Patient Perspective in the Development of Electronic Patient-Reported Outcomes (ePROs) in Seizure Disorders: A Patient-Centric Approach.

BACKGROUND: Patient-centered outcomes research (PCOR) emphasizes the patient perspective and input to inform the research process with the aim to improve the quality of care. Given PCOR's emphasis on the patient perspective, methods to incorporate patient-reported outcomes (PROs) are important. Electronic PROs (ePROs) have been implemented successfully in many populations; however, many of these measurements do not incorporate patient perspective in the development of ePROs. For epilepsy and seizure disorders, user perspectives are key to developing measurements that capture real-time data, as seizures are not timed events; therefore, patients can wait days or even weeks and then try to recall their experience which can lead to variations in recall. ePRO can provide the necessary assurance that data were entered by the patient at the time the episode occurs. The aim of the present study was to assess patient perceptions of completing ePROs, expectations of ePRO devices for PCOR and on-site clinical visit in order to guide the development of successful ePRO deployment in seizure-related disorders. METHODS: This study used a naturalistic cohort design. A sample of 713 persons completed an online survey which consisted of 11 situational questions. Of the 713 individuals, results from 640 participants were included. Results were compared using a Wilcoxon signed-rank test. RESULTS: Most participants (71.9%) were able to accurately identify a seizure and 86.3% of participants felt it would be beneficial to have a short training on seizure symptoms prior to completing a daily seizure diary, and seizures should be reasonably reported within 10 mins (n = 426, 66.6%). Participants endorsed that repetitive movements and loss of consciousness as the most predominant symptoms they would look for in an ePRO. A majority of participants, 67.0% indicated that they regularly use accessibility features on using smartphones and tablets, and 38.6% indicated they would like to see more than one item per screen but only if they are related and to see all text in a larger size with scrolling features using fingers (n = 246; 38.4%). CONCLUSION: This study has demonstrated the importance of developing ePROs that satisfy the needs of the participants and caregivers without compromising the scientific and clinical aspects of the disease construct. Developing tools using participant needs, observations, characteristics and input is essential to putting the participant perspective in patient-centered outcomes research.

Training Subjects On Key Concepts From Patient-Reported Outcomes (PROs) Improves Understanding And Data Accuracy.

OBJECTIVES: The majority of subjects do not understand how to accurately report PRO data due to conceptual misunderstandings. This study demonstrates how even a short 2-sentence instruction can improve subject understanding. METHODS: For this study, 613 subjects completed an online survey, in which they were asked to provide responses to commonly seen PRO questions from various therapeutic areas. Demographic data were also collected. RESULTS: Subjects were provided with scenarios relating to pain severity, the definition of a rescue laxative, reporting stool counts, reporting a bleeding event, and itch severity. After subjects provided an initial response to the question, they were provided with minimal training information consisting of 1-2 sentences and asked to provide a response again to the same question. A 16% increase in mean response accuracy was found amongst all 5 questions evaluated by subjects. CONCLUSION: Patient understanding of PRO items often seen as key endpoints in clinical trials was shown to increase with minimal training thus increasing the accuracy of data collected.

Preferences for Use and Design of Electronic Patient-Reported Outcomes in Patients with Chronic Obstructive Pulmonary Disease.

OBJECTIVES: Collection of patient-reported outcome (PRO) measures is critical to fully understand chronic obstructive pulmonary disease (COPD) management and progression, as the impact on health-related quality of life is not well understood by objective measures alone. Electronic PROs (ePROs) are increasingly used because of their advantages over paper data collection, including elimination of transcription errors, increased accuracy and data quality, real-time data reporting, and increased compliance. The objective of this study was to characterize how patients with COPD prefer to use various types of technology to report disease symptoms, and their preferences for ePRO design and display. METHODS: The sample consisted of subjects with COPD (N = 103) who completed in-person surveys on their ePRO preferences. RESULTS: The majority of subjects prefer to use a form of electronic media over paper to report their disease symptoms. Of these electronic methods, subjects most often prefer to use a smartphone provided by their physician. Subjects were also interested in ePRO features, such as knowing estimated PRO completion time at the outset, tracking their progress in real time as they complete a questionnaire, seeing the data that they report in order to track their health status, being encouraged to complete their diary if they fall behind by positive messaging, and being thanked for their completion of a daily diary. CONCLUSIONS: Investigators should consider including these preferences when designing ePRO assessments. Incorporating patient preferences for ePRO design can ultimately help reduce patient burden and increase engagement, compliance, and improve data quality.

Reduced interhemispheric executive control network coupling in men during early cocaine abstinence: A pilot study.

