Research methods in performance validity testing studies: Criterion grouping approach impacts study outcomes

Objective: Performance validity test (PVT) research studies commonly utilize a known-groups design, but the criterion grouping approaches within the design vary greatly from one study to another. At the present time, it is unclear as to what degree different criterion grouping approaches might impact PVT classification accuracy statistics. Method: To analyze this, the authors used three different criterion grouping approaches to examine how classification accuracy statistics of a PVT (Word Choice Test; WCT) would differ. The three criterion grouping approaches included: (1) failure of 2+ PVTs versus failure of 0 PVTs, (2) failure of 2+ PVTs versus failure of 0–1 PVT, and (3) failure of a stand-alone PVT versus passing of a stand-alone PVT (Test of Memory Malingering). Results: When setting specificity at ≥.90, WCT cutoff scores ranged from 41 to 44 and associated sensitivity values ranged from .64 to .88, depending on the criterion grouping approach that was utilized. Conclusions: When using a stand-alone PVT to define criterion group status, classification accuracy rates of the WCT were higher than expected, likely due to strong correlations between the reference PVT and the WCT. This held true even when considering evidence that this grouping approach results in higher rates of criterion group misclassification. Conversely, when using criterion grouping approaches that utilized failure of 2+ PVTs, accuracy rates were more consistent with expectations. These findings demonstrate that criterion grouping approaches can impact PVT classification accuracy rates and resultant cutoff scores. Strengths, weaknesses, and practical implications of each of the criterion grouping approaches are discussed.     

Depression and glioblastoma,complicated concomitant diseases: a systemic review of published literature

Glioblastoma multiforme (GBM) is the most common primary brain cancer. Depression is a common co-morbidity of this condition. Despite this common interaction, relatively little research has been performed on the development of GBM-associated depression. We performed a literary search of the PubMed database for articles published relating to GBM and depression. A total of 85 articles were identified with 46 meeting inclusion criteria. Depression significantly impacts care, decreasing medication compliance, and patient survival. Diagnostically, because depression and GBM share intricate neuro-connectivity in a way that effect functionality, these diseases can be mistaken for alternative psychological or pathological disorders, complicating care. Therapeutically, anti-depressants have anti-tumor properties; yet, some have been shown to interfere with GBM treatment. One reason for this is that the pathophysiological development of depression and GBM share several pathways including altered regulation of the 5-HT receptor, norepinephrine, and 3′:5′-cyclic monophosphate. Over time, depression can persist after GBM treatment, affecting patient quality of life. Together, depression and GBM are complicated concomitant diseases. Clinicians must be aware of their co-existence. Because of overlapping molecular pathways involved in both diseases, careful medication selection is imperative to avoid potential adverse interactions. Since GBMs are the most common primary brain cancer, physicians dealing with this disease should be prepared for the development of depression as a potential sequela of this condition, given the related pathophysiology and the known poor outcomes.     

Preclinical Profile of BI 224436, a Novel HIV-1 Non-Catalytic-Site Integrase Inhibitor

BI 224436 is an HIV-1 integrase inhibitor with effective antiviral activity that acts through a mechanism that is distinct from that of integrase strand transfer inhibitors (INSTIs). This 3-quinolineacetic acid derivative series was identified using an enzymatic integrase long terminal repeat (LTR) DNA 3′-processing assay. A combination of medicinal chemistry, parallel synthesis, and structure-guided drug design led to the identification of BI 224436 as a candidate for preclinical profiling. It has antiviral 50% effective concentrations (EC₅₀s) of <15 nM against different HIV-1 laboratory strains and cellular cytotoxicity of >90 μM. BI 224436 also has a low, ∼2.1-fold decrease in antiviral potency in the presence of 50% human serum and, by virtue of a steep dose-response curve slope, exhibits serum-shifted EC₉₅ values ranging between 22 and 75 nM. Passage of virus in the presence of inhibitor selected for either A128T, A128N, or L102F primary resistance substitutions, all mapping to a conserved allosteric pocket on the catalytic core of integrase. BI 224436 also retains full antiviral activity against recombinant viruses encoding INSTI resistance substitutions N155S, Q148H, and E92Q. In drug combination studies performed in cellular antiviral assays, BI 224436 displays an additive effect in combination with most approved antiretrovirals, including INSTIs. BI 224436 has drug-like in vitro absorption, distribution, metabolism, and excretion (ADME) properties, including Caco-2 cell permeability, solubility, and low cytochrome P450 inhibition. It exhibited excellent pharmacokinetic profiles in rat (clearance as a percentage of hepatic flow [CL], 0.7%; bioavailability [F], 54%), monkey (CL, 23%; F, 82%), and dog (CL, 8%; F, 81%). Based on the excellent biological and pharmacokinetic profile, BI 224436 was advanced into phase 1 clinical trials.     

Anspruch und Wirklichkeit selektiver Vertragsmöglichkeiten

Selective contracts are an important component in addition to the total healthcare concept in order to introduce process-related innovations into the healthcare system. Since 2011 the Berufsverband der Deutschen Urologen (BDU, Professional Association of German Urologists) has held negotiations with individual health insurance companies and care providers in order to view selective contracts as collective contracts, not only as pilot projects but also as additional forms of care.This article illustrates the experiences of the BDU in the initiation and finalizing of selective contracts as well as existing weak points in the framework conditions.     

Zertifizierungssysteme in der urologischen Versorgung

There have been function and organ-related certification systems in urology for a long time. The aim of such certificates is the optimization of patient care above the defined minimum standards and intensification of interdisciplinary cooperation. Whether such certificates have led to better patient care has not been proven. The obligatory documentation in epidemiological cancer registries, which has been taken up by legislature, will in future lead to so-called clinical cancer registries in which the complete course of treatment must be entered. With these registries the quality of healthcare can be compared between individual institutions. Until now, quality of care data outside oncology are lacking. Urology would also benefit from a registry with quality of care data for these patients.     

The Parental Concerns Questionnaire: A Brief Screening Instrument for Potentially Severe Behavior Problems in Infants and Toddlers At-Risk for Developmental Delays

The Parental Concerns Questionnaire (PCQ) was designed as a parent-interview screening instrument for young children with developmental concerns at risk for potentially severe behavior problems (SBDs). Parents of 262 young children (4 to 48 months) answered to the 15 dichotomous PCQ items interviewed by trained staff. Cluster analysis for items revealed three item clusters, which we labeled Developmental/Social (8 items), Biomedical (3 items), and Behavior Problems (3 items). This paper discussed primarily the Behavior Problems cluster, with items referring to self-injurious, aggressive, and destructive behaviors. Parents’ concerns about behavior problems were high, with item-endorsements of the Behavior Problems cluster ranging from 41.8 % to 68.8 %. The Behavior Problems cluster was significantly correlated with all three subscales of the Behavior Problems Inventory (BPI-01), with select subscales of the Aberrant Behavior Checklist (ABC), and with the Repetitive Behavior Scale-Revised (RBS-R) providing some evidence for concurrent validity. Sensitivity and specificity data were computed for the three PCQ items as well as for the cluster score in comparison with the BPI-01, ABC, and RBS-R showing strong sensitivity. The PCQ Behavior Problems cluster is a useful screening checklist with high sensitivity for potential SBDs in young children at-risk for developmental delays.