scholarly journals Revisiting FDA’s 1995 Guidance on Bioequivalence Establishment of Topical Dermatologic Corticosteroids: New Research Based Recommendations

2018 ◽  
Vol 21 ◽  
pp. 413-428 ◽  
Author(s):  
Deniz Ozdin ◽  
Naveen Sharma ◽  
Jorge Lujan-Zilbermann ◽  
Philippe Colucci ◽  
Isadore Kanfer ◽  
...  
Keyword(s):  
Normal Distribution ◽  
Population Analysis ◽  
Population Modeling ◽  
Individual Variability ◽  
Mixed Effect ◽  
Pilot Studies ◽  
Fda Guidance ◽  
Emax Model ◽  
New Research ◽  
The Impact

Purpose: As per the US FDA guidance issued on June 2, 1995, the establishment of bioequivalence for topical dermatologic corticosteroids is based on comparing the pharmacodynamic (PD) effects of Test and Reference products at the dose duration corresponding to the population ED50, determined either by naïve pooled data or nonlinear mixed effect modeling (NLME). The guidance was introduced using a study case example where the expectation maximization (EM) NLME algorithm, as implemented in P-PHARM®, was used. Although EM methods are relatively common, other methods such as the First-Order Conditional Estimation (FOCE) as implemented in the NONMEM® software are even more common. The objective of this study was to investigate the impact of using different parametric population modeling/analysis methods and distribution assumptions on population analysis results. Methods: The dose duration-response data from 11 distinct skin blanching blinded pilot studies were fitted using FOCE (NONMEM®) and an EM algorithm (ADAPT5® (MLEM)). Three different Emax models were tested for each method. Population PD estimates and associated CV%, and the agreement between model predicted values and observed data were compared between the two methods. The impact of assuming different distributions of PD parameters was also investigated. Results: The simple Emax model, as proposed in the FDA guidance, appeared to best characterize the data compared to more complex alternatives. The MLEM method in general appeared to provide better results than FOCE; lower population PD estimates with less inter-individual variability, and no variance shrinkage issues. The results also favored ln-normal versus normal distribution assumptions. Conclusions: The population ED50 estimates were influenced by both the type of population modeling methods and the distribution assumptions. We recommend updating the FDA guidance with more specific instructions related to the population approach to be used (EM-like versus FOCE-like methods) and to the normality assumptions that need to be set (ln-normal versus normal distribution).

State Medical Board Disciplinary Hearings as Tools for Teaching Professionalism in Medical Education

2011 ◽  
Vol 97 (3) ◽  
pp. 8-12
Author(s):  
Onelia G. Lage ◽  
Sydney F. Pomenti ◽  
Edwin Hayes ◽  
Kristen Barrie ◽  
Nancy Baker
Keyword(s):  
Medical Students ◽  
Ethics Education ◽  
Faculty Members ◽  
Specific Method ◽  
Pilot Studies ◽  
Medical Board ◽  
Medical Institutions ◽  
State Medical Boards ◽  
State Medical Board ◽  
The Impact

ABSTRACT This article proposes a partnership of state medical boards with medical schools to supplement professionalism and ethics education for medical students, residents, physicians and faculty members of medical institutions. The importance of professionalism has been recognized by several studies, but a specific method of teaching and developing professionalism has yet to emerge. Studies suggest that there is an association between a lack of professionalism in medical school and future disciplinary actions by medical boards. However, there has been little collaboration between these institutions in addressing unprofessional behaviors. One collaborative concept that holds promise, however, is the idea of inviting medical students to attend physician disciplinary hearings. Students and physicians alike report that watching a hearing can significantly impact attitudes about professionalism as a part of medical practice. While formal research is scarce, the positive response of individual students who experience disciplinary hearings firsthand suggests that further pilot studies may be useful. Presented in this paper are the perspectives of three individuals — a medical student, a faculty member and a medical board chair — who discuss the impact and potential of attending disciplinary hearings in developing professionalism and ethics. Also included is a review of the current literature.

