The ability to remotely monitor cognitive skills is increasing with the ubiquity of smartphones. The Mobile Toolbox (MTB) is a new measurement system that includes measures assessing Executive Functioning (EF) and Processing Speed (PS): Arrow Matching, Shape-Color Sorting, and Number-Symbol Match. The purpose of this study was to assess their psychometric properties.

MTB measures were developed for smartphone administration based on constructs measured in the NIH Toolbox® (NIHTB). Psychometric properties of the resulting measures were evaluated in three studies with participants ages 18 to 90. In Study 1 (N = 92), participants completed MTB measures in the lab and were administered both equivalent NIH TB measures and other external measures of similar cognitive constructs. In Study 2 (N = 1,021), participants completed the equivalent NIHTB measures in the lab and then took the MTB measures on their own, remotely. In Study 3 (N = 168), participants completed MTB measures twice remotely, two weeks apart.

All three measures exhibited very high internal consistency and strong test-retest reliability, as well as moderately high correlations with comparable NIHTB tests and moderate correlations with external measures of similar constructs. Phone operating system (iOS vs. Android) had a significant impact on performance for Arrow Matching and Shape-Color Sorting, but no impact on either validity or reliability.

Results support the reliability and convergent validity of MTB EF and PS measures for use across the adult lifespan in remote, self-administered designs.

Diagnosis of acute ischemia typically relies on evidence of ischemic lesions on magnetic resonance imaging (MRI), a limited diagnostic resource. We aimed to determine associations of clinical variables and acute infarcts on MRI in patients with suspected low-risk transient ischemic attack (TIA) and minor stroke and to assess their predictive ability.

We conducted a post-hoc analysis of the Diagnosis of Uncertain-Origin Benign Transient Neurological Symptoms (DOUBT) study, a prospective, multicenter cohort study investigating the frequency of acute infarcts in patients with low-risk neurological symptoms. Primary outcome parameter was defined as diffusion-weighted imaging (DWI)-positive lesions on MRI. Logistic regression analysis was performed to evaluate associations of clinical characteristics with MRI-DWI-positivity. Model performance was evaluated by Harrel’s c-statistic.

In 1028 patients, age (Odds Ratio (OR) 1.03, 95% Confidence Interval (CI) 1.01–1.05), motor (OR 2.18, 95%CI 1.27–3.65) or speech symptoms (OR 2.53, 95%CI 1.28–4.80), and no previous identical event (OR 1.75, 95%CI 1.07–2.99) were positively associated with MRI-DWI-positivity. Female sex (OR 0.47, 95%CI 0.32–0.68), dizziness and gait instability (OR 0.34, 95%CI 0.14–0.69), normal exam (OR 0.55, 95%CI 0.35–0.85) and resolved symptoms (OR 0.49, 95%CI 0.30–0.78) were negatively associated. Symptom duration and any additional symptoms/symptom combinations were not associated. Predictive ability of the model was moderate (c-statistic 0.72, 95%CI 0.69–0.77).

Detailed clinical information is helpful in assessing the risk of ischemia in patients with low-risk neurological events, but a predictive model had only moderate discriminative ability. Patients with clinically suspected low-risk TIA or minor stroke require MRI to confirm the diagnosis of cerebral ischemia.

Pediatric medical devices lag behind adult devices due to economic barriers, smaller patient populations, changing anatomy and physiology of patients, regulatory hurdles, and especially difficulties in executing clinical trials. We investigated the requirements, challenges, associated timeline, and costs of conducting a multi-site pivotal clinical trial for a Class II pediatric physiologic monitoring device.

This case study focused on the negotiation of clinical trial agreements (CTAs), budgets, and Institutional Review Board (IRB) processing times for a pediatric device trial. We identified key factors contributing to delays in clinical trial execution and potential best practices to expedite the process while maintaining safety, ethics, and efficacy.

The total time from site contact to first patient enrollment averaged 14 months. CTA and budget negotiations were the most time-consuming processes, averaging nearly 10 and 9 months, respectively. Reliance and local IRB processing also contributed significantly to the timeline, overall adding an average of 6.5 months across institutions. Nearly half of all costs were devoted to regulatory oversight. The COVID-19 pandemic caused significant slowdowns and delays at multiple institutions during study enrollment. Despite these pandemic-induced delays, it is important to note that the issues and themes highlighted remain relevant and have post-pandemic applicability.

Our case study results underscore the importance of establishing efficient and standardized processing of CTAs, budget negotiations, and use of reliance IRBs to expedite clinical trial execution for pediatric devices. The findings also highlight the need for a national clinical trials network to streamline the clinical trial process.

