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Main Objective: Cognitive difficulties are some of the most frequently experienced symptoms following mild-to-moderate traumatic brain injuries (TBIs). There is meta-analytic evidence that cognitive rehabilitation improves cognitive functioning after TBI in nonveteran populations but not specifically within the veteran and service member (V/SM) population. The purpose of the current meta-analysis was to examine the effect of cognitive rehabilitation interventions for V/SMs with a history of mild-to-moderate TBI., Design and Main Measures: This meta-analysis was preregistered with PROSPERO (CRD42021262902) and used the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) checklist for reporting guidelines. Inclusion criteria required studies to have (1) randomized controlled trials; (2) used adult participants (aged 18 years or older) who were US veterans or active-duty service members who had a history of mild-to-moderate TBI; (3) cognitive rehabilitation treatments designed to improve cognition and/or everyday functioning; (4) used objective neuropsychological testing as a primary outcome measure; and (5) been published in English. At least 2 reviewers independently screened all identified abstracts and full-text articles and coded demographic and effect size data. The final search was run on February 24, 2023, using 4 databases (PubMed, PsycINFO, Web of Science, and Google Scholar). Study quality and bias were examined using the revised Cochrane Risk-of-Bias Tool for Randomized Trials., Results: We identified 8 articles meeting full criteria (total participants = 564; 97% of whom had a history of mild TBI). Compared with control groups, participants showed a small, but significant, improvement in overall objective neuropsychological functioning after cognitive rehabilitation interventions. Interventions focusing on teaching strategies had a larger effect size than did those focusing on drill-and-practice approaches for both objective neuropsychological test performance and performance-based measures of functional capacity., Conclusion: There is evidence of cognitive improvement in V/SMs with TBI histories after participation in cognitive rehabilitation. Clinician-administered interventions focusing on teaching strategies may yield the greatest cognitive improvement in this population., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

To effectively diagnose and treat subjective cognitive symptoms in post-acute sequalae of COVID-19 (PASC), it is important to understand objective cognitive impairment across the range of acute COVID-19 severity. Despite the importance of this area of research, to our knowledge, there are no current meta-analyses of objective cognitive functioning following non-severe initial SARS-CoV-2 infection. The aim of this meta-analysis is to describe objective cognitive impairment in individuals with non-severe (mild or moderate) SARS-CoV-2 cases in the post-acute stage of infection. This meta-analysis was pre-registered with Prospero (CRD42021293124) and utilized the PRISMA checklist for reporting guidelines, with screening conducted by at least two independent reviewers for all aspects of the screening and data extraction process. Fifty-nine articles (total participants = 22,060) with three types of study designs met our full criteria. Individuals with non-severe (mild/moderate) initial SARS-CoV-2 infection demonstrated worse objective cognitive performance compared to healthy comparison participants. However, those with mild (nonhospitalized) initial SARS-CoV-2 infections had better objective cognitive performance than those with moderate (hospitalized but not requiring ICU care) or severe (hospitalized with ICU care) initial SARS-CoV-2 infections. For studies that used normative data comparisons instead of healthy comparison participants, there was a small and nearly significant effect when compared to normative data. There were high levels of heterogeneity (88.6 to 97.3%), likely reflecting small sample sizes and variations in primary study methodology. Individuals who have recovered from non-severe cases of SARS-CoV-2 infections may be at risk for cognitive decline or impairment and may benefit from cognitive health interventions., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Secondary crashes or crashes that occur in the wake of a preceding or primary crash are among the most critical incidents occurring on highways, due to the exceptional danger they present to the first responders and victims of the primary crash. In this work, we developed a self-exciting temporal point process to analyze crash events data and classify it into primary and secondary crashes. Our model uses a self-exciting function to describe secondary crashes while primary crashes are modeled using a background rate function. We fit the model to crash incidents data from the Florida Department of Transportation, on Interstate-4 (I-4) highway for the years 2015-2017, to determine the model parameters. These are used to estimate the probability that a given crash is secondary crash and to find queue times. To represent the periodically varying traffic levels and crash incidents, we model the background rate, as a stationary function, a sinusoidal non-stationary function, and a piecewise non-stationary function. We show that the sinusoidal non-stationary background rate fits the traffic data better and replicates the daily and weekly peaks in crash events due to traffic rush hours. Secondary crashes are found to account for up to 15.09% of traffic incidents, depending on the city on the I-4 Highway., Competing Interests: There are no competing interests for this study., (Copyright: © 2023 Motagi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Competing Interests: Disclosures of conflicts of interest: J.C. No relevant relationships. S.P. National Science Foundation Graduate Research Fellowship, paid for through Brown University as part of the computer science department, additional stipend from Brown itself; consultant for Spellcraft AI (minor fees [<1000 dollars] for relatively unrelated consulting for a startup, the topic was similar: foundation models, although not in a medical context).

