Rat Video-Electroencephalography as a Model to Assess Early Stage Safety Assessment of Sleep Disturbance and Seizurogenic Potential

2016 ◽  
Author(s):  
Saivishal Daripelli
Keyword(s):  
Sleep Disturbance ◽  
Safety Assessment ◽  
Early Stage

Rat Video-Electroencephalography as a Model to Assess Early Stage Safety Assessment of Sleep Disturbance and Seizurogenic Potential

2017 ◽  
Vol 88 ◽  
pp. 190-191
Author(s):  
Gopinadh Bhyrapuneni ◽  
Saivishal Daripelli ◽  
Vijay Benade ◽  
Nageswararao Muddana ◽  
Vinod Goyal ◽  
...  
Keyword(s):  
Sleep Disturbance ◽  
Safety Assessment ◽  
Early Stage

scholarly journals Inflammation and Behavioral Symptoms After Breast Cancer Treatment: Do Fatigue, Depression, and Sleep Disturbance Share a Common Underlying Mechanism?

2011 ◽  
Vol 29 (26) ◽  
pp. 3517-3522 ◽  
Author(s):  
Julienne E. Bower ◽  
Patricia A. Ganz ◽  
Michael R. Irwin ◽  
Lorna Kwan ◽  
Elizabeth C. Breen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Depressive Symptoms ◽  
Cancer Treatment ◽  
Sleep Disturbance ◽  
Plasma Levels ◽  
Inflammatory Markers ◽  
Breast Cancer Survivors ◽  
Early Stage ◽  
Self Report ◽  
Behavioral Symptoms

Purpose Fatigue, depression, and sleep disturbance are common adverse effects of cancer treatment and frequently co-occur. However, the possibility that inflammatory processes may underlie this constellation of symptoms has not been examined. Patients and Methods Women (N = 103) who had recently finished primary treatment (ie, surgery, radiation, chemotherapy) for early-stage breast cancer completed self-report scales and provided blood samples for determination of plasma levels of inflammatory markers: soluble tumor necrosis factor (TNF) receptor II (sTNF-RII), interleukin-1 receptor antagonist, and C-reactive protein. Results Symptoms were elevated at the end of treatment; greater than 60% of participants reported clinically significant problems with fatigue and sleep, and 25% reported elevated depressive symptoms. Women treated with chemotherapy endorsed higher levels of all symptoms and also had higher plasma levels of sTNF-RII than women who did not receive chemotherapy (all P < .05). Fatigue was positively associated with sTNF-RII, particularly in the chemotherapy-treated group (P < .05). Depressive symptoms and sleep problems were correlated with fatigue but not with inflammatory markers. Conclusion This study confirms high rates of behavioral symptoms in breast cancer survivors, particularly those treated with chemotherapy, and indicates a role for TNF-α signaling as a contributor to postchemotherapy fatigue. Results also suggest that fatigue, sleep disturbance, and depression may stem from distinct biologic processes in post-treatment survivors, with inflammatory signaling contributing relatively specifically to fatigue.

Regulatory considerations, challenges and risk-based approach in nanomedicine development

2021 ◽  
Vol 28 ◽  
Author(s):  
Ildikó Csóka ◽  
Ruba Ismail ◽  
Orsolya Jójárt-Laczkovich ◽  
Edina Pallagi
Keyword(s):  
Safety Assessment ◽  
Multidisciplinary Approach ◽  
Early Stage ◽  
Scale Up ◽  
Physicochemical Characteristics ◽  
The Novel ◽  
Safety And Efficacy ◽  
The Status ◽  
Regulatory Bodies