Evidence for necrotising otitis externa (NOE) diagnosis and management is limited, and outcome reporting is heterogeneous. International best practice guidelines were used to develop consensus diagnostic criteria and a core outcome set (COS).

The study was pre-registered on the Core Outcome Measures in Effectiveness Trials (COMET) database. Systematic literature review identified candidate items. Patient-centred items were identified via a qualitative study. Items and their definitions were refined by multidisciplinary stakeholders in a two-round Delphi exercise and subsequent consensus meeting.

The final COS incorporates 36 items within 12 themes: Signs and symptoms; Pain; Advanced Disease Indicators; Complications; Survival; Antibiotic regimes and side effects; Patient comorbidities; Non-antibiotic treatments; Patient compliance; Duration and cessation of treatment; Relapse and readmission; Multidisciplinary team management.

Consensus diagnostic criteria include 12 items within 6 themes: Signs and symptoms (oedema, otorrhoea, granulation); Pain (otalgia, nocturnal otalgia); Investigations (microbiology [does not have to be positive], histology [malignancy excluded], positive CT and MRI); Persistent symptoms despite local and/or systemic treatment for at least two weeks; At least one risk factor for impaired immune response; Indicators of advanced disease (not obligatory but mut be reported when present at diagnosis). Stakeholders were unanimous that there is no role for secondary, graded, or optional diagnostic items. The consensus meeting identified themes for future research.

The adoption of consensus-defined diagnostic criteria and COS facilitates standardised research reporting and robust data synthesis. Inclusion of patient and professional perspectives ensures best practice stakeholder engagement.

Psychological therapies can be effective in reducing symptoms of depression and anxiety in people living with dementia (PLWD). However, factors associated with better therapy outcomes in PLWD are currently unknown.

To investigate whether dementia-specific and non-dementia-specific factors are associated with therapy outcomes in PLWD.

National linked healthcare records were used to identify 1522 PLWD who attended psychological therapy services across England. Associations between various factors and therapy outcomes were explored.

People with frontotemporal dementia were more likely to experience reliable deterioration in depression/anxiety symptoms compared with people with vascular dementia (odds ratio 2.98, 95% CI 1.08–8.22; P = 0.03) or Alzheimer's disease (odds ratio 2.95, 95% CI 1.15–7.55; P = 0.03). Greater depression severity (reliable recovery: odds ratio 0.95, 95% CI 0.92–0.98, P < 0.001; reliable deterioration: odds ratio 1.73, 95% CI 1.04–2.90, P = 0.04), lower work and social functioning (recovery: odds ratio 0.98, 95% CI 0.96–0.99, P = 0.002), psychotropic medication use (recovery: odds ratio 0.67, 95% CI 0.51–0.90, P = 0.01), being of working age (recovery: odds ratio 2.03, 95% CI 1.10–3.73, P = 0.02) and fewer therapy sessions (recovery: odds ratio 1.12, 95% CI 1.09–1.16, P < 0.001) were associated with worse therapy outcomes in PLWD.

Dementia type was generally not associated with outcomes, whereas clinical factors were consistent with those identified for the general population. Additional support and adaptations may be required to improve therapy outcomes in PLWD, particularly in those who are younger and have more severe depression.

Incidence of first-episode psychosis (FEP) varies substantially across geographic regions. Phenotypes of subclinical psychosis (SP), such as psychotic-like experiences (PLEs) and schizotypy, present several similarities with psychosis. We aimed to examine whether SP measures varied across different sites and whether this variation was comparable with FEP incidence within the same areas. We further examined contribution of environmental and genetic factors to SP.

We used data from 1497 controls recruited in 16 different sites across 6 countries. Factor scores for several psychopathological dimensions of schizotypy and PLEs were obtained using multidimensional item response theory models. Variation of these scores was assessed using multi-level regression analysis to estimate individual and between-sites variance adjusting for age, sex, education, migrant, employment and relational status, childhood adversity, and cannabis use. In the final model we added local FEP incidence as a second-level variable. Association with genetic liability was examined separately.

Schizotypy showed a large between-sites variation with up to 15% of variance attributable to site-level characteristics. Adding local FEP incidence to the model considerably reduced the between-sites unexplained schizotypy variance. PLEs did not show as much variation. Overall, SP was associated with younger age, migrant, unmarried, unemployed and less educated individuals, cannabis use, and childhood adversity. Both phenotypes were associated with genetic liability to schizophrenia.

Schizotypy showed substantial between-sites variation, being more represented in areas where FEP incidence is higher. This supports the hypothesis that shared contextual factors shape the between-sites variation of psychosis across the spectrum.

