Daratumumab-based therapies in transplant-ineligible patients with untreated multiple myeloma and hepatic dysfunction: A systematic review of subgroup analyses

Introduction There is subgroup analysis suggesting a lack of benefit of daratumumab use in multiple myeloma (MM) and hepatic disease (HD). The objectives of this study were to conduct a systematic review and interpretation of daratumumab-based regimen efficacy in transplant-ineligible patients with untreated MM and HD. Methods A systematic search in Pubmed® database about randomized clinical trials (RCTs) with subgroup analysis regarding hepatic function for overall survival (OS) or progression-free survival (PFS) were developed. Two methodologies were applied. One of them considered statistical interaction, prespecification, biological support and consistency of subgroup results. Second methodology was two-part validated tool: preliminary questions to reject subset analysis without minimal relevance, and a checklist relating a recommendation for applicability in clinical practice. Results It was included three records. About first methodology, statistical interaction among subgroups was found for PFS in one RCT. Subsets were prespecified in all RCTs. Biological support of efficacy differences could be reasonable. Inconsistent results were found. Second methology directly rejected applicability of subset analysis in two records. Checklist recommended “null” application of results in the remaining RCT. Conclusions No consistent heterogeneity for daratumumab-based regimen efficacy was observed among subgroups regarding hepatic function in transplant-ineligible patients with untreated MM. Patients with normal hepatic function and HD could benefit from these treatments.

Influence of the Multiple Layers Application and the Heating of Silane on the Bond Strength between Lithium Disilicate Ceramics and Resinous Cement

Objective The study aimed to evaluate the bond strength between lithium disilicate ceramic and resinous cement when silane (Prosil, FGM) was applied in different amounts of layers under heating or not. Materials and Methods Sixty IPS E-max CAD ceramic (Ivoclar) was used. They were conditioned with 10% hydrofluoric acid for 20 seconds. The samples were distributed in six groups (n = 10): 1Sil, 1 layer of silane without heating; 1SilAq, 1 layer of silane with heating; 2Sil, 2 layers without heating; 2SilAq, 2 layers with heating; 3Sil, 3 layers without heating; and 3SilAq, 3 layers with heating. After each layer, a jet of cold air was applied for 20 seconds in groups 1Sil, 2Sil, 3Sil, and jet of hot air (50°C) in groups 1SilAq, 2SilAq, and 3SilAq. Subsequently, an adhesive layer was applied, and fourcylinders were made on the ceramic with a resin cement AllCemVeneer and photoactivated for 20 seconds. The samples were stored at 37°C for 24 hours and analyzed to the microshear test at EMIC. Statistical Analysis Data were submitted to ANOVA and Tukey’s test (α = 0.05). Results The results showed that there was no statistical interaction between the factors studied. The “heating” factor was not statistically significant; however, the “silane layers” factor showed differences between groups. The analysis of the results showed that the use of one (66%) or two layers (67%) of silane regardless of heating, produced higher values of bond strength, when compared with the group of three layers (62%). Conclusion The use of silane with one or two layers provided a greater bond strength between lithium disilicate ceramic and resinous cement and that the heating did not influence the results.

The effect of comorbidities on glycemic control among Colombian adults with diabetes mellitus: a longitudinal approach with real-world data

Background Achieving an optimal glycemic control has been described to reduce the incidence of diabetes mellitus (DM) related complications. The association between comorbidities and glycemic control remains unclear. Our aim is to evaluate the effect of comorbidities on glycemic control in people living with DM. Methods A retrospective longitudinal study on data from the National Registry of Chronic Kidney Disease from 2014 to 2019 in Colombia. The outcome was poor glycemic control (PGC = HbA1c ≥7.0%). The association between each comorbidity (hypertension (HTN), chronic kidney disease (CKD) or obesity) and PGC was evaluated through multivariate mixed effects logistic regression models. The measures of effect were odds ratios (OR) and their 95% confidence intervals (CI). We also evaluated the main associations stratified by gender, insurance, and early onset diabetes as well as statistical interaction between each comorbidity and ethnicity. Results From 969,531 people at baseline, 85% had at least one comorbidity; they were older and mostly female. In people living with DM and CKD, the odds of having a PGC were 78% (OR: 1.78, CI 95%: 1.55-2.05) higher than those without CKD. Same pattern was observed in obese for whom the odds were 52% (OR: 1.52, CI 95%: 1.31-1.75) higher than in non-obese. Non-significant association was found between HTN and PGC. We found statistical interaction between comorbidities and ethnicity (afro descendant) as well as effect modification by health insurance and early onset DM. Conclusions Prevalence of comorbidities was high in adults living with DM. Patients with concomitant CKD or obesity had significantly higher odds of having a PGC.

Designing Bivariate Auto-Regressive Timeseries with Controlled Granger Causality

In this manuscript, we analyze a bivariate vector auto-regressive (VAR) model in order to draw the design principle of a timeseries with a controlled statistical inter-relationship. We show how to generate bivariate timeseries with given covariance and Granger causality (or, equivalently, transfer entropy), and show the trade-off relationship between these two types of statistical interaction. In principle, covariance and Granger causality are independently controllable, but the feasible ranges of their values which allow the VAR to be proper and have a stationary distribution are constrained by each other. Thus, our analysis identifies the essential tri-lemma structure among the stability and properness of VAR, the controllability of covariance, and that of Granger causality.

Designing bivariate timeseries with controlled Granger causality

In this manuscript, we analyzed vector auto-regressive (VAR) model in order to draw a design principle for bivariate timeseries with a controlled statistical inter-relationship. We show how to generate bivariate timeseries with given covariance and Granger causality, and showed the trade-off relationship between these two types of statistical interaction. In principle, covariance and Granger causality are controllable independently, but the ranges of their values, which let VAR be proper and have stationary distribution, are constrained by each other. Thus, there is an essential tri-lemma among the stability and properness of VAR, the controllability of covariance, and that of Granger causality.

Psychopathy as an Emergent Interpersonal Syndrome: What Is the Function of Fearlessness?

Lilienfeld and colleagues (this issue) propose that some personality disorders can be conceptualized as emergent interpersonal syndromes (EIS). An EIS elicits negative interpersonal reactions in others. Further, an EIS results from statistical interactions between symptom dimensions that are uncorrelated. As a prototypical EIS, psychopathy is an interaction between boldness (or fearlessness) and interpersonal antagonism. The authors marshal many threads of research to develop an intriguing idea that suggests the “whole” of psychopathy is more than the sum of its parts. Unfortunately, the authors focus primarily on psychopathy, and fail to provide convincing quantitative data for the statistical interaction that forms the basis for their theory. Also missing from this model of personality pathology is a consideration of what function boldness serves; viewing boldness as a means to accomplish the (maladaptive) rewarding goals that motivate the individual high in antagonism and disinhibition may serve to flesh out this theory and our conceptualization of personality pathology more broadly.