Devick, Katrina L.

AbstractThe role of collaborative biostatisticians and epidemiologists in academic medical centres and how their degree type, supervisor type and sex influences recognition and feelings of respect is poorly understood. We conducted a cross‐sectional survey of self‐identified biostatisticians and epidemiologists working in academic medical centres in the United States or Canada. The survey was sent to 341 contacts at 125 institutions who were asked to forward the survey invitation to faculty and staff at their institution and posted on Community sections of the American Statistical Association website. Participants were asked a variety of questions including if they felt pressured to produce specific results, whether they had intellectual and ethical freedom to pursue appropriate use of statistical methods in collaborative research and if they felt their contributions were appropriately recognized by collaborators. We received responses from 314 biostatisticians or related methodologists. A majority were female (59%), had a doctorate degree (52%) and reported to a statistician or biostatistician supervisor (69%). Overall, most participants felt valued by their collaborators, but that they did not have sufficient calendar time to meet deadlines. Doctoral‐level participants reported more autonomy in their collaborations than master's level participants. Females were less likely to feel recognized and respected compared with males. The survey results suggest that while most respondents felt valued by their collaborators, they have too many projects and need more time to critically review research. Further research is needed to understand why response differs by sex and how these responses fluctuate over time.

AbstractMagnetic resonance imaging (MRI) is a valuable imaging modality for the assessment of both cardiac and non‐cardiac structures. With a growing population of patients with cardiovascular implantable electronic devices (CIEDs), 50%–75% of these patients will need an MRI. MRI‐conditional CIEDs have demonstrated safety of MRI scanning with such devices, yet non‐conditional devices such as hybrid CIEDs which have generator and lead brand mismatch may pose a safety risk. In this retrospective study, we examined the outcomes of patients with hybrid CIEDs undergoing MRI compared to those patients with non‐hybrid CIEDs. A total of 349 patients were included, of which 24 patients (7%) had hybrid CIEDs. The primary endpoint was the safety of MRI for patients with hybrid CIEDs as compared to those with non‐hybrid devices, measured by the rate of adverse events, including death, lead or generator failure needing immediate replacement, loss of capture, new onset arrhythmia, or power‐on reset. Secondary endpoints consisted of pre‐ and post‐MRI changes of decreased P‐wave or R‐wave sensing by ≥50%, changes in pacing lead impedance by ≥50 ohms, increase in pacing thresholds by ≥ 0.5 V at 0.4 ms, and decreasing battery voltage of ≥ 0.04 V. The primary endpoint of any adverse reaction was present in 1 (4.2%) patient with a hybrid device, and consistent of atrial tachyarrhythmia, and in 10 (3.1%) patients with a non‐hybrid device, and consisted of self‐limited atrial and non‐sustained ventricular arrhythmias; this was not statistically significant. No significant differences were found in the secondary endpoints. This study demonstrates that MRI in patients with hybrid CIEDs does not result in increased patient risk or significant device changes when compared to those patients who underwent MRI with non‐hybrid CIEDs.

Greater understanding of the pathways through which an environmental mixture operates is important to design effective interventions. We present new methodology to estimate natural direct and indirect effects and controlled direct effects of a complex mixture exposure on an outcome through a mediator variable. We implement Bayesian Kernel Machine Regression (BKMR) to allow for all possible interactions and nonlinear effects of (1) the co‐exposures on the mediator, (2) the co‐exposures and mediator on the outcome, and (3) selected covariates on the mediator and/or outcome. From the posterior predictive distributions of the mediator and outcome, we simulate counterfactuals to obtain posterior samples, estimates, and credible intervals of the mediation effects. Our simulation study demonstrates that when the exposure‐mediator and exposure‐mediator‐outcome relationships are complex, BKMR‐Causal Mediation Analysis performs better than current mediation methods. We applied our methodology to quantify the contribution of birth length as a mediator between in utero co‐exposure to arsenic, manganese, and lead, and children's neurodevelopmental scores, in a prospective birth cohort in Bangladesh. Among younger children, we found a negative (adverse) association between the metal mixture and neurodevelopment. We also found evidence that birth length mediates the effect of exposure to the metal mixture on neurodevelopment for younger children. If birth length were fixed to its percentile value, the harmful effect of the metal mixture on neurodevelopment is attenuated, suggesting nutritional interventions to help increase fetal growth, and thus birth length, could potentially block the harmful effect of the metal mixture on neurodevelopment.

AbstractIntroductionCaregivers of patients with frontotemporal lobar degeneration (FTLD) spectrum disorders experience tremendous burden, which has been associated with the neuropsychiatric and behavioral features of the disorders.MethodsIn a sample of 558 participants with FTLD spectrum disorders, we performed multiple‐variable regressions to identify the behavioral features that were most strongly associated with caregiver burden, as measured by the Zarit Burden Interview, at each stage of disease.ResultsApathy and disinhibition, as rated by both clinicians and caregivers, as well as clinician‐rated psychosis, showed the strongest associations with caregiver burden, a pattern that was consistent when participants were separated cross‐sectionally by disease stage. In addition, behavioral features appeared to contribute most to caregiver burden in patients with early dementia.DiscussionCaregivers should be provided with early education on the management of the behavioral features of FTLD spectrum disorders. Interventions targeting apathy, disinhibition, and psychosis may be most useful to reduce caregiver burden.

