scholarly journals Bias factor, maximum bias and the E-value: insight and extended applications

2020 ◽  
Vol 49 (5) ◽  
pp. 1509-1516
Author(s):  
Alexandre Cusson ◽  
Claire Infante-Rivard
Keyword(s):  
Odds Ratio ◽  
Sensitivity Analyses ◽  
Unmeasured Confounding ◽  
Unmeasured Confounder ◽  
Maximum Value ◽  
Bias Factor ◽  
Maximum Bias ◽  
The Relationship ◽  
Value Measure ◽  
Insight Into

Abstract Background Unmeasured confounding can bias the relationship between exposure and outcome. Sensitivity analyses generate bias-adjusted measures but these are not much used; this may change with the availability of the E-value (for evidence for causality in observational studies), appealing for its ease of calculation. However, as currently proposed, the E-value has some practical limitations that may reduce its use. Methods We first provide some insight into the relationship between two established measures for unmeasured confounding: ‘the bias factor’ and the maximum value this bias factor can take (‘the B bias’). These measures are the statistical foundation for the E-value. We use them to develop new E-value formulas for situations when it is not currently applicable such as e.g. when, not unusually, a negative relation between unmeasured confounder and outcome and a positive one with exposure are postulated. We also provide E-values on the odds ratio scale because, currently, even when using the odds ratio as the study measure in the calculation of E-value, the result is to be interpreted as a relative risk, which is somewhat inconvenient. Results The additional formulas for the E-value measure make it applicable in all possible scenarios defined by the combined directions between unmeasured confounder and both the exposure and outcome. In addition, E-value measures can now be interpreted as odds ratios if the observed results are reported on the same scale. Conclusions The E-value is part of newer sensitivity analyses methods for unmeasured confounding. We provide insight into its structure, underscoring its advantages and limitations, and expand its applications.

scholarly journals New Insights on the Mechanism of Fatty Acids as Buccal Permeation Enhancers

Pharmaceutics ◽  
2018 ◽  
Vol 10 (4) ◽  
pp. 201 ◽  
Author(s):  
Cristina Padula ◽  
Silvia Pescina ◽  
Sara Nicoli ◽  
Patrizia Santi
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Fluorescein Isothiocyanate ◽  
Penetration Enhancers ◽  
Systemic Delivery ◽  
Permeation Enhancers ◽  
Maximum Value ◽  
The Relationship ◽  
Insight Into ◽  
The Ideal

Buccal mucosa has recently received much attention as a potential route for systemic delivery of drugs, including biologics and vaccines. The aim of this work was to gain insight into the mechanism of fatty acids as buccal permeation enhancers, by studying the effect of a series of medium and long chain fatty acids on the permeation of a model high molecular weight and hydrophilic molecule, fluorescein isothiocyanate labelled dextran (FD-4, m.w. 4 kDa) across porcine esophageal epithelium. A parabolic relationship between fatty acid lipophilicity and enhancement was obtained, regardless of the presence and number of double bonds. The relationship, which resembles the well-known relationship between permeability and lipophilicity of transdermal delivery, presents a maximum value in correspondence of C10 (logP approx. 4). This is probably the ideal lipophilicity for the fatty acid to interact with the lipid domains of the mucosa. When the same analysis was performed on skin data, the same trend was observed, although the maximum value was reached for C12 (logP approx. 5), in agreement with the higher lipophilicity of the skin. The results obtained in the present work represent a significant advancement in the understanding of the mechanisms of action of fatty acids as buccal penetration enhancers.

scholarly journals D-Dimer Determination to Assess Regression of Deep Venous Thrombosis

1997 ◽  
Vol 78 (02) ◽  
pp. 799-802 ◽  
Author(s):  
M C H Janssen ◽  
H Verbruggen ◽  
H Wollersheim ◽  
B Hoogkamer ◽  
H van Langen ◽  
...  
Keyword(s):  
Venous Thrombosis ◽  
Deep Venous Thrombosis ◽  
Odds Ratio ◽  
Initial Treatment ◽  
Heparin Therapy ◽  
Duplex Scanning ◽  
Fibrinolytic Parameters ◽  
The Relationship ◽  
Insight Into ◽  
D Dimer

