorescence microscopy shows an identical fluorescence pattern for normal bladders at both concentrations and tumor bladders at 8mM with bright spots. Tumor bladders at 16 mM exhibit a more diffuse cytoplasmic fluorescence distribution. The different response to PDT with regard to the initial pro-drug concentration can thus be attributed to the different cellular localization.

Keywords: bladder cancer, hexyl-aminolevulinate, photobleaching, confocal fluorescence microscopy

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1 Prevalence, Median Time, and Associated Factors with the Likelihood of Initial Antidepressant Change: A Cross-Sectional Study

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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