: The translation of nanomedicines from the lab level into marketed product face several challenges including characterization of physicochemical properties, pharmacodynamics, pharmacokinetics, process control, biocompatibility and nanotoxicity, scale-up as well as reproducibility. The challenges of nanomedicine development are in connection with the different requirements from the patient (clinical and therapeutic use), industry (production) and regulatory bodies (authorization process). This paper aims at reviewing the status and regulatory aspects of nano-based drug delivery systems with a focus on the Food and Drug Administration (FDA) and the European Medicine Agency (EMA) regulations. In addition to discussing the risks accompanied by the development of nanomedicine, the potential of following a risk-based methodology from the early stage of the R&D phase is emphasized here to ensure safety and efficacy when developing novel nano-based dosage forms. Nanomedicines R&D is a complex and multidisciplinary approach and there are still many challenges in their regulation and legislation. In general, the most critical considerations for nanomedicines are the product quality assessment (physicochemical characteristics, quality control, manufacturing process) and product safety assessment (pharmacokinetics, biodegradation, accumulation and nanotoxicity). The paper presents a promising paradigm in the development and marketing authorization of nanomedicines, namely the Quality by Design (QbD) approach. Sufficient knowledge on the quality, safety, and efficacy of nanomedicines is necessary to obtain with a significant focus on establishing robust, standardized methods to evaluate the critical quality attributes of nanomedicines. The QbD-based submission is highly recommended and required by the regulatory authorities and will enable a smooth clinical translation of the novel nanomedicines.

scholarly journals Impact of COVID-19 pandemic on mental health among general Bangladeshi population: a cross-sectional study

BMJ Open ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. e045727
Author(s):  
Rajesh Das ◽  
Md Rakib Hasan ◽  
Sohel Daria ◽  
Md Rabiul Islam
Keyword(s):  
Mental Health ◽  
Los Angeles ◽  
Sleep Disturbance ◽  
Mental Health Problems ◽  
Early Stage ◽  
Health Problems ◽  
Cross Sectional Survey ◽  
Cross Sectional ◽  
Bangladeshi Population ◽  
The Impact

ObjectivesMental health problems significantly increased worldwide during the coronavirus (COVID-19) pandemic. At the early stage of the outbreak, the government of Bangladesh imposed lockdown and quarantine approaches to prevent the spread of the virus, which impacted people’s daily life and health. The COVID-19 pandemic has also affected people’s economic status, healthcare facilities and other lifestyle factors in Bangladesh. We aimed to assess the impact of the COVID-19 pandemic on mental health among the Bangladeshi population.MethodsWe conducted an online cross-sectional survey among 672 Bangladeshi people aged between 15 and 65 years all over the country from 15 April to 10 May 2020. After obtaining electronic consent, we conducted a survey assessing people’s sociodemographic profiles and psychometric measures. We used The University of California, Los Angeles (UCLA) Loneliness Scale-8, Patient Health Questionnaire-9, Generalized Anxiety Disorder 7-Item Scale and Pittsburgh Sleep Quality Index to assess loneliness, depression, anxiety and sleep disturbance, respectively.ResultsThe prevalence of loneliness, depression, anxiety and sleep disturbance was estimated at 71% (mild: 32%, moderate: 29%, severe: 10%), 38% (mild: 24%, moderate: 11%, severe: 3%), 64% (mild: 30%, moderate: 17%, severe: 17%) and 73% (mild: 50%, moderate: 18%, severe: 5%), respectively. In Bangladesh, the key factors associated with poor mental health during COVID-19 were female sex, unemployment, being a student, obesity and living without a family. The present study also identified statistically significant interrelationships among the measured mental health issues.ConclusionsA large portion of respondents reported mental health problems during the COVID-19 pandemic in Bangladesh. The present study suggests longitudinal assessments of mental health among Bangladeshi people to determine the gravity of this issue during and after the pandemic. Appropriate supportive programmes and interventional approaches would address mental health problems in Bangladesh during the COVID-19 pandemic.

Design Workflow for Electronic Product With Safety Assessment Concept at the Early Stage

2009 ◽  
Author(s):  
Jingyuan Huang ◽  
Xiang Wang
Keyword(s):  
Product Design ◽  
Design Process ◽  
Safety Assessment ◽  
Early Stage ◽  
Practical Experience ◽  
Life Cycles ◽  
Additional Time ◽  
Electronic Product ◽  
Safety Parameters ◽  
Product Design Process

Today, the interdisciplinary design approach has been quickly adopted as a new trend in the modern product design process. Whereas, it is believed that manufacturers try to make shortcuts in order to reduce the time-to-market. Therefore, many inherent or uncertain safety parameters and factors are normally ignored in the early stage of the process until problems occur during the life cycles of products. This is very harmful to users. Enterprises may face liability claims and recalls of those products. In addition to the claims, additional time and cost are required to investigate the root cause of problems and to redesign the products and. Those problems mostly happen in some developing countries in which their product design and manufacturing process is still in a labor-intensive mode. Systematic and knowledge-based design approaches have not yet been popularly adopted. In order to have a better consideration, in terms of safety at the early stage of design process, the integration of practical experience of safety assessment concept and analysis methods into the traditional electronic product design process is the key proposed idea in this paper. A new design workflow with safety assessment concept at the early stage is generated, with a result of saving redesign cost and time.