SummaryA number of studies evaluating deep venous thrombosis (DVT) have demonstrated that plasma levels of thrombotic and fibrinolytic parameters change during treatment, but the relationship between thrombus regression and evolution of these markers remains unknown. The objective of the present study was to correlate levels of D-Dimer (DD) with thrombus regression as assessed by duplex scanning.From 44 patients treated for acute DVT, DD were determined at diagnosis and at the end of initial heparin therapy of at least 5 days. Thrombus regression was measured by repeated duplex scanning at diagnosis and after 1 and 3 months.DD significantly decreased during heparin treatment as compared with values at presentation. DD levels were significantly higher in the group of patients without normalization of the DVT after 3 months (p = 0.003). A ninefold excess tendency was seen for DD levels > 1200 ng/ml at the end of initial treatment to be associated with poor resolution of the DVT [odds ratio 9.0, 0.95 confidence interval (CI) 2.3-35.4]. When the patients with an established malignancy were excluded, the differences were even more significant (p = 0.0004 for DD levels after initial treatment and an odds ratio of 17.5, 0.95 CI 3.3-92.5).These results suggest that increased DD levels after the initial phase of treatment are related to poor resolution of DVT after 3 months. These findings contribute to further insight into the process of thrombus regression. Furthermore high DD levels might help to identify the patients with a poor prognosis and could be useful to judge the efficacy of anticoagulant treatment.

scholarly journals Conducting sensitivity analysis for unmeasured confounding in observational studies using E-values: The evalue package

2020 ◽  
Vol 20 (1) ◽  
pp. 162-175 ◽  
Author(s):  
Ariel Linden ◽  
Maya B. Mathur ◽  
Tyler J. VanderWeele
Keyword(s):  
Observational Studies ◽  
Specific Treatment ◽  
Sensitivity Analyses ◽  
Unmeasured Confounding ◽  
Unmeasured Confounder ◽  
Point Estimates ◽  
Hazard Ratios ◽  
Mean Differences ◽  
Rate Ratios ◽  
Strength Of Association

In this article, we introduce the evalue package, which performs sensitivity analyses for unmeasured confounding in observational studies using the methodology proposed by VanderWeele and Ding (2017, Annals of Internal Medicine 167: 268–274). evalue reports E-values, defined as the minimum strength of association on the risk-ratio scale that an unmeasured confounder would need to have with both the treatment assignment and the outcome to fully explain away a specific treatment-outcome association, conditional on the measured covariates. evalue computes E-values for point estimates (and optionally, confidence limits) for several common outcome types, including risk and rate ratios, odds ratios with common or rare outcomes, hazard ratios with common or rare outcomes, standardized mean differences in outcomes, and risk differences.

scholarly journals Assessing the impact of unmeasured confounders for credible and reliable real-world evidence

2020 ◽  
Author(s):  
Xiang Zhang ◽  
James Stamey ◽  
Maya B Mathur
Keyword(s):  
Sensitivity Analysis ◽  
Statistical Methods ◽  
Real World ◽  
Sensitivity Analyses ◽  
Real World Data ◽  
Unmeasured Confounding ◽  
Suggested Approach ◽  
Unmeasured Confounder ◽  
The Impact ◽  
Unmeasured Confounders

Purpose: We review statistical methods for assessing the possible impact of bias due to unmeasured confounding in real world data analysis and provide detailed recommendations for choosing among the methods. Methods: By updating an earlier systematic review, we summarize modern statistical best practices for evaluating and correcting for potential bias due to unmeasuredconfounding in estimating causal treatment effect from non-interventional studies. Results: We suggest a hierarchical structure for assessing unmeasured confounding.First, for initial sensitivity analyses, we strongly recommend applying a recently developed method, the E-value, that is straightforward to apply and does not require prior knowledge or assumptions about the unmeasured confounder(s). When some such knowledge is available, the E-value could be supplemented by the rule-out or array method at this step. If these initial analyses suggest results may not be robust to unmeasured confounding, subsequent analyses could be conducted using more specialized statistical methods, which we categorize based on whether they requireaccess to external data on the suspected unmeasured confounder(s), internal data, or no data. Other factors for choosing the subsequent sensitivity analysis methods arealso introduced and discussed, including the types of unmeasured confounders and whether the subsequent sensitivity analysis is intended to provide a corrected causaltreatment effect. Conclusion: Various analytical methods have been proposed to address unmeasured confounding, but little research has discussed a structured approach to select appropriate methods in practice. In providing practical suggestions for choosing appropriate initial and, potentially, more specialized subsequent sensitivity analyses, we hopeto facilitate the widespread reporting of such sensitivity analyses in non-interventional studies. The suggested approach also has the potential to inform pre-specificationof sensitivity analyses before executing the analysis, and therefore increase the transparency and limit selective study reporting.

