Hyperlocal lessons from the COVID-19 pandemic: Toward an equity-centered implementation science approach.

COVID-19 vaccination campaigns across the US were implemented to mitigate the disproportionate hospitalizations and unnecessary deaths across many communities that experienced unequal gaps in initial vaccine distribution rollout and uptake. In parallel, the COVID-19 pandemic created declines in routine vaccination coverage for adults, adolescents, and children; particularly, in communities experiencing overlapping social disadvantage. Community-based efforts offer a solution to narrow immunization gaps but have not been replicated consistently nor demonstrated widespread success during the pandemic as evidenced by prevailing disparities in immunization uptake. We offer an equity centered implementation science approach that involves co-designing, co-implementing, and co-evaluating solutions with the community and all partners investing in the shared goal of sustainable improvement in health outcomes.

What is the environmental impact of a blood transfusion? A life cycle assessment of transfusion services across England.

BACKGROUND: Healthcare activities significantly contribute to greenhouse gas (GHG) emissions. Blood transfusions require complex, interlinked processes to collect, manufacture, and supply. Their contribution to healthcare emissions and avenues for mitigation is unknown. STUDY DESIGN AND METHODS: We performed a life cycle assessment (LCA) for red blood cell (RBC) transfusions across England where 1.36 million units are transfused annually. We defined the process flow with seven categories: donation, transportation, manufacturing, testing, stockholding, hospital transfusion, and disposal. We used direct measurements, manufacturer data, bioengineering databases, and surveys to assess electrical power usage, embodied carbon in disposable materials and reagents, and direct emissions through transportation, refrigerant leakage, and disposal. RESULTS: The central estimate of carbon footprint per unit of RBC transfused was 7.56 kg CO2 equivalent (CO2eq). The largest contribution was from transportation (2.8 kg CO2eq, 36% of total). The second largest was from hospital transfusion processes (1.9 kg CO2eq, 26%), driven mostly by refrigeration. The third largest was donation (1.3 kg CO2eq, 17%) due to the plastic blood packs. Total emissions from RBC transfusion are ~10.3 million kg CO2eq/year. DISCUSSION: This is the first study to estimate GHG emissions attributable to RBC transfusion, quantifying the contributions of each stage of the process. Primary areas for mitigation may include electric vehicles for the blood service fleet, improving the energy efficiency of refrigeration, using renewable sources of electricity, changing the plastic of blood packs, and using methods of disposal other than incineration.

Natural capital accounting of land resources based on ecological footprint and ecosystem services value.

Land resources are the material basis for human survival and development. Rapid economic development in the past has resulted in the over-utilization of land, and the undervaluation of land in market transactions has further exacerbated the loss of land benefits. This calls for monitoring the quantity and quality of land and reversing the undervaluation of land to reduce the waste of land resources. Based on this, a scientific natural capital accounting system of land resources should be established to understand the quantity and value of land resources in time. In order to provide a comprehensive evaluation of land utilization, this paper introduces the idea of compiling the land resources balance sheet. First, the physical quantity of land is calculated through the ecological footprint method improved by net primary productivity. Second, the value quantity of land is calculated through the equivalent factor method which is improved by the biologically productive land area obtained above, and then using ArcGIS to further demonstrate spatial and temporal changes in land resources. Taking the relevant data of Chongqing from 2000 to 2020 as an example, the land status is comprehensively evaluated from multiple perspectives, including quantity, value and spatial distribution. The results show that: (1) Under the dual impact of changes in the physical quantity and the unit price of land, the value quantity of land assets and equity in Chongqing realized 5.9 times and 5.1 times growth respectively during the study period. (2) Grassland was the most productive land type in Chongqing. Over a long time period, Chongqing prioritized the development of animal husbandry, placing too much emphasis on the production function of grassland and neglecting ecological protection, which was caused by an imbalance in the pasture area. In 2020, grassland utilization exceeded 40.9 % of the carrying capacity. (3) The value quantity of land in Chongqing existed in a spatial distribution pattern that was high in the southeast and northeast and low in the center and west, and there was a great imbalance in its growth rate among regions. The research results are helpful to the rational utilization and standardized transaction of land resources in Chongqing, and provide references for the inclusion of land resources in the management of state-owned assets.

"My Blood, You Know, My Biology Being out There ": Consent and Participant Control of Biological Samples.