Clinical Pharmacokinetic Studies in Pregnant Women and the Relevance of Pharmacometric Tools

2019 ◽  
Vol 25 (5) ◽  
pp. 483-495 ◽  
Author(s):  
André Dallmann ◽  
Paola Mian ◽  
Johannes Van den Anker ◽  
Karel Allegaert
Keyword(s):  
Pregnant Women ◽  
Clinical Pharmacokinetic ◽  
Individual Variability ◽  
Current Status ◽  
Pharmacokinetic Studies ◽  
Full Potential ◽  
Pbpk Models ◽  
Pregnancy And Postpartum ◽  
Population Pk ◽  
The Impact

Background: In clinical pharmacokinetic (PK) studies, pregnant women are significantly underrepresented because of ethical and legal reasons which lead to a paucity of information on potential PK changes in this population. As a consequence, pharmacometric tools became instrumental to explore and quantify the impact of PK changes during pregnancy. Methods: We explore and discuss the typical characteristics of population PK and physiologically based pharmacokinetic (PBPK) models with a specific focus on pregnancy and postpartum. Results: Population PK models enable the analysis of dense, sparse or unbalanced data to explore covariates in order to (partly) explain inter-individual variability (including pregnancy) and to individualize dosing. For population PK models, we subsequently used an illustrative approach with ketorolac data to highlight the relevance of enantiomer specific modeling for racemic drugs during pregnancy, while data on antibiotic prophylaxis (cefazolin) during surgery illustrate the specific characteristics of the fetal compartments in the presence of timeconcentration profiles. For PBPK models, an overview on the current status of reports and papers during pregnancy is followed by a PBPK cefuroxime model to illustrate the added benefit of PBPK in evaluating dosing regimens in pregnant women. Conclusions: Pharmacometric tools became very instrumental to improve perinatal pharmacology. However, to reach their full potential, multidisciplinary collaboration and structured efforts are needed to generate more information from already available datasets, to share data and models, and to stimulate cross talk between clinicians and pharmacometricians to generate specific observations (pathophysiology during pregnancy, breastfeeding) needed to further develop the field.

A New Narrative?

2018 ◽  
Author(s):  
Natalia Nowakowska
Keyword(s):  
Master Narratives ◽  
European Context ◽  
Early Signs ◽  
Research Findings ◽  
New Research ◽  
The Impact ◽  
Different Sources

Our three existing master narratives of the early Reformation in Poland are all over a century old and mutually contradictory, drawing on different sources to serve differing confessional and national/ist agendas. This chapter offers a fresh narrative of the impact of Lutheranism on the Polish composite monarchy to c.1540, synthesizing these older accounts and updating them with new research findings. This is a narrative in three parts: early signs (1517–24), the great Reformation year (1525), and aftershocks (1526–40). The chapter discusses the challenges of measuring ‘Lutheran’ sentiment, sets these Polish-Prussian events clearly in their comparative European context, and considers what implications they might have for that bigger, familiar tale. It stresses the precocity of Sigismund I’s monarchy, which saw the most far-reaching urban and violent Reformation in 1520s Europe (Danzig), a peasant Reformation rising, and Christendom’s first territorial-princely Reformation, in Ducal Prussia.

How Does Public Debt Affect the Indian Macroeconomy? A Structural VAR Approach

2020 ◽  
Vol 14 (3) ◽  
pp. 253-284
Author(s):  
Ranjan Kumar Mohanty ◽  
Sidheswar Panda
Keyword(s):  
Economic Growth ◽  
Interest Rate ◽  
Public Debt ◽  
Positive Impact ◽  
Decomposition Analysis ◽  
Structural Var ◽  
Adverse Impact ◽  
Mixed Effect ◽  
Domestic Debt ◽  
The Impact

The study investigates the macroeconomic effects of public debt in India during 1980–2017 using a structural vector autoregression framework. The objective is to examine the impact of public debt on the interest rate, investment, inflation and economic growth in India. The results of the impulse response functions show that public debt has an adverse impact on economic growth but a positive impact on the long-term interest rate in the short run and a mixed effect (both negative and positive) on investment and inflation. We also find that domestic debt has a more adverse impact on the economy than external debt. The estimated variance decomposition analysis finds that much of the variation in selected macro variables are explained by public debt and growth in India. This study suggests that public debt especially domestic debt should be controlled and channelled productively to have a favourable impact on the economy. JEL Classification: H63, O40, C40

scholarly journals Salt Intake in Nigeria: a nationwide population survey

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
A.N Odili ◽  
B.S Chori ◽  
B Danladi ◽  
P.C Nwakile ◽  
J.O Ogedengbe ◽  
...  
Keyword(s):  
Salt Intake ◽  
Sodium Intake ◽  
Population Analysis ◽  
Cost Effective ◽  
Rural Site ◽  
Urban Site ◽  
Funding Source ◽  
Salt Reduction ◽  
High Salt Intake ◽  
The Impact

