Dysnomia may be one of the earlier neuropsychological signs of Alzheimer’ disease (Cullum & Liff, 2014), making it an essential part of dementia evaluations. The Verbal Naming (VNT) is a verbal naming-to-definition task designed to assess possible dysnomia in older adults (Yochim et al., 2015) and has been used as an alternative to tasks that predominately rely on picture-naming paradigms. These researchers investigated the influences of age, educational level, cognitive diagnosis, educational quality, and race to examine if race would be a remaining significant factor in the performance of the VNT.

Black (n=57) and White (n=127) participant data were collected during clinical neuropsychological evaluations, which included the VNT alongside other cognitive measures. A multiple regression was utilized controlling for age, educational level, cognitive diagnosis, educational quality via reading level, and race to investigate if race would remain a significant predictor of test performance.

Results suggested that race was still a significant predictor (p = .003) of VNT scores despite efforts to control other sources of variance. Additionally, other cognitive measures such as WAIS-IV Block Design (p = .004) and D-KEFS Tower Test (p = .004) also showed statistically significant relationships with race in the same model, whereas verbal memory (CVLT) and verbal fluency (D-KEFS) did not. The NAB Naming analysis violated the assumption of homoscedasticity; therefore, results with the NAB Naming test were not further interpreted.

These results suggest that race is a significant predictor of performance on some cognitive measures, including the VNT. However, it did not predict performance on verbal memory or verbal fluency. Future investigations of racial differences on neuropsychological test performance would benefit from consideration of variables that may account for discrepancies between White and Black examinees. Several proxy variables could include educational quality, acculturation, and economic status.

Real-world data, such as administrative claims and electronic health records, are increasingly used for safety monitoring and to help guide regulatory decision-making. In these settings, it is important to document analytic decisions transparently and objectively to assess and ensure that analyses meet their intended goals.

The Causal Roadmap is an established framework that can guide and document analytic decisions through each step of the analytic pipeline, which will help investigators generate high-quality real-world evidence.

In this paper, we illustrate the utility of the Causal Roadmap using two case studies previously led by workgroups sponsored by the Sentinel Initiative – a program for actively monitoring the safety of regulated medical products. Each case example focuses on different aspects of the analytic pipeline for drug safety monitoring. The first case study shows how the Causal Roadmap encourages transparency, reproducibility, and objective decision-making for causal analyses. The second case study highlights how this framework can guide analytic decisions beyond inference on causal parameters, improving outcome ascertainment in clinical phenotyping.

These examples provide a structured framework for implementing the Causal Roadmap in safety surveillance and guide transparent, reproducible, and objective analysis.

Recent well-powered genome-wide association studies have enhanced prediction of substance use outcomes via polygenic scores (PGSs). Here, we test (1) whether these scores contribute to prediction over-and-above family history, (2) the extent to which PGS prediction reflects inherited genetic variation v. demography (population stratification and assortative mating) and indirect genetic effects of parents (genetic nurture), and (3) whether PGS prediction is mediated by behavioral disinhibition prior to substance use onset.

PGSs for alcohol, cannabis, and nicotine use/use disorder were calculated for Minnesota Twin Family Study participants (N = 2483, 1565 monozygotic/918 dizygotic). Twins' parents were assessed for histories of substance use disorder. Twins were assessed for behavioral disinhibition at age 11 and substance use from ages 14 to 24. PGS prediction of substance use was examined using linear mixed-effects, within-twin pair, and structural equation models.

Nearly all PGS measures were associated with multiple types of substance use independently of family history. However, most within-pair PGS prediction estimates were substantially smaller than the corresponding between-pair estimates, suggesting that prediction is driven in part by demography and indirect genetic effects of parents. Path analyses indicated the effects of both PGSs and family history on substance use were mediated via disinhibition in preadolescence.

PGSs capturing risk of substance use and use disorder can be combined with family history measures to augment prediction of substance use outcomes. Results highlight indirect sources of genetic associations and preadolescent elevations in behavioral disinhibition as two routes through which these scores may relate to substance use.

The Verbal Naming Test (VNT) is an auditory-based measure of naming or word finding. The current multisite study sought to evaluate the reliability and validity of the VNT in the detection of major and mild neurocognitive disorder (NCD).

This study analyzed clinical data from two outpatient neuropsychology clinics (N = 188 and N = 77) and a geriatric primary care clinic (N = 104). Cronbach’s alpha and Spearman correlations with other measures were calculated. ROC analyses were used to calculate sensitivity, specificity, positive predictive power, and negative predictive power for the detection of major and mild NCD per DSM-5 (Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition) criteria.

The VNT was found to have strong reliability (Cronbach’s alpha = .90) and high convergent validity with a commonly used picture-naming task (NAB Naming, Spearman’s rho = .65, p < .001). The VNT showed good sensitivity and specificity for the detection of NCDs, particularly major NCD, with an area under the curve of .85, sensitivity of .80, and specificity of .75. A possible discontinue rule is also suggested for clinicians to use.

These findings provide compelling evidence for the use of the VNT to detect neurocognitive impairment in a clinical setting. The VNT provides a reliable alternative to picture-naming tasks, which may be advantageous when working with visually impaired patients or conducting evaluations over telehealth.