BACKGROUND: Individuals who use cocaine have fewer cognitive resources needed to maintain abstinence. This is evidenced by blunted brain function during cognitive control tasks and reduced communication between brain regions associated with cognitive function. For instance, relapse vulnerability is heightened in individuals with less communication between the right and left frontoparietal executive control network (ECN). Given that recent cocaine use enhances such communication, it is plausible that recency of cocaine use influences interhemispheric ECN communication. However, it is unclear whether ECN communication weakens over the course of early cocaine abstinence, which may then enhance relapse risk. METHODS: In ten men with cocaine use disorder, we conducted a preliminary assessment of the relationship between the number of days since last cocaine use (1-3days) and interhemispheric ECN coupling using resting state functional magnetic resonance imaging (fMRI). RESULTS: Reduced interhemispheric ECN coupling was associated with increasing days since last cocaine use; weaker coupling was also associated with lower urine cocaine metabolite concentrations. This association was more prominent in prefrontal than parietal ECN-subregions. CONCLUSIONS: Preliminary results indicate that resting state interhemispheric ECN coupling weakens within the first few days following last cocaine use. Because of the known link between reduced ECN interhemispheric coupling and relapse vulnerability, these results suggest that relapse risk may increase the longer an individual abstains during an early quit attempt. Treatments focused on reversing this coupling deficit may facilitate abstinence.

Attentional bias in adults with cannabis use disorders.

There has been modest examination of attentional bias in individuals with cannabis use disorders. Clinical implications of this work are directly relevant to better informing extant evidence-based treatment for substance use disorders (e.g., relapse prevention) and/or developing novel interventions. The overarching aim of this investigation was to examine a novel attentional bias task in adults with cannabis use disorders. Participants were comprised of 25 adults (8 women: M age = 31, SD = 6.8; range = 22-45) with cannabis use disorders (n = 12) and controls (n = 13) without any current (past month) psychopathology. Relative to controls, adults with cannabis use disorders had greater attentional bias scores. These differences were present only at the 125-ms probe time, where the cannabis use disorders group showed greater attentional bias to cannabis cues than the control group (adjusted p = .001, cannabis use disorders mean = 59.9, control mean = -24.8, Cohen's d-effect size for 125 ms = 1.03). The cannabis use disorders group also reported significantly greater perceived stress and post-task stress scores than the control group, but stress was not related to attentional bias. This study informs understanding of the influence of cannabis cues on visual detection and reaction time under different cue-target onset times, as attentional bias was most prevalent under time pressure to detect the probe.

Anti-saccade error rates as a measure of attentional bias in cocaine dependent subjects.

Cocaine-dependent (CD) subjects show attentional bias toward cocaine-related cues, and this form of cue-reactivity may be predictive of craving and relapse. Attentional bias has previously been assessed by models that present drug-relevant stimuli and measure physiological and behavioral reactivity (often reaction time). Studies of several CNS diseases outside of substance use disorders consistently report anti-saccade deficits, suggesting a compromise in the interplay between higher-order cortical processes in voluntary eye control (i.e., anti-saccades) and reflexive saccades driven more by involuntary midbrain perceptual input (i.e., pro-saccades). Here, we describe a novel attentional-bias task developed by using measurements of saccadic eye movements in the presence of cocaine-specific stimuli, combining previously unique research domains to capitalize on their respective experimental and conceptual strengths. CD subjects (N = 46) and healthy controls (N = 41) were tested on blocks of pro-saccade and anti-saccade trials featuring cocaine and neutral stimuli (pictures). Analyses of eye-movement data indicated (1) greater overall anti-saccade errors in the CD group; (2) greater attentional bias in CD subjects as measured by anti-saccade errors to cocaine-specific (relative to neutral) stimuli; and (3) no differences in pro-saccade error rates. Attentional bias was correlated with scores on the obsessive-compulsive cocaine scale. The results demonstrate increased saliency and differential attentional to cocaine cues by the CD group. The assay provides a sensitive index of saccadic (visual inhibitory) control, a specific index of attentional bias to drug-relevant cues, and preliminary insight into the visual circuitry that may contribute to drug-specific cue reactivity.

Demographic and psychological factors associated with lifetime cocaine use: An exploratory factor analysis of baseline questionnaires.

