Safety Profile of Niraparib as Maintenance Therapy for Ovarian Cancer: A Systematic Review and Meta-Analysis

Background: Patients with epithelial ovarian cancer (EOC), treated with niraparib maintenance, present with haematological and gastrointestinal toxicities. Limited data exist on niraparib safety assessment. Objective: To evaluate niraparib safety profile, as maintenance therapy, in women with platinum-sensitive EOC. Methods: PubMed and Cochrane searches were carried out up to April 2021 for randomised controlled trials (RCTs) evaluating niraparib versus placebo in EOC patients with a response to platinum-based chemotherapy. Regarding the meta-analysis, for dichotomous data, the pooled risk ratio (RR) was calculated. Results: A total of 1539 patients from three RCTs revealed that niraparib-treated patients are associated with a significantly higher risk of any grade of nausea (RR, 2.15; 95% CI, 1.86 to 2.48), fatigue (RR, 1.26; 95% CI, 1.05 to 1.52, p < 0.00001), anemia (RR, 6.86; 95% CI, 2.54 to 18.52, p = 0.0001), thrombocytopenia (RR, 7.02; 95% CI, 1.68 to 29.38, p < 0.00001), vomiting (RR, 2.51; 95% CI, 1.50 to 4.19, p = 0.0005), neutropenia (RR, 2.96; 95% CI, 1.13 to 7.73, p < 0.00001), headache (RR, 2.08; 95% CI, 1.57 to 2.74, p < 0.00001), constipation (RR, 2.10; 95% CI, 1.72 to 2.57, p < 0.00001) and insomnia (RR, 2.48; 95% CI, 1.52 to 2.89, p = 0.0003) when compared with placebo. For grade 3 or 4 adverse effects, significantly higher risk was only noted for fatigue (RR,6.25; 95% CI, 1.70 to 23.05, p = 0.006), anemia (RR, 16.23; 95% CI, 4.86 to 54.17, p < 0.00001), thrombocytopenia (RR, 35.12; 95% CI, 12.23 to 100.82, p < 0.00001) and neutropenia episodes (RR, 6.35; 95% CI, 2.08 to 19.39, p = 0.001) for those taking niraparib. Notably, incidents of adverse effects and discontinuation rates were substantially lower among patients treated with an individualised niraparib dose than those treated with the standard one. Efficacy was not reduced, and no treatment-related deaths occurred during the included trials. Conclusion: Niraparib is considered an effective and well-tolerated choice, with an improved safety profile, for the maintenance treatment of EOC patients.

Analysis of zero inflated dichotomous variables from a Bayesian perspective: application to occupational health

Background Zero-inflated models are generally aimed to addressing the problem that arises from having two different sources that generate the zero values observed in a distribution. In practice, this is due to the fact that the population studied actually consists of two subpopulations: one in which the value zero is by default (structural zero) and the other is circumstantial (sample zero). Methods This work proposes a new methodology to fit zero inflated Bernoulli data from a Bayesian approach, able to distinguish between two potential sources of zeros (structural and non-structural). Results The proposed methodology performance has been evaluated through a comprehensive simulation study, and it has been compiled as an R package freely available to the community. Its usage is illustrated by means of a real example from the field of occupational health as the phenomenon of sickness presenteeism, in which it is reasonable to think that some individuals will never be at risk of suffering it because they have not been sick in the period of study (structural zeros). Without separating structural and non-structural zeros one would be studying jointly the general health status and the presenteeism itself, and therefore obtaining potentially biased estimates as the phenomenon is being implicitly underestimated by diluting it into the general health status. Conclusions The proposed methodology is able to distinguish two different sources of zeros (structural and non-structural) from dichotomous data with or without covariates in a Bayesian framework, and has been made available to any interested researcher in the form of the bayesZIB R package (https://cran.r-project.org/package=bayesZIB).

High prevalence of hip lesions secondary to arthroscopic over- or undercorrection of femoroacetabular impingement in patients with postoperative pain