Evidence development for medical devices is often focused on satisfying regulatory requirements with the result that health professional and payer expectations may not be met, despite considerable investment in clinical trials. Early engagement with payers and health professionals could allow companies to understand these expectations and reflect them in clinical study design, increasing chances of positive coverage determination and adoption into clinical practice.

An example of early engagement through the EXCITE International model using an early technology review (ETR) is described which includes engagement with payers and health professionals to better inform companies to develop data that meet their expectations. ETR is based on an early evidence review, a framework of expectations that guides the process and identified gaps in evidence. The first fourteen ETRs were reviewed for examples of advice to companies that provided additional information from payers and health professionals that was thought likely to impact on downstream outcomes or strategic direction. Given that limitations were imposed by confidentiality, examples were genericized.

Advice through early engagement can inform evidence development that coincides with expectations of payers and health professionals through a structured, objective, evidence-based approach. This could reduce the risk of business-related adverse outcomes such as failure to secure a positive coverage determination and/or acceptance by expert health professionals.

Early engagement with key stakeholders exemplified by the ETR approach offers an alternative to the current approach of focusing on regulatory expectations. This could reduce the time to reimbursement and clinical adoption and benefit patient outcomes and/or health system efficiencies.

Return to driving after moderate-to-severe traumatic brain injury (TBI) is often a key step in recovery to regain independence. Survivors are often eager to resume driving and may do so despite having residual cognitive limitations from their injury. A better understanding is needed of how cognition and self-awareness impact survivors’ driving after injury. This study examined the influence of cognition and self-awareness on driving patterns following moderate-to-severe TBI.

Participants were 350 adults aged 19-87 years (mean age = 46 years; 70% male) with history of moderate-to-severe TBI, who resumed driving and were enrolled in the TBI Model System. Cross-sectional data were obtained ranging 1-30 years post injury, including questions on driving practices, the Brief Test of Adult Cognition by Telephone (BTACT), and the Functional Independence Measure (FIM). Self-awareness of cognitive function was measured via the discrepancy between dichotomized ratings (intact versus impaired) of objective cognitive testing (BTACT) and self-reported cognitive function (FIM Cognition subscale). Driving patterns included frequency (driving 'more than once a week’ versus 'once a week or less') and restricted driving behavior (total number of driving situations the survivor described as restricted, ranging 0-15). Regression analyses were conducted to examine the relationships between cognition, self-awareness, and each driving outcome (frequency and restriction), followed by causal mediation analyses to examine the mediating effect of self-awareness. Demographics (age, sex, education), injury characteristics (time since injury, injury severity, history of seizures in past year), and medical/social factors (family income, motor function, urban-rural classification) were included in the models as covariates.

Thirty-nine percent of survivors had impaired self-awareness, 88% of survivors drove numerous times per week, and the average survivor reported limited driving in 6 situations (out of 15 total situations). Cognition was inversely related to impaired self-awareness (OR = 0.03, p < 0.001) and inversely related to restricted driving behavior (b = -0.79, p < 0.001). Motor function was positively related to impaired self-awareness (OR = 1.28, p < 0.01). Cognition was not related to driving frequency, and self-awareness did not mediate the relationships between cognition and driving patterns (all p > 0.05).

Most survivors who drive after their injury are driving frequently, but the situations they drive in differ based on their cognitive ability. Impaired self-awareness of cognitive deficits is common after TBI, and self-awareness of cognitive function does not affect driving patterns. Future research needs to focus on how cognition affects nuanced aspects of driving behavior after injury (i.e., types of situations survivors drive in).

A critical need in the neuropsychology field is development and validation of efficient, scalable assessments of cognition. The Mobile Toolbox (MTB), a novel suite of mobile device-compatible, app-based cognitive assessments, was developed to address this need. The goals of this study were (1) To collect longitudinal normative data for the MTB assessments in a large, ethnoculturally and educationally diverse cohort; (2) To assess the feasibility and usability of remote assessment using MTB.

Participants were recruited from the UCSF Brain Health Registry (BHR), an online cohort (N>100,000) that collects longitudinal cognitive, functional, behavioral, and health data using online neuropsychological tests and self- and study-partner report surveys. BHR participants who opted to learning about additional research opportunities were sent automated email invitations to enroll in the MTB study. Those who indicated study interest were provided instructions within the BHR online portal for downloading the MTB app. All participants had the opportunity to complete a single baseline administration of MTB (Word Meaning, Sequences, Spelling, Arranging Pictures, Arrow Matching, Faces and Names, Shape-Color Sorting, Number Match). Those who completed the baseline assessment within three days were invited to continue into the longitudinal study, where they complete MTB assessments at a single, short-term timepoint (day 7, 14, or 21; study arms sequentially assigned), and then at 6-month intervals. Enrollment across demographic groups was monitored, and study invitations were sent to specific demographic groups, with the goal of enrolling a sample of 800 participants in the longitudinal study: equal distribution across eight, 10-year age bands (ages 18-80+); 60% with <16 years of education; 10% non-Latinx Black, 15% Latinx, and 5% non-White other ethnocultural identity.