scholarly journals COVID-19 Uncertainty and Sleep: The Roles of Perceived Stress and Intolerance of Uncertainty during the Early Stage of the COVID-19 Outbreak

2021 ◽  
Author(s):  
Dan Wu ◽  
Tingzhong Yang ◽  
Daniel Hall ◽  
Guihua Jiao ◽  
Can Jiao
Keyword(s):  
Sleep Quality ◽  
Sleep Disturbance ◽  
Perceived Stress ◽  
Structural Equation ◽  
Early Stage ◽  
Intolerance Of Uncertainty ◽  
Self Report ◽  
Equation Modeling ◽  
Poor Sleep ◽  
Cross Sectional

Abstract Background. The COVID-19 pandemic brings unprecedented uncertainty and stress. This study aimed to characterize sleep behaviors among Chinese residents during the early stage of the outbreak and to test the extent to which sleep quality was driven by COVID-19 uncertainty, intolerance of uncertainty, and perceived stress. Methods. A cross-sectional correlational survey was conducted online. A total of 2,534 Chinese residents were recruited from February 7 to 14, 2020, the third week of lockdown. Self-report measures assessed uncertainty about COVID-19, intolerance of uncertainty, perceived stress, and sleep quality. Structural equation modeling was applied to test the relationships among uncertainty about COVID-19, intolerance of uncertainty, perceived stress, and sleep quality. Results. Sleep disturbance was common, with approximately half of participants (47.1%) reporting going to bed after 12:00am, 23.0% taking 30 minutes or longer to fall asleep, and 30.3% sleeping a total of 7 hours or less. Higher uncertainty about COVID-19 was significantly positively correlated with higher intolerance of uncertainty (r = 0.506, p < 0.001). Uncertainty about COVID-19 had a weak direct effect on poor sleep (β = 0.043, p < 0.05); however, there was a robust indirect effect on poor sleep through intolerance of uncertainty (β = 0.506, p < 0.001) and perceived stress (β = 0.479, p < 0.001). Conclusions. These findings suggest that intolerance of uncertainty and perceived stress are critical targets for reducing sleep disturbance during the COVID-19 pandemic. Given the sustained uncertainties and challenges managing COVID-19, it is likely that, if unmanaged, COVID-19 related uncertainty will persist and continue to impact sleep outcomes.

A Validation Study of PROMIS Sleep Disturbance (PROMIS-SD) and Sleep Related Impairment (PROMIS-SRI) Item Banks in Individuals with Idiopathic Parkinson’s Disease and Matched Controls

2021 ◽  
Vol 11 (2) ◽  
pp. 877-883
Author(s):  
Jolynn Jones ◽  
Spencer A. Nielson ◽  
Jonathan Trout ◽  
Mckaella Swenson ◽  
Joseph Reiley ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Sleep Disturbance ◽  
Internal Consistency ◽  
Early Stage ◽  
Strong Correlations ◽  
Divergent Validity ◽  
Item Banks ◽  
Daytime Impairment ◽  
Disease Questionnaire

Background: Parkinson’s disease (PD) is associated with sleep disturbance (SD) and sleep-related impairment (SRI). Validation of self-report measures of these problems is needed in PD. The Patient-Reported Outcomes Measurement Information System (PROMIS) includes tools that assess these problems (PROMIS-SD and PROMIS-SRI, respectively). Objective: This study aimed to further validate these measures in individuals with PD and matched controls. Methods: Individuals with early-stage PD (n=50) and matched controls (n=48) completed measures of SD including the PROMIS-SD, Pittsburgh Sleep Quality Index (PSQI), and Insomnia Severity Index (ISI). They also completed measures of daytime impairment including the PROMIS-SRI, Epworth Sleepiness Scale, State-Trait Anxiety Inventory, Beck Depression Inventory 2nd edition, and Parkinson’s Disease Questionnaire-39. Internal consistency for the PROMIS measures were assessed using Cronbach’s α coefficient and item-total correlations in the total sample. Convergent and divergent validity of the PROMIS item banks were assessed using Spearman correlations. Results: The PROMIS item banks had excellent internal consistency (α>0.94). Supporting convergent validity, the PROMIS-SD had strong correlations with other measures of SD (ρ>0.68, for PSQI and ISI) and the PROMIS-SRI had moderate to strong correlations with all measures of daytime impairment (ρ=0.41–0.72). Supporting divergent validity within the PD group, the PROMIS-SD correlated more strongly with SRI than with the Parkinson’s Disease Questionnaire total score, a metric of PD related impairment. Conclusion: In middle-aged and older adults, with and without early-stage PD, the PROMIS-SD and PROMIS-SRI are reliable and valid measures of SD and SRI, respectively.

