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Decentralized clinical trials (DCTs) have the potential to increase pace and reach of recruitment as well as to improve sample representation, compared to traditional in-person clinical trials. However, concerns linger regarding data integrity in DCTs due to threats of fraud and sampling bias. The purpose of this report is to describe two tools that we have developed and successfully implemented to combat these threats. Cheatblocker and QuotaConfig are two external modules that we have made publicly available within the REDCap data capture system to target fraud and sampling bias, respectively. We describe the modules, present two case examples in which we used the modules successfully, and discuss the potential impact of tools such as these on data integrity in DCTs. We situate this discussion within the broader landscape of translational science wherein we strive to improve research rigor and efficiency to maximize public health benefit.
Decentralized clinical trials (DCTs) are often hindered by challenges in remotely capturing biomarkers. To address this gap, we developed MyTrials, a mobile application integrated with REDCap, designed to facilitate the remote capture of biomarkers via Bluetooth-enabled remote patient monitoring (RPM) devices. The purpose of the present study was to evaluate the feasibility and acceptability of MyTrials among participants within a DCT design.
Methods:
In this four-arm randomized trial, 47 participants were allocated to receive zero, one, two, or three RPM devices. Participants were asked to use their devices once per week for a total of four weeks to remotely provide biomarkers via MyTrials. Feasibility was assessed using objective metrics of successful biomarker submission (i.e., valid device data accompanied by a video confirming participant identity) alongside the participant-reported Feasibility of Intervention Measure (FIM). Acceptability was evaluated via the Acceptability of Intervention Measure (AIM) and the System Usability Scale (SUS).
Results:
Among participants assigned at least one device, the successful biomarker submission rate was 74% across all study weeks. FIM and AIM scores exceeded prespecified feasibility benchmarks across all conditions except the zero-device condition. SUS scores consistently indicated high usability across all conditions (range: 77.29–94.29).
Conclusions:
The MyTrials platform is a feasible and acceptable solution for remote biomarker capture in DCTs. These findings support the potential of MyTrials to advance remote data collection in clinical research.
We investigated differences in cognition between variants of progressive supranuclear palsy (PSP) including PSP-Richardson (PSP-RS) and subcortical and cortical variants using updated diagnostic criteria and comprehensive neuropsychological assessment.
Method:
We recruited 140 participants with PSP (age = 71.3 ± 6.9 years; education = 15.0 ± 2.8 years; 49.3% female) who completed neurological and neuropsychological assessment. Participants received diagnoses of PSP clinical variants at their evaluation (or retrospectively if evaluated before 2017) according to the Movement Disorder Society PSP criteria. We grouped variants as PSP-RS (62 participants), PSP-Cortical (25 with PSP-speech/language and 9 with PSP-corticobasal syndrome), and PSP-Subcortical (27 with PSP-parkinsonism, 11 with PSP-progressive gait freezing, and 6 with PSP-postural instability). Analysis of covariance adjusted for age assessed for differences in neuropsychological performance between variants across cognitive domains.
Results:
PSP-Cortical participants performed worst on measures of visual attention/working memory (Spatial Span Forward/Backward/Total), executive function (Frontal Assessment Battery), and language (Letter Fluency). PSP-RS participants performed worst on verbal memory (Camden Words). There were no significant group differences for the MoCA or indices of visuospatial function. There were no sex or education differences between PSP groups; however, there were differences in age at visit and disease duration.
Conclusions:
In a large sample of participants with PSP, there were differences in cognition across PSP-RS, PSP-Subcortical, and PSP-Cortical variants, with PSP-Cortical and, to a lesser extent, PSP-RS, performing worse on tests of attention and executive function. These findings suggest cognitive distinctions among PSP clinical variants and highlight the value of neuropsychological assessment in differential diagnosis of PSP subtypes for more accurate and timely clinical classification.
