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.

Outer membrane translocation of pyocins via the copper regulated TonB-dependent transporter CrtA.

Pseudomonas aeruginosa is a common cause of serious hospital-acquired infections, the leading proven cause of mortality in people with cystic fibrosis and is associated with high levels of antimicrobial resistance. Pyocins are narrow-spectrum protein antibiotics produced by P. aeruginosa that kill strains of the same species and have the potential to be developed as therapeutics targeting multi-drug resistant isolates. We have identified two novel pyocins designated SX1 and SX2. Pyocin SX1 is a metal-dependent DNase while pyocin SX2 kills cells through inhibition of protein synthesis. Mapping the uptake pathways of SX1 and SX2 shows these pyocins utilize a combination of the common polysaccharide antigen (CPA) and a previously uncharacterized TonB-dependent transporter (TBDT) PA0434 to traverse the outer membrane. In addition, TonB1 and FtsH are required by both pyocins to energize their transport into cells and catalyze their translocation across the inner membrane, respectively. Expression of PA0434 was found to be specifically regulated by copper availability and we have designated PA0434 as Copper Responsive Transporter A, or CrtA. To our knowledge these are the first S-type pyocins described that utilize a TBDT that is not involved in iron uptake.

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.

PF-431396 hydrate inhibition of kinase phosphorylation during adherent-invasive Escherichia coli infection inhibits intra-macrophage replication and inflammatory cytokine release.

Adherent-invasive Escherichia coli (AIEC) have been implicated in the aetiology of Crohn's disease (CD). They are characterized by an ability to adhere to and invade intestinal epithelial cells, and to replicate intracellularly in macrophages resulting in inflammation. Proline-rich tyrosine kinase 2 (PYK2) has previously been identified as a risk locus for inflammatory bowel disease and a regulator of intestinal inflammation. It is overexpressed in patients with colorectal cancer, a major long-term complication of CD. Here we show that Pyk2 levels are significantly increased during AIEC infection of murine macrophages while the inhibitor PF-431396 hydrate, which blocks Pyk2 activation, significantly decreased intramacrophage AIEC numbers. Imaging flow cytometry indicated that Pyk2 inhibition blocked intramacrophage replication of AIEC with no change in the overall number of infected cells, but a significant reduction in bacterial burden per cell. This reduction in intracellular bacteria resulted in a 20-fold decrease in tumour necrosis factor α secretion by cells post-AIEC infection. These data demonstrate a key role for Pyk2 in modulating AIEC intracellular replication and associated inflammation and may provide a new avenue for future therapeutic intervention in CD.

Diversity of Participation in Clinical Trials and Influencing Factors: Findings from the Health Information National Trends Survey 2020.

BACKGROUND: Clinical trial diversity is critical to advance health and health equity. Research addressing the discrepancy between goals of achieving clinical trial diversity and realities of study enrollment remains underdeveloped. OBJECTIVE: This study aims to examine the association between race/ethnicity and clinical trial invitation, participation, knowledge, and sources of influence on clinical trial participation. DESIGN AND PARTICIPANTS: A cross-sectional, observational study using nationally representative data from 3689 US adults (≥ 18 years of age) who responded to the Health Information National Trends Survey fielded from February 24 to June 15, 2020. MAIN MEASURES: Primary outcomes included clinical trial invitation, participation, knowledge, and sources of influence on participation. The independent variable of interest is self-reported race/ethnicity. KEY RESULTS: Respondents identifying as non-Hispanic Black (relative to non-Hispanic White) had higher odds of being invited into a clinical trial (adjusted odds ratio: 2.0, 95% confidence interval (CI): 1.1, 3.7), but no differences in odds of participation were observed by race/ethnicity. Respondents from all races/ethnicities reported that personal healthcare providers were the most trusted source of clinical trial information. Hispanic (marginal effect (ME): - 0.09; 95% CI: - 0.16, - 0.03), non-Hispanic Black (ME: - 0.11; 95% CI: - 0.18, - 0.04), and non-Hispanic other (ME: - 0.11; 95% CI: - 0.19, - 0.02) respondents had lower odds than non-Hispanic White respondents of saying they would be influenced "a lot" by their doctor encouraging participation. Non-Hispanic Black respondents had significantly lower odds (relative to non-Hispanic White) of indicating family encouragement would influence their clinical trial participation decision "a lot" (ME: - 0.09; 95%: CI: - 0.14, - 0.03). CONCLUSION: While personal healthcare providers were trusted sources of information, racial/ethnic minority populations noted lower odds of clinical trial participation influence from providers and family. Thus, it is imperative for the healthcare, government, and industry organizations to build trust in medicine and science.

Association of Living in a Food Desert and Poor Periconceptional Diet Quality in a Cohort of Nulliparous Pregnant Individuals.

BACKGROUND: A poor diet can result from adverse social determinants of health and increases the risk of adverse pregnancy outcomes. OBJECTIVE: We aimed to assess, using data from the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be prospective cohort, whether nulliparous pregnant individuals who lived in a food desert were more likely to experience poorer periconceptional diet quality compared with those who did not live in a food desert. