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There is a clinical need to appropriately apply large language model (LLM)-based systems for use in infectious diseases. We sought to use LLM and machine learning for extracting antibiotic susceptibility from clinical microbiology free-text reports, allowing use for outbreak detection, increasing information gathering efficiency, and public health reporting.
Multicenter clinical trials are essential for evaluating interventions but often face significant challenges in study design, site coordination, participant recruitment, and regulatory compliance. To address these issues, the National Institutes of Health’s National Center for Advancing Translational Sciences established the Trial Innovation Network (TIN). The TIN offers a scientific consultation process, providing access to clinical trial and disease experts who provide input and recommendations throughout the trial’s duration, at no cost to investigators. This approach aims to improve trial design, accelerate implementation, foster interdisciplinary teamwork, and spur innovations that enhance multicenter trial quality and efficiency. The TIN leverages resources of the Clinical and Translational Science Awards (CTSA) program, complementing local capabilities at the investigator’s institution. The Initial Consultation process focuses on the study’s scientific premise, design, site development, recruitment and retention strategies, funding feasibility, and other support areas. As of 6/1/2024, the TIN has provided 431 Initial Consultations to increase efficiency and accelerate trial implementation by delivering customized support and tailored recommendations. Across a range of clinical trials, the TIN has developed standardized, streamlined, and adaptable processes. We describe these processes, provide operational metrics, and include a set of lessons learned for consideration by other trial support and innovation networks.
The consent process for research studies can be burdensome for potential participants due to complex information and lengthy consent forms. This pragmatic study aimed to improve the consent experience and evaluate its impact on participant decision making, study knowledge, and satisfaction with the In Our DNA SC program, a population-based genomic screening initiative. We compared two consent procedures: standard consent (SC) involving a PDF document and enhanced consent (EC) incorporating a pictograph and true or false questions. Decision-making control, study knowledge, satisfaction, and time to consent were assessed. We analyzed data for 109 individuals who completed the SC and 96 who completed the EC. Results indicated strong decision-making control and high levels of knowledge and satisfaction in both groups. While no significant differences were found between the two groups, the EC experience took longer for participants to complete. Future modifications include incorporating video modules and launching a Spanish version of the consent experience. Overall, this study contributes to the growing literature on consent improvements and highlights the need to assess salient components and explore participant preferences for receiving consent information.
Pandemic-related restrictions in nursing homes have undermined the critical role that family and friend caregivers play in enhancing resident quality of life. We examined how family caregiver access restrictions in nursing homes were implemented and how they impacted the mutual well-being of and relationships between residents and their caregivers over time. Between March 2021 and March 2022, 24 ‘designated caregivers’ in Atlantic Canada were interviewed three times. We identified changes in family relationships and activities over time, constricted support networks, the increasing need for advocacy and monitoring, and the generally negative cumulative impacts of restrictions, especially during residents’ end-of-life. Subsequent adaptations to access restrictions allowed caregivers to contribute to essential monitoring, care relationships, and advocacy roles. We argue that the role of designated caregivers in nursing homes must be maintained during public health emergencies to ensure resident’s supportive family relationships and general well-being.
In 2023, Henrietta Lacks’ family won a settlement from Thermo Fisher Scientific on the grounds that the company had been “unjustly enriched” by the sale of products developed with Henrietta’s cells. Given that hundreds of thousands of people have tissue stored in the United States, this article explores how today’s patients might fare if they similarly sued professionals and companies that undertake unauthorized research on or commercialization of their tissue on the grounds of conversion, unjust enrichment, lack of informed consent, breach of fiduciary duty and, where government entities are involved, Fourteenth Amendment claims. The article notes that the practices that were subsequently seen as unethical in Henrietta Lacks’ care continue in some health care institutions today. It also analyzes how research and commercialization without consent can lead to a lack of trust in the research enterprise and the unwillingness of people to participate in research.
Giant coronary artery aneurysms and myocardial fibrosis after Kawasaki disease may lead to devastating cardiovascular outcomes. We characterised the vascular and myocardial outcomes in five selected Kawasaki disease patients with a history of giant coronary artery aneurysms that completely regressed.
Methods:
Five patients were selected who had giant coronary artery aneurysm in early childhood that regressed when studied 12–33 years after Kawasaki disease onset. Coronary arteries were imaged by coronary CT angiography, and coronary artery calcium volume scores were determined. We used endocardial strain measurements from CT imaging to assess myocardial regional wall function. Calprotectin and galectin-3 (gal-3) as biomarkers of inflammation and myocardial fibrosis were measured by enzyme-linked immunosorbent assay.
Results:
The five selected patients with regressed giant coronary artery aneurysms had calcium scores of zero, normal levels of calprotectin and gal-3, and normal appearance of the coronary arteries by coronary computed tomography angiography. CT strain demonstrated normal peak systolic and diastolic strain patterns in four of five patients. In one patient with a myocardial infarction at the time of Kawasaki disease diagnosis at the age of 10 months, CT strain showed altered global longitudinal strain, reduced segmental peak strain, and reduced diastolic relaxation patterns in multiple left ventricle segments.
Conclusions:
These patients illustrate that regression of giant aneurysms after Kawasaki disease is possible with no detectable calcium, normal biomarkers of inflammation and fibrosis, and normal myocardial function. Individuals with regressed giant coronary artery aneurysm still require longitudinal surveillance to assess the durability of this favourable outcome.
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.
Attention-deficit/hyperactivity disorder (ADHD) is a neurobehavioral disorder characterized by pervasive impairment in symptoms of inattention, hyperactivity, and impulsivity. Psychopharmacologic treatment is targeted at the management of symptoms of ADHD, and evidence exists that ADHD persists into adulthood. Clinical practice guidelines recommend a combination of behavior therapy and psychostimulant medication for the treatment of ADHD in children, adolescents, and adults. Psychostimulants are often prescribed for ADHD in adults, and amphetamine long has been considered a mainstay of treatment for this population. As adult patients seek relief from ADHD symptoms early in the workday and into the early evening hours, with fewer required doses, extended-release formulations with an early onset of efficacy and an extended duration of effect are considered very desirable. The amphetamine-extended release tablet (AMPH ER TAB) was developed to provide a portable, easy-to-use amphetamine tablet dosage option that can be chewed or swallowed whole.
Objectives
To evaluate the efficacy and safety of an Amphetamine Extended-Release Tablet (AMPH ER TAB) in adults with ADHD aged 18 to 60 years. Methods: In a 5-week forced dose-titration phase, eligible subjects were randomized to either oral double-blind AMPH ER TAB 5 mg starting dose or matching placebo, once daily in the morning beginning the day after the Baseline Visit. Subjects were titrated up (5 mg increments) each week. Safety and efficacy assessments were done weekly. After Visit 3, subjects received 20 mg for 14 (3) days before Visit 5 (V5). Subjects who could not tolerate study drugs discontinued. A Permanent Product Measure of Performance (PERMP) placement test was done at Screening or Baseline. At V5, efficacy assessments included the administration of serial PERMPs predose, 0.5, 1, 2, 4, 8, 10, 12, 13, and 14 hours postdose. The primary efficacy endpoint was the mean PERMP-T score across postdose time points during the Visit 5 serial PERMPs. Safety was monitored by AEs assessed at each visit, C-SSRS, vital signs, weight, and assessment of sleep, appetite, mood, and psychotic AEs.
Results
The mean postdose PERMP-T score over all postdose time points at V5 was statistically significantly higher in the AMPH ER TAB group vs placebo (302.8 vs 279.6; P = .0043). Common adverse events were decreased appetite, insomnia, and dry mouth. The majority of TEAEs were mild to moderate in severity, and no SAEs were reported.
Conclusion
The AMPH ER TAB demonstrated efficacy in the treatment of symptoms of ADHD in adults, with an anticipated safety profile.
Disasters of all varieties have been steadily increasing in frequency. Simultaneously, “big data” has seen explosive growth as a tool in business and private industries while opportunities for robust implementation in disaster management remain nascent. To more explicitly ascertain the current status of big data as applied to disaster recovery, we conducted an integrative literature review.
