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Evaluation of benefits beyond quantitative academic outputs is essential in determining translational research value. We used the Translational Science Benefits Model (TSBM) to examine the impact of the QUARTET USA trial using 30 benefits across 4 domains: Clinical, Community, Economic, and Policy. We found that the QUARTET USA trial demonstrated impact in six areas within the Clinical, and Community domains and had potential impact in two additional areas within the Community and Economic domains. Use of the TSBM supports the value of the QUARTET USA trial, which can be used as a template for future cardiovascular trials.
Young people with a first episode of psychosis can achieve full remission with prompt treatment. Throughout Canada, early psychosis intervention programs are implementing policies to ensure timely delivery of services. One of Canada’s first early intervention services, the Prevention and Early Intervention for Psychosis program, set the guideline that all youth referred should receive an appointment within 72 hours. The availability of early intervention programs has increased significantly but the standards these programs have adopted to ensure timely delivery of services remains unknown.
Objectives
This project aims to identify the policies and practices in early intervention programs that ensure timely delivery of services. Secondly, the project aims to understand the level of awareness of the 72-hour recommendation and the level of adoption of this recommendation. Thirdly, the project aims to identify the factors that facilitate and hinder a program’s ability to reach and maintain their benchmarks for timely delivery of services.
Methods
Participants included 17 service delivery providers from four early intervention programs located in socio-culturally distinct regions in Canada. Participants completed a survey about their program’s service delivery policies and practices. We led individual semi-structured interviews with seven service providers to identify the barriers and facilitators to delivering timely care. We conducted frequency analyses of the survey data and thematic analysis of the interviews to identify emerging themes.
Results
Forty-one percent of survey respondents indicated that their program implemented formal policies to minimize the delay to the first appointment, with benchmarks ranging from 72 hours to 12 weeks. The majority of program managers interviewed were aware of the 72-hour benchmark, voiced satisfaction with standards, and felt that establishing standards was helpful to delivering quality services. Average time between referral and first appointment ranged from 10 days to 12 weeks; however, more than half of survey respondents were unaware of the average delay in their program. Notable barriers to implementation included patient non-responsiveness, insufficient staffing, and missing patient contact information from referrals. The service providers reported engaged staff, flexible schedules, and team-based care as facilitators to meeting service delivery benchmarks.
Conclusions
Benchmarks such as the 72-hour recommendation are an excellent step in improving timeliness of delivery of early intervention services. Common barriers to meeting benchmarks, such as patient adherence and staff resources may be difficult to overcome; however, implementing standardized referral forms and processes, increasing staff engagement, providing flexible schedules, and encouraging team-based care could improve timely delivery of services.
Although chemical and radiological agents cause toxicity through different mechanisms, the multiorgan injuries caused by these threats share similarities that convene on the level of basic biological responses. This publication will discuss these areas of convergence and explore “multi-utility” approaches that could be leveraged to address common injury mechanisms underlying actions of chemical and radiological agents in a threat-agnostic manner. In addition, we will provide an overview of the current state of radiological and chemical threat research, discuss the US Government’s efforts toward medical preparedness, and identify potential areas for collaboration geared toward enhancing preparedness and response against radiological and chemical threats. We also will discuss previous regulatory experience to provide insight on how to navigate regulatory paths for US Food and Drug Administration (FDA) approval/licensure/clearance for products addressing chemical or radiological/nuclear threats. This publication follows a 2022 trans-agency meeting titled, “Overlapping Science in Radiation and Sulfur Mustard Exposures of Skin and Lung: Consideration of Models, Mechanisms, Organ Systems, and Medical Countermeasures,” sponsored by the National Institute of Allergy and Infectious Diseases (NIAID), a part of the National Institutes of Health (NIH). Discussions from this meeting explored the overlapping nature of radiation and chemical injury and spurred increased interest in how preparedness for one threat leads to preparedness for the other. Herein, subject matter experts from the NIAID and the Biomedical Advanced Research and Development Authority (BARDA), a part of the Administration for Strategic Preparedness and Response (ASPR), summarize the knowledge gained from recently funded biomedical research, as well as insights from the 2022 meeting. These topics include identification of common areas for collaboration, potential use of biomarkers of injury to identify injuries caused by both hazards, and common and widely available treatments that could treat damage caused by radiological or chemical threats.
