We use cookies to distinguish you from other users and to provide you with a better experience on our websites. Close this message to accept cookies or find out how to manage your cookie settings.
To save content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about saving content to .
To save content items to your Kindle, first ensure no-reply@cambridge.org
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about saving to your Kindle.
Note you can select to save to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
Nearly 25% of people with intellectual disability (PwID) have epilepsy compared to 1% of the UK general population. PwID are commonly excluded from research, eventually affecting their care. Understanding seizures in PwID is particularly challenging because of reliance on subjective external observation and poor objective validation. Remote electroencephalography (EEG) monitoring could capture objective data, but particular challenges and implementation strategies for this population need to be understood.
Aim
This co-production aimed to explore the accessibility and potential impact of a remote, long-term EEG tool (UnEEG 24/7 SubQ) for PwID and epilepsy.
Method
We conducted six, 2-hour long workshops; three with people with mild intellectual disability and three with families/carers of people with moderate–profound intellectual disability. Brief presentations, easy read information and model demonstrations were used to explain the problem and device. A semi-structured guide developed by a communication specialist and art-based techniques facilitated discussion with PwID. For family/carers, active listening was employed. All conversations were recorded and transcribed. Artificial intelligence-based coding and thematic analysis (ATLAS.ti and ChatGPT) were synthesised with manual theming to generate insights.
Results
Co-production included four PwID, five family members and seven care professionals. Three main themes were identified: (1) perceived benefits for improving seizure understanding, informing care and reducing family and carer responsibility to accurately identify seizures; (2) the device was feasible for some PwID but not all; and (3) appropriate person-centred communication is essential for all stakeholders to reduce concerns.
Conclusions
The workshops identified key benefits and implementing barriers to SubQ in PwID.
Involving participants in the design of clinical trials should improve the overall success of a study. For this to occur, streamlined mechanisms are needed to connect the populations potentially impacted by a given study or health topic with research teams in order to inform trial design in a meaningful and timely manner. To address this need, we developed an innovative mechanism called the “ResearchMatch Expert Advice Tool” that quickly obtains volunteer perspectives from populations with specific health conditions or lived experiences using the national recruitment registry, ResearchMatch. This tool does not ask volunteers to participate in the trial but allows for wider community feedback to be gathered and translated into actionable recommendations used to inform the study’s design. We describe early use cases that shaped the current Expert Advice Tool workflow, how results from this tool were incorporated and implemented by studies, and feedback from volunteers and study teams regarding the tool’s usefulness. Additionally, we present a set of lessons learned during the development of the Expert Advice Tool that can be used by other recruitment registries seeking to obtain volunteer feedback on study design and operations.
To assess the potential contribution of large-scale food fortification (LSFF) towards meeting dietary micronutrient requirements in Tanzania.
Design:
We used household food consumption data from the National Panel Survey 2014–15 to estimate fortifiable food vehicle coverage and consumption (standardised using the adult female equivalent approach) and the prevalence at risk of inadequate apparent intake of five micronutrients included in Tanzania’s fortification legislation. We modelled four LSFF scenarios: no fortification, status quo (i.e. compliance with current fortification contents) and full fortification with and without maize flour fortification.
Setting:
Tanzania.
Participants:
A nationally representative sample of 3290 Tanzanian households.
Results:
The coverage of edible oils and maize and wheat flours (including products of wheat flour and oil such as bread and cakes) was high, with 91 percent, 88 percent and 53 percent of households consuming these commodities, respectively. We estimated that vitamin A-fortified oil could reduce the prevalence of inadequate apparent intake of vitamin A (retinol activity equivalent) from 92 percent without LSFF to 80 percent with LSFF at current fortification levels. Low industry LSFF compliance of flour fortification limits the contribution of other micronutrients, but a hypothetical full fortification scenario shows that LSFF of cereal flours could substantially reduce the prevalence at risk of inadequate intakes of iron, zinc, folate and vitamin B12.