Methods:
Eleven databases were searched using iteratively developed keywords to target big data in a disaster recovery context. All studies were dual-screened by title and abstract followed by dual full-text review to determine if they met inclusion criteria. Articles were included if they focused on big data in a disaster recovery setting and were published in the English-language peer-reviewed literature.
Results:
After removing duplicates, 25,417 articles were originally identified. Following dual title/abstract review and full-text review, 18 studies were included in the final analysis. Among those, 44% were United States-based and 39% focused on hurricane recovery. Qualitative themes emerged surrounding geographic information systems (GIS), social media, and mental health.
Conclusions:
Big data is an evolving tool for recovery from disasters. More research, particularly in real-time applied disaster recovery settings, is needed to further expand the knowledge base for future applications.
Modern digital strategies, including Internet of Things, machine learning, and mobile applications, have revolutionized situational awareness during disaster management. Despite their importance, no review of digital strategies to support emergency food security efforts has been conducted. This scoping review fills that gap.
Methods:
Keywords were defined within the concepts of food assistance, digital technology, and disasters. After the database searches, PRISMA guidelines were followed to perform a partnered, 2-round scoping literature review.
Results:
The search identified 3201 articles, and 26 articles met criteria and were included in the analysis. The data types used to describe the tools were text/opinion (42.3%), qualitative (23.1%), system architecture (19.2%), quantitative and qualitative (11.5 %), and quantitative (3.8%). The tools’ main functions were Resource Allocation (41.7%), Data Collection and Management (33%), Interagency Communications (15.4 %), Beneficiary Communications (11.5%), and Fundraising (7.7%). The platforms used to achieve these goals were Mobile Application (36%), Internet of Things (20%), Website (20%), and Mobile Survey (8%); 92% covered the disaster response phase.
Conclusions:
Digital tools for planning, situational awareness, client choice, and recovery are needed to support emergency food assistance, but there is a lack of these tools and research on their effectiveness across all disaster phases.
We examine the impact of asset allocation and contribution rates on the risk of defined benefit (DB) pension schemes, using both a run-off and a shorter 3-year time horizon. Using the 3-year horizon, which is typically preferred by regulators, a high bond allocation reduces the spread of the distribution of surplus. However, this result is reversed when examined on a run-off basis. Furthermore, under both the 3-year horizon and the run-off, the higher bond allocation reduces the median level of surplus. Pressure on the affordability of DB schemes has led to widespread implementation of the so-called de-risking strategies, such as moving away from predominantly equity investments to greater bond investments. If the incentives produced by shorter term risk assessments are contributing to this shift, they might be harming the long-term financial health of the schemes. Contribution rates have relatively lower impact on the risk.
Whether maternal obesity and gestational weight gain (GWG) are associated with early-childhood development in low-income, urban, minority populations, and whether effects differ by child sex remain unknown. This study examined the impact of prepregnancy BMI and GWG on early childhood neurodevelopment in the Columbia Center for Children’s Environmental Health Mothers and Newborns study. Maternal prepregnancy weight was obtained by self-report, and GWG was assessed from participant medical charts. At child age 3 years, the Psychomotor Development Index (PDI) and Mental Development Index (MDI) of the Bayley Scales of Infant Intelligence were completed. Sex-stratified linear regression models assessed associations between prepregnancy BMI and pregnancy weight gain z-scores with child PDI and MDI scores, adjusting for covariates. Of 382 women, 48.2% were normal weight before pregnancy, 24.1% overweight, 23.0% obese, and 4.7% underweight. At 3 years, mean scores on the PDI and MDI were higher among girls compared to boys (PDI: 102.3 vs. 97.2, P = 0.0002; MDI: 92.8 vs. 88.3, P = 0.0001). In covariate-adjusted models, maternal obesity was markedly associated with lower PDI scores in boys [b = −7.81, 95% CI: (−13.08, −2.55), P = 0.004], but not girls. Maternal BMI was not associated with MDI in girls or boys, and GWG was not associated with PDI or MDI among either sex (all-P > 0.05). We found that prepregnancy obesity was associated with lower PDI scores at 3 years in boys, but not girls. The mechanisms underlying this sex-specific association remain unclear, but due to elevated obesity exposure in urban populations, further investigation is warranted.