A Review of the Main Considerations for Formulation Development in Preclinical Toxicology Studies

2021 ◽  
pp. 109158182110437
Author(s):  
Matt D. Saunders
Keyword(s):  
Safety Assessment ◽  
Early Stage ◽  
Clinical Work ◽  
Careful Consideration ◽  
Formulation Development ◽  
Regulatory Requirements ◽  
Test Species ◽  
Preclinical Species ◽  
High Doses ◽  
The Stability

The main considerations for the development of a formulation for preclinical safety assessment testing are explored. Intravenous, inhalation, oral and dermal dosing are given focus and although different dose routes do present their own individual challenges there are common themes that emerge. In each case it is necessary to maximise exposure to achieve high doses to satisfy regulatory requirements for safety assessment testing. This often involves producing formulations that are at the limits of solubility and maximum volumes possible for administration to different test species by the chosen route. It is concluded that for all routes it is important to thoroughly explore the stability of the test item in the proposed formulation matrix well ahead of dosing any animals, giving careful consideration to which excipients are used and what their underlying toxicity profile may be for the relevant preclinical species. In addition, determining the maximum achievable concentrations and weighing that against the maximum volumes that can be given by the chosen route in all the test species at an early stage will also give a read on whether it would be theoretically possible to achieve suitably high enough doses to support clinical work. Not doing so can cause delays in the development programme and may have ethical repercussions.

scholarly journals Variations in COMT and NTRK2 Influence Symptom Burden in Women Undergoing Breast Cancer Treatment

2017 ◽  
Vol 19 (3) ◽  
pp. 318-328 ◽  
Author(s):  
Erin E. Young ◽  
Debra Lynch Kelly ◽  
Insop Shim ◽  
Kyle M. Baumbauer ◽  
Angela Starkweather ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tyrosine Kinase ◽  
Sleep Disturbance ◽  
Early Stage ◽  
Symptom Burden ◽  
Breast Cancer Diagnosis ◽  
Tyrosine Kinase Receptor ◽  
Patient Symptom ◽  
Chemotherapy Patients ◽  
Specific Symptoms

Women with breast cancer frequently report distressing symptoms during and after treatment that can significantly erode quality of life (QOL). Symptom burden among women with breast cancer is of complex etiology and is likely influenced by disease, treatment, and environmental factors as well as individual genetic differences. The purpose of the present study was to examine the relationships between genetic polymorphisms within Neurotrophic tyrosine kinase receptor 1 (NTRK1), Neurotrophic tyrosine kinase receptor 2 (NTRK2), and catechol-O-methyltransferase ( COMT) and patient symptom burden of QOL, pain, fatigue, anxiety, depression, and sleep disturbance before, during, and after treatment for breast cancer in a subset of participants ( N = 51) in a randomized clinical trial of a novel symptom-management modality for women with breast cancer undergoing chemotherapy. Patients were recruited at the time of initial breast cancer diagnosis and completed all survey measures at the time of recruitment, after the initiation of treatment (surgery and/or chemotherapy), and then following treatment conclusion. Multiple linear regression analyses revealed significant associations between NTRK2 and COMT single nucleotide polymorphism (SNP) genotype and symptom burden. Two COMT variants were associated with the specific symptoms of anxiety and QOL measures prior to the initiation of chemotherapy as well as pain interference and severity during and after treatment. Genotype at the NTRK2 SNP rs1212171 was associated with both sleep disturbance and fatigue. These findings, while exploratory, indicate that the genotypes of NTRK2 and COMT may contribute to relative risk for symptom burden during and shortly after the period of chemotherapy in women with early stage breast cancer.

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