Conclusions:
The current Tanzania LSFF programme likely contributes to reducing vitamin A inadequacy. Policies that support increased compliance could improve the supply of multiple nutrients, but the prominence of small-scale maize mills restricts this theoretical benefit.
Personalised management of recurrent depression, considering individual patient characteristics, is crucial.
Aims
This study evaluates the potentially different mediating role of mindfulness skills in managing recurrent depression using mindfulness-based cognitive therapy (MBCT) among people with varying depression severity.
Method
Data from the Prevention of Depressive Relapse or Recurrence (PREVENT) trial, comparing MBCT (with antidepressant medication (ADM) tapering support, MBCT-tapering support) versus maintenance-ADM, were used. The study included pre, post, 9-, 12-, 18- and 24-month follow-ups. Adults with ≥3 previous major depressive episodes, in full/partial remission (below threshold for a current episode), on ADM, were assessed for eligibility in primary care practices in the UK. People were randomised (1:1) to MBCT-tapering support or maintenance-ADM. We used the Beck Depression Inventory-II to evaluate depressive symptom changes over the six time points. Pre-post treatment, we employed the Five Facets of Mindfulness Questionnaire to gauge mindfulness skills. Baseline symptom and history variables were used to identify individuals with varying severity profiles. We conducted Latent Profile Moderated-Mediation Growth Mixture Models.
Results
A total of 424 people (mean (s.d.) age = 49.44 (12.31) years; with 325 (76.7%) self-identified as female) were included. A mediating effect of mindfulness skills, between trial arm allocation and the linear rate of depressive symptoms change over 24 months, moderated by depression severity, was observed (moderated-mediation index = −0.27, 95% CI = −0.66, −0.03). Conditional indirect effects were −0.42 (95% CI = −0.78, −0.18) for higher severity (expected mean BDI-II reduction = 10 points), and −0.15 (95% CI = −0.35, −0.02) for lower severity (expected mean BDI-II reduction = 3.5 points).
Conclusions
Mindfulness skills constitute a unique mechanism driving change in MBCT (versus maintenance-ADM). Individuals with higher depression severity may benefit most from MBCT-tapering support for residual symptoms. It is unclear if these effects apply to those with a current depressive episode. Future research should investigate individuals who are not on medication. This study provides preliminary evidence for personalised management of recurrent depression.
Integrating community expertise into scientific teams and research endeavors can holistically address complex health challenges and grand societal problems. An in-depth understanding of the integration of team science and community engagement principles is needed. The purpose of this scoping review was to identify how and where team science and community engagement approaches are being used simultaneously in research.
Methods:
We followed Levac’s enhancement of Arksey and O’Malley’s Scoping Review Framework and systematically searched PubMed, CINAHL, Scopus, ERIC, and Embase for team science and community engagement terms through January 2024.
Results:
Sixty-seven articles were reviewed. Publications describing integrated team science and community-engaged research have increased exponentially since 2004. Over half were conducted outside of the U.S., utilized qualitative methods, included community-researcher co-development of research question and study design, and described team partnership goals, roles, and management. Fewer studies evaluated partnership, built community capacity, described financial compensation to communities, or described team dynamics facilitation.
Conclusion:
As researchers continue to integrate community engagement and team science, common criteria and strategies for integrating the approaches are needed. We provide 19 recommendations for research teams, research institutions, journals, and funding bodies in service of advancing the science and practice of this integration.
The field of healthcare epidemiology is increasingly focused on identifying, characterizing, and addressing social determinants of health (SDOH) to address inequities in healthcare quality. To identify evidence gaps, we examined recent systematic reviews examining the association of race, ethnicity, and SDOH with inpatient quality measures.
