Salinaspower7547

Chemistry, Manufacturing and Control Post-Approval Changes are an intrinsic part of the lifecycle of pharmaceutical products. In this paper, the authors examine the potential impact of such changes on product quality, safety and efficacy of biologics. Comparability studies and more specifically analytical comparability are introduced as one of the tools that can support both biomanufacturers and health agencies in ensuring that patient safety, product safety and efficacy is maintained through the proposed changes. Together with a scientific risk-based review approach based on product and process knowledge and the definition of acceptance criteria that will ensure that the product is 'essentially similar', what constitutes a holistic comparability study is detailed. ICH Guidelines principles and definitions are used throughout the paper to aid the reader with other appropriate references. Finally, three case studies are presented change to the manufacturing facility of the drug substance, change to the manufacturing process of a drug substance intermediate and manufacturing facility, and justification of not including drug product in analytical compatibility. Copyright © 2020, Parenteral Drug Association.It is generally acknowledged that quantitation in extractables and leachables (E&L) can be variably reproducible and accurate, depending on the quantitation approach taken. This is especially true for ″simple″ quantitation, which is the practice of estimating an analyte's concentration based on its response relative to that of an internal standard which has been added to the sample in a known amount. Simple quantitation is prone to error and variation as it is based on the largely false premise that the response factors for all extractables, leachables and internal standard candidates are the same. It has been proposed that this uncertainty (inaccuracy and variation) be accounted for by adjusting two key parameters in E&L assessment, the reported concentrations themselves and the Analytical Evaluation Threshold (AET) via an Uncertainty Factor (UF). This Correspondence examines quantitation variation, and discusses the means of establishing and utilizing the UF to adjust the AET to lower values and adjust reported concentrations to higher values, enabling an impact assessment performed with this data to be more protective of patient safety. Although adjustment of the AET lower with the UF is supported, flaws in the concept of using the UF to adjust reported concentration upward are considered and it is recommended that the UF not be used in this manner. Rather, E&L quantitation should be based on compound-specific relative response factors, collected and collated in an E&L database. Copyright © 2020, Parenteral Drug Association.BACKGROUND AND PURPOSE Conflicts in nursing workplace are frequent and can be resolved by individuals or groups. The purpose of this study was to develop a valid and reliable measure for the Workplace Conflicts among Emergency Department Nurses (WCEDN). METHODS A three-stage mixed methods study was conducted (a) In-depth interviews with emergency department (ED) nurses were performed and themes were extracted from the data (b) Findings of the content analysis in combination with results of a literature review were examined, and preliminary instrument items were developed. The initial instrument comprised 50 items. (c) Content validity, face validity, content validity ratio, content validity index, and construct validity using exploratory factor analysis were performed. RESULTS Subscales in the final instrument included Intrapersonal Conflict, Intragroup Conflict, Intergroup Conflict, and Causes of Conflict. Reliability of the instrument was .86, and the feasibility was 96.8%. CONCLUSIONS The final 40-item WCEDN demonstrated strong psychometric properties. © Copyright 2020 Springer Publishing Company, LLC.BACKGROUND AND PURPOSE Trauma-informed care (TIC) acknowledges the lasting effects of trauma on individuals. The Attitudes Related to Trauma-Informed Care (ARTIC-35) scale was developed to examine healthcare providers' attitudes related to TIC. Here, we present an item-level analysis of the ARTIC-35 scale for use with nurses and compare our findings to the current ARTIC-35 structure. METHODS Principal components analysis, qualitative inter-item analysis, and qualitative intra-item analysis of the ARTIC-35. FINDINGS Our principal component analysis structure supported a nine-factor solution, inter-item qualitative analysis structure supported five subscales, and intra-item qualitative analysis identified 13 acceptable items and 22 items requiring revision for use with nurses. DISCUSSION When used with nurses, there are important considerations regarding scale validity and challenges with the design of the original ARTIC-35 scale. © Copyright 2020 Springer Publishing Company, LLC.BACKGROUND AND PURPOSE The Health Risk Screening Tool (HRST) is a 22-item instrument specifically designed to assess the health risk of persons with developmental disabilities. The predictive validity of the HRST was investigated by examining its ability to predict mortality. METHODS The sample consisted of 12,582 people with an intellectual or developmental disability residing in Georgia (U.S.). this website Data were analyzed using survival analysis (Kaplan-Meier estimate and Cox regression) and a binary logistic regression. RESULTS All models supported the prognostic value of the six-level health risk classification. The Kaplan-Meier procedure showed clear separation among functions. The Cox proportional hazard regression revealed that hazard is inversely