The aim of the present study was to evaluate the association between depression and SSRI monotherapy and frailty both baseline and prospectively in older adults.

Prospective cohort study, 12-month follow-up.

Geriatric outpatient clinic in São Paulo, Brazil.

A total of 811 elderly adults aged 60 or older.

Depression was diagnosed as follows: (1) a diagnosis of major depression disorder (MDD) according to DSM-5; or (2) an incomplete diagnosis of MDD, referred to as minor or subsyndromic depression, plus Geriatric Depression Scale 15-itens ≥ 6 points, and social or functional impairment secondary to depressive symptoms and observed by relatives. Frailty evaluation was performed through the FRAIL questionnaire, which is a self-rated scale. Trained investigators blinded to the baseline assessment conducted telephone calls to evaluate frailty after 12-month follow-up. The association between depression and the use of SSRI with frailty was estimated through a generalized estimating equation adjusted for age, gender, total drugs, and number of comorbidities.

Depression with SSRI use was associated with frailty at baseline (OR 2.82, 95% CI = 1.69–4.69) and after 12 months (OR 2.75, 95% CI = 1.84–4.11). Additionally, depression with SSRI monotherapy was also associated with FRAIL subdomains Physical Performance (OR 1.99, 95% CI = 1.29–3.07) and Health Status (OR 4.64, 95% CI = 2.11–10.21). SSRI use, without significant depressive symptoms, was associated with subdomain Health Status (OR 1.52, 95% CI = 1.04–2.23).

It appears that depression with SSRI is associated to frailty, and this association cannot be explained only by antidepressant use.

Rapid identification of esophageal intubations is critical to avoid patient morbidity and mortality. Continuous waveform capnography remains the gold standard for endotracheal tube (ETT) confirmation, but it has limitations. Point-of-care ultrasound (POCUS) may be a useful alternative for confirming ETT placement. The objective of this study was to determine the accuracy of paramedic-performed POCUS identification of esophageal intubations with and without ETT manipulation.

A prospective, observational study using a cadaver model was conducted. Local paramedics were recruited as subjects and each completed a survey of their demographics, employment history, intubation experience, and prior POCUS training. Subjects participated in a didactic session in which they learned POCUS identification of ETT location. During each study session, investigators randomly placed an ETT in either the trachea or esophagus of four cadavers, confirmed with direct laryngoscopy. Subjects then attempted to determine position using POCUS both without and with manipulation of the ETT. Manipulation of the tube was performed by twisting the tube. Descriptive statistics and logistic regression were used to assess the results and the effects of previous paramedic experience.

During 12 study sessions, from March 2014 through December 2015, 57 subjects participated, evaluating a total of 228 intubations: 113 tracheal and 115 esophageal. Subjects were 84.0% male, mean age of 39 years (range: 22 - 62 years), with median experience of seven years (range: 0.6 - 39 years). Paramedics correctly identified ETT location in 158 (69.3%) cases without and 194 (85.1%) with ETT manipulation. The sensitivity and specificity of identifying esophageal location without ETT manipulation increased from 52.2% (95% confidence interval [CI], 43.0-61.0) and 86.7% (95% CI, 81.0-93.0) to 87.0% (95% CI, 81.0-93.0) and 83.2% (95% CI, 0.76-0.90) after manipulation (P<.0001), without affecting specificity (P=.45). Subjects correctly identified 41 previously incorrectly identified esophageal intubations. Paramedic experience, previous intubations, and POCUS experience did not correlate with ability to identify tube location.

Paramedics can accurately identify esophageal intubations with POCUS, and manipulation improves identification. Further studies of paramedic use of dynamic POCUS to identify inadvertent esophageal intubations are needed.

LemaPC, O’BrienM, WilsonJ, St. JamesE, LindstromH, DeAngelisJ, CaldwellJ, MayP, ClemencyB.Avoid the Goose! Paramedic Identification of Esophageal Intubation by Ultrasound. Prehosp Disaster Med.2018;33(4):406–410

A stepped care approach involves patients first receiving low-intensity treatment followed by higher intensity treatment. This two-step randomized controlled trial investigated the efficacy of a sequential stepped care approach for the psychological treatment of binge-eating disorder (BED).

In the first step, all participants with BED (n = 135) received unguided self-help (USH) based on a cognitive-behavioral therapy model. In the second step, participants who remained in the trial were randomized either to 16 weeks of group psychodynamic-interpersonal psychotherapy (GPIP) (n = 39) or to a no-treatment control condition (n = 46). Outcomes were assessed for USH in step 1, and then for step 2 up to 6-months post-treatment using multilevel regression slope discontinuity models.

In the first step, USH resulted in large and statistically significant reductions in the frequency of binge eating. Statistically significant moderate to large reductions in eating disorder cognitions were also noted. In the second step, there was no difference in change in frequency of binge eating between GPIP and the control condition. Compared with controls, GPIP resulted in significant and large improvement in attachment avoidance and interpersonal problems.

The findings indicated that a second step of a stepped care approach did not significantly reduce binge-eating symptoms beyond the effects of USH alone. The study provided some evidence for the second step potentially to reduce factors known to maintain binge eating in the long run, such as attachment avoidance and interpersonal problems.