Between January-June 2022, 48,110 BHR participants were invited to the MTB study. Of those, 8294 (17%) expressed interest, 3401 (7%) completed the baseline assessment, 850 (1.8%) were assigned to the longitudinal study, and 782 (1.6%) completed a short-term longitudinal assessment. Study staff received 797 help tickets submitted by participants asking for email support to complete MTB. The baseline cohort had and average age of 64 years and an average of 16.6 years of education, 76.2% female, 2.1% non-Latinx Black, 7.1% Latinx, 86.8% non-Latinx White, and 4% from other ethnocultural groups. The longitudinal cohort had an average age of 62.3 years and an average of 16.1 years of education, 80% female, 2.8% non-Latinx Black, 8.5% Latinx, 83.5% non-Latinx White; and 5% other ethnocultural group. Compared to those invited to the study, those who enrolled in the longitudinal study were older, had higher educational attainment, and were more likely to be female and self-identify as non-Latinx White (p<0.05 for all).

Efficient enrollment and task completion of a large cohort in a novel, app-based mobile cognitive assessment is feasible in a completely remote setting. Most participants were able to complete MTB without individual support, indicating good usability. This approach can be scaled up to efficiently assess cognition in many research and healthcare settings. A remaining challenge is achieving robust ethnocultural and educational diversity.

Essential tremor (ET) is the most common movement disorder, characterized by bilateral action tremors of the upper extremities. Surgical interventions can be considered for severe cases that are refractory to medication. Magnetic resonance-guided focused ultrasound (MRgFUS) of the ventral intermediate nucleus of the thalamus (Vim) is a recently approved, minimally invasive treatment for unilateral tremor. While patients are generally pleased with unilateral treatment, many patients are bothered by tremor on the untreated side. Historically, bilateral thalamotomy has been associated with a higher rate of adverse events, including cognitive impairment. MRgFUS Vim thalamotomy for bilateral tremor is currently being investigated. The goal of the present study was to evaluate the effect of bilateral MRgFUS Vim thalamotomy on cognition.

Twelve patients with medication-refractory essential tremor (mean age = 68.77 +/- 11.78 years, mean education = 14.34 +/- 2.71 years, 8 male) were included in the present study. Three of the 12 patients met criteria for mild cognitive impairment (MCI). All patients successfully underwent unilateral MRgFUS thalamotomy at least 48 weeks before the second thalamotomy. A battery of neuropsychological tests was administered to patients before (considered baseline in the present study) and three months following the second thalamotomy. Baseline evaluations occurred on average 144.64 +/- 91.53 weeks (range: 55.00 - 346.58) after the first thalamotomy. The neuropsychological battery assessed domains of processing speed (Oral Symbol Digit Modalities Test, D-KEFS Color-Word Naming and Reading), attention (WAIS-IV Digit Span Forward), executive function (D-KEFS Color-Word Inhibition and Inhibition/Switching), working memory (WAIS-IV Digit Span Backward and Sequencing), verbal fluency (D-KEFS Letter Fluency and Animal Fluency), confrontation naming (Boston Naming Test), verbal memory (Hopkins Verbal Learning Test-Revised), and visuospatial perception (Judgment of Line Orientation). Alternate versions of tests were used when possible. Cognitive changes were analyzed at the group and individual level. Group level changes were assessed with paired sample t-tests (corrected for multiple comparisons). At the individual level, postoperative declines > 1.5 SD from baseline were considered clinically significant.

Participants’ baseline intellectual functioning ranged from low average to superior (as measured by the WTAR). The mean baseline score on the Montreal Cognitive Assessment was 24.58 (range: 17 - 30). At the group level, there were no significant changes in cognitive scores from baseline to follow-up (all p values > 0.635). At the individual level, one patient with MCI declined > 1.5 SD on the verbal memory composite. No other patients showed declines > 1.5 SD.

Our preliminary findings suggest that bilateral MRgFUS Vim thalamotomy is relatively safe from a cognitive perspective. However, a single patient with MCI exhibited clinically significant postoperative decline in verbal memory. Future studies with larger sample sizes are needed to investigate the factors that increase the risk of postoperative cognitive decline, including pre-existing cognitive impairment, older age, and lesion size.