scholarly journals Sensitivity analysis for unmeasured confounding in meta-analyses

2017 ◽  
Author(s):  
Maya B Mathur ◽  
Tyler VanderWeele
Keyword(s):  
Random Effects ◽  
Observational Studies ◽  
R Package ◽  
Sensitivity Analyses ◽  
Unmeasured Confounding ◽  
Confounding Bias ◽  
Point Estimates ◽  
Bias Factor ◽  
Meta Analyses ◽  
Biased Estimates

Random-effects meta-analyses of observational studies can produce biased estimates if the synthesized studies are subject to unmeasured confounding. We propose sensitivity analyses quantifying the extent to which unmeasured confounding of specified magnitude could reduce to below a certain threshold the proportion of true effect sizes that are scientifically meaningful. We also develop converse methods to estimate the strength of confounding capable of reducing the proportion of scientifically meaningful true effects to below a chosen threshold. These methods apply when a "bias factor'' is assumed to be normally distributed across studies or is assessed across a range of fixed values. Our estimators are derived using recently proposed sharp bounds on confounding bias within a single study that do not make assumptions regarding the unmeasured confounders themselves or the functional form of their relationships to the exposure and outcome of interest. We provide an R package, EValue, and a free website that compute point estimates and inference and produce plots for conducting such sensitivity analyses. These methods facilitate principled use of random-effects meta-analyses of observational studies to assess the strength of causal evidence for a hypothesis.

Skeletal elements of crinoid echinoderms: High-resolution structural and microanalytical results

1983 ◽  
Vol 41 ◽  
pp. 194-195
Author(s):  
D. F. Blake ◽  
L. F. Allard ◽  
D. R. Peacor
Keyword(s):  
High Resolution ◽  
Marine Invertebrates ◽  
Sea Urchins ◽  
Structural Features ◽  
Sea Stars ◽  
High Resolution Tem ◽  
Relationship Of ◽  
The Relationship ◽  
Insight Into

Echinodermata is a phylum of marine invertebrates which has been extant since Cambrian time (c.a. 500 m.y. before the present). Modern examples of echinoderms include sea urchins, sea stars, and sea lilies (crinoids). The endoskeletons of echinoderms are composed of plates or ossicles (Fig. 1) which are with few exceptions, porous, single crystals of high-magnesian calcite. Despite their single crystal nature, fracture surfaces do not exhibit the near-perfect {10.4} cleavage characteristic of inorganic calcite. This paradoxical mix of biogenic and inorganic features has prompted much recent work on echinoderm skeletal crystallography. Furthermore, fossil echinoderm hard parts comprise a volumetrically significant portion of some marine limestones sequences. The ultrastructural and microchemical characterization of modern skeletal material should lend insight into: 1). The nature of the biogenic processes involved, for example, the relationship of Mg heterogeneity to morphological and structural features in modern echinoderm material, and 2). The nature of the diagenetic changes undergone by their ancient, fossilized counterparts. In this study, high resolution TEM (HRTEM), high voltage TEM (HVTEM), and STEM microanalysis are used to characterize tha ultrastructural and microchemical composition of skeletal elements of the modern crinoid Neocrinus blakei.

On Metaphysics and the Political: A Polemics of Reading Baudelaire in the 1930s

2019 ◽  
Vol 58 (2) ◽  
pp. 249-259
Author(s):  
Joseph Acquisto
Keyword(s):  
Twentieth Century ◽  
Political Crisis ◽  
The Political ◽  
Modern Poetry ◽  
Progressive Politics ◽  
The World ◽  
Relationship Of ◽  
The Relationship ◽  
Insight Into

This essay examines a polemic between two Baudelaire critics of the 1930s, Jean Cassou and Benjamin Fondane, which centered on the relationship of poetry to progressive politics and metaphysics. I argue that a return to Baudelaire's poetry can yield insight into what seems like an impasse in Cassou and Fondane. Baudelaire provides the possibility of realigning metaphysics and politics so that poetry has the potential to become the space in which we can begin to think the two of them together, as opposed to seeing them in unresolvable tension. Or rather, the tension that Baudelaire animates between the two allows us a new way of thinking about the role of esthetics in moments of political crisis. We can in some ways see Baudelaire as responding, avant la lettre, to two of his early twentieth-century readers who correctly perceived his work as the space that breathes a new urgency into the questions of how modern poetry relates to the world from which it springs and in which it intervenes.