Better indicators of prognosis are needed to personalise post-traumatic stress disorder (PTSD) treatments.
Aims
We aimed to evaluate early symptom reduction as a predictor of better outcome and examine predictors of early response.
Method
Patients with PTSD (N = 134) received sertraline or prolonged exposure in a randomised trial. Early response was defined as 20% PTSD symptom reduction by session two and good end-state functioning defined as non-clinical levels of PTSD, depression and anxiety.
Results
Early response rates were similar in prolonged exposure and sertraline (40 and 42%), but in sertraline only, early responders were four times more likely to achieve good end-state functioning at post-treatment (Number Needed to Treat = 1.8, 95% CI 1.28–3.00) and final follow-up (Number Needed to Treat = 3.1, 95% CI 1.68–16.71). Better outcome expectations of sertraline also predicted higher likelihood of early response.
Conclusions
Higher expectancy of sertraline coupled with early response may produce a cascade-like effect for optimal conditions for long-term symptom reduction. Therefore, assessing expectations and providing clear treatment rationales may optimise sertraline effects.
The use of scouting and economic thresholds has not been accepted as readily for managing weeds as it has been for insects, but the economic threshold concept is the basis of most weed management decision models available to growers. A World Wide Web survey was conducted to investigate perceptions of weed science professionals regarding the value of these models. Over half of the 56 respondents were involved in model development or support, and 82% thought that decision models could be beneficial for managing weeds, although more as educational rather than as decision-making tools. Some respondents indicated that models are too simple because they do not include all factors that influence weed competition or all issues a grower considers when deciding how to manage weeds. Others stated that models are too complex because many users do not have time to obtain and enter the required information or are not necessary because growers use a zero threshold or because skilled decision makers can make better and quicker recommendations. Our view is that economic threshold–based models are, and will continue to be, valuable as a means of providing growers with the knowledge and experience of many experts for field-specific decisions. Weed management decision models must be evaluated from three perspectives: biological accuracy, quality of recommendations, and ease of use. Scientists developing and supporting decision models may have hindered wide-scale acceptance by overemphasizing the capacity to determine economic thresholds, and they need to explain more clearly to potential users the tasks for which models are and are not suitable. Future use depends on finding cost-effective methods to assess weed populations, demonstrating that models use results in better decision making, and finding stable, long-term funding for maintenance and support. New technologies, including herbicide-resistant crops, will likely increase rather than decrease the need for decision support.
Speech is commonly claimed to relate to mirror neurons because of the alluring surface analogy of mirror neurons to the Motor Theory of speech perception, which posits that perception and production draw upon common motor-articulatory representations. We argue that the analogy fails and highlight examples of systems-level developmental approaches that have been more fruitful in revealing perception–production associations.
Outcome of moderate to severe traumatic brain injury (TBI) includes impaired emotion regulation. Emotion regulation has been associated with amygdala and rostral anterior cingulate (rACC). However, functional connectivity between the two structures after injury has not been reported. A preliminary examination of functional connectivity of rACC and right amygdala was conducted in adolescents 2 to 3 years after moderate to severe TBI and in typically developing (TD) control adolescents, with the hypothesis that the TBI adolescents would demonstrate altered functional connectivity in the two regions. Functional connectivity was determined by correlating fluctuations in the blood oxygen level dependent (BOLD) signal of the rACC and right amygdala with that of other brain regions. In the TBI adolescents, the rACC was found to be significantly less functionally connected to medial prefrontal cortices and to right temporal regions near the amygdala (height threshold T = 2.5, cluster level p < .05, FDR corrected), while the right amygdala showed a trend in reduced functional connectivity with the rACC (height threshold T = 2.5, cluster level p = .06, FDR corrected). Data suggest disrupted functional connectivity in emotion regulation regions. Limitations include small sample sizes. Studies with larger sample sizes are necessary to characterize the persistent neural damage resulting from moderate to severe TBI during development. (JINS, 2013, 19, 1–14)