Objectives To compare the prevalence of pre- and postoperative osseous deformities and intra-articular lesions in patients with persistent pain following arthroscopic femoroacetabular impingement (FAI) correction and to identify imaging findings associated with progressive cartilage damage. Methods Retrospective study evaluating patients with hip pain following arthroscopic FAI correction between 2010 and 2018. Pre- and postoperative imaging studies were analyzed independently by two blinded readers for osseous deformities (cam-deformity, hip dysplasia, acetabular overcoverage, femoral torsion) and intra-articular lesions (chondro-labral damage, capsular lesions). Prevalence of osseous deformities and intra-articular lesions was compared with paired t-tests/McNemar tests for continuous/dichotomous data. Association between imaging findings and progressive cartilage damage was assessed with logistic regression. Results Forty-six patients (mean age 29 ± 10 years; 30 female) were included. Postoperatively, 74% (34/46) of patients had any osseous deformity including 48% (22/46) acetabular and femoral deformities. Ninety-six percent (44/46) had an intra-articular lesion ranging from 20% (9/46) for femoral to 65% (30/46) for acetabular cartilage lesions. Prevalence of hip dysplasia increased (2 to 20%, p = 0.01) from pre- to postoperatively while prevalence of cam-deformity decreased (83 to 28%, p < 0.001). Progressive cartilage damage was detected in 37% (17/46) of patients and was associated with extensive preoperative cartilage damage > 2 h, i.e., > 60° (OR 7.72; p = 0.02) and an incremental increase in postoperative alpha angles (OR 1.18; p = 0.04). Conclusion Prevalence of osseous deformities secondary to over- or undercorrrection was high. Extensive preoperative cartilage damage and higher postoperative alpha angles increase the risk for progressive degeneration. Key Points • The majority of patients presented with osseous deformities of the acetabulum or femur (74%) and with intra-articular lesions (96%) on postoperative imaging. • Prevalence of hip dysplasia increased (2 to 20%, p = 0.01) from pre- to postoperatively while prevalence of a cam deformity decreased (83 to 28%, p < 0.001). • Progressive cartilage damage was present in 37% of patients and was associated with extensive preoperative cartilage damage > 2 h (OR 7.72; p = 0.02) and with an incremental increase in postoperative alpha angles (OR 1.18; p = 0.04).

Proposal of the Dichotomous STATIS DUAL Method: Software and Application for the Analysis of Dichotomous Data, Applied to the Test of Learning Styles in University Students

The present work analyzed a review of methods for analyzing sequences of matrices or dichotomous data. A new method for a sequence of dichotomous matrices with a different number of rows is presented; the Dichotomous STATIS DUAL. Suppose we match the sequence of matrices by different years, with this method. In that case, we can graphically represent the relations among the different columns of all the matrices, and the relations between those columns and the different years, because everything can be represented in the same plots. As in all STATIS methods, three different plots can get: (i) the interstructure, with the relations among the years; (ii) the compromise, with the stable part of the relations between the columns; and (iii) the intrastructure (also known as trajectories), with the relations between columns and years, in other words, the evolution of the columns through the time. This new mathematical method can be used with all kinds of dichotomous data, thanks to the software we propose. In the present work, the software was applied to the assessment of learning styles.

Effect of Dichotomization on the Latent Structure of Data

We investigated whether dichotomous data showed the same latent structure as the interval-level data from which they originated. Given constancy of dimensionality and factor loadings reflecting the latent structure of data, the focus was on the variance of the latent variable of a confirmatory factor model. This variance was shown to summarize the information provided by the factor loadings. The results of a simulation study did not reveal exact correspondence of the variances of the latent variables derived from interval-level and dichotomous data but shrinkage. Since shrinkage occurred systematically, methods for recovering the original variance were fleshed out and evaluated.

Echocardiographic E/e for the prediction of recurrent atrial fibrillation after ablation or electrical cardioversion: a systematic review and meta-analysis

Background Atrial Fibrillation (AF) is the most common arrhythmia, with important sequelae if left untreated. Markers help to predict the recurrence of AF after an intervention like ablation or electrical cardioversion (ECV). E/e' ratio is an echocardiographic marker which is potentially useful in predicting AF recurrence, however, present data is conflicting. Adding a simple tool like E/e' ratio to evaluation of patients for AF intervention may help in advising patients better about their risk for recurrent AF after intervention without adding much cost to the diagnostic work-up. Purpose To determine if there is a significant difference in pooled mean E/e' ratio among AF patients with recurrence after ablation or ECV compared to those who maintained sinus rhythm, and to determine the odds ratio of recurrent AF given an abnormal E/e' ratio. Methods The investigators systematically searched Pubmed, Medline, Cochrane Database, and Google Scholar for articles on patients undergoing catheter ablation or ECV for AF and who were adjudicated on recurrence of the arrhythmia. We calculated the weighted mean difference of E/e' ratio between those with recurring AF and those who maintained sinus rhythm, and the odds ratio of AF recurrence given an abnormal E/e' ratio. Statistical analysis was done using RevMan 5.4.1 software. Results A total of 38 studies involving 7048 patients were included in the initial analysis (26 studies on ablation with continuous data and 2 with dichotomous data based on a set cutoff, and 10 studies on ECV). One study was excluded due to absence of a blanking period and and another due to outlaying data in funnel plot analysis. The remaining 36 studies with 6910 patients were analyzed. There was a significant difference in the weighted mean E/e' ratio between the two groups in AF patients undergoing ablation (Mean Difference (MD)=0.60 (95% CI [0.20,1.00] p=0.003, I2=63%]), and ECV (MD=2.07 (95% CI [1.66, 2.49] p&lt;0.ehab724.0361, I2=12%), with an odds ratio of 1.88 (95% CI [1.04, 3.37] p=0.04, I2=52%) among those with dichotomous data. Subgroup analyses were done to reduce heterogeneity. E/e' ratio was not significantly different in the population of paroxysmal AF undergoing ablation (MD=0.64, 95% CI [−0.55, 1.83], p=0.29, I2=76%) but significantly different in patients with non-paroxysmal AF undergoing ECV (MD=2.19, 95% CI [1.82, 2.56], I2=0%). Conclusion This analysis suggests that a higher E/e' ratio may be used to predict recurrence of AF after ablation or ECV, especially in patients undergoing ECV. The heterogeneity of the data for E/e' ratio in AF ablation and the variety of co-morbid conditions to atrial fibrillation limits its clinical applicability. Further studies are recommended to determine the optimal cutoff of this ratio that would predict AF recurrence. FUNDunding Acknowledgement Type of funding sources: None. Forest plot for studies on Ablation Forest plot for studies on ECV