Evidence of myelosuppression has been negatively correlated with patient outcomes following cases of high dose sulfur mustard (SM) exposure. These hematologic complications can negatively impact overall immune function and increase the risk of infection and life-threatening septicemia. Currently, there are no approved medical treatments for the myelosuppressive effects of SM exposure.
Methods:
Leveraging a recently developed rodent model of SM-induced hematologic toxicity, post-exposure efficacy testing of the granulocyte colony-stimulating factor drug Neupogen® was performed in rats intravenously challenged with SM. Before efficacy testing, pharmacokinetic/pharmacodynamic analyses were performed in naïve rats to identify the apparent human equivalent dose of Neupogen® for efficacy evaluation.
Results:
When administered 1 d after SM-exposure, daily subcutaneous Neupogen® treatment did not prevent the delayed onset of hematologic toxicity but significantly accelerated recovery from neutropenia. Compared with SM controls, Neupogen®-treated animals recovered body weight faster, resolved toxic clinical signs more rapidly, and did not display transient febrility at time points generally concurrent with marked pancytopenia.
Conclusions:
Collectively, this work corroborates the results of a previous pilot large animal study, validates the utility of a rodent screening model, and provides further evidence for the potential clinical utility of Neupogen® as an adjunct treatment following SM exposure.
The Eighth World Congress of Pediatric Cardiology and Cardiac Surgery (WCPCCS) will be held in Washington DC, USA, from Saturday, 26 August, 2023 to Friday, 1 September, 2023, inclusive. The Eighth World Congress of Pediatric Cardiology and Cardiac Surgery will be the largest and most comprehensive scientific meeting dedicated to paediatric and congenital cardiac care ever held. At the time of the writing of this manuscript, The Eighth World Congress of Pediatric Cardiology and Cardiac Surgery has 5,037 registered attendees (and rising) from 117 countries, a truly diverse and international faculty of over 925 individuals from 89 countries, over 2,000 individual abstracts and poster presenters from 101 countries, and a Best Abstract Competition featuring 153 oral abstracts from 34 countries. For information about the Eighth World Congress of Pediatric Cardiology and Cardiac Surgery, please visit the following website: [www.WCPCCS2023.org]. The purpose of this manuscript is to review the activities related to global health and advocacy that will occur at the Eighth World Congress of Pediatric Cardiology and Cardiac Surgery.
Acknowledging the need for urgent change, we wanted to take the opportunity to bring a common voice to the global community and issue the Washington DC WCPCCS Call to Action on Addressing the Global Burden of Pediatric and Congenital Heart Diseases. A copy of this Washington DC WCPCCS Call to Action is provided in the Appendix of this manuscript. This Washington DC WCPCCS Call to Action is an initiative aimed at increasing awareness of the global burden, promoting the development of sustainable care systems, and improving access to high quality and equitable healthcare for children with heart disease as well as adults with congenital heart disease worldwide.
During your call duty, a healthy 40-year-old primigravida with a spontaneous dichorionic pregnancy presents, accompanied by her husband, to the obstetric emergency assessment unit of your hospital center at 33+1 weeks’ gestation with new-onset abdominal pain and vomiting after a two-day history of nausea and general malaise. She has no obstetric complaints, and fetal viabilities are ascertained upon presentation. Her face appears yellow tinged relative to her last clinical visit one week ago. You recall that routine prenatal laboratory investigations, aneuploidy screening, morphology surveys of the male fetuses, and serial sonograms have all been unremarkable.