The widespread and persistent underrepresentation of groups experiencing health disparities in research involving biospecimens is a barrier to scientific knowledge and advances in health equity. To ensure that all groups have the opportunity to participate in research and feel welcome and safe doing so, we must understand how research studies may be shaped to promote inclusion. In this study, we explored the decision to participate in hypothetical research scenarios among African American adults (n = 169) that varied on the basis of four attributes (form of consent, reason for research, institutional affiliation and race of the researcher). Findings indicate that participants were largely willing to contribute to biobanks but significantly preferred opportunities where they had control over the use of their biological samples through tiered or study-specific forms of consent. Broad consent procedures, although common and perhaps preferred by participants with high trust in researchers, may amount to an exclusionary practice.

Global Learning for Health Equity: A Survey of Five Global Learning Sites in the United States.

Global learning is the practice of adopting and adapting global ideas to local challenges. To advance the field of global learning, we performed a case study of five communities that had implemented global health models to advance health equity in a U.S. setting. Surveys were developed using a Consolidated Framework for Implementation Research (CFIR) framework, and each site completed surveys to characterize their global learning experience with respect to community context, the learning and implementation process, implementation science considerations, and health equity. The immense diversity of sites and their experiences underscored the heterogenous nature of global learning. Nonetheless, all cases highlighted core themes of addressing social determinants of health through strong community engagement. Cross-sector participation and implementation science evaluation were strategies applied by many but not all sites. We advocate for continued global learning that advances health equity and fosters equitable partnerships with mutual benefits to origination and destination sites.

Development of A Standardized Opsonophagocytosis Killing Assay for Group B Streptococcus and Assessment in an Interlaboratory Study.

The placental transfer of antibodies that mediate bacterial clearance via phagocytes is likely important for protection against invasive group B Streptococcus (GBS) disease. A robust functional assay is essential to determine the immune correlates of protection and assist vaccine development. Using standard reagents, we developed and optimized an opsonophagocytic killing assay (OPKA) where dilutions of test sera were incubated with bacteria, baby rabbit complement (BRC) and differentiated HL60 cells (dHL60) for 30 min. Following overnight incubation, the surviving bacteria were enumerated and the % bacterial survival was calculated relative to serum-negative controls. A reciprocal 50% killing titer was then assigned. The minimal concentrations of anti-capsular polysaccharide (CPS) IgG required for 50% killing were 1.65-3.70 ng/mL (depending on serotype). Inhibition of killing was observed using sera absorbed with homologous CPS but not heterologous CPS, indicating specificity for anti-CPS IgG. The assay performance was examined in an interlaboratory study using residual sera from CPS-conjugate vaccine trials with international partners in the Group B Streptococcus Assay STandardisatiON (GASTON) Consortium. Strong correlations of reported titers between laboratories were observed: ST-Ia r = 0.88, ST-Ib r = 0.91, ST-II r = 0.91, ST-III r = 0.90 and ST-V r = 0.94. The OPKA is an easily transferable assay with accessible standard reagents and will be a valuable tool to assess GBS-specific antibodies in natural immunity and vaccine studies.

Measuring dengue illness intensity: Development and content validity of the dengue virus daily diary (DENV-DD).

BACKGROUND: Dengue is the most prevalent arboviral infection causing an estimated 50-60 million cases of febrile illness globally per year, exacting considerable disease burden. Few instruments exist to assess the patient illness experience, with most based on healthcare provider assessment, lacking standardization in timepoints and symptom assessment. This study aimed to evaluate the content validity of the novel 'Dengue Virus Daily Diary (DENV-DD)', designed to measure symptom intensity and disease burden within outpatient infant to adult populations. METHODS: The Dengue Illness Index Report Card was used as a foundation to create the DENV-DD, consisting of patient- and observer-reported outcome (PRO/ObsRO) instruments. In two South American dengue-endemic communities, qualitative combined concept elicitation and cognitive debriefing interviews were conducted among individuals and caregivers of children with symptomatic laboratory-confirmed dengue. Interviews were conducted across two rounds allowing DENV-DD modifications. A small-scale quantitative assessment of the DENV-DD was also conducted with data from an independent Dengue Human Infection Model (DHIM) to generate early evidence of feasibility of DENV-DD completion, instrument performance and insight into the sign/symptom trajectory over the course of illness. RESULTS: Forty-eight participants were interviewed (20 adults, 20 older children/adolescents with their caregivers, 8 caregivers of younger children). A wide spectrum of signs/symptoms lasting 3-15 days were reported with fever, headache, body ache/pain, loss of appetite, and body weakness each reported by > 70% participants. DENV-DD instructions, items and response scales were understood, and items were considered relevant across ages. DHIM data supported feasibility of DENV-DD completion. CONCLUSIONS: Findings demonstrate content validity of the DENV-DD (PRO/ObsRO instruments) in dengue-endemic populations. Psychometric and cultural validity studies are ongoing to support use of the DENV-DD in clinical studies.