Abstract Background Population wide salt reduction programmes are cost effective strategies for control of cardiovascular diseases (CVDs). Obtaining a nationwide salt consumption data in a multi-cultural setting as Nigeria's is key for proper implementation and monitoring of such strategy. Methods We measured sodium in 24-hour urine of free-living adult Nigerians selected from an urban and a rural site each from the 6 geopolitical zones of Nigeria to evaluate patterns of salt intake and its associations with blood pressures (BP). Results Across the 12 sites, sodium intake ranged from 97.9 in the rural South-South to 210 mmol/day in the urban site of the same zone. Overall, the median (IQR) daily sodium intake was 143.5 (97.8) mmol; with higher (p=0.0028) levels among the urban 149.7 (113.8) compared to the rural 133.1 (105.2) dwellers. Overall, 20% of the subjects consumed less than the recommended 2g (86mmol) of sodium daily. After adjustment for age, sex and BMI; sodium intake and BP (systolic and diastolic) were positively associated in 8 out of the 12 sites; significantly so in 2 (p<0.05) for systolic. Within population analysis; which included 973 individuals, increasing sodium intake tended (not significantly) to increase SBP but decrease DBP. However, among subjects whose sodium intake was in excess of 257mmol/day, a 100 mmol/day increase in sodium intake was significantly (p=0.04) associated with a 3.3 mmHg increase in SBP. Conclusion Salt intake among Nigerians is higher than the recommended. The impact of sodium intake on BP appears to be evident only among individuals with high salt intake. Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): Wellcome Trust

scholarly journals The Effects of Social Distancing Policies on non-SARS-CoV-2 Respiratory Pathogens

2021 ◽  
Author(s):  
Jeff Nawrocki ◽  
Katherine Olin ◽  
Martin C Holdrege ◽  
Joel Hartsell ◽  
Lindsay Meyers ◽  
...  
Keyword(s):  
Public Health ◽  
Influenza A ◽  
Detection Rate ◽  
Respiratory Illness ◽  
Respiratory Pathogens ◽  
Public Health Response ◽  
Mixed Effect ◽  
Detection Rates ◽  
Social Distancing ◽  
The Impact

Abstract Background The initial focus of the US public health response to COVID-19 was the implementation of numerous social distancing policies. While COVID-19 was the impetus for imposing these policies, it is not the only respiratory disease affected by their implementation. This study aimed to assess the impact of social distancing policies on non-SARS-CoV-2 respiratory pathogens typically circulating across multiple US states. Methods Linear mixed-effect models were implemented to explore the effects of five social distancing policies on non-SARS-CoV-2 respiratory pathogens across nine states from January 1 through May 1, 2020. The observed 2020 pathogen detection rates were compared week-by-week to historical rates to determine when the detection rates were different. Results Model results indicate that several social distancing policies were associated with a reduction in total detection rate, by nearly 15%. Policies were associated with decreases in pathogen circulation of human rhinovirus/enterovirus and human metapneumovirus, as well as influenza A, which typically decrease after winter. Parainfluenza viruses failed to circulate at historical levels during the spring. Total detection rate in April 2020 was 35% less than historical average. Many of the pathogens driving this difference fell below historical detection rate ranges within two weeks of initial policy implementation. Conclusion This analysis investigated the effect of multiple social distancing policies implemented to reduce transmission of SARS-CoV-2 on non-SARS-CoV-2 respiratory pathogens. These findings suggest that social distancing policies may be used as an impactful public health tool to reduce communicable respiratory illness.

The Impact of Personality Disorders on Longitudinal Change in Relationship Satisfaction in Long-Term Married Couples

2020 ◽  
Vol 34 (4) ◽  
pp. 439-458 ◽  
Author(s):  
Susan C. South ◽  
Michael J. Boudreaux ◽  
Thomas F. Oltmanns
Keyword(s):  
Marital Satisfaction ◽  
Relationship Satisfaction ◽  
Personality Disorders ◽  
Married Couples ◽  
Structured Interview ◽  
Individual Variability ◽  
Self Report ◽  
Longitudinal Change ◽  
The Impact

Personality disorders (PDs) are significantly, negatively related to marital satisfaction. We examine how maladaptive personality is related to change in marital satisfaction over time utilizing data from the St. Louis Personality and Aging Network (SPAN), a longitudinal, community-based study of personality and health in older adults. Participants were assessed at baseline for PD (self-report, informant-report, and structured interview); self- and spouse-reported relationship satisfaction assessed at baseline and five follow-ups was analyzed with latent growth curve modeling. Higher levels of PD at baseline were associated with lower self and spouse relationship satisfaction at baseline. On average, satisfaction did not change significantly over the study period, but there was significant individual variability. Higher levels of schizoid PD were protective of declines in partner's perception of satisfaction. Findings suggest that partners in long-term married unions may have adapted to the presence of their own or their spouse's level of personality pathology.

Effect of education on migration decisions in Ghana: a rural-urban perspective

2016 ◽  
Vol 43 (2) ◽  
pp. 336-356 ◽  
Author(s):  
Franklin Amuakwa-Mensah ◽  
Louis Boakye-Yiadom ◽  
William Baah-Boateng
Keyword(s):  
Educational Attainment ◽  
Rural Areas ◽  
Migration Decision ◽  
Skilled Workers ◽  
Mixed Effect ◽  
Content Type ◽  
Rural And Urban ◽  
Migration Decisions ◽  
Negative Effect ◽  
The Impact

Purpose – The purpose of this paper is to investigate the effect of education on migration decisions focusing on rural and urban in-migrants by comparing the 2005/2006 and 2012/2013 rounds of the Ghana Living Standards Survey (GLSS5 and GLSS6). After correcting for selectivity bias, the authors observed that anticipated welfare gain and socio-economic variables such as sector of employment, sex, experience, age, educational level and marital status significantly affect an individual’s migration decision. Design/methodology/approach – The authors made use of Sjaastad’s (1962) human capital framework as a basis for examining the impact of education on migration. The migration decision equation was based on the Heckman two stage procedure. Findings – While educational attainment is observed to have a positive effect on migration decision in the period 2005/2006, the authors find a negative effect of educational attainment on migration decision in the period 2012/2013. The effect of educational attainment on migration decision in 2005/2006 for urban in-migrant is higher than the effect for rural in-migrant, with its significance varying for the different stages of educational attainment. In absolute terms, whereas the effect of secondary educational attainment on migration decisions for urban in-migrant is higher than that of rural in-migrant, the reverse holds for higher educational attainment during the period 2012/2013. Social implications – Based on the mixed effect of education on migration decision as evident from the study, policies to enhance the educational system in Ghana should be complemented with job creations in the entire country. Moreover, special attention should be given to the rural sector in such a way that the jobs to be created in the sector do not require skilled workers. With quality education and job creation, the welfare of individuals living in urban and rural areas will be enhanced. Originality/value – In spite of the importance of education in migration decisions, there is scanty literature on the rural-urban dimension. To the best of the author’s knowledge there is no literature in the Ghanaian context which examines the rural and urban perspective of the impact of education on migration with a much recent data. Further, the author consider how the determinants of migration decision have changed over time focusing on rural and urban perspectives.

Reflections on the biochemistry ofEchinococcus: past, present and future

Parasitology ◽  
2009 ◽  
Vol 136 (12) ◽  
pp. 1643-1652 ◽  
Author(s):  
D. P. McMANUS
Keyword(s):  
Hydatid Disease ◽  
Biochemical Analysis ◽  
Species Variation ◽  
Research Directions ◽  
Future Studies ◽  
Tegumental Surface ◽  
Research Areas ◽  
General Metabolism ◽  
New Research ◽  
The Impact

SUMMARYThis review discusses 5 of my earliest papers on the biochemistry of larvalEchinococcuspublished inParasitologyin the 1970s and 1980s. Two of the publications consider aspects of the basic biochemistry, intermediary metabolism and the regulation of respiratory pathways inE. granulosusandE. multilocularis, and emphasize the existence of inter- and intra-species variation in their general metabolism. The third reports on the detailed biochemical analysis of the tegumental surface of the protoscolex ofE. granulosus, and the final 2 papers describe the genomic cloning ofEchinococcusDNA fragments and their use, along with other DNA markers, in molecular identification ofE. granulosusisolates collected worldwide from areas endemic for hydatid disease. A number of years have elapsed since these publications inParasitologyand, in this Centenary Issue article, I reflect briefly on some of the subsequent studies undertaken in these research areas that have advanced the field. As well, I provide brief insight on new research directions, emphasizing the impact of molecular biology and associated techniques on future studies ofEchinococcusand hydatid disease.

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