The continuous spread of coronavirus disease 2019 (COVID-19) has highlighted the need for simple and reliable diagnostic technologies for point-of-care (POC) virus detection applications. Here, we report a COVID-19 diagnostic platform based on aerosol jet-printed antibody-functionalized organic electrochemical transistors (OECTs) for rapidly identifying severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) antigens. Selective sensing of SARS-CoV-2 spike S1 protein is achieved in phosphate-buffered saline (PBS) with a detectable range of 1 fg mL -1 to 1 μg mL -1 . We used the sensors to detect the antigens in unprocessed patient nasopharyngeal swab samples in universal transport medium (UTM) and achieved an overall accuracy of 70%. In addition, these patient sample tests clearly demonstrate that our OECT threshold voltage shift is correlated with the sample SARS-CoV-2 viral load. Hence, we have demonstrated an accurate POC biosensor for detecting SARS-CoV-2 antigens, which holds great promise towards developing on-site and at-home rapid SARS-CoV-2 infection screening and COVID-19 prognosis.

Background: Hereditary transthyretin amyloidosis (ATTRv) is an ultra-rare, life-shortening disease with a high unmet need. This study examined ATTRv caregiver health-related quality of life (HRQoL) and productivity., Methods: A cross-sectional online survey, including EQ-5D-3L, Hospital anxiety and depression scale (HADS), and caregiver and patient characteristics questions, was developed to assess ATTRv caregiver burden. A companion general population survey collected EQ-5D-3L, HADS and chronic health conditions data. Caregiver-control group differences in HRQoL were assessed using t-tests and chi-square tests. Ordinary Least Squares regression was used to estimate the disutility of being a caregiver compared to controls stratified by patient ambulatory status., Results: Thirty-six caregivers and matched controls completed the survey (n = 72). The disease severity of patients they cared for was varied: 33% required no assistance walking, 58% required assistance with walking and 9% required a wheelchair/were bedridden. On average, caregivers spent 6 h daily on practical care and 4 h daily on emotional support. Fifty-six percent indicated that they had changed their employment due to providing ATTRv care. Caregivers reported lower HRQoL, as indicated by lower EQ-5D 3L utility scores (M = 0.772, SD = 0.178 vs. M = 0.849, SD = 0.218) and higher HADS anxiety (9.3 vs. 6.1, p < 0.01) and depression (7.6 vs. 4.4, p < 0.01) scores, compared with matched controls. Caregivers were also more likely to report sleep problems (33% vs. 8%, p < 0.01) and stress (42% vs. 0%, p < 0.001) as chronic conditions than controls., Conclusions: The study results indicate that caring for a person with ATTRv can have a considerable negative impact on caregivers' HRQoL and productivity. The study findings provide important information for economic evaluations of ATTRv treatments., (© 2023. The Author(s).)

Aim: To describe the strength of a cross-sector and multi-university collaboration in co-designing an extended nursing placement innovation in rural and remote Australia., Context: Registered nurses are Australia's largest health workforce. Short-duration placements can limit nursing student exposure to rural and remote practice, impacting student capacity to tailor and contextualise their practice, navigate complex inequities, establish a sense of belonging and consider rural practice post-registration. Extended nursing placements have been recommended to address these challenges, but there are no guidelines governing their development and limited resources to support implementation., Approach: Methods adopted in program development included the following: (1) collaboration establishment; (2) co-defining challenges confronting nurse education in these contexts; (3) co-developing guiding principles; (4) co-designing a new approach to nurse education, the Extended Nursing Placement Program (ENPP); and (5) the co-contribution of stakeholders to program design, implementation and evaluation. Regional stakeholders include a NSW and Victorian Local Health District/Service, three Aboriginal health services and the Royal Flying Doctor Service of Australia. University participants include two metropolitan universities, a University Department of Rural Health and final-year Bachelor of Nursing students. Program implementation in Semester 1 of 2022 with seven final-year nursing students., Conclusion: The authors propose that the adoption of collaborative approaches can contribute to re-framing student nurse education and the development of a rural-ready nursing workforce. These approaches can provide regions and universities with the opportunity to avoid student churn whilst promoting the attainment of skills required to work, live and thrive in these locations., (© 2022 National Rural Health Alliance Ltd.)