Dengue is the most common viral infection transmitted to humans by mosquitos, and affects an estimated 50­60 million individuals globally per year. However, there are few resources for understanding and capturing the patient experience of dengue throughout illness. Most research studies are based on healthcare provider assessment, which lack consistency in terms of assessment time points and the signs/symptoms assessed. The 'Dengue Illness Index Report Card (DII-RC)' was used as a foundation to create the new 'Dengue Virus Daily Diary (DENV-DD)' to better capture the patient experience of symptom intensity and dengue disease burden for the duration of illness. Forty-eight individuals and caregivers of younger children from Peru and Ecuador who recently had symptomatic dengue were interviewed to understand the patient experience over the time of illness and to test whether the DENV-DD is understood by patients and caregivers and includes all relevant and important signs/symptoms and health-related quality of life impacts. Nine individuals with active dengue infection also completed the DENV-DD daily for 28-days as part of a clinical study. We found that > 70% of patients experienced fever, headache, body ache/pain, loss of appetite and body weakness. The DENV-DD instructions, questions and response option(s) were well understood, feasible to complete and the concepts assessed by the DENV-DD were relevant to the dengue experience. Our study adds to the understanding of the dengue illness experience and supports the DENV-DD for use in future dengue studies as an assessment of signs/symptoms throughout the duration of illness.

Making the invisible visible: Using a qualitative system dynamics model to map disparities in cumulative environmental stressors and children's neurodevelopment.

BACKGROUND: The combined effects of multiple environmental toxicants and social stressor exposures are widely recognized as important public health problems, likely contributing to health inequities. However, US policy makers at state and federal levels typically focus on one stressor exposure at a time and have failed to develop comprehensive strategies to reduce multiple co-occurring exposures, mitigate cumulative risks and prevent harm. This research aimed to move from considering disparate environmental stressors in isolation to mapping the links between environmental, economic, social and health outcomes as a dynamic complex system using children's exposure to neurodevelopmental toxicants as an illustrative example. Such a model can be used to support a broad range of child developmental and environmental health policy stakeholders in improving their understanding of cumulative effects of multiple chemical, physical, biological and social environmental stressors as a complex system through a collaborative learning process. METHODS: We used system dynamics (SD) group model building to develop a qualitative causal theory linking multiple interacting streams of social stressors and environmental neurotoxicants impacting children's neurodevelopment. A 2 1/2-day interactive system dynamics workshop involving experts across multiple disciplines was convened to develop the model followed by qualitative survey on system insights. RESULTS: The SD causal map covered seven interconnected themes: environmental exposures, social environment, health status, education, employment, housing and advocacy. Potential high leverage intervention points for reducing disparities in children's cumulative neurotoxicant exposures and effects were identified. Workshop participants developed deeper level of understanding about the complexity of cumulative environmental health risks, increased their agreement about underlying causes, and enhanced their capabilities for integrating diverse forms of knowledge about the complex multi-level problem of cumulative chemical and non-chemical exposures. CONCLUSION: Group model building using SD can lead to important insights to into the sociological, policy, and institutional mechanisms through which disparities in cumulative impacts are transmitted, resisted, and understood.

Development of multidimensional water poverty in the Yangtze River Economic Belt, China.