The Annual Reports of the Prison Commissioners for Scotland and Religion, 1903–1931

2019 ◽  
Vol 48 (1) ◽  
pp. 83-101
Author(s):  
Cameron McKay
Keyword(s):  
Annual Report ◽  
Annual Reports ◽  
Individual Choice ◽  
Drinking Habits ◽  
Parental Neglect ◽  
Late Nineteenth ◽  
Causes Of Crime ◽  
Criminological Theories ◽  
The Relationship ◽  
Insight Into

During the late nineteenth and early twentieth century penologists began to explore the possibility that environment and upbringing, as opposed to individual choice, were the causes criminality. The Prison Commissioners for Scotland, the devolved body who administered prisons north of the border, were not immune to this wider trend. Smith has argued that from the 1890s onwards the Commissioners began to accept that criminality was caused by social problems, namely alcoholism, but also parental neglect, poor education and poverty. In their efforts to test these new criminological theories, the Commissioners began to make more careful enquiries into the backgrounds of their charges. From 1896 to 1931 the Commissioners interviewed a sample of prisoners each year and included the findings in their annual report. Although the main focus of these interviews was on the upbringing and drinking habits of prisoners; by the 1900s the Commissioners seem to have added irreligion to the growing list of etiological causes of crime, and from 1903 onwards prisoners were asked to give details on their religious habits. Although it is debateable how much the Prison Commissioners revealed about the relationship between religion and crime, they did however provide a useful insight into the religiosity of the average prisoner.

The Relationship between Seeker and Spiritual Guide as portrayed in contemporary Western Sufi Autobiographies

2011 ◽  
Vol 5 (2) ◽  
pp. 297-332
Author(s):  
Kate Zebiri
Keyword(s):  
Life Writing ◽  
New Age ◽  
The Self ◽  
Individual Autonomy ◽  
Religious Authority ◽  
The Face ◽  
The Relationship ◽  
Insight Into ◽  
Continuity And Discontinuity

This article aims to explore the Shaykh-mur?d (disciple) or teacher-pupil relationship as portrayed in Western Sufi life writing in recent decades, observing elements of continuity and discontinuity with classical Sufism. Additionally, it traces the influence on the texts of certain developments in religiosity in contemporary Western societies, especially New Age understandings of religious authority. Studying these works will provide an insight into the diversity of expressions of contemporary Sufism, while shedding light on a phenomenon which seems to fly in the face of contemporary social and religious trends which deemphasize external authority and promote the authority of the self or individual autonomy.

Is there a relationship between gestational diabetes and postpartum depression?

2020 ◽  
Vol 16 ◽  
Author(s):  
Salman Khazaei ◽  
Erfan Ayubi ◽  
Saeid Bashirian ◽  
Ronak Hamzehei ◽  
Ensiyeh Jenabi
Keyword(s):  
Gestational Diabetes ◽  
Postpartum Depression ◽  
Odds Ratio ◽  
Depression Scale ◽  
Binary Logistic Regression ◽  
Cross Sectional Study ◽  
University Education ◽  
P Value ◽  
Cross Sectional ◽  
The Relationship

Background: The relationship between gestational diabetes and postpartum depression (PPD) is poorly understood and seldom studied. Objective: In an effort to explore this issue, the present study investigated the relationship between gestational diabetes and PPD. Methods: The present cross-sectional study was performed with 342 women who were referred to four urban health centers of Hamadan city, west of Iran. We used convenience sampling as a method to recruit women in each health center. We used a researcher-made checklist for gathering data on socio-demographic characteristics and potential risk factors of PPD. The Persian validated version of the Edinburgh Postnatal Depression Scale (EPDS) was used to assess PPD. Univariate and multivariable binary logistic regression was applied to estimate the odds ratio (OR) (95% confidence interval [CI]). Results: Gestational diabetes was identified as the most important risk factor for PPD with OR (95% CI) of 2.19 (1.11, 4.31); P-value=0.02 after adjusting for other variables. Moreover, the adjusted odds ratio showed that PPD among lesseducated women (primary school) was 3.5 times higher compared to women with a university education (OR=3.54, 95% CI: 1.27, 9.84; P-value=0.01). Conclusion: Our findings suggested that PPD is more likely among women with gestational diabetes and those who were less educated. Interventional and educational activities for reducing the risk of PPD can be targeted for use with this population.

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