Canada’s National Microbiology Laboratory offers diagnostic testing of Creutzfeldt-Jakob disease (CJD) and related prion diseases. Since 2016, the highly sensitive and specific end-point quaking-induced conversion assay (EP-QuIC) of CSF samples has been used for antemortem CJD diagnostic testing alongside tests for surrogate biomarkers 14-3-3 and hTau. To assess EP-QuIC’s utility, we undertook a retrospective study of Canadian CJD diagnostic testing conducted between 2016 and 2024.
Methods:
Using CJD CSF test results collected between 2016 and 2024, we analyzed the CJD incidence in Canada, estimated based on positive EP-QuIC tests. Multivariate regression models were used to further evaluate CJD CSF testing between CJD subtypes, genders, age groups and codon 129 genotypes.
Results:
From 2016 to 2024, the CJD incidence across Canada was estimated at 1.51 cases per million population per year. CJD incidence did not vary significantly across provinces, although a slight increase in CJD incidence was detected in New Brunswick due to increased sampling rates. EP-QuIC offered higher test sensitivity than both surrogate biomarker tests. Analysis of biomarker abundances and test positivity rates across biochemical subtypes revealed significant differences. We also detected variation in CSF test positivity rates across age groups and a trend of increasing biomarker abundance with age within EP-QuIC-negative cases. No significant variation was detected between males and females.
Conclusion:
EP-QuIC exhibits exceptional specificity and sensitivity for antemortem diagnosis of CJD, providing a valuable tool for the diagnosis of human prion diseases and for improved surveillance.
Mass casualty incidents (MCI) overwhelm health care systems; however, MCIs are infrequent and require ongoing preparatory efforts. Although there is dedicated disaster medicine education in emergency medicine, most pediatric emergency medicine (PEM) fellows complete pediatric residencies. Pediatric residents have variable exposure to disaster training as part of their curriculum. To improve this, a quality improvement (QI) initiative was implemented to increase MCI comfort and knowledge amongst PEM fellows.
Methods
This study took place in a single-center tertiary pediatric hospital, amongst 1 cohort of PEM fellows. Following a baseline survey, a key driver diagram was developed to guide Plan-Do-Study-Act (PDSA) cycles. A focused disaster curriculum was provided to fellows and specific quick references were developed. Knowledge application interventions included mock triage, response scavenger hunt, and tabletop MCI exercise.
Results
PEM fellow comfort and knowledge of MCI response improved from an average of 2.93 to 6.56 on a 10-point Likert scale, and 3.71 to 6.58 on 10-point Likert scale respectively following the active intervention cycle and showed sustained results over a 6-month period without further interventions.
Conclusions
Utilizing QI methodology, PEM fellow comfort with MCI response, and knowledge of MCI response increased. As MCIs are a rare occurrence, ongoing assessment is necessary to evaluate the need for further interventions to maintain knowledge and comfort levels.
To say that any one person changed the way we think about the way we operationalize economic geography obfuscates the collaborative and iterative ways in which change actually happens in academic disciplines. Considering the contribution of any individual to an academic discipline involves asserting a deterministic role that almost certainly overstates the causality between the individual work and the collective change. Indeed, change is a both a process and a project involving many hands. Thus, naming Susan Christopherson's unique and specific contribution to economic geography must reflect a core argument in her work itself: economic geography is a team sport and further to note that Christopherson played it that way.
That said, Christopherson made a substantial individual contribution to economic geography. This contribution was especially remarkable given that she participated in economic geography from a position literally ‘outside the project’ as a Professor of City and Regional Planning rather than within a Geography department. For most of her faculty career Christopherson sat beyond the formal boundaries of the Geography discipline or its academic departments. And this liminal status has particular significance because it was not unusual for women in US economic geography at the time (and nor is it now) to hold positions in departments of public policy or urban planning rather than geography. Economic geography has closely guarded its membership rolls – and continues to – creating hard boundaries between insiders and outsiders.