As a basic natural and strategic resource, water is of great significance to the sustainable development of economies and societies. Owing to population growth, industrialization, the acceleration of urbanization, and global warming, water poverty is gradually increasing in some parts of the world. Effectively assessing water poverty from different dimensions is still a serious challenge for global water resources planning. This paper establishes a framework of multidimensional water poverty (MWP) from six dimensions: water management, water technology, water assets, water welfare, water resources, and water environment. The measurement model of MWP is built based on the Back Propagation Neural Network (BPNN), and the Spatial Correlation Analysis tool is used to visualize the spatial effects of MWP. The Yangtze River Economic Belt (YREB) was used as a case study and the main factors affecting the MWP of the YREB were determined by the Geodetector. When analyzing the results the following observations were made: (1) In terms of time distribution, the level of MWP in the YREB has gradually increased, and the poverty gap between the upper reaches, as well as the middle and lower reaches, shows an increasing trend. (2) With respect to spatial distribution, there is a continuously increasing agglomeration effect that shows a gradient-increasing distribution pattern of "West-Central-East." (3) The MWP in the YREB is mainly affected by these indicators in the three dimensions consisting of water resources, water technology, and water management. Specifically, R&D expenditure as a percentage of GDP, the proportion of water-saving irrigation area in the cultivable land area, the urban daily wastewater treatment capacity, the land surface water resources per capita, and the groundwater resources per capita play an important role in the MWP. Based on the above findings, targeted policy recommendations are proposed to alleviate the MWP in the YREB.

Particle Property Characterization and Data Curation for Effective Powder Property Modeling in the Pharmaceutical Industry.

Computational modeling, machine learning, and statistical data analysis are increasingly utilized to mitigate chemistry, manufacturing, and control failures related to particle properties in solid dosage form manufacture. Advances in particle characterization techniques and computational approaches provide unprecedented opportunities to explore relationships between particle morphology and drug product manufacturability. Achieving this, however, has numerous challenges such as producing and appropriately curating robust particle size and shape data. Addressing these challenges requires a harmonized strategy from material sampling practices, characterization technique selection, and data curation to provide data sets which are informative on material properties. Herein, common sources of error in particle characterization and data compression are reviewed, and a proposal for providing robust particle morphology (size and shape) data to support modeling efforts, approaches for data curation, and the outlook for modeling particle properties are discussed.

Racial Discrimination and Health-Related Quality of Life: An Examination Among Asian American Immigrants.

OBJECTIVES: We aimed to examine the relationship between everyday and major racial discrimination with health-related quality of life (HRQOL), which consists of self-rated health, days of poor physical health, mental health, and activity limitation. DESIGN: In a cross-sectional analytic sample of 524 foreign-born Asian adults, aged 18 years and older, we conducted multivariable logistic regression and multivariable negative binomial regression to examine associations between discrimination and HRQOL. Furthermore, potential effect modification was tested by gender, ethnicity, and social support. RESULTS: Associations were found between everyday racial discrimination and days of poor physical health (incidence rate ratio, IRR = 1.05), mental health (IRR = 1.03), and activity limitation (IRR = 1.05). Stronger significant associations were observed between major racial discrimination and days of poor physical health (IRR = 1.21), mental health (IRR = 1.16), and activity limitation (IRR = 1.53), adjusting for all covariates. Racial discrimination was not associated with poor self-rated health. In addition, gender significantly modified the relationship between continuous racial discrimination and activity limitation days with associations of greater magnitude among men, while social support significantly modified the association between categorized major racial discrimination and physically unhealthy days. When stratified, the association was only significant among those with low social support (IRR = 3.04; 95% CI: 1.60, 5.79) as opposed to high social support. CONCLUSIONS: This study supports the association between racial discrimination and worse HRQOL among Asian Americans, which can inform future interventions, especially among men and those with low social support, aimed at improving the quality of life in this population.

Total Hospital Costs and Readmission Rate of Patient-Specific Instrument in Total Knee Arthroplasty Patients.

