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The development of modified‐release (MR) drug products aims to address a clinical need such as improving patient compliance. There are multiple pathways and development strategies for the registration and approval of MR products. The development strategy of an MR product is usually dependent on the availability and pharmacokinetic/pharmacodynamics (PK/PD) characteristics of the reference drug product, that is, an immediate‐release (IR) product or a reference MR. Compared with a reference IR product, an MR product is likely to have a different PK profile over the least common dosing time due to unequal dosing intervals. In case of differences in PK profiles between the MR product and the reference product, confirmatory efficacy and safety studies may be needed to support registration. In some cases, however, a thorough clinical PK/PD characterization may provide sufficient basis to support the approval of the proposed MR product without the need for additional safety and efficacy studies. This article summarizes the US Food and Drug Administration experience and the regulatory considerations supporting the approval of MR products in the past 6 years and discusses cases in which clinical pharmacology and PK/PD information were leveraged to support approval without the need for additional clinical studies. Details of all these cases are available in the public domain. In 2 cases a well‐characterized exposure‐response relationship provided sufficient justification that differences in the shape of the PK profiles were not clinically relevant. In the remaining 3 cases a thorough characterization of the PK profile along with a risk‐based approach provided bases for approval. [ABSTRACT FROM AUTHOR]

Evolution of technology has brought a revolution in various fields of sciences and amongst them, healthcare is one of the most critical and sensitive areas because of its connection with common masses' quality of life. The notion of integrating the healthcare system with the latest data repositories is to make disease prediction efficient, transparent, and reusable. Due to data heterogeneity, data repositories along with optimum classifiers help stakeholders to predict the disease more accurately without compromising the interpretability. Evolutionary algorithms have shown great efficacy, accuracy, and interpretability in improving disease prediction for several datasets. However, the quest for the best classifier is still in evolution. In this research, a state‐of‐the‐art medical data repository has been developed to give researchers of medical domain great ease of use in utilizing different datasets governed by a multi‐objective evolutionary algorithm using fuzzy genetics. The proposed model called 'MEAF' is evaluated on various public repositories. A subset of these repositories includes breast cancer, heart, diabetes, liver, and hepatitis datasets. The results have been analyzed, which show competitive accuracy, sensitivity, and interpretability as compared to relevant research. A customised software application named 'MediHealth' is developed to supplement the proposed model that will facilitate the domain users. [ABSTRACT FROM AUTHOR]

Background: Unhealthy weight control behaviors are a serious concern, impairing the quality of life in adolescents. Although recent epidemiological studies indicate a high level of disordered eating in developing countries, such data in Ethiopia are scarce. Thus, this study aimed to determine the extent of unhealthy weight control behaviors (i.e., purging and nonpurging) and corresponding associated factors among urban Ethiopian adolescents. Method: A cross‐sectional study using self‐administered questionnaires was applied to 690 randomly selected female high school adolescents in Addis Ababa, Ethiopia in 2017. Measures included unhealthy weight control behaviors, body mass index, subjective perception of body weight, appearance satisfaction, depressive symptoms, and socio‐demographic factors. Logistic regression was applied for data analyses, that is, adjusted odds ratio (aOR) with 95% confidence interval (CI). Results: The level of unhealthy weight control behaviors (i.e., a score of at least once a week in the last 1 month) was 30.7% (N = 208). Specifically, the extent of purging and nonpurging weight control behaviors was 1.5% (N = 10) and 29.8% (N = 202), respectively. Factors that were significantly associated with unhealthy weight control behaviors were perception of being overweight [aOR = 3.01; 95%CI: 1.11–8.11], being overweight [aOR = 3.28; 95%CI: 1.54–7.01], severe depression [aOR = 4.09; 95%CI: 1.73–9.96], and high socio‐economic status [aOR = 2.07; 95%CI: 1.30–2.80]. Conclusion: This study reveals a considerable level of unhealthy weight control behaviors among female adolescents in an urban setting in Ethiopia. Researchers and policy makers should focus their attention upon this emerging public health challenge and develop associated strategies. [ABSTRACT FROM AUTHOR]

ABSTRACT The aim of this work was to compare the intestinal absorption kinetics and the bioavailability of γ-tocotrienol (γ-T3) and α-tocopherol (α-Tph) administered separately as oil solutions to rats in vivo. Also, to explain the significant difference in the oral bioavailability of the compounds: (1) the release profiles using the dynamic in vitro lipolysis model, (2) the intestinal permeability and (3) carrier-mediated uptake by Niemann-Pick C1-like 1 (NPC1L1) transporter were examined. Absolute bioavailability studies were conducted after oral administration of γ-T3 or α-Tph prepared in corn oil to rats. In situ rat intestinal perfusion with ezetimibe (a NPC1L1 inhibitor) was performed to compare intestinal permeability. The in vitro interaction kinetics with NPC1L1 was examined in NPC1L1 transfected cells. While the in vitro release studies demonstrated a significantly higher release rate of γ-T3 in the aqueous phase, the oral bioavailability of α-Tph (36%) was significantly higher than γ-T3 (9%). Consequent in situ studies revealed significantly higher intestinal permeability for α-Tph compared with γ-T3 in rats. Moreover, the NPC1L1 kinetic studies demonstrated higher Vmax and Km values for α-Tph compared with γ-T3. Collectively, these results indicate that intestinal permeability is the main contributing factor for the higher bioavailability of α-Tph. Also, these results emphasize the potentially important role of intestinal permeability in the bioavailability of γ-T3, suggesting that enhancing its permeability would increase its oral bioavailability. Copyright © 2012 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]