Outdoor air pollution is a complex system that is responsible for the deaths of millions of people annually, yet the integration of interdisciplinary data necessary to assess air quality's multiple metrics is still lacking. This case study integrates atmospheric indicators (concentrations of criteria pollutants including particulate matter and gaseous pollutants), traffic indicators (permanent traffic monitoring station data), and social indicators (community responses in Twitter archives) representing the interplay of the three critical pillars of the United Nations' Triple Bottom Line: environment, economy, and society. During the watershed moment of the COVID-19 pandemic lockdowns in Florida, urban centers demonstrated the gaps and opportunities for understanding the relationships, through correlations rather than causations, between urban air quality, traffic emissions, and public perceptions. The relationship between the perception and the traffic variables were strongly correlated, however no correlation was observed between the perception and actual air quality indicators, except for NO 2 . These observations might consequently infer that traffic serves as people's proxy for air quality, regardless of actual air quality, suggesting that social media messaging around asthma may be a way to monitor traffic patterns in areas where no infrastructure currently exists or is prohibited to build. It also indicates that people are less likely to be reliable sensors to accurately measure air quality due to bias in their observations of traffic volume and/or confirmation biases in broader social discourse. Results presented herein are of significance in demonstrating the capacity for interdisciplinary studies to consider the predictive capacities of social media and air pollution, its use as both lever and indicator of public support for air quality legislation and clean-air transitions, and its ability to overcome limitations of surface monitoring stations., Competing Interests: Declaration of competing interest Heather O'Leary reports financial support was provided by USF COVID-19 Rapid Response Grants in Research & Innovation at the University of South Florida, grant from the Pandemic Response Research Network (PRRN). Scott Parr reports financial support was provided by United States Department of Transportation. Scott Parr reports financial support was provided by Center for Advanced Transportation Mobility at North Carolina A&T University. Marwa M.H. El-Sayed reports financial support was provided by Embry-Riddle Aeronautical University., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

This article presents a framework to analyse the gendered impact of COVID-19 on workers in global value chains (GVCs) in the business process outsourcing, garment and electronics industries. Distinguishing between the health and lockdown effects of the pandemic, and between its supply- and demand-related impacts, the authors' gendered analysis focuses on multidimensional aspects of well-being, understands the economy as encompassing production and social reproduction spheres, and examines the social norms and structures of power that produce gender inequalities. Their findings suggest that the pandemic exposes and amplifies the existing vulnerabilities of women workers in GVCs., (© The authors 2021 Journal compilation © International Labour Organization 2021.)

US ports and container/intermodal terminals are critical links in the marine transportation system. Disruption at a port can have a crippling economic effect in the coastal zone as well as the rest of the nation. Port stakeholders have a vested interest in the long-term function and viability of ports, but no standardized measures for performance or resilience exist for ports. The goal of this research is to demonstrate the utility of a predictive port resilience assessment tool. The developed tool encompasses a microscopic traffic simulation model (VISSIM) based hybrid multimodal analyzes of port operations and provides a quantifiable assessment of resilience. The application of this tool is shown on six ports in the Southeast US. The waterside port simulation models were developed using vessel automatic identification system data and programed within a VISSIM simulation of landside operations. This hybrid modeling approach was used to visualize vessels and allow them to interact in both time and space with each other and landside infrastructure. Local and regional resilience was quantified through the analysis of time-dependent resilience plots and used as a performance measure in this study. The utility of the predictive port resilience assessment was demonstrated in response to Hurricane Matthew (2016). However, the novel procedure described herein can be applied to any port hazard. This research grows the understanding of the regional consequences of hurricane events and enhances the knowledge in the development of a stakeholder-focused tool to assess resilience., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2021.)

Background: Successful development of new treatments for rare diseases (RDs) and their sustainable patient access require overcoming a series of challenges related to research and health technology assessment (HTA). These impediments, which may be unique to RDs or also apply to common diseases but are particularly pertinent in RDs, are diverse and interrelated., Objective: To develop for the first time a catalog of primary impediments to RD research and HTA, and to describe the cause and effect of individual challenges., Methods: Challenges were identified by an international 22-person expert working group and qualitative outreach to colleagues with relevant expertise. A broad range of stakeholder perspectives is represented. Draft results were presented at annual European and North American International Society for Pharmacoeconomics and Outcomes Research (ISPOR) congresses, and written comments were received by the 385-strong ISPOR Rare Disease Review Group from two rounds of review. Findings were refined and confirmed via targeted literature search., Results: Research-related challenges linked to the low prevalence of RDs were categorized into those pertaining to disease recognition and diagnosis, evaluation of treatment effect, and patient recruitment for clinical research. HTA-related challenges were classified into issues relating to the lack of a tailored HTA method for RD treatments and uncertainty for HTA agencies and health care payers., Conclusions: Identifying and highlighting diverse, but interrelated, key challenges in RD research and HTA is an essential first step toward developing implementable and sustainable solutions. A collaborative multistakeholder effort is required to enable faster and less costly development of safe, efficacious, and appropriate new RD therapies that offer value for money., (Copyright © 2018 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.)

Background: It has been suggested that ultra-rare diseases should be recognized as distinct from more prevalent rare diseases, but how drugs developed to treat ultra-rare diseases (DURDs) might be distinguished from drugs for 'other' rare diseases (DORDs) is not clear. We compared the characteristics of DURDs to DORDs from a health technology assessment (HTA) perspective in submissions made to the CADTH Common Drug Review. We defined a DURD as a drug used to treat a disease with a prevalence ≤ 1 patient per 100,000 people, a DORD as a drug used to treat a disease with a prevalence > 1 and ≤ 50 patients per 100,000 people. We assessed differences in the level and quantity of evidence supporting each HTA submission, the molecular basis of treatment agents, annual treatment cost per patient, type of reimbursement recommendation made by CADTH, and reasons for negative recommendations., Results: We analyzed 14 DURD and 46 DORD submissions made between 2004 and 2016. Compared to DORDs, DURDs were more likely to be biologic drugs (OR = 6.06, 95%CI 1.25 to 38.58), to have been studied in uncontrolled clinical trials (OR = 23.11, 95%CI 2.23 to 1207.19), and to have a higher annual treatment cost per patient (median difference = CAN$243,787.75, 95%CI CAN$83,396 to CAN$329,050). Also, submissions for DURDs were associated with a less robust evidence base versus DORDs, as DURD submissions were less likely to include data from at least one double-blinded randomized controlled trial (OR = 0.13, 95%CI 0.02 to 0.70) and have smaller patient cohorts in clinical trials (median difference = -108, 95%CI -234 to -50). Furthermore, DURDs are less likely to receive a positive reimbursement recommendation (OR = 0.22, 95%CI 0.05 to 0.91), and low level of evidence was the major contributor for a negative recommendation., Conclusions: The results suggest that DURDs could be viewed as distinct category from an HTA perspective. Applying the same HTA decision-making framework to DURDs and DORDs might have contributed the higher rate of negative reimbursement recommendations made for DURDs. Recognition of DURDs as a distinct subgroup of DRDs by explicitly defining DURDs based on objective criteria may facilitate the implementation of HTA assessment process that accounts for the issues associated with DURD.