Despite advancements in surgical technique and component design, implant loosening, stiffness, and instability remain leading causes of total knee arthroplasty (TKA) failure. Patient-specific instruments (PSI) aid in surgical precision and in implant positioning and ultimately reduce readmissions and revisions in TKA. The objective of the study was to evaluate total hospital cost and readmission rate at 30, 60, 90, and 365 days in PSI-guided TKA patients. We retrospectively reviewed patients who underwent a primary TKA for osteoarthritis from the Premier Perspective Database between 2014 and 2017 Q2. TKA with PSI patients were identified using appropriate keywords from billing records and compared against patients without PSI. Patients were excluded if they were < 21 years of age; outpatient hospital discharges; evidence of revision TKA; bilateral TKA in same discharge or different discharges. 1:1 propensity score matching was used to control patients, hospital, and clinical characteristics. Generalized Estimating Equation model with appropriate distribution and link function were used to estimate hospital related cost while logistic regression models were used to estimate 30, 60, and 90 days and 1-year readmission rate. The study matched 3,358 TKAs with PSI with TKA without PSI patients. Mean total hospital costs were statistically significantly (p < 0.0001) lower for TKA with PSI ($14,910; 95% confidence interval [CI]: $14,735-$15,087) than TKA without PSI patients ($16,018; 95% CI: $15,826-$16,212). TKA with PSI patients were 31% (odds ratio [OR]: 0.69; 95% CI: 0.51-0.95; p-value = 0.0218) less likely to be readmitted at 30 days; 35% (OR: 0.65; 95% CI: 0.50-0.86; p-value = 0.0022) less likely to be readmitted at 60 days; 32% (OR: 0.68; 95% CI: 0.53-0.88; p-value = 0.0031) less likely to be readmitted at 90 days; 28% (OR: 0.72; 95% CI: 0.60-0.86; p-value = 0.0004) less likely to be readmitted at 365 days than TKA without PSI patients. Hospitals and health care professionals can use retrospective real-world data to make informed decisions on using PSI to reduce hospital cost and readmission rate, and improve outcomes in TKA patients.

Entomological Risk Assessment for Dengue Virus Transmission during 2016-2020 in Kamphaeng Phet, Thailand.

Individual houses with high risks of dengue virus (DENV) transmission might be a source of virus transmission within the neighborhood. We conducted an entomological risk assessment for DENV transmission at the household level, comprising family cohort members residing in the same location, to assess the risk for dengue virus transmitted by mosquito vectors. The studies were conducted in Kamphaeng Phet Province, Thailand, during 2016-2020. Entomological investigations were performed in 35 cohort families on day 1 and day 14 after receiving dengue case reports. DENV was found in 22 Aedes samples (4.9%) out of 451 tested samples. A significantly higher DENV infection rate was detected in vectors collected on day 1 (6.64%) compared to those collected on day 14 (1.82%). Annual vector surveillance was carried out in 732 houses, with 1002 traps catching 3653 Aedes females. The majority of the 13,228 water containers examined were made from plastic and clay, with used tires serving as a primary container, with 59.55% larval abundance. Larval indices, as indicators of dengue epidemics and to evaluate disease and vector control approaches, were calculated. As a result, high values of larval indices indicated the considerably high risk of dengue transmission in these communities.

Common patterns in the public reporting of waiting time and waiting list information: Findings from a sample of OECD jurisdictions.

We present findings from a review of published literature and administrative documentation on waiting time and waiting list reporting models for elective treatment in a sample of international jurisdictions (a subset of OECD countries, with regional reporting regimes treated as distinct jurisdictions). In this paper we identified common patterns in the measurement and reporting of waiting time and waiting list information for elective treatment. We mapped the waiting time, waiting list, and key performance indicator statistics reported by 15 English-speaking international jurisdictions. Three distinct patterns of maximum waiting time target measures for elective treatment were identified amongst our international sample following our patient pathway event time-point analysis: (i) full-pathway maximum wait time targets; (ii) separate wait time targets for "time-to-diagnosis" and "time-to-treatment"; and (iii) "Time-to-Treatment" waiting time target only. Our review also revealed common patterns in the reporting of waiting time and waiting list statistics as well as KPI measures amongst a sub-sample of English-speaking jurisdictions. These common patterns provide a starting point towards more standardised measurement and reporting of waiting time and waiting list statistics in benchmarking access to elective care internationally.

Palliative radiotherapy combined with stent insertion to reduce recurrent dysphagia in oesophageal cancer patients: the ROCS RCT.

BACKGROUND: Most patients with oesophageal cancer present with incurable disease. For those with advanced disease, the mean survival is 3-5 months. Treatment emphasis is therefore on effective palliation, with the majority of patients requiring intervention for dysphagia. Insertion of a self-expanding metal stent provides rapid relief but dysphagia may recur within 3 months owing to tumour progression. Evidence reviews have called for trials of interventions combined with stenting to better maintain the ability to swallow. OBJECTIVES: The Radiotherapy after Oesophageal Cancer Stenting (ROCS) study examined the effectiveness of palliative radiotherapy, combined with insertion of a stent, in maintaining the ability to swallow. The trial also examined the impact that the ability to swallow had on quality of life, bleeding events, survival and cost-effectiveness. DESIGN: A pragmatic, multicentre, randomised controlled trial with follow-up every 4 weeks for 12 months. An embedded qualitative study examined trial experiences in a participant subgroup. SETTING: Participants were recruited in secondary care, with all planned follow-up at home. PARTICIPANTS: Patients who were referred for stent insertion as the primary management of dysphagia related to incurable oesophageal cancer. INTERVENTIONS: Following stent insertion, the external beam radiotherapy arm received palliative oesophageal radiotherapy at a dose of 20 Gy in five fractions or 30 Gy in 10 fractions. MAIN OUTCOME MEASURES: The primary outcome was the difference in the proportion of participants with recurrent dysphagia, or death, at 12 weeks. Recurrent dysphagia was defined as deterioration of ≥ 11 points on the dysphagia scale of the European Organisation of Research and Treatment of Cancer Quality of Life Questionnaire oesophago-gastric module questionnaire. Secondary outcomes included quality of life, bleeding risk and survival. RESULTS: The study recruited 220 patients: 112 were randomised to the usual-care arm and 108 were randomised to the external beam radiotherapy arm. There was no evidence that radiotherapy reduced recurrence of dysphagia at 12 weeks (48.6% in the usual-care arm compared with 45.3% in the external beam radiotherapy arm; adjusted odds ratio 0.82, 95% confidence interval 0.40 to 1.68; p = 0.587) and it was less cost-effective than stent insertion alone. There was no difference in median survival or key quality-of-life outcomes. There were fewer bleeding events in the external beam radiotherapy arm. Exploration of patient experience prompted changes to trial processes. Participants in both trial arms experienced difficulty in managing the physical and psychosocial aspects of eating restriction and uncertainties of living with advanced oesophageal cancer. LIMITATIONS: Change in timing of the primary outcome to 12 weeks may affect the ability to detect a true intervention effect. However, consistency of results across sensitivity analyses is robust, including secondary analysis of dysphagia deterioration-free survival. CONCLUSIONS: Widely accessible palliative external beam radiotherapy in combination with stent insertion does not reduce the risk of dysphagia recurrence at 12 weeks, does not have an impact on survival and is less cost-effective than inserting a stent alone. Reductions in bleeding events should be considered in the context of patient-described trade-offs of fatigue and burdens of attending hospital. Trial design elements including at-home data capture, regular multicentre nurse meetings and qualitative enquiry improved recruitment/data capture, and should be considered for future studies. FUTURE WORK: Further studies are required to identify interventions that improve stent efficacy and to address the multidimensional challenges of eating and nutrition in this patient population. TRIAL REGISTRATION: Current Controlled Trials ISRCTN12376468 and Clinicaltrials.gov NCT01915693. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 31. See the NIHR Journals Library website for further project information.

Most people are diagnosed with oesophageal (gullet) cancer when it is already at an advanced stage. Losing the ability to swallow food and even fluids is very common when patients are approaching the last months of life. Placing a flexible metal tube, or stent, in the gullet opens it up and improves the ability to swallow quickly. Unfortunately this can fail after around 3 months because the cancer grows and presses on the stent. We designed this trial to see if giving a small dose of radiotherapy alongside insertion of the stent would allow more people to remain swallowing well after 3 months. This could then improve their quality of life and reduce hospitalisation towards the end of life. It may also reduce bleeding from the gullet, as well as other symptoms. We recruited 220 people across the UK, randomly assigning them to have the stent as usual or the stent and a low dose of radiotherapy. We collected a lot of information from the participants at home on how the cancer, the stent and the radiotherapy affected their ability to swallow and their quality of life. Overall, the study showed that the radiotherapy did not improve the ability to swallow 3 months following stent insertion and was less cost-effective than stent insertion alone. It seemed to reduce the risk of bleeding from the tumour itself, but patients found that radiotherapy made them tired and attending extra hospital visits could be troublesome. We also learned that, even after a stent was inserted, patients still struggled with food and needed more support with managing daily life with the stent. The trial results are important. They show that, to answer questions such as these, studies should use different ways of assessing what works, particularly focusing on patients' and families' viewpoints. The results will guide doctors to not routinely give radiotherapy in this situation. The results also suggest that, after the insertion of a stent, patients need extra help in managing their diet, their worries about the stent and their worries about the future.

