Stratifying macrophages based on their infectious burden identifies novel host targets for intervention during Crohn's disease associated adherent-invasive Escherichia coli infection.

Bacterial infection is a dynamic process resulting in a heterogenous population of infected and uninfected cells. These cells respond differently based on their bacterial load and duration of infection. In the case of infection of macrophages with Crohn's disease (CD) associated adherent-invasive Escherichia coli (AIEC), understanding the drivers of pathogen success may allow targeting of cells where AIEC replicate to high levels. Here we show that stratifying immune cells based on their bacterial load identifies novel pathways and therapeutic targets not previously associated with AIEC when using a traditional homogeneous infected population approach. Using flow cytometry-based cell sorting we stratified cells into those with low or high intracellular pathogen loads, or those which were bystanders to infection. Immune cells transcriptomics revealed a diverse response to the varying levels of infection while pathway analysis identified novel intervention targets that were directly related to increasing intracellular AIEC numbers. Chemical inhibition of identified targets reduced AIEC intracellular replication or inhibited secretion of tumour necrosis factor alpha (TNFα), a key cytokine associated with AIEC infection. Our results have identified new avenues of intervention in AIEC infection that may also be applicable to CD through the repurposing of already available inhibitors. Additionally, they highlight the applicability of immune cell stratification post-infection as an effective approach for the study of microbial pathogens.

Reducing perceived barriers to scaling up overdose education and naloxone distribution and medications for opioid use disorder in the United States in the HEALing (Helping End Addiction Long-Term®) communities study.

BACKGROUND: Scaling up overdose education and naloxone distribution (OEND) and medications for opioid use disorder (MOUD) is needed to reduce opioid overdose deaths, but barriers are pervasive. This study examines whether the Communities That HEAL (CTH) intervention reduced perceived barriers to expanding OEND and MOUD in healthcare/behavioral health, criminal-legal, and other/non-traditional venues. METHODS: The HEALing (Helping End Addiction Long-Term®) Communities Study is a parallel, wait-list, cluster randomized trial testing the CTH intervention in 67 communities in the United States. Surveys administered to coalition members and key stakeholders measured the magnitude of perceived barriers to scaling up OEND and MOUD in November 2019-January 2020, May-June 2021, and May-June 2022. Multilevel linear mixed models compared Wave 1 (intervention) and Wave 2 (wait-list control) respondents. Interactions by rural/urban status and research site were tested. RESULTS: Wave 1 respondents reported significantly greater reductions in mean scores for three outcomes: perceived barriers to scaling up OEND in Healthcare/Behavioral Health Venues (-0.26, 95% confidence interval, CI: -0.48, -0.05, p = 0.015), OEND in Other/Non-traditional Venues (-0.53, 95% CI: - 0.84, -0.22, p = 0.001) and MOUD in Other/Non-traditional Venues (-0.34, 95% CI: -0.62, -0.05, p = 0.020). There were significant interactions by research site for perceived barriers to scaling up OEND and MOUD in Criminal-Legal Venues. There were no significant interactions by rural/urban status. DISCUSSION: The CTH Intervention reduced perceived barriers to scaling up OEND and MOUD in certain venues, with no difference in effectiveness between rural and urban communities. More research is needed to understand facilitators and barriers in different venues.

Does Climate Change Affect Health? Beliefs from the Health Information National Trends Survey.

Climate change is currently and will continue impacting human health, however, beliefs about the level of threat vary by demographics, region, and ideology. The purpose of this study was to assess factors related to climate change and health beliefs using cross-sectional data from the Health Information National Trends Survey (HINTS). Data from 5,075 respondents in the 2022 iteration of HINTS was used for this study. Chi-square tests were used to evaluate demographic differences among those who believe climate change will harm health a lot compared to some, a little, or not at all. Generalized ordinal logistic regression models were used to examine the relationship between the belief that climate change will harm health and independent variables regarding trust in scientists, health recommendations from experts, and demographic characteristics. Female, Black, Hispanic, and college graduate respondents had higher odds and people in the Southern U.S. those aged 35-49, 50-64, and 75years or older had significantly lower odds of believing climate change would harm their health. Those who trust information about cancer from scientists and those that believe health recommendations from experts conflict or change had higher odds of believing climate change would harm health. Our analysis highlights factors that impact climate change and health beliefs, which may provide targets for tailoring public health messages to address this issue.

The relationship between hospital patient safety culture and performance on Centers for Medicare & Medicaid Services value-based purchasing metrics.

BACKGROUND: Despite the intense policy focus on reducing health-care-associated conditions, adverse events in health care settings persist. Therefore, evaluating patient safety efforts and related health policy initiatives remains critical. PURPOSE: The aim of this study was to explore the relationship between hospital patient safety culture and hospital performance on Centers for Medicare & Medicaid Services (CMS) Hospital Value-Based Purchasing (HVBP) metrics. METHODOLOGY/APPROACH: A pooled cross-sectional study design was used utilizing three secondary datasets from 2018 and 2021: the Hospital Survey on Patient Safety Culture, the American Hospital Association annual survey, and the Hospital Compare data from CMS. We used two multivariable linear regression models to examine the relationship between organizational patient safety culture and hospital performance. The dependent variables included the overall CMS total performance score (TPS) and the four individual TPS domain scores. Hospital patient safety culture, the independent variable, was operationalized using two measures from the Hospital Survey on Patient Safety Culture: (a) the domain score of overall perceptions of patient safety and (b) the patient safety grade. RESULTS: We observed positive and significant associations between hospital patient safety culture and a hospital's overall TPS and the "patient and community engagement" and "safety" domains. CONCLUSION: Findings suggest that building a strong patient safety culture has the potential to lead health care organizations to achieve high performance on HVBP metrics. PRACTICE IMPLICATIONS: Our findings have important policy implications for both the future of CMS HVBP as a motivator of patient safety and how health care managers integrate culture change into programs to meet external quality metrics.

Differences by Race in Outcomes of an In-Person Training Intervention on Use of an Inpatient Portal: A Secondary Analysis of a Randomized Clinical Trial.

Importance: Differences in patient use of health information technologies by race can adversely impact equitable access to health care services. While this digital divide is well documented, there is limited evidence of how health care systems have used interventions to narrow the gap. Objective: To compare differences in the effectiveness of patient training and portal functionality interventions implemented to increase portal use among racial groups. Design, Setting, and Participants: This secondary analysis used data from a randomized clinical trial conducted from December 15, 2016, to August 31, 2019. Data were from a single health care system and included 6 noncancer hospitals. Participants were patients who were at least 18 years of age, identified English as their preferred language, were not involuntarily confined or detained, and agreed to be provided a tablet to access the inpatient portal during their stay. Data were analyzed from September 1, 2022, to October 31, 2023. Interventions: A 2 × 2 factorial design was used to compare the inpatient portal training intervention (touch, in-person [high] vs built-in video tutorial [low]) and the portal functionality intervention (technology, full functionality [full] vs a limited subset of functions [lite]). Main Outcomes and Measures: Primary outcomes were inpatient portal use, measured by frequency and comprehensiveness of use, and use of specific portal functions. A logistic regression model was used to test the association of the estimators with the comprehensiveness use measure. Outcomes are reported as incidence rate ratios (IRRs) for the frequency outcomes or odds ratios (ORs) for the comprehensiveness outcomes with corresponding 95% CIs. Results: Of 2892 participants, 550 (19.0%) were Black individuals, 2221 (76.8%) were White individuals, and 121 (4.2%) were categorized as other race (including African, American Indian or Alaska Native, Asian or Asian American, multiple races or ethnicities, and unknown race or ethnicity). Black participants had a significantly lower frequency (IRR, 0.80 [95% CI, 0.72-0.89]) of inpatient portal use compared with White participants. Interaction effects were not observed between technology, touch, and race. Among participants who received the full technology intervention, Black participants had lower odds of being comprehensive users (OR, 0.76 [95% CI, 0.62-0.91), but interaction effects were not observed between touch and race. Conclusions and Relevance: In this study, providing in-person training or robust portal functionality did not narrow the divide between Black participants and White participants with respect to their inpatient portal use. Health systems looking to narrow the digital divide may need to consider intentional interventions that address underlying issues contributing to this inequity. Trial Registration: ClinicalTrials.gov Identifier: NCT02943109.

Differences in perceptions of community stigma towards opioid use disorder between community substance use coalition members and the general public.

INTRODUCTION: To examine differences in perceptions about community stigma towards individuals with opioid use disorder (OUD) between community members involved in the opioid response (i.e., coalition members) and the general public, and how community geography may moderate this relationship. METHODS: This study administered identical cross-sectional surveys about perceived community opioid-related stigma to two distinct populations in 66 communities participating in the HEALing Communities Study prior to the intervention period (i.e., coalition members, November 2019-January 2020; residents, March-April 2020). Linear-mixed models compared survey responses of populations, including the moderating effect of community rural/urban location. RESULTS: A total of 826 coalition members and 1131 residents completed the surveys. The study found no differences between the coalition members and residents for general perceived community opioid-related stigma. In both urban and rural communities, coalition members reported greater perceived community stigma than residents reported towards medication for opioid use disorder (MOUD), naloxone, and drug treatment as an alternative to incarceration. CONCLUSION: Our findings suggest similar perceived community opioid-related stigma between coalition members and residents, yet differences emerge related to evidence-based practices (i.e., MOUD, naloxone, and drug treatment as an alternative to incarceration) to reduce opioid overdose deaths. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04111939.

Association of Socioeconomic Status With Life's Essential 8 in the National Health and Nutrition Examination Survey: Effect Modification by Sex.

BACKGROUND: Higher scores for the American Heart Association Life's Essential 8 (LE8) metrics, blood pressure, cholesterol, glucose, body mass index, physical activity, smoking, sleep, and diet, are associated with lower risk of chronic disease. Socioeconomic status (SES; employment, insurance, education, and income) is associated with LE8 scores, but there is limited understanding of potential differences by sex. This analysis quantifies the association of SES with LE8 for each sex, within Hispanic Americans, non-Hispanic Asian Americans, non-Hispanic Black Americans, and non-Hispanic White Americans. METHODS AND RESULTS: Using cross-sectional data from the National Health and Nutrition Examination Survey, years 2011 to 2018, LE8 scores were calculated (range, 0-100). Age-adjusted linear regression quantified the association of SES with LE8 score. The interaction of sex with SES in the association with LE8 score was assessed in each racial and ethnic group. The US population representatively weighted sample (13 529 observations) was aged ≥20 years (median, 48 years). The association of education and income with LE8 scores was higher in women compared with men for non-Hispanic Black Americans and non-Hispanic White Americans (P for all interactions <0.05). Among non-Hispanic Asian Americans and Hispanic Americans, the association of SES with LE8 was not different between men and women, and women had greater LE8 scores than men at all SES levels (eg, high school or less, some college, and college degree or more). CONCLUSIONS: The factors that explain the sex differences among non-Hispanic Black Americans and non-Hispanic White Americans, but not non-Hispanic Asian Americans and Hispanic Americans, are critical areas for further research to advance cardiovascular health equity.

'ThinkCancer!' - Randomised feasibility trial of a novel practice-based early cancer diagnosis intervention.

BACKGROUND: UK cancer deaths remain high; primary care is key for earlier cancer diagnosis as half of avoidable delays occur here. Improvement is possible through lower referral thresholds, better guideline adherence, and better safety netting systems. Few interventions target whole practice teams. We developed a novel whole practice team intervention to address this. AIM: To test the feasibility and acceptability of a novel, complex behavioural intervention 'ThinkCancer!' for assessment in a subsequent Phase III trial. DESIGN & SETTING: Pragmatic, superiority pilot RCT with an embedded process evaluation and feasibility economic analysis in Welsh general practices. METHOD: Clinical outcome data were collected from practices (the unit of randomisation). Practice characteristics and cancer safety netting systems were assessed. Individual practice staff completed evaluation and feedback forms, and qualitative interviews. The intervention was adapted and refined. RESULTS: Trial recruitment and workshop deliveries took place between March 2020 to May 2021. Trial progression criteria for recruitment, intervention fidelity and routine data collection were met. Staff-level fidelity, retention and individual level data collection processes were reviewed and amended. Interviews highlighted positive participant views on all aspects of the intervention. All practices set out to liberalise referral thresholds appropriately, implement guidelines, and address safety netting plans in detail. CONCLUSION: 'ThinkCancer!' appears feasible and acceptable; the new iteration of the workshops was completed, and the Phase III trial has been funded to assess the effectiveness and cost effectiveness of this novel professional behaviour change intervention. Delivery at scale to multiple practices will likely improve fidelity and reach.

Diet quality, community food access, and glycemic control among nulliparous individuals with diabetes.

Better diet quality regardless of community food access was associated with a higher likelihood of glycemic control in early pregnancy among nulliparous individuals with pregestational diabetes. These findings highlight the need for interventions that address nutrition insecurity for pregnant individuals living with diabetes.

Effects of the Communities that Heal (CTH) intervention on perceived opioid-related community stigma in the HEALing Communities Study: results of a multi-site, community-level, cluster-randomized trial.

