scholarly journals Leveraging the Variability of Pharmacovigilance Disproportionality Analyses to Improve Signal Detection Performances

2021 ◽  
Vol 12 ◽  
Author(s):  
Charles Khouri ◽  
Thuy Nguyen ◽  
Bruno Revol ◽  
Marion Lepelley ◽  
Antoine Pariente ◽  
...  
Keyword(s):  
Signal Detection ◽  
Regression Models ◽  
Roc Curves ◽  
Sensitivity Analyses ◽  
Drug Event ◽  
Event Pair ◽  
Safety Surveillance ◽  
Binomial Regression ◽  
Sensitivity Specificity ◽  
The Impact

Background: A plethora of methods and models of disproportionality analyses for safety surveillance have been developed to date without consensus nor a gold standard, leading to methodological heterogeneity and substantial variability in results. We hypothesized that this variability is inversely correlated to the robustness of a signal of disproportionate reporting (SDR) and could be used to improve signal detection performances.Methods: We used a validated reference set containing 399 true and false drug-event pairs and performed, with a frequentist and a Bayesian disproportionality method, seven types of analyses (model) for which the results were very unlikely to be related to actual differences in absolute risks of ADR. We calculated sensitivity, specificity and plotted ROC curves for each model. We then evaluated the predictive capacities of all models and assessed the impact of combining such models with the number of positive SDR for a given drug-event pair through binomial regression models.Results: We found considerable variability in disproportionality analysis results, both positive and negative SDR could be generated for 60% of all drug-event pairs depending on the model used whatever their truthfulness. Furthermore, using the number of positive SDR for a given drug-event pair largely improved the signal detection performances of all models.Conclusion: We therefore advocate for the pre-registration of protocols and the presentation of a set of secondary and sensitivity analyses instead of a unique result to avoid selective outcome reporting and because variability in the results may reflect the likelihood of a signal being a true adverse drug reaction.

scholarly journals Identification of the most specific markers to differentiate primary pulmonary carcinoma from metastatic gastrointestinal carcinoma to the lung

2022 ◽  
Vol 17 (1) ◽  
Author(s):  
Bachar Alabdullah ◽  
Amir Hadji-Ashrafy
Keyword(s):  
Gastrointestinal Tract ◽  
Predictive Value ◽  
Regression Models ◽  
Area Under The Curve ◽  
Roc Curves ◽  
Multivariate Models ◽  
Gastrointestinal Carcinoma ◽  
Lung Tumours ◽  
Napsin A ◽  
Sensitivity Specificity

Abstract Background A number of biomarkers have the potential of differentiating between primary lung tumours and secondary lung tumours from the gastrointestinal tract, however, a standardised panel for that purpose does not exist yet. We aimed to identify the smallest panel that is most sensitive and specific at differentiating between primary lung tumours and secondary lung tumours from the gastrointestinal tract. Methods A total of 170 samples were collected, including 140 primary and 30 non-primary lung tumours and staining for CK7, Napsin-A, TTF1, CK20, CDX2, and SATB2 was performed via tissue microarray. The data was then analysed using univariate regression models and a combination of multivariate regression models and Receiver Operating Characteristic (ROC) curves. Results Univariate regression models confirmed the 6 biomarkers’ ability to independently predict the primary outcome (p < 0.001). Multivariate models of 2-biomarker combinations identified 11 combinations with statistically significant odds ratios (ORs) (p < 0.05), of which TTF1/CDX2 had the highest area under the curve (AUC) (0.983, 0.960–1.000 95% CI). The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 75.7, 100, 100, and 37.5% respectively. Multivariate models of 3-biomarker combinations identified 4 combinations with statistically significant ORs (p < 0.05), of which CK7/CK20/SATB2 had the highest AUC (0.965, 0.930–1.000 95% CI). The sensitivity, specificity, PPV, and NPV were 85.1, 100, 100, and 41.7% respectively. Multivariate models of 4-biomarker combinations did not identify any combinations with statistically significant ORs (p < 0.05). Conclusions The analysis identified the combination of CK7/CK20/SATB2 to be the smallest panel with the highest sensitivity (85.1%) and specificity (100%) for predicting tumour origin with an ROC AUC of 0.965 (p < 0.001; SE: 0.018, 0.930–1.000 95% CI).

scholarly journals The impact of political instability upon the increase of terrorism in the Middle East

2021 ◽  
pp. 43-62
Author(s):  
Andrey Vadimovich Novikov
Keyword(s):  
Regression Models ◽  
Negative Binomial ◽  
Political Instability ◽  
Negative Binomial Regression ◽  
Severe Form ◽  
Political Regime ◽  
Level Of Education ◽  
Binomial Regression ◽  
Different Types ◽  
The Impact

The key goal of the article is to examine whether the domestic political instability associated with the &ldquo;Arab Spring&rdquo; caused the subsequent surge of global terrorism, which reached its peak in 2014. The author reviews six different types of domestic political instability: antigovernment demonstrations, national strikes, government crises, government repression, disturbances, and revolutions. Using the regression models, the author clarifies the impact of such factors as the level of education, Internet access, economic development, democratization indexes, and the degree of religious and ethnic fragmentariness. Analysis is conducted on the results of the models separately for different types of political regimes, forms of domestic political instability, and global regions. The results of construction and analysis a number of negative binomial regression models testify to the support of &ldquo;escalation effect&rdquo;, which implies that heightened intensity of domestic political instability leads to the surge of terrorist attacks. More severe forms of domestic political instability, namely repression and disturbances, generate a higher level of terrorism; however, revolution, as the most severe form of domestic political instability does not produce such effect. The formulated conclusions are also substantiated by the fact that certain forms of political instability have a different impact upon terrorism and its peculiarities, depending on the geographical region and the type of political regime.

scholarly journals The impact of database restriction on pharmacovigilance signal detection of selected cancer therapies

2017 ◽  
Vol 8 (5) ◽  
pp. 145-156 ◽  
Author(s):  
Manfred Hauben ◽  
Eric Hung ◽  
Jennifer Wood ◽  
Amit Soitkar ◽  
Daniel Reshef
Keyword(s):  
Adverse Event ◽  
Signal Detection ◽  
Safety Information ◽  
Adverse Event Reporting System ◽  
Package Insert ◽  
The United States ◽  
Drug Event ◽  
Reference Set ◽  
Oncology Drug ◽  
The Impact

Background: The aim of this study was to investigate whether database restriction can improve oncology drug pharmacovigilance signal detection performance. Methods: We used spontaneous adverse event (AE) reports in the United States (US) Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database. Positive control (PC) drug medical concept (DMC) pairs were selected from safety information not included in the product’s first label but subsequently added as label changes. These medical concepts (MCs) were mapped to the Medical Dictionary for Regulatory Activities (MedDRA) preferred terms (PTs) used in FAERS to code AEs. Negative controls (NC) were MCs with circumscribed PTs not included in the corresponding US package insert (USPI). We calculated shrinkage-adjusted observed-to-expected (O/E) reporting frequencies for the aforementioned drug–PT pairs. We also formulated an adjudication framework to calculate performance at the MC level. Performance metrics [sensitivity, specificity, positive and negative predictive value (PPV, NPV), signal/noise (S/N), F and Matthews correlation coefficient (MCC)] were calculated for each analysis and compared. Results: The PC reference set consisted of 11 drugs, 487 PTs, 27 MCs, 37 drug–MC combinations and 638 drug–event combinations (DECs). The NC reference set consisted of 11 drugs, 9 PTs, 5 MCs, 40 drug–MC combinations and 67 DECs. Most drug–event pairs were not highlighted by either analysis. A small percentage of signals of disproportionate reporting were lost, more noise than signal, with no gains. Specificity and PPV improved whereas sensitivity, NPV, F and MCC decreased, but all changes were small relative to the decrease in sensitivity. The overall S/N improved. Conclusion: This oncology drug restricted analysis improved the S/N ratio, removing proportionately more noise than signal, but with significant credible signal loss. Without broader experience and a calculus of costs and utilities of correct versus incorrect classifications in oncology pharmacovigilance such restricted analyses should be optional rather than a default analysis.

scholarly journals The Impact of the COVID-19 Pandemic on Cross-Border Mergers and Acquisitions’ Determinants: New Empirical Evidence from Quasi-Poisson and Negative Binomial Regression Models

Economies ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 184
Author(s):  
Han-Sol Lee ◽  
Ekaterina A. Degtereva ◽  
Alexander M. Zobov
Keyword(s):  
Mergers And Acquisitions ◽  
Empirical Evidence ◽  
Regression Models ◽  
Negative Binomial ◽  
Negative Binomial Regression ◽  
Entry Modes ◽  
Cross Sectional ◽  
Cross Border ◽  
Binomial Regression ◽  
The Impact

The cross-border movement of capital has suffered due to the COVID-19 pandemic since December 2019. Nevertheless, it is unrealistic for multinational companies to withdraw giant global value chains (GVCs) overnight because of the pandemic. Instead, active discussions and achievements of deals in cross-border mergers and acquisitions (M&As) are expected in the post-COVID-19 era among various other market entry modes, considering the growing demand in high technologies in societies. This paper analyzes particular determinants of cross-border mergers and acquisitions (M&As) during the pandemic year (2020) based on cross-sectional datasets by employing quasi-Poisson and negative binomial regression models. According to the empirical evidence, COVID-19 indices do not hamper M&A deals in general. This indicates that managerial capabilities of the coronavirus, not the outbreak itself, determined locational decisions of M&A deals during the pandemic. In this vein, it is expected that the vaccination rate will become a key factor of locational decision for M&A deals in the near future. Furthermore, countries that have been outstanding in coping with COVID-19 and thus serve as a good example for other nations may seize more opportunities to take a leap forward. In addition, as hypothesized, the results present positive and significant associations with M&A deals and the SDG index, confirming the resource-based theory of internationalization. In particular, the achievement of SDGs seems to exercise much influence in developing countries for M&A bidders during the pandemic year. This indicates that the pandemic demands a new zeitgeist that pursues growth while resolving existing but disregarded environmental issues and cherishes humanitarian values, for all countries, non-exceptionally, standing at the start line of the post-COVID-19 era.

FAKTOR DETERMINAN PENYALURAN KREDIT BANK PERSERO

2018 ◽  
Vol 23 (1) ◽  
pp. 60-71
Author(s):  
Wigiyanti Masodah
Keyword(s):  
Interest Rate ◽  
Linear Regression ◽  
Interest Rates ◽  
Regression Models ◽  
Linear Regression Models ◽  
Negative Impacts ◽  
Main Activity ◽  
The Impact ◽  
The Given ◽  
Multiple Linear Regression Models

Offering credit is the main activity of a Bank. There are some considerations when a bank offers credit, that includes Interest Rates, Inflation, and NPL. This study aims to find out the impact of Variable Interest Rates, Inflation variables and NPL variables on credit disbursed. The object in this study is state-owned banks. The method of analysis in this study uses multiple linear regression models. The results of the study have shown that Interest Rates and NPL gave some negative impacts on the given credit. Meanwhile, Inflation variable does not have a significant effect on credit given. Keywords: Interest Rate, Inflation, NPL, offered Credit.

The impact of SPY angiography on intraoperative decision making and outcomes for post-mastectomy reconstruction

2019 ◽  
pp. 1-5
Keyword(s):  
Decision Making ◽  
Logistic Regression ◽  
Skin Necrosis ◽  
Regression Models ◽  
Multivariable Analysis ◽  
P Value ◽  
Flap Necrosis ◽  
Single Institution ◽  
Logistic Regression Models ◽  
The Impact

Objective: While the use of intraoperative laser angiography (SPY) is increasing in mastectomy patients, its impact in the operating room to change the type of reconstruction performed has not been well described. The purpose of this study is to investigate whether SPY angiography influences post-mastectomy reconstruction decisions and outcomes. Methods and materials: A retrospective analysis of mastectomy patients with reconstruction at a single institution was performed from 2015-2017.All patients underwent intraoperative SPY after mastectomy but prior to reconstruction. SPY results were defined as ‘good’, ‘questionable’, ‘bad’, or ‘had skin excised’. Complications within 60 days of surgery were compared between those whose SPY results did not change the type of reconstruction done versus those who did. Preoperative and intraoperative variables were entered into multivariable logistic regression models if significant at the univariate level. A p-value <0.05 was considered significant. Results: 267 mastectomies were identified, 42 underwent a change in the type of planned reconstruction due to intraoperative SPY results. Of the 42 breasts that underwent a change in reconstruction, 6 had a ‘good’ SPY result, 10 ‘questionable’, 25 ‘bad’, and 2 ‘had areas excised’ (p<0.01). After multivariable analysis, predictors of skin necrosis included patients with ‘questionable’ SPY results (p<0.01, OR: 8.1, 95%CI: 2.06 – 32.2) and smokers (p<0.01, OR:5.7, 95%CI: 1.5 – 21.2). Predictors of any complication included a change in reconstruction (p<0.05, OR:4.5, 95%CI: 1.4-14.9) and ‘questionable’ SPY result (p<0.01, OR: 4.4, 95%CI: 1.6-14.9). Conclusion: SPY angiography results strongly influence intraoperative surgical decisions regarding the type of reconstruction performed. Patients most at risk for flap necrosis and complication post-mastectomy are those with questionable SPY results.