Abstract At present, no research criteria exist for the diagnosis of prodromal behavioural variant frontotemporal dementia (bvFTD), though early detection is of high research importance. Thus, we sought to develop and validate a proposed set of research criteria for prodromal bvFTD, termed ‘mild behavioural and/or cognitive impairment in bvFTD’ (MBCI-FTD). Participants included 72 participants deemed to have prodromal bvFTD; this comprised 55 carriers of a pathogenic mutation known to cause frontotemporal lobar degeneration, and 17 individuals with autopsy-confirmed frontotemporal lobar degeneration. All had mild behavioural and/or cognitive changes, as judged by an evaluating clinician. Based on extensive clinical workup, the prodromal bvFTD group was divided into a Development Group (n = 22) and a Validation Group (n = 50). The Development Group was selected to be the subset of the prodromal bvFTD group for whom we had the strongest longitudinal evidence of conversion to bvFTD, and was used to develop the MBCI-FTD criteria. The Validation Group was the remainder of the prodromal bvFTD group and was used as a separate sample on which to validate the criteria. Familial non-carriers were included as healthy controls (n = 165). The frequencies of behavioural and neuropsychiatric features, neuropsychological deficits, and social cognitive dysfunction in the prodromal bvFTD Development Group and healthy controls were assessed. Based on sensitivity and specificity analyses, seven core features were identified: apathy without moderate-severe dysphoria, behavioural disinhibition, irritability/agitation, reduced empathy/sympathy, repetitive behaviours (simple and/or complex), joviality/gregariousness, and appetite changes/hyperorality. Supportive features include a neuropsychological profile of impaired executive function or naming with intact orientation and visuospatial skills, reduced insight for cognitive or behavioural changes, and poor social cognition. Three core features or two core features plus one supportive feature are required for the diagnosis of possible MBCI-FTD; probable MBCI-FTD requires imaging or biomarker evidence, or a pathogenic genetic mutation. The proposed MBCI-FTD criteria correctly classified 95% of the prodromal bvFTD Development Group, and 74% of the prodromal bvFTD Validation Group, with a false positive rate of <10% in healthy controls. Finally, the MBCI-FTD criteria were tested on a cohort of individuals with prodromal Alzheimer’s disease, and the false positive rate of diagnosis was 11–16%. Future research will need to refine the sensitivity and specificity of these criteria, and incorporate emerging biomarker evidence.

Percutaneous transendocardial injections of therapeutic agents into the myocardium may not always be effective. We used an animal model for assessing the efficacy of the injections using linoleic acid as a testing agent. Efficacious delivery into the myocardium of a beating heart was indicated by rapidly developed local myocardial necrosis and wall motion abnormalities using echocardiography. We employed this experimental model to test our innovative technology, an acoustically active injection catheter. The Doppler ultrasound‐guided acoustically active injection catheter effectively delivers the substance to the myocardium but needs further technical improvements to minimize an unwanted systemic distribution of the agent.

AbstractBackgroundOne nonpharmacological intervention for persons with amnestic Mild Cognitive Impairment (MCI) is development of a compensatory memory notebook/planner system. De Wit et al. (2019) showed that global cognitive status is the primary predictor of learning success with training on a memory notebook system and that learning success predicts ongoing adherence to the tool. The purpose of our work is to validate their analysis in a new sample and evaluate whether or not patient or partner personality traits predict learning success over and above that explained by cognitive status.MethodTraining in the Memory Support System (MSS) is one component of the multi‐disciplinary behavioral intervention program called Healthy Action to Benefit Independence and Thinking (HABIT) offered at Mayo Clinic. 183 patient and partner dyads completed the HABIT program and enrolled in our IRB approved ongoing research registry to allow use of their clinical data for research purposes. Personality traits were measured with the self‐report Ten Item Personality Inventory (TIPI) based on the five‐factor model of personality (Agreeableness, Conscientiousness, Emotional Stability, Openness, and Extraversion) completed by both the patient and the partner. For our analyses, we fit logistic regression models to predict full MSS mastery at the end of the two‐week program and dichotomized TIPI into “high” or “low” for each trait based on its median (low was the reference group).ResultConsistent with De Wit et al. (2019), global cognitive status again was the only significant predictor of MSS learning mastery when considering age, education, baseline depression score and baseline global cognitive status (Table 2). When adding patient personality traits, only openness significantly added to the model with higher openness predicting learning success (Table 3). Adding both patient and partner personality traits resulted in a significant interaction between patient and partner openness (Table 4). The direction of this interaction indicates that learning success is highest when either the partner or patient is high in openness (but not both).ConclusionHigh openness to experience in the patient with MCI or their partner (but not both) significantly improves learning success for a cognitive rehabilitation memory support tool in patients with MCI.