Alternative Tendon Coaptations to the Pulvertaft Weave Technique: A Systematic Review and Meta-Analysis of Biomechanical Studies

Background The Pulvertaft weave technique (PT) is frequently used during tendon repairs and transfers. However, this technique is associated with limitations. In this systematic review and meta-analysis, quantitative and qualitative analyses were performed on in vitro, biomechanical studies that compared the PT with alternative techniques. Methods Articles included for qualitative and/or qualitative analysis were identified following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Studies included in the meta-analysis were analyzed either as continuous data with inverse variance and random effects or as dichotomous data using a Mantel-Haenszel analysis assuming random effects to calculate an odds ratio. Results A comprehensive electronic search yielded 8 studies meeting inclusion criteria for meta-analysis. Two studies with a total of 65 tendon coaptations demonstrated no significant difference in strength between the PT and traditional side-to-side (STS) techniques ( P = .92). Two studies with a total of 43 tendon coaptations showed that the STS with 1 weave has a higher yield strength than the PT ( P = .03). Two studies with a total of 62 tendon repairs demonstrated no significant difference in strength between the PT and the step-cut (SC) techniques ( P = .70). The final 2 studies included 46 tendon repairs and demonstrated that the wrap around (WA) technique has a higher yield strength than the PT ( P < .001). Conclusions The STS, SC, and WA techniques are preferred for improving tendon form. The STS and WA techniques have superior yield strengths than the PT, and the SC technique withstands similar stress to failure as the PT.

IRTGUI: An R Package for Unidimensional item response theory Analysis With a Graphical User Interface

In the last decade, many R packages were published to perform item response theory (IRT) analysis. Some researchers and practitioners have difficulty in using these functional tools because of their insufficient coding skills. The IRTGUI package provides these researchers a user-friendly GUI where they can perform unidimensional IRT analysis without coding skills. Using the IRTGUI package, person and item parameters, model and item fit indices can be obtained. Dimensionality and local independence assumptions can be tested. With the IRTGUI package, users can generate dichotomous data sets with customizable conditions. Also, Wright Maps, item characteristics and information curves can be graphically displayed. All outputs can be easily downloaded by users.

The efficacy of Tranexamic Acid Administration in Patients Undergoing Tonsillectomy: An Updated Meta-Analysis

Objective: There is controversy regarding the efficacy and safety of tranexamic acid (TXA) in reducing tonsillectomy-related hemorrhage. We conducted a systematic review and meta-analysis to evaluate the prophylactic role of TXA in tonsillectomy. Methods: We searched 6 databases to identify studies that directly compare the effect of TXA versus controls in tonsillectomy patients. Standardized mean difference was applied to summate the findings across the studies. Dichotomous data were expressed as relative risk. Results: Ten studies representing a total of 111 898 patients were included. The pooled results showed a significant reduction of intraoperative blood loss by 39.02 ml (SMD = −1.05, 95% CI: −1.91 to −0.20, P = .016) and the rate of post-tonsillectomy hemorrhage (RR = 0.42, 95% CI: 0.28 to 0.65, P < .0001), with no significant difference in reduction of further intervention risk (RR = 0.78, 95% CI: 0.45 to 1.35, P = .373). Conclusions: Overall, this study indicates that TXA may reduce blood loss and frequency of post-operative hemorrhage associated with tonsillectomy. Further large, high-quality clinical trials are still needed to explore TXA’s effect on post-tonsillectomy hemorrhage and the safety of its use.