Defining and Intervening on Cumulative Environmental Neurodevelopmental Risks: Introducing a Complex Systems Approach.

BACKGROUND: The combined effects of multiple environmental toxicants and social stressor exposures are widely recognized as important public health problems contributing to health inequities. However cumulative environmental health risks and impacts have received little attention from U.S. policy makers at state and federal levels to develop comprehensive strategies to reduce these exposures, mitigate cumulative risks, and prevent harm. An area for which the inherent limitations of current approaches to cumulative environmental health risks are well illustrated is children's neurodevelopment, which exhibits dynamic complexity of multiple interdependent and causally linked factors and intergenerational effects. OBJECTIVES: We delineate how a complex systems approach, specifically system dynamics, can address shortcomings in environmental health risk assessment regarding exposures to multiple chemical and nonchemical stressors and reshape associated public policies. DISCUSSION: Systems modeling assists in the goal of solving problems by improving the "mental models" we use to make decisions, including regulatory and policy decisions. In the context of disparities in children's cumulative exposure to neurodevelopmental stressors, we describe potential policy insights about the structure and behavior of the system and the types of system dynamics modeling that would be appropriate, from visual depiction (i.e., informal maps) to formal quantitative simulation models. A systems dynamics framework provides not only a language but also a set of methodological tools that can more easily operationalize existing multidisciplinary scientific evidence and conceptual frameworks on cumulative risks. Thus, we can arrive at more accurate diagnostic tools for children's' environmental health inequities that take into consideration the broader social and economic environment in which children live, grow, play, and learn. https://doi.org/10.1289/EHP7333.

Palliative radiotherapy after oesophageal cancer stenting (ROCS): a multicentre, open-label, phase 3 randomised controlled trial.

BACKGROUND: Patients with advanced oesophageal cancer have a median survival of 3-6 months, and most require intervention for dysphagia. Self-expanding metal stent (SEMS) insertion is the most typical form of palliation in these patients, but dysphagia deterioration and re-intervention are common. This study examined the efficacy of adjuvant external beam radiotherapy (EBRT) compared with usual care alone in preventing dysphagia deterioration and reducing service use after SEMS insertion. METHODS: This was a multicentre, open-label, phase 3 randomised controlled trial based at cancer centres and acute care hospitals in England, Scotland, and Wales. Patients (aged ≥16 years) with incurable oesophageal carcinoma receiving stent insertion for primary management of dysphagia were randomly assigned (1:1) to receive usual care alone or EBRT (20 Gy in five fractions or 30 Gy in ten fractions) plus usual care after stent insertion. Usual care was implemented according to need as identified by the local multidisciplinary team (MDT). Randomisation was via the method of minimisation stratified by treating centre, stage at diagnosis (I-III vs IV), histology (squamous or non-squamous), and MDT intent to give chemotherapy (yes vs no). The primary outcome was difference in proportions of participants with dysphagia deterioration (>11 point decrease on patient-reported European Organisation for Research and Treatment of Cancer quality of life questionnaire-oesophagogastric module [QLQ-OG25], or a dysphagia-related event consistent with such a deterioration) or death by 12 weeks in a modified intention-to-treat (ITT) population, which excluded patients who did not have a stent inserted and those without a baseline QLQ-OG25 assessment. Secondary outcomes included survival, quality of life (QoL), morbidities (including time to first bleeding event or hospital admission for bleeding event and first dysphagia-related stent complications or re-intervention), and cost-effectiveness. Safety analysis was undertaken in the modified ITT population. The study is registered with the International Standard Randomised Controlled Trial registry, ISRCTN12376468, and ClinicalTrials.gov, NCT01915693, and is completed. FINDINGS: 220 patients were randomly assigned between Dec 16, 2013, and Aug 24, 2018, from 23 UK centres. The modified ITT population (n=199) comprised 102 patients in the usual care group and 97 patients in the EBRT group. Radiotherapy did not reduce dysphagia deterioration, which was reported in 36 (49%) of 74 patients receiving usual care versus 34 (45%) of 75 receiving EBRT (adjusted odds ratio 0·82 [95% CI 0·40-1·68], p=0·59) in those with complete data for the primary endpoint. No significant difference was observed in overall survival: median overall survival was 19·7 weeks (95% CI 14·4-27·7) with usual care and 18·9 weeks (14·7-25·6) with EBRT (adjusted hazard ratio 1·06 [95% CI 0·78-1·45], p=0·70; n=199). Median time to first bleeding event or hospital admission for a bleeding event was 49·0 weeks (95% CI 33·3-not reached) with usual care versus 65·9 weeks (52·7-not reached) with EBRT (adjusted subhazard ratio 0·52 [95% CI 0·28-0·97], p=0·038; n=199). No time versus treatment interaction was observed for prespecified QoL outcomes. We found no evidence of differences between trial group in time to first stent complication or re-intervention event. The most common (grade 3-4) adverse event was fatigue, reported in 19 (19%) of 102 patients receiving usual care alone and 22 (23%) of 97 receiving EBRT. On cost-utility analysis, EBRT was more expensive and less efficacious than usual care. INTERPRETATION: Patients with advanced oesophageal cancer having SEMS insertion for the primary management of their dysphagia did not gain additional benefit from concurrent palliative radiotherapy and it should not be routinely offered. For a minority of patients clinically considered to be at high risk of tumour bleeding, concurrent palliative radiotherapy might reduce bleeding risk and the need for associated interventions. FUNDING: National Institute for Health Research Health Technology Assessment Programme.