Methods:
We searched Medline via OVID for English language systematic reviews from 2010 to 2022 addressing race, ethnicity, or SDOH domains and inpatient quality measures in adults using specific topic questions. We imported all citations to Covidence (www.covidence.org, Veritas Health Innovation) and removed duplicates. Two blinded reviewers assessed all articles for inclusion in 2 phases: title/abstract, then full-text review. Discrepancies were resolved by a third reviewer.
Results:
Of 472 systematic reviews identified, 39 were included. Of these, 23 examined all-cause mortality; 6 examined 30-day readmission rates; 4 examined length of stay, 4 examined falls, 2 examined surgical site infections (SSIs) and one review examined risk of venous thromboembolism. The most evaluated SDOH measures were sex (n = 9), income and/or employment status (n = 9), age (n = 6), race and ethnicity (n = 6), and education (n = 5). No systematic reviews assessed medication use errors or healthcare-associated infections. We found very limited assessment of other SDOH measures such as economic stability, neighborhood, and health system access.
Conclusion:
A limited number of systematic reviews have examined the association of race, ethnicity and SDOH measures with inpatient quality measures, and existing reviews highlight wide variability in reporting. Future systematic evaluations of SDOH measures are needed to better understand the relationships with inpatient quality measures.
Our team of core and higher psychiatry trainees aimed to improve secondary mental health service detection of and response to gender-based violence (GBV) in South East London. We audited home treatment team (HTT), drug and alcohol (D&A) service and in-patient ward clinical records (n = 90) for female and non-binary patients. We implemented brief, cost-neutral staff engagement and education interventions at service, borough and trust levels before re-auditing (n = 86), completing a plan–do–study–act cycle.
Results
Documented enquiry about exposure to GBV increased by 30% (HTT), 15% (ward) and 7% (D&A), post-intervention. We identified staff training needs and support for improving GBV care. Up to 56% of records identified psychiatric symptoms related to GBV exposure.
Clinical implications
Moves to make mental healthcare more trauma-informed rely on services first being supportive environments for enquiry, disclosure and response to traumatic stressors. Our collaborative approach across clinical services increased GBV enquiry and documentation. The quality of response is more difficult to measure and requires concerted attention.
Higher educational attainment is associated with reduced risk for Alzheimer's disease (AD) dementia, and its protective effect may act through alterations in cerebral blood flow (CBF) that allow for better coping with accumulating neuropathology. Additionally, there are sex differences in both the risk of developing AD as well as the potential protective effects of education. We therefore sought to investigate whether education moderates the association of hippocampal CBF and memory in cognitively unimpaired older adults, and to examine if these interactions were moderated by sex.
Participants and Methods:
Cognitively unimpaired older adults from the Alzheimer's Disease Neuroimaging Initiative (ADNI; 51 men, 50 women) underwent neuropsychological evaluation and arterial spin labeling MRI, which was used to quantify bilateral hippocampal CBF. Sex was defined as sex at birth. Multiple linear regressions assessed (1) the independent associations among education, CBF, and memory performance separately in men and women and (2) the three-way interactions among CBF, sex, and education, followed by sex-stratified analyses. Three outcome measures were examined: Logical Memory Story A immediate and delayed recall, and Rey Auditory Verbal Learning Test (RAVLT) intrusions. All models adjusted for age and APOE epsilon-4 allele frequency, and all models with CBF additionally adjusted for cerebral metabolism (baseline FDG-PET composite) and pulse pressure.
Results:
CBF was not associated with education or memory in either women or men. There was a positive association between education and delayed memory in women (ß=0.14, t=2.64, p=0.008) as well as trending, positive associations between education and immediate memory in women (ß=0.09, t=1.79, p=0.074) and education and delayed memory in men (ß=0.09, t=1.94, p=0.054). Three-way interactions among sex, CBF, and education were significant on immediate recall (ß=2.55, t=2.53, p=0.013), delayed recall (ß=2.56, t=2.44, p=0.017), and RAVLT intrusions (ß=-2.28, t=-2.27, p=0.026). In women, there were interactions between education and hippocampal CBF on both immediate (ß=2.49, t=2.90, p=0.006) and delayed recall (ß=2.30, t=2.78, p=0.009), such that as education increased, the strength of the association between CBF and immediate memory increased. There was also an interaction between education and hippocampal CBF on RAVLT intrusions in women (ß=-2.42, t=-3.05, p=0.004), such that as education increased, the strength of the association between CBF and number of intrusions decreased; there was a main effect where in women with lower education, as CBF increased, the number of intrusions increased (ß=0.76, t=2.59, p=0.032); in women with higher education, there was no association between CBF and intrusions. In men, none of these two-way interactions were significant.