related to the health risk level, even after controlling for potential confounding by gender, ethnicity, and race. CONCLUSIONS The HRST can predict mortality. Therefore, it can serve as a basis for establishing healthcare needs and determining nursing care acuity. © Copyright 2020 Springer Publishing Company, LLC.OBJECTIVE Patients with dermatomyositis (DM) and polymyositis (PM) have reduced muscle endurance. The aim of this study was to streamline the Functional Index-2 (FI-2) by developing the Functional Index-3 (FI-3) and to evaluate its measurement properties, content and construct validity, intra- and inter-rater reliability. METHODS A data set of the previously performed and validated FI-2 (n=63) was analyzed for internal redundancy, floor and ceiling effects. The content of the FI-2 was revised into the FI-3. Construct validity and intra-rater reliability of FI-3 were tested on 43 DM and PM patients at two rheumatology centers. Inter-rater reliability was tested in 25 patients. The construct validity was compared with the Myositis Activities Profile (MAP), Health Assessment Questionnaire (HAQ), and Borg CR-10 using Spearman's correlation coefficient. RESULTS Spearman's correlation coefficients of 63 patients performing FI-3 revealed moderate to high correlations between shoulder flexion and hip flexion tasks and similar correlations with MAP and HAQ scores; there were lower correlations for neck flexion task. All FI-3 tasks had very low to moderate correlations with the Borg scale. Intra-class correlation coefficients (ICC) of FI-3 tasks for intra-rater reliability (n = 25) were moderate to good (range 0.88-0.96). ICC of FI-3 tasks for inter-rater reliability (n = 17) were fair to good (range 0.83-0.96). link2 CONCLUSION The FI-3 is an efficient and valid method for clinically assessing muscle endurance in DM and PM patients. FI-3's construct validity is supported by the significant correlations between functional tasks and the MAP, HAQ, and Borg CR-10 scores.OBJECTIVE The frequency of end stage renal disease from SLE in the United States has not improved over the last few decades in large population datasets. Understanding the risk factors for renal failure in SLE could lead to earlier detection of lupus nephritis and potentially more effective treatments in those with markers of poor prognosis. METHODS The Hopkins Lupus Cohort, comprised of 2,528 patients was used. 151 patients experienced renal failure after SLE diagnosis, defined as dialysis or renal transplant. We estimated the risk of renal failure in subgroups defined by demographics, laboratory tests and ACR/SLICC Classification criteria satisfied within one year of SLE diagnosis. RESULTS The overall incidence of renal failure within 20 years of SLE diagnosis was 8.4%. The risk was much higher (20.0%) among those who experienced proteinuria within the first year of diagnosis. Demographic predictors included African American ethnicity (rate ratio 1.82, p=0.0012) and age less than 30 years at SLE diagnosis (rate ratio 1.96 vs. those with diagnosis over 40 years of age, p=0.019). Among immunologic markers, low C3 was a strong predictor of renal failure (Rate ratio 2.00, p=0.0011). link3 CONCLUSION Proteinuria within the first year of diagnosis of SLE is one of the most important predictors of end stage renal disease. Our data also confirm African American ethnicity, younger age at SLE diagnosis and low C3 as strong predictors of renal failure.Cognitive impairment (CI) is one of the most prevalent neuropsychiatric syndromes. In Systemic Lupus Erythematosus (SLE) Patients often report CI as the most bothersome disease-related manifestation with a great impact on their quality of life. Nevertheless, studies focusing on CI remain scarce and no effective targeted therapy has been identified. We herein present murine models of CI in lupus with insights into the pathogenesis of this condition as well as the role of the renin angiotensin system in microglial activation. We will discuss the role of neuroimaging as a useful objective assessment tool describing our experience in previous and ongoing clinical trials of CI in SLE patients.We thank Dr. Lambova for her interesting comment1 on our recent article published in The Journal 2 We reported that a systemic sclerosis (SSc) or scleroderma-like capillaroscopic pattern is common in patients with Raynaud phenomenon, and can be frequently observed in patients with connective tissue diseases (CTD) other than SSc.Epithelial cells such as liver-resident hepatocytes rely heavily on the Rab family of small GTPases to perform membrane trafficking events that dictate cell physiology and metabolism. Not surprisingly, disruption of several Rabs can manifest in metabolic diseases or cancer. Rab32 is expressed in many secretory epithelial cells but its role in cellular metabolism is virtually unknown. In this study, we find that Rab32 associates with lysosomes and regulates proliferation and cell size of Hep3B hepatoma and HeLa cells. Specifically, we identify that Rab32 supports mTORC1 signaling under basal and amino acid stimulated conditions. Consistent with inhibited mTORC1, an increase in nuclear TFEB localization and lysosome biogenesis is also observed in Rab32-depleted cells. Finally, we find that Rab32 interacts with mTOR kinase and that loss of Rab32 reduces the association of mTOR and mTORC1 pathway proteins with lysosomes, suggesting that Rab32 regulates lysosomal mTOR trafficking. In summary, these findings suggest that Rab32 functions as a novel regulator of cellular metabolism through supporting mTORC1 signaling. © 2020. Published by The Company of Biologists Ltd.