Assessment of US Healthcare Personnel Attitudes Towards Coronavirus Disease 2019 (COVID-19) Vaccination in a Large University Healthcare System.

BACKGROUND: As a priority group, healthcare personnel (HCP) will be key to the success of coronavirus disease 2019 (COVID-19) vaccination programs. This study assessed HCP willingness to get vaccinated and identified specific concerns that would undermine vaccination efforts. METHODS: We conducted a cross-sectional survey of HCP, including clinical and nonclinical staff, researchers, and trainees, between 23 November and 5 December 2020. The survey evaluated attitudes, beliefs, and willingness to get vaccinated. RESULTS: There were 5287 respondents with a mean (SD) age of 42.5 (13.56) years; 72.8% were female (n = 3842). Overall, 57.5 % of individuals expressed intent to receive COVID-19 vaccine; 80.4% were physicians and scientists representing the largest group. 33.6% of registered nurses, 31.6% of allied health professionals, and 32% of master's level clinicians were unsure they would take the vaccine (P < .001). Respondents who were older, male, White, or Asian were more likely to get vaccinated than other groups. Vaccine safety, potential adverse events, efficacy, and speed of vaccine development dominated concerns listed by participants. Fewer (54.0%) providers of direct care versus non-care providers (62.4%) and 52.0% of those who had provided care for COVID-19 patients (vs 60.6% of those who had not) indicated they would take the vaccine if offered (P < .001). CONCLUSIONS: We observed that self-reported willingness to receive vaccination against COVID-19 differs by hospital roles, with physicians and research scientists showing the highest acceptance. These findings highlight important heterogeneity in personal attitudes among HCPs around COVID-19 vaccines and highlight a need for tailored communication strategies.

A Phase 1, Open-Label Assessment of a Dengue Virus-1 Live Virus Human Challenge Strain.

BACKGROUND: Dengue human infection models (DHIM) have been used as a safe means to test the viability of prophylaxis and therapeutics. METHODS: A phase 1 study of 12 healthy adult volunteers using a challenge virus, DENV-1-LVHC strain 45AZ5, was performed. A dose escalating design was used to determine the safety and performance profile of the challenge virus. Subjects were evaluated extensively until 28 days and then out to 6 months. RESULTS: Twelve subjects received the challenge virus: 6 with 0.5 mL of 6.5 × 103 plaque-forming units (PFU)/mL (low-dose group) and 6 with 0.5 mL of 6.5 × 104 PFU/mL (mid-dose group). All except 1 in the low-dose group developed detectable viremia. For all subjects the mean incubation period was 5.9 days (range 5-9 days) and mean time of viremia was 6.8 days (range 3-9 days). Mean peak for all subjects was 1.6 × 107 genome equivalents (GE)/mL (range 4.6 × 103 to 5 × 107 GE/mL). There were no serious adverse events or long-term safety signals noted. CONCLUSIONS: We conclude that DENV-1-LVHC was well-tolerated, resulted in an uncomplicated dengue illness, and may be a suitable DHIM for therapeutic and prophylactic product testing. CLINICAL TRIALS REGISTRATION: NCT02372175.