Conclusions:
These results suggest that, in cognitively unimpaired older women, the relationship between hippocampal CBF and memory is moderated by education level, even when adjusting for several other factors. Specifically, higher education may serve as a protective factor in the hippocampal CBF-memory relationship, and this relationship was sex-dependent, occurring in women only. Further research is needed to examine these relationships longitudinally across the clinical continuum of AD. Additionally, this work needs to be conducted in more diverse samples to allow for analyses investigating the impact of education on the intersection of race/ethnicity and sex/gender.
In 2016, the National Center for Advancing Translational Science launched the Trial Innovation Network (TIN) to address barriers to efficient and informative multicenter trials. The TIN provides a national platform, working in partnership with 60+ Clinical and Translational Science Award (CTSA) hubs across the country to support the design and conduct of successful multicenter trials. A dedicated Hub Liaison Team (HLT) was established within each CTSA to facilitate connection between the hubs and the newly launched Trial and Recruitment Innovation Centers. Each HLT serves as an expert intermediary, connecting CTSA Hub investigators with TIN support, and connecting TIN research teams with potential multicenter trial site investigators. The cross-consortium Liaison Team network was developed during the first TIN funding cycle, and it is now a mature national network at the cutting edge of team science in clinical and translational research. The CTSA-based HLT structures and the external network structure have been developed in collaborative and iterative ways, with methods for shared learning and continuous process improvement. In this paper, we review the structure, function, and development of the Liaison Team network, discuss lessons learned during the first TIN funding cycle, and outline a path toward further network maturity.
Clinical trials face many challenges with meeting projected enrollment and retention goals. A study’s recruitment materials and messaging convey necessary key information and therefore serve as a critical first impression with potential participants. Yet study teams often lack the resources and skills needed to develop engaging, culturally tailored, and professional-looking recruitment materials. To address this gap, the Recruitment Innovation Center recently developed a Recruitment & Retention Materials Content and Design Toolkit, which offers research teams guidance, actionable tips, resources, and customizable templates for creating trial-specific study materials. This paper seeks to describe the creation and contents of this new toolkit.
New technologies and disruptions related to Coronavirus disease-2019 have led to expansion of decentralized approaches to clinical trials. Remote tools and methods hold promise for increasing trial efficiency and reducing burdens and barriers by facilitating participation outside of traditional clinical settings and taking studies directly to participants. The Trial Innovation Network, established in 2016 by the National Center for Advancing Clinical and Translational Science to address critical roadblocks in clinical research and accelerate the translational research process, has consulted on over 400 research study proposals to date. Its recommendations for decentralized approaches have included eConsent, participant-informed study design, remote intervention, study task reminders, social media recruitment, and return of results for participants. Some clinical trial elements have worked well when decentralized, while others, including remote recruitment and patient monitoring, need further refinement and assessment to determine their value. Partially decentralized, or “hybrid” trials, offer a first step to optimizing remote methods. Decentralized processes demonstrate potential to improve urban-rural diversity, but their impact on inclusion of racially and ethnically marginalized populations requires further study. To optimize inclusive participation in decentralized clinical trials, efforts must be made to build trust among marginalized communities, and to ensure access to remote technology.