Gait, balance, and cognitive impairment make travel cumbersome for People with Parkinson’s disease (PwPD). About 75% of PwPD cared for at the University of Arkansas for Medical Sciences’ Movement Disorders Clinic reside in medically underserved areas (MUAs). Validated remote evaluations could help improve their access to care. Our goal was to explore the feasibility of telemedicine research visits for the evaluation of multi-modal function in PwPD in a rural state.
Methods:
In-home telemedicine research visits were performed in PwPD. Motor and non-motor disease features were evaluated and quantified by trained personnel, digital survey instruments for self-assessments, digital voice recordings, and scanned and digitized Archimedes spiral drawings. Participant’s MUA residence was determined after evaluations were completed.
Results:
Twenty of the fifty PwPD enrolled resided in MUAs. The groups were well matched for disease duration, modified motor UPDRS, and Montreal Cognitive assessment scores but MUA participants were younger. Ninety-two percent were satisfied with their visit, and 61% were more likely to participate in future telemedicine research. MUA participants traveled longer distances, with higher travel costs, lower income, and education level. While 50% of MUA participants reported self-reliance for in-person visits, 85% reported self-reliance for the telemedicine visit. We rated audio-video quality highly in approximately 60% of visits in both groups. There was good correlation with prior in-person research assessments in a subset of participants.
Conclusions:
In-home research visits for PwPD in MUAs are feasible and could help improve access to care and research participation in these traditionally underrepresented populations.
An unusual combination of three types of interatrial communications – coronary sinus defect, primum defect, and secundum defect – occurring together in a 3-year-old child is presented.
Pharyngocutaneous fistulae are dreaded complications following total laryngectomy. This paper presents our experience using 3–5 ml gastrografin to detect pharyngeal leaks following total laryngectomy, and compares post-operative videofluoroscopy with clinical follow-up findings in the detection of pharyngocutaneous fistulae.
Methods
A retrospective case–control study was conducted of total laryngectomy patients. The control group (n = 85) was assessed clinically for development of pharyngocutaneous fistulae, while the study group (n = 52) underwent small-volume (3–5 ml) post-operative gastrografin videofluoroscopy.
Results
In the control group, 24 of 85 patients (28 per cent) developed pharyngocutaneous fistulae, with 6 requiring surgical correction. In the study group, 24 of 52 patients (46 per cent) had videofluoroscopy-detected pharyngeal leaks; 4 patients (8 per cent) developed pharyngocutaneous fistulae, but all cases resolved following non-surgical management. Patients who underwent videofluoroscopy had a significantly lower risk of developing pharyngocutaneous fistulae; sensitivity and specificity in the detection of pharyngocutaneous fistulae were 58 per cent and 100 per cent respectively.
Conclusion
Small-volume gastrografin videofluoroscopy reliably identified small pharyngeal leaks. Routine use in total laryngectomy combined with withholding feeds in cases of early leaks may prevent the development of pharyngocutaneous fistulae.
Comparing the feasibility of ovine and synthetic temporal bones for simulating endoscopic ear surgery against the ‘gold standard’ of human cadaveric tissue.
Methods
A total of 10 candidates (5 trainees and 5 experts) performed endoscopic tympanoplasty on 3 models: Pettigrew temporal bones, ovine temporal bones and cadaveric temporal bones. Candidates completed a questionnaire assessing the face validity, global content validity and task-specific content validity of each model.
Results
Regarding ovine temporal bone validity, the median values were 4 (interquartile range = 4–4) for face validity, 4 (interquartile range = 4–4) for global content validity and 4 (interquartile range = 4–4) for task-specific content validity. For the Pettigrew temporal bone, the median values were 3.5 (interquartile range = 2.25–4) for face validity, 3 (interquartile range = 2.75–3) for global content validity and 3 (interquartile range = 2.5–3) for task-specific content validity. The ovine temporal bone was considered significantly superior to the Pettigrew temporal bone for the majority of validity categories assessed.
Conclusion
Tympanoplasty is feasible in both the ovine temporal bone and the Pettigrew temporal bone. However, the ovine model was a significantly more realistic simulation tool.
Currently no national guidelines exist for the management of scabies outbreaks in residential or nursing care homes for the elderly in the United Kingdom. In this setting, diagnosis and treatment of scabies outbreaks is often delayed and optimal drug treatment, environmental control measures and even outcome measures are unclear. We undertook a systematic review to establish the efficacy of outbreak management interventions and determine evidence-based recommendations. Four electronic databases were searched for relevant studies, which were assessed using a quality assessment tool drawing on STROBE guidelines to describe the quality of observational data. Nineteen outbreak reports were identified, describing both drug treatment and environmental management measures. The quality of data was poor; none reported all outcome measures and only four described symptom relief measures. We were unable to make definitive evidence-based recommendations. We draw on the results to propose a framework for data collection in future observational studies of scabies outbreaks. While high-quality randomised controlled trials are needed to determine optimal drug treatment, evidence on environmental measures will need augmentation through other literature studies. The quality assessment tool designed is a useful resource for reporting of outcome measures including patient-reported measures in future outbreaks.
Eigenmodes of averaged small-amplitude perturbations to a turbulent channel flow – which is one of the most fundamental canonical flows – are identified for the first time via an extensive set of high-fidelity graphics processing unit accelerated direct numerical simulations. While the system governing averaged small-amplitude perturbations to turbulent channel flow remains unknown, the fact such eigenmodes can be identified constitutes direct evidence that it is linear. Moreover, while the eigenvalue associated with the slowest-decaying anti-symmetric eigenmode mode is found to be real, the eigenvalue associated with the slowest-decaying symmetric eigenmode mode is found to be complex. This indicates that the unknown linear system governing the evolution of averaged small-amplitude perturbations cannot be self-adjoint, even for the case of a uni-directional flow. In addition to elucidating aspects of the flow physics, the findings provide guidance for development of new unsteady Reynolds-averaged Navier–Stokes turbulence models, and constitute a new and accessible benchmark problem for assessing the performance of existing models, which are used widely throughout industry.
At GE Research, we are combining “physics” with artificial intelligence and machine learning to advance manufacturing design, processing, and inspection, turning innovative technologies into real products and solutions across our industrial portfolio. This article provides a snapshot of how this physical plus digital transformation is evolving at GE.
Elderly patients have been consistently shown to receive suboptimal therapy for cancers of the head and neck. This study was performed to determine the peri-operative outcomes of these patients and compare them with those of younger patients.
Methods
In this retrospective analysis, 115 patients aged 70 years or more undergoing major surgery for head and neck cancers were matched with 115 patients aged 50–60 years, and univariate analysis was performed.
Results
Elderly patients had a reduced performance status (p < 0.001) and more co-morbid illnesses (p = 0.007), but a comparable intra-operative course. They had a longer median hospital stay (p = 0.016), longer intensive care unit stay (p = 0.04), longer median tracheostomy dependence (p = 0.04) and were more often discharged with feeding tubes (p < 0.001). They also had a higher incidence of post-operative non-fatal cardiac events (p = 0.045).
Conclusion
Elderly patients with good performance status should receive curative-intent surgery. Although hospital stay and tube dependence are longer, morbidity and mortality are comparable with younger patients.
Metal–graphene composites are sought after for various applications. A hybrid light-weight foam of nickel (Ni) and reduced graphene oxide (rGO), called Ni-rGO, is reported here for small molecule oxidations and thereby their sensing. Methanol oxidation and non-enzymatic glucose sensing are attempted with the Ni-rGO foam via electrocatalytically, and an enhanced methanol oxidation current density of 4.81 mA/cm2 is achieved, which is ~1.7 times higher than that of bare Ni foam. In glucose oxidation, the Ni-rGO electrode shows a better sensitivity over bare Ni foam electrode where it could detect glucose linearly over a concentration range of 10 µM to 4.5 mM with a very low detection limit of 3.6 µM. This work demonstrates the synergistic effects of metal and graphene in oxidative processes, and also shows the feasibility of scalable metal–graphene composite inks development for small molecule printable sensors and fuel cell catalysts.
In many parts of the world, mostly low- and middle-income countries, timely diagnosis and repair of congenital heart diseases (CHDs) is not feasible for a variety of reasons. In these regions, economic growth has enabled the development of cardiac units that manage patients with CHD presenting later than would be ideal, often after the window for early stabilisation – transposition of the great arteries, coarctation of the aorta – or for lower-risk surgery in infancy – left-to-right shunts or cyanotic conditions. As a result, patients may have suffered organ dysfunction, manifest signs of pulmonary vascular disease, or the sequelae of profound cyanosis and polycythaemia. Late presentation poses unique clinical and ethical challenges in decision making regarding operability or surgical candidacy, surgical strategy, and perioperative intensive care management.
Commonly thought of as a disease of poverty and overcrowding in resource-poor settings globally, scabies is also an important public health issue in residential care facilities for the elderly (RCFE) in high-income countries such as the UK. We compared and contrasted current local Health Protection Team (HPT) guidelines for the management of scabies outbreaks in RCFE throughout England. We performed content analysis on 20 guidelines, and used this to create a quantitative report of their variation in key dimensions. Although the guidelines were generally consistent on issues such as the treatment protocols for individual patients, there was substantial variation in their recommendations regarding the prophylactic treatment of contacts, infection control measures and the roles and responsibilities of individual stakeholders. Most guidelines did not adequately address the logistical challenges associated with mass treatment in this setting. We conclude that the heterogeneous nature of the guidelines reviewed is an argument in favour of national guidelines being produced.
Quasi-one-dimensional (quasi-1D) tools developed for capturing flow and acoustic dynamics in non-segmented solid rocket motors are evaluated using multi-dimensional computational fluid dynamic simulations and used to characterise damping of modal perturbations. For motors with high length-to-diameter ratios (of the order of 10), remarkably accurate estimates of frequencies and damping rates of lower modes can be obtained using the the quasi-1D approximation. Various grain configurations are considered to study the effect of internal geometry on damping rates. Analysis shows that lower cross-sectional area at the nozzle entry plane is found to increase damping rates of all the modes. The flow-turning loss for a mode increases if the more mass addition due to combustion is added at pressure nodes. For the fundamental mode, this loss is, therefore, maximum if burning area is maximum at the centre. The insights from this study in addition to recommendations made by Blomshield(1) based on combustion considerations would be very helpful in realizing rocket motors free from combustion instability.
The Fontan connection, originally described in 1971, is used to provide palliation for patients with many forms of CHDs that cannot support a biventricular circulation. An increasing number of females who have undergone these connections in childhood are now surviving into adulthood and some are becoming pregnant. We report a case of a 29-year-old woman who presented with a twin pregnancy at 33 weeks of gestation. She had significant deterioration of her cardiovascular status before the twin babies were delivered by emergency caesarean section owing to associated obstetric complications. This report also highlights the various maternal and fetal complications occurring in pregnancy of Fontan-palliated patients and suggests the need for meticulous pre-conception counselling and strict perinatal care.
In this study, we present the case of a neonate with obstructed infracardiac total anomalous pulmonary venous connection with severe pulmonary hypertension and a patent ductus arteriosus with right-to-left shunting. The patient had an unusual finding of pandiastolic flow reversal in the upper descending thoracic aorta. He underwent emergency surgical re-routing of the pulmonary veins to the left atrium, and postoperative echocardiography showed disappearance of the descending aortic flow reversal. We hypothesise that in severely obstructed total anomalous pulmonary venous connection the left ventricular output may be extremely low, resulting in flow reversal in the descending aorta.