Background: Rare diseases (RDs) affect a small number of people within a population. About 5000 to 8000 distinct RDs have been identified, with an estimated 6% to 8% of people worldwide suffering from an RD. Approximately 75% of RDs affect children. Frequently, these conditions are heterogeneous; many are progressive. Regulatory incentives have increased orphan drug designations and approvals., Objective: To develop emerging good practices for RD outcomes research addressing the challenges inherent in identifying, selecting, developing, adapting, and implementing patient-reported outcome (PRO) and observer-reported outcome (ObsRO) assessments for use in RD clinical trials., Good Practices for Outcomes Research: This report outlines the challenges and potential solutions in determining clinical outcomes for RD trials. It follows the US Food and Drug Administration Roadmap to Patient-Focused Outcome Measurement in Clinical Trials. The Roadmap consists of three columns: 1) Understanding the Disease or Condition, 2) Conceptualizing Treatment Benefit, and 3) Selecting/Developing the Outcome Measure. Challenges in column 1 include factors such as incomplete natural history data and heterogeneity of disease presentation and patient experience. Solutions include using several information sources, for example, clinical experts and patient advocacy groups, to construct the condition's natural history and understand treatment patterns. Challenges in column 2 include understanding and measuring treatment benefit from the patient's perspective, especially given challenges in defining the context of use such as variations in age or disease severity/progression. Solutions include focusing on common symptoms across patient subgroups, identifying short-term outcomes, and using multiple types of COA instruments to measure the same constructs. Challenges in column 3 center around the small patient population and heterogeneity of the condition or study sample. Few disease-specific instruments for RDs exist. Strategies include adapting existing instruments developed for a similar condition or that contain symptoms of importance to the RD patient population, or using a generic instrument validated for the context of use., Conclusions: This report provides state-of-the-art solutions to patient-reported outcome (PRO) and observer-reported outcome (ObsRO) assessments challenges in clinical trials of patients with RDs. These recommended solutions are both pragmatic and creative and posed with clear recognition of the global regulatory context used in RD clinical development programs., (Copyright © 2017. Published by Elsevier Inc.)

Background: At present, there is no universal definition of rare disease., Objective: To provide an overview of rare disease definitions currently used globally., Methods: We systematically searched for definitions related to rare disease from organizations in 32 international jurisdictions. Descriptive statistics of definitions were generated and prevalence thresholds were calculated., Results: We identified 296 definitions from 1109 organizations. The terms "rare disease(s)" and "orphan drug(s)" were used most frequently (38% and 27% of the definitions, respectively). Qualitative descriptors such as "life-threatening" were used infrequently. A prevalence threshold was specified in at least one definition in 88% of the jurisdictions. The average prevalence threshold across organizations within individual jurisdictions ranged from 5 to 76 cases/100,000 people. Most jurisdictions (66%) had an average prevalence threshold between 40 and 50 cases/100,000 people, with a global average of 40 cases/100,000 people. Prevalence thresholds used by different organizations within individual jurisdictions varied substantially. Across jurisdictions, umbrella patient organizations had the highest (most liberal) average prevalence threshold (47 cases/100,000 people), whereas private payers had the lowest threshold (18 cases/100,000 people)., Conclusions: Despite variation in the terminology and prevalence thresholds used to define rare diseases among different jurisdictions and organizations, the terms "rare disease" and "orphan drug" are used most widely and the average prevalence threshold is between 40 and 50 cases/100,000 people. These findings highlight the existing diversity among definitions of rare diseases, but suggest that any attempts to harmonize rare disease definitions should focus on standardizing objective criteria such as prevalence thresholds and avoid qualitative descriptors., (Copyright © 2015 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.)

Background: Evidence-based practice has become fundamentally important in the field of musculoskeletal physiotherapy, which include clinical practice guidelines, such as those developed by National Institute for Health and Clinical Excellence (NICE) for low back pain., Objectives: To gauge whether musculoskeletal physiotherapist working in the UK are compliant with the NICE guidelines for back pain, and if they believe them to be practical and relevant to their current practice., Design: Descriptive cross-sectional voluntary electronic survey., Methods: A survey of musculoskeletal physiotherapists currently working in the UK was conducted through an anonymous online data collection website over a two month data collection period. Data was collected about demographic details of participants, and their views about the NICE guidelines through a specially designed questionnaire, and are presented descriptively., Results: Two hundred and twenty-three therapists participated. Following a thematic content analysis seven key themes were identified about the guidelines: they facilitated evidence-based practice; they were unrealistic and idealistic; they did not facilitate a multimodal approach; they promoted largely a passive approach; they challenged therapist autonomy; they were outdated; they lacked relevance and specificity., Conclusion: Musculoskeletal physiotherapists strongly believe in the principles of EBP, and thought the NICE back pain guidelines were relevant to their practice. However the recommendations made within the guidelines were not realistic in day to day practice and they impacted negatively on the practice in a number of ways., (Copyright © 2013 Chartered Society of Physiotherapy. Published by Elsevier Ltd. All rights reserved.)