Susan Christopherson's contribution to the discipline of economic geography involved expanding the field to include a broader set of epistemologies, methodologies and sites of inquiry. In other words, Christopherson challenged both what counts as an economic geography question and what is considered an economic geography explanation. Christopherson was part of a cohort of academics who pushed the analytical focus beyond the formal functions of traditional economic actors to unpack how institutions and intermediaries operate within regional and national economies to produce different spatial outcomes. And her work exhibited a sustained concern for labour.
Christopherson's work brought contingent and precarious labour into focus before it was a central concern of the discipline. And her work sustained that focus on labour and labour markets across a variety of sectors and industries, including film and new media, energy, high technology, and manufacturing.
Dual modality feeding (DMF) – feeding human milk interchangeably from the breast and from a bottle – comes with unique practical, emotional and relational challenges, as well as support needs. Yet, there is little research that explores the experiences of individuals who use DMF in the Canadian context. The aim of this study is to explore the practices, challenges, reasons and enablers of DMF.
Design:
Repeat, semi-structured one-on-one interviews were conducted at 8 weeks and 22 weeks postpartum. Interview transcripts were thematically analysed using a critical feminist lens.
Setting:
Nova Scotia, Canada.
Participants:
Ten DMF mothers.
Results:
DMF practices were influenced by a mix of social and material circumstances, including breast-feeding challenges, the involvement of support persons, finances and access to lactation support. Individuals who predominantly fed at the breast expressed milk strategically to mitigate transitory breast-feeding challenges, for convenience under specific circumstances, and to share feeding responsibilities with other caregivers for personal and practical reasons. Individuals who mainly bottle-fed did so due to long-term breast-feeding challenges or a need to return to employment. Enablers of successful DMF were consistent between the two groups and included practical, personal and relational aspects.
Conclusions:
DMF is a unique practice compared to feeding human milk solely from the breast or bottle. Despite the potential growing prevalence of DMF, it is currently understudied and inadequately addressed in existing support programmes in Nova Scotia. Tailored programming and public messaging are needed to support DMF families.
Post-traumatic stress disorder (PTSD) after traumatic birth can have a debilitating effect on parents already adapting to significant life changes during the post-partum period. Cognitive therapy for PTSD (CT-PTSD) is a highly effective psychological therapy for PTSD which is recommended in the NICE guidelines (National Institute for Health and Care Excellence, 2018) as a first-line intervention for PTSD. In this paper, we provide guidance on how to deliver CT-PTSD for birth-related trauma and baby loss and how to address common cognitive themes.
Key learning aims
(1) To recognise and understand the development of PTSD following childbirth and baby loss.
(2) To understand how Ehlers and Clark’s (2000) cognitive model of PTSD can be applied to post-partum PTSD.
(3) To be able to apply cognitive therapy for PTSD to patients with perinatal PTSD, including traumatic baby loss through miscarriage or birth.
(4) To discover common personal meanings associated with birth trauma and baby loss and the steps to update them.
Community-Research Advisory Councils (C-RAC) provide a unique mechanism for building sustainable community-academic partnership, fostering bidirectional understanding of complex research issues, disseminating timely research findings, and thereby improving public trust in science. Created in 2009, the Johns Hopkins C-RAC has a mission to achieve diversity, equity, and inclusion (DEI) of stakeholders across the entire research continuum. It has nurtured over a decade of partnership among community and academic stakeholders toward addressing health disparity, health equity, structural racism, and discrimination. Evidence of successful strategies to ensure DEI in partnership and lessons learned are illustrated in this special communication.
We agree with Grossmann that fear often builds cooperative relationships. Yet he neglects much extant literature. Prior researchers have discussed how fear (and other emotions) build cooperative relationships, have questioned whether fear per se evolved to serve this purpose, and have emphasized that human cooperation takes many forms. Grossmann's theory would benefit from a wider consideration of this work.
Patients with social anxiety disorder (SAD) have a range of negative thoughts and beliefs about how they think they come across to others. These include specific fears about doing or saying something that will be judged negatively (e.g. ‘I’ll babble’, ‘I’ll have nothing to say’, ‘I’ll blush’, ‘I’ll sweat’, ‘I’ll shake’, etc.) and more persistent negative self-evaluative beliefs such as ‘I am unlikeable’, ‘I am foolish’, ‘I am inadequate’, ‘I am inferior’, ‘I am weird/different’ and ‘I am boring’. Some therapists may take the presence of such persistent negative self-evaluations as being a separate problem of ‘low self-esteem’, rather than seeing them as a core feature of SAD. This may lead to a delay in addressing the persistent negative self-evaluations until the last stages of treatment, as might be typically done in cognitive therapy for depression. It might also prompt therapist drift from the core interventions of NICE recommended cognitive therapy for social anxiety disorder (CT-SAD). Therapists may be tempted to devote considerable time to interventions for ‘low self-esteem’. Our experience from almost 30 years of treating SAD within the framework of the Clark and Wells (1995) model is that when these digressions are at the cost of core CT-SAD techniques, they have limited value. This article clarifies the role of persistent negative self-evaluations in SAD and shows how these beliefs can be more helpfully addressed from the start, and throughout the course of CT-SAD, using a range of experiential techniques.
Key learning aims
(1) To recognise persistent negative self-evaluations as a key feature of SAD.
(2) To understand that persistent negative self-evaluations are central in the Clark and Wells (1995) cognitive model and how to formulate these as part of SAD.
(3) To be able to use all the experiential interventions in cognitive therapy for SAD to address these beliefs.
Surveys are a powerful technique in cognitive behavioural therapy (CBT). A form of behavioural experiment, surveys can be used to test beliefs, normalise symptoms and experiences, and generate compassionate perspectives. In this article, we discuss why and when to use surveys in CBT interventions for a range of psychological disorders. We also present a step-by-step guide to collaboratively designing surveys with patients, selecting the appropriate recipients, sending out surveys, discussing responses and using key learning as a part of therapy. In doing so, we hope to demonstrate that surveys are a flexible, impactful, time-efficient, individualised technique which can be readily and effectively integrated into CBT interventions.
Key learning aims
After reading this article, it is hoped that readers will be able to:
(1) Conceptualise why surveys can be useful in cognitive behavioural therapy.
(2) Implement collaborative and individualised survey design, delivery and feedback as part of a CBT intervention.
Therapist cognitions about trauma-focused psychological therapies can affect our implementation of evidence-based therapies for post-traumatic stress disorder (PTSD), potentially reducing their effectiveness. Based on observations gleaned from teaching and supervising one of these treatments, cognitive therapy for PTSD (CT-PTSD), ten common ‘misconceptions’ were identified. These included misconceptions about the suitability of the treatment for some types of trauma and/or emotions, the need for stabilisation prior to memory work, the danger of ‘retraumatising’ patients with memory-focused work, the risks of using memory-focused techniques with patients who dissociate, the remote use of trauma-focused techniques, and the perception of trauma-focused CBT as inflexible. In this article, these misconceptions are analysed in light of existing evidence and guidance is provided on using trauma-focused CT-PTSD with a broad range of presentations.
Key learning aims
(1) To recognise common misconceptions about trauma-focused CBT for PTSD and the evidence against them.
(2) To widen understanding of the application of cognitive therapy for PTSD (CT-PTSD) to a broad range of presentations.
(3) To increase confidence in the formulation-driven, flexible, active and creative delivery of CT-PTSD.
Cognitive therapy for social anxiety disorder (CT-SAD) is recommended by NICE (2013) as a first-line intervention. Take up in routine services is limited by the need for up to 14 ninety-min face-to-face sessions, some of which are out of the office. An internet-based version of the treatment (iCT-SAD) with remote therapist support may achieve similar outcomes with less therapist time.
Methods
102 patients with social anxiety disorder were randomised to iCT-SAD, CT-SAD, or waitlist (WAIT) control, each for 14 weeks. WAIT patients were randomised to the treatments after wait. Assessments were at pre-treatment/wait, midtreatment/wait, posttreatment/wait, and follow-ups 3 & 12 months after treatment. The pre-registered (ISRCTN 95 458 747) primary outcome was the social anxiety disorder composite, which combines 6 independent assessor and patient self-report scales of social anxiety. Secondary outcomes included disability, general anxiety, depression and a behaviour test.
Results
CT-SAD and iCT-SAD were both superior to WAIT on all measures. iCT-SAD did not differ from CT-SAD on the primary outcome at post-treatment or follow-up. Total therapist time in iCT-SAD was 6.45 h. CT-SAD required 15.8 h for the same reduction in social anxiety. Mediation analysis indicated that change in process variables specified in cognitive models accounted for 60% of the improvements associated with either treatment. Unlike the primary outcome, there was a significant but small difference in favour of CT-SAD on the behaviour test.
Conclusions
When compared to conventional face-to-face therapy, iCT-SAD can more than double the amount of symptom change associated with each therapist hour.
Early in the COVID-19 pandemic, the World Health Organization stressed the importance of daily clinical assessments of infected patients, yet current approaches frequently consider cross-sectional timepoints, cumulative summary measures, or time-to-event analyses. Statistical methods are available that make use of the rich information content of longitudinal assessments. We demonstrate the use of a multistate transition model to assess the dynamic nature of COVID-19-associated critical illness using daily evaluations of COVID-19 patients from 9 academic hospitals. We describe the accessibility and utility of methods that consider the clinical trajectory of critically ill COVID-19 patients.
To characterize and compare the neuropsychological profiles of patients with primary progressive apraxia of speech (PPAOS) and apraxia of speech with progressive agrammatic aphasia (AOS-PAA).
Method:
Thirty-nine patients with PPAOS and 49 patients with AOS-PAA underwent formal neurological, speech, language, and neuropsychological evaluations. Cognitive domains assessed included immediate and delayed episodic memory (Wechsler Memory Scale-Third edition; Logical Memory; Visual Reproduction; Rey Auditory Verbal Learning Test), processing speed (Trail Making Test A), executive functioning (Trail Making Test B; Delis-Kaplan Executive Functioning Scale – Sorting), and visuospatial ability (Rey-Osterrieth Complex Figure copy).
Results:
The PPAOS patients were cognitively average or higher in the domains of immediate and delayed episodic memory, processing speed, executive functioning, and visuospatial ability. Patients with AOS-PAA performed more poorly on tests of immediate and delayed episodic memory and executive functioning compared to those with PPAOS. For every 1 unit increase in aphasia severity (e.g. mild to moderate), performance declined by 1/3 to 1/2 a standard deviation depending on cognitive domain. The degree of decline was stronger within the more verbally mediated domains, but was also notable in less verbally mediated domains.
Conclusion:
The study provides neuropsychological evidence further supporting the distinction of PPAOS from primary progressive aphasia and should be used to inform future diagnostic criteria. More immediately, it informs prognostication and treatment planning.
The existence of a shared constraint hierarchy is one of the criteria that defines and delimits speech communities. In particular, women and men are thought to differ only in their rates of variable usage, not in the constraints governing their variation; that is, women and men are typically considered to belong to the same speech community. We find that in early twentieth century Southland, New Zealand, women and men had different constraint hierarchies for rhoticity, with a community grammar of rhoticity only developing later. These results may be a product of a particular set of sociohistorical facts thatare not peculiar to Southland. We suggest that further research in other geographical locations may indeed reveal that men and women have different constraint hierarchies for other variables. Speech communities may thus be delimited along social lines in ways that have not been previously considered.