Body mass index and risk of all-cause mortality in normotensive and hypertensive adults: The Rural Chinese Cohort Study

2021 ◽  
pp. 1-25
Author(s):  
Qionggui Zhou ◽  
Xuejiao Liu ◽  
Yang Zhao ◽  
Pei Qin ◽  
Yongcheng Ren ◽  
...  
Keyword(s):  
Cohort Study ◽  
Population Based ◽  
Normal Weight ◽  
Sensitivity Analyses ◽  
Hypertension Status ◽  
Moderation Effect ◽  
Increased Risk ◽  
All Cause Mortality ◽  
Chinese Cohort ◽  
The Impact

Abstract Objective: The impact of baseline hypertension status on the BMI–mortality association is still unclear. We aimed to examine the moderation effect of hypertension on the BMI–mortality association using a rural Chinese cohort. Design: In this cohort study, we investigated the incident of mortality according to different BMI categories by hypertension status. Setting: Longitudinal population-based cohort Participants: 17,262 adults ≥18 years were recruited from July to August of 2013 and July to August of 2014 from a rural area in China. Results: During a median 6-year follow-up, we recorded 1109 deaths (610 with and 499 without hypertension). In adjusted models, as compared with BMI 22-24 kg/m2, with BMI ≤18, 18-20, 20-22, 24-26, 26-28, 28-30 and >30 kg/m2, the HRs (95% CI) for mortality in normotensive participants were 1.92 (1.23-3.00), 1.44 (1.01-2.05), 1.14 (0.82-1.58), 0.96 (0.70-1.31), 0.96 (0.65-1.43), 1.32 (0.81-2.14), and 1.32 (0.74-2.35) respectively, and in hypertensive participants were 1.85 (1.08-3.17), 1.67 (1.17-2.39), 1.29 (0.95-1.75), 1.20 (0.91-1.58), 1.10 (0.83-1.46), 1.10 (0.80-1.52), and 0.61 (0.40-0.94) respectively. The risk of mortality was lower in individuals with hypertension with overweight or obesity versus normal weight, especially in older hypertensives (≥60 years old). Sensitivity analyses gave consistent results for both normotensive and hypertensive participants. Conclusions: Low BMI was significantly associated with increased risk of all-cause mortality regardless of hypertension status in rural Chinese adults, but high BMI decreased the mortality risk among individuals with hypertension, especially in older hypertensives.

scholarly journals Impact of Preharvest and Postharvest on Color Changes during Convective Drying of Mangoes

Foods ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 490
Author(s):  
Alioune Diop ◽  
Jean–Michel Méot ◽  
Mathieu Léchaudel ◽  
Frédéric Chiroleu ◽  
Nafissatou Diop Ndiaye ◽  
...  
Keyword(s):  
Regression Models ◽  
Convective Drying ◽  
Color Changes ◽  
Ripening Time ◽  
Physico Chemical ◽  
C 30 ◽  
The Impact

The purpose of this study was to evaluate the impact of the harvest stage, ripening conditions and maturity on color changes of cv. ‘Cogshall’ and cv. ‘Kent’ variety mangoes during drying. A total of four harvests were undertaken, and the fruits were ripened at 20 and 35 °C for five different ripening times at each temperature. At each ripening time, mangoes were dried at 60 °C/30% RH/1.5 m/s for 5 h. A wide physico-chemical and color variability of fresh and dry pulp was created. The relationships according to the L*, H* and C* coordinates were established using mixed covariance regression models in relation to the above pre- and postharvest (preprocess) parameters. According to the L* coordinate results, browning during drying was not affected by the preprocess parameters. However, dried slices from mangoes ripened at 35 °C exhibited better retention of the initial chroma, and had a greater decrease in hue than dried slices from mangoes ripened at 20 °C. However, fresh mango color, successfully managed by the pre- and postharvest conditions, had more impact on dried mango color than the studied parameters. The preprocess parameters were effective levers for improving fresh mango color, and consequently dried mango color.

scholarly journals The Impact of Narrow-band Imaging on the Pre- and Intra- operative Assessments of Neoplastic and Preneoplastic Laryngeal Lesions. A Systematic Review