One challenge for multisite clinical trials is ensuring that the conditions of an informative trial are incorporated into all aspects of trial planning and execution. The multicenter model can provide the potential for a more informative environment, but it can also place a trial at risk of becoming uninformative due to lack of rigor, quality control, or effective recruitment, resulting in premature discontinuation and/or non-publication. Key factors that support informativeness are having the right team and resources during study planning and implementation and adequate funding to support performance activities. This communication draws on the experience of the National Center for Advancing Translational Science (NCATS) Trial Innovation Network (TIN) to develop approaches for enhancing the informativeness of clinical trials. We distilled this information into three principles: (1) assemble a diverse team, (2) leverage existing processes and systems, and (3) carefully consider budgets and contracts. The TIN, comprised of NCATS, three Trial Innovation Centers, a Recruitment Innovation Center, and 60+ CTSA Program hubs, provides resources to investigators who are proposing multicenter collaborations. In addition to sharing principles that support the informativeness of clinical trials, we highlight TIN-developed resources relevant for multicenter trial initiation and conduct.
OBJECTIVES/GOALS: Patients who have experienced conjunctive mild traumatic brain injuries (mTBIs) suffer from a number of comorbidities, including chronic pain. Despite extensive studies investigating the underlying mechanisms of mTBI-associated chronic pain, the role of inflammation after mTBI and its contribution to long-term pain are still poorly understood. METHODS/STUDY POPULATION: Given the shifting dynamics of inflammation, it is important to understand the spatial-longitudinal changes and their effects on TBI-related pain. Utilizing a recently developed transgenic caspase-1 luciferase reporter mouse, we characterized the bioluminescence signal evident in both in vivo and ex vivo tissues following repetitive closed head mTBIs. This allowed us to reveal the spatiotemporal dynamics of caspase-1 activation in individual animals over time. Furthermore, we utilize various proteomic and behavioral assays to evaluate the role of caspase-1 mediated inflammation in the development and progression of injury-associated chronic pain. Lastly, by blocking inflammasome caspase-1 activation with a specific inhibitor, we assess its clinical potential as the next therapeutic approach to pain. RESULTS/ANTICIPATED RESULTS: We established that there were significant increases in bioluminescent signals upon protease cleavage in the brain, thorax, abdomen, and paws in vivo, which lasted for at least one week after each injury. Enhanced inflammation was also observed in ex vivo brain slice preparations following injury events that lasted for at least 3 days. Concurrent with the in vivo detection of the bioluminescent signal were persistent decreases in mouse hind paw withdrawal thresholds that lasted for more than two months postinjury. Using MCC950, a potent small molecule inhibitor of NLRP3 inflammasome-caspase 1 activity, we observed reductions in both caspase-1 bioluminescent signals in vivo and caspase-1 p45 expression by immunoblotting and an increase in hind paw withdrawal thresholds. DISCUSSION/SIGNIFICANCE: Overall, these findings suggest that neuroinflammation in the brain following repeated mTBIs is coincidental with a chronic nociplastic pain state, and repeated mTBI-associated events can be ameliorated by a highly specific small molecule inhibitor of NLRP3 inflammasome activation.
Risk of suicide-related behaviors is elevated among military personnel transitioning to civilian life. An earlier report showed that high-risk U.S. Army soldiers could be identified shortly before this transition with a machine learning model that included predictors from administrative systems, self-report surveys, and geospatial data. Based on this result, a Veterans Affairs and Army initiative was launched to evaluate a suicide-prevention intervention for high-risk transitioning soldiers. To make targeting practical, though, a streamlined model and risk calculator were needed that used only a short series of self-report survey questions.
Methods
We revised the original model in a sample of n = 8335 observations from the Study to Assess Risk and Resilience in Servicemembers-Longitudinal Study (STARRS-LS) who participated in one of three Army STARRS 2011–2014 baseline surveys while in service and in one or more subsequent panel surveys (LS1: 2016–2018, LS2: 2018–2019) after leaving service. We trained ensemble machine learning models with constrained numbers of item-level survey predictors in a 70% training sample. The outcome was self-reported post-transition suicide attempts (SA). The models were validated in the 30% test sample.
Results
Twelve-month post-transition SA prevalence was 1.0% (s.e. = 0.1). The best constrained model, with only 17 predictors, had a test sample ROC-AUC of 0.85 (s.e. = 0.03). The 10–30% of respondents with the highest predicted risk included 44.9–92.5% of 12-month SAs.
Conclusions
An accurate SA risk calculator based on a short self-report survey can target transitioning soldiers shortly before leaving service for intervention to prevent post-transition SA.
Racially and ethnically minoritized populations have been historically excluded and underrepresented in research. This paper will describe best practices in multicultural and multilingual awareness-raising strategies used by the Recruitment Innovation Center to increase minoritized enrollment into clinical trials. The Passive Immunity Trial for Our Nation will be used as a primary example to highlight real-world application of these methods to raise awareness, engage community partners, and recruit diverse study participants.
Exclusion of special populations (older adults; pregnant women, children, and adolescents; individuals of lower socioeconomic status and/or who live in rural communities; people from racial and ethnic minority groups; individuals from sexual or gender minority groups; and individuals with disabilities) in research is a pervasive problem, despite efforts and policy changes by the National Institutes of Health and other organizations. These populations are adversely impacted by social determinants of health (SDOH) that reduce access and ability to participate in biomedical research. In March 2020, the Northwestern University Clinical and Translational Sciences Institute hosted the “Lifespan and Life Course Research: integrating strategies” “Un-Meeting” to discuss barriers and solutions to underrepresentation of special populations in biomedical research. The COVID-19 pandemic highlighted how exclusion of representative populations in research can increase health inequities. We applied findings of this meeting to perform a literature review of barriers and solutions to recruitment and retention of representative populations in research and to discuss how findings are important to research conducted during the ongoing COVID-19 pandemic. We highlight the role of SDOH, review barriers and solutions to underrepresentation, and discuss the importance of a structural competency framework to improve research participation and retention among special populations.
Healthcare disparities and inequities exist in a variety of environments and manifest in diagnostic and therapeutic measures. In this commentary, we highlight our experience examining our organization’s urgent care respiratory encounter antibiotic prescribing practices. We identified differences in prescribing based on several individual characteristics including patient age, race, ethnicity, preferred language, and patient and/or clinician gender. Our approach can serve as an electronic health record (EHR)–based methodology for disparity and inequity audits in other systems and for other conditions.
Through a case study of small-scale Kaqchikel Maya farmers involved in non-traditional export agriculture (NTAX) in the Central Guatemalan highlands, this article examines the tensions between the mostly positive perceptions of farmers and the negative assessments of many who study NTAX production. In a context of severe political-economic structural inequalities and potentially high social and cultural costs, quantitative household survey results demonstrate a modest decrease in concentration of land in favour of Maya smallholders; more gender-egalitarian relations of production than expected; and largely positive local perceptions of economic and social change. Qualitative analysis interprets these findings in light of Maya-affective ties to land, preferences for continuity in traditional labor organization and subsistence maize production, perceptions of risk, and the transfer of traditional marketing skills. We find that Kaqchikeles are shaping alternative modernities as they deal with new sets of political-economic and social constraints.
The Recruitment Innovation Center (RIC) has created a toolkit of novel strategies to engage potential participants in response to recruitment and retention challenges associated with COVID-19 studies. The toolkit contains pragmatic, generalizable resources to help research teams increase awareness of clinical trials and opportunities to participate; produce culturally sensitive and engaging recruitment materials; improve consent and return of results processes; and enhance recruitment of individuals from populations disproportionately impacted by COVID-19. This resource, the “RIC COVID-19 Recruitment and Retention Toolkit,” is available free online. We describe the toolkit and the community feedback used to author and curate this resource.