OBJECTIVES: Underlying heterogeneity among individuals with cocaine dependence is widely postulated in the literature, however, identification of a group of factors that explain risk of cocaine use severity has yet to be confirmed. METHODS: Latent mixture modeling evaluated 338 cocaine-dependent individuals recruited from the community to assess the evidence for the presence of distinct subgroups. Variables included 5 baseline questionnaires measuring cognitive function (Shipley), impulsivity (BIS), mood (BDI), affective lability (ALS), and addiction severity (ASI). Results failed to suggest multiple subgroups. Given a lack of evidence for discrete latent classes, an exploratory factor analysis (EFA) followed by exploratory structural equation modeling (ESEM) was implemented to identify functional dimensions to enhance interpretation of these variables. RESULTS: Findings from the EFA indicated a 3-factor model as the best fit, and the subsequent ESEM solution resulted in associations with lifetime cocaine use. Factor 1, best characterized by demographic factors (gender, age), is associated with less lifetime cocaine use. Psychological problems best characterize factor 2, which is associated with higher lifetime cocaine use. Finally, factor 3 is characterized by other substance use (alcohol and marijuana). Although this factor did not demonstrate a statistically reliable relation with self-reported, lifetime cocaine use, it did indicate a potentially meaningful positive association. CONCLUSIONS: These 3 factors delineate dimensions of functioning that likewise help characterize the variability found in previously established associations with self-reported cocaine use.

Optimizing estimation of hemispheric dominance for language using magnetic source imaging.

The efficacy of magnetoencephalography (MEG) as an alternative to invasive methods for investigating the cortical representation of language has been explored in several studies. Recently, studies comparing MEG to the gold standard Wada procedure have found inconsistent and often less-than accurate estimates of laterality across various MEG studies. Here we attempted to address this issue among normal right-handed adults (N=12) by supplementing a well-established MEG protocol involving word recognition and the single dipole method with a sentence comprehension task and a beamformer approach localizing neural oscillations. Beamformer analysis of word recognition and sentence comprehension tasks revealed a desynchronization in the 10-18Hz range, localized to the temporo-parietal cortices. Inspection of individual profiles of localized desynchronization (10-18Hz) revealed left hemispheric dominance in 91.7% and 83.3% of individuals during the word recognition and sentence comprehension tasks, respectively. In contrast, single dipole analysis yielded lower estimates, such that activity in temporal language regions was left-lateralized in 66.7% and 58.3% of individuals during word recognition and sentence comprehension, respectively. The results obtained from the word recognition task and localization of oscillatory activity using a beamformer appear to be in line with general estimates of left hemispheric dominance for language in normal right-handed individuals. Furthermore, the current findings support the growing notion that changes in neural oscillations underlie critical components of linguistic processing.

Trinuclear silver(I) complexes of fluorinated pyrazolates.

Silver pyrazolates [[3-(CF3)Pz]Ag]3, [[3-(CF3),5-(CH3)Pz]Ag]3, [[3-(CF3),5-(Ph)Pz]Ag]3, [[3-(CF3),5-(But)Pz]Ag]3, and [[3-(C3F7),5-(But)Pz]Ag]3 have been synthesized by treatment of the corresponding pyrazole with a slight molar excess of silver(I) oxide. This economical and convenient route gives silver pyrazolates in high (>80%) yields. X-ray crystal structures of [[3-(CF3),5-(CH3)Pz]Ag]3, [[3-(CF3),5-(But)Pz]Ag]3, and [[3-(C3F7),5-(But)Pz]Ag]3 show that these molecules have trinuclear structures with essentially planar to highly distorted Ag3N6 metallacycles. [[3-(CF3),5-(CH3)Pz]Ag]3 forms extended columns via intertrimer argentophilic contacts (the closest Ag...Ag separation between the neighboring trimers are 3.355 and 3.426 A). The trinuclear [[3-(CF3),5-(But)Pz]Ag]3 units crystallize in pairs, basically forming "dimers of trimers", with the six silver atom core of the adjacent trimers adopting a chair conformation. However, in these dimers of trimers, even the shortest intertrimer Ag...Ag distance (3.480 A) is slightly longer than the van der Waals contact of silver (3.44 A). [[3-(C3F7),5-(But)Pz]Ag]3, which has two bulky groups on each pyrazolyl ring, shows no close intertrimer Ag...Ag contacts (closest intertrimer Ag...Ag distance = 5.376 A). The Ag-N bond distances and the intratrimer Ag...Ag separations of the silver pyrazolates do not show much variation. However, their N-Ag-N angles are sensitive to the nature (especially, the size) of substituents on the pyrazolyl rings. The pi-acidic [[3,5-(CF3)2Pz]Ag]3 and [[3-(C3F7),5-(But)Pz]Ag]3 form adducts with the pi-base toluene. X-ray data show that they adopt extended columnar structures of the type [[Ag3]2.[toluene]]infinity and [[Ag3]'.[toluene]]infinity ([[3,5-(CF3)2Pz]Ag]3 = [Ag3],[[3-(C3F7),5-(But)Pz]Ag]3 = [Ag3]'), in which toluene interleaves and makes face-to-face contacts with [[3-(C3F7),5-(But)Pz]Ag]3 or dimers of [[3,5-(CF3)2Pz]Ag]3.