2020 ◽  
Author(s):  
Carmelo Saraniti ◽  
Enzo Chianetta ◽  
Giuseppe Greco ◽  
Norhafiza Mat Lazim ◽  
Barbara Verro
Keyword(s):  
White Light ◽  
Diagnostic Tool ◽  
Narrow Band ◽  
Narrow Band Imaging ◽  
Resection Margins ◽  
Predictive Values ◽  
White Light Endoscopy ◽  
Laryngeal Lesions ◽  
Sensitivity Specificity ◽  
The Impact

Introduction Narrow-band imaging is an endoscopic diagnostic tool that, focusing on superficial vascular changes, is useful to detect suspicious laryngeal lesions, enabling their complete excision with safe and tailored resection margins. Objectives To analyze the applications and benefits of narrow-band imaging in detecting premalignant and malignant laryngeal lesions through a comparison with white-light endoscopy. Data Synthesis A literature search was performed in the PubMed, Scopus and Web of Science databases using strict keywords. Then, two authors independently analyzed the articles, read the titles and abstracts, and read completely only the relevant studies according to certain eligibility criteria. In total, 14 articles have been included in the present review; the sensitivity, specificity, positive and negative predictive values, and accuracy of pre- and/or intraoperative narrow-band imaging were analyzed. The analysis showed that narrow-band imaging is better than white-light endoscopy in terms of sensitivity, specificity, positive and negative predictive values, and accuracy regarding the ability to identify cancer and/or precancerous laryngeal lesions. Moreover, the intraoperative performance of narrow-band imaging resulted more effective than the in-office performance. Conclusion Narrow-band imaging is an effective diagnostic tool to detect premalignant and malignant laryngeal lesions and to define proper resection margins. Moreover, narrow-band imaging is useful in cases of leukoplakia that may cover a possible malignant lesion and that cannot be easily assessed with white-light endoscopy. Finally, a shared, simple and practical classification of laryngeal lesions, such as that of the European Laryngological Society, is required to identify a shared lesion management strategy. Key Points

scholarly journals TIRADS, SRE and SWE in INDETERMINATE thyroid nodule characterization: Which has better diagnostic performance?

2021 ◽  
Author(s):  
Ilaria Celletti ◽  
Daniele Fresilli ◽  
Corrado De Vito ◽  
Marco Bononi ◽  
Sara Cardaccio ◽  
...  
Keyword(s):  
Thyroid Nodule ◽  
Preoperative Staging ◽  
Shear Wave Elastography ◽  
Roc Curves ◽  
Strain Ratio ◽  
Multicenter Studies ◽  
Increased Sensitivity ◽  
Bonferroni Test ◽  
Indeterminate Cytology ◽  
Sensitivity Specificity

Abstract Purpose To assess Strain Ratio (SRE) and Shear Wave Elastography (SWE) accuracy alone and with TIRADS classification, for the risk stratification of indeterminate thyroid nodules. Materials and methods 128 Patients with 128 indeterminate nodules candidates for thyroidectomy underwent preoperative staging neck ultrasound and were classified according to K-TIRADS score. After TIRADS evaluation, semi-quantitative (SRE) and quantitative (SWE expressed in kPa) elastosonography were performed and relative diagnostic performances, alone and in combination, were compared through ROC curves analysis. In order to maximize the SRE and SWE sensitivity and specificity, their cut-off values were calculated using the Liu test. Bonferroni test was used to evaluate statistically significant differences with a p value < 0.05. Results Sensitivity, specificity, PPV and NPV were, respectively, 71.4%, 82.4%, 62.5%, 87.5% for K-TIRADS baseline US, 85.7%, 94.1%, 85.7%, 94.1% for SRE and 57.1%, 79.4%, 53.3%, 81.8% for SWE (kPa expressed). SRE evaluation showed the best diagnostic accuracy compared to the SWE (kPa expressed) (p < 0.05) and to the K-TIRADS (p > 0.05). The association of SRE with conventional ultrasound with K-TIRADS score increased sensitivity (92.9% vs 71.4%) but decreased the specificity than conventional US alone (76.5% vs 82.4%). Conclusion Strain Elastosonography can be associated with K-TIRADS US examination in the thyroid nodule characterization with indeterminate cytology; in fact, adding the SRE to K-TIRADS assessment significantly increases its sensitivity and negative predictive value. However, further multicenter studies on larger population are warranted.

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