Background: Community stigma against people with opioid use disorder (OUD) and intervention stigma (e.g., toward naloxone) exacerbate the opioid overdose crisis. We examined the effects of the Communities that HEAL (CTH) intervention on perceived opioid-related community stigma by stakeholders in the HEALing Communities Study (HCS). Methods: We collected three surveys from community coalition members in 66 communities across four states participating in HCS. Communities were randomized into Intervention (Wave 1) or Wait-list Control (Wave 2) arms. We conducted multilevel linear mixed models to compare changes in primary outcomes of community stigma toward people treated for OUD, naloxone, and medication for opioid use disorder (MOUD) by arm from time 1 (before the start of the intervention) to time 3 (end of the intervention period in the Intervention arm). Findings: Intervention stakeholders reported a larger decrease in perceived community stigma toward people treated for OUD (adjusted mean change (AMC) -3.20 [95% C.I. -4.43, -1.98]) and toward MOUD (AMC -0.33 [95% C.I. -0.56, -0.09]) than stakeholders in Wait-list Control communities (AMC -0.18 [95% C.I. -1.38, 1.02], p = 0.0007 and AMC 0.11 [95% C.I. -0.09, 0.31], p = 0.0066). The relationship between intervention status and change in stigma toward MOUD was moderated by rural-urban status (urban AMC -0.59 [95% CI, -0.87, -0.32], rural AMC not sig.) and state. The difference in stigma toward naloxone between Intervention and Wait-list Control stakeholders was not statistically significant (p = 0.18). Interpretation: The CTH intervention decreased stakeholder perceptions of community stigma toward people treated for OUD and stigma toward MOUD. Implementing the CTH intervention in other communities could decrease OUD stigma across diverse settings nationally. Funding: US National Institute on Drug Abuse.

Embedding Big Qual and Team Science into Qualitative Research: Lessons from a Large-scale, Cross-site Research Study.

Background: A major part of the HEALing Communities Study (HCS), launched in 2019 to address the growing opioid epidemic, is evaluating the study's intervention implementation process through an implementation science (IS) approach. One component of the IS approach involves teams with more than 20 researchers collaborating across four research sites to conduct in-depth qualitative interviews with over 300 participants at four time points. After completion of the first two rounds of data collection, we reflect upon our qualitative data collection and analysis approach. We aim to share our lessons learned about designing and applying qualitative methods within an implementation science framework. Methods: The HCS evaluation is based on the RE-AIM/PRISM framework and incorporates interviews at four timepoints. At each timepoint, the core qualitative team of the Intervention Work Group drafts an interview guide based on the framework and insights from previous round(s) of data collection. Researchers then conduct interviews with key informants and coalition members within their respective states. Data analysis involves drafting, iteratively refining, and finalizing a codebook in a cross-site and within-site consensus processes. Interview transcripts are then individually coded by researchers within their respective states. Results: Successes in the evaluation process includes having structured procedures for communication, data collection, and analysis, all of which are critical for ensuring consistent data collection and for achieving consensus during data analysis. Challenges include recognizing and accommodating the diversity of training and knowledge between researchers, and establishing reliable ways to securely store, manage, and share the large volumes of data. Conclusion: Qualitative methods using a team science approach have been limited in their application in large, multi-site randomized controlled trials of health interventions. Our experience provides practical guidance for future studies with large, experientially and disciplinarily diverse teams, and teams seeking to incorporate qualitative or mixed-methods components for their evaluations.

Contribución genética a la mortalidad embrionaria en 2 poblaciones de roedores no consanguíneos / Genetic contribution to embrionary mortality in 2 population of non-consanguineous rodents

Se calcularon los porcientos de genes letales recesivos que en estado homocigótico, provocan mortalidad embrionaria tomando como base poblaciones de ratas y ratones no consanguíneos. El aporte de los genes letales recesivos se halló por la diferencia de la mortalidad embrionaria entre 2 grupos con diferentes variantes de apareamiento: sistema rotatorio y cruzamiento consanguíneo. Se comparó al efecto el número de cuerpos lúteos, fetos vivos y reabsorciones en 200 ratones y 160 ratas en los días 15 y 17 del embarazo. Solamente en las ratas se encontraron diferencias significativas entre ambos sistemas debido al efecto de los genes letales recesivos. La mortalidad embrionaria después de la implantación y en general fue de 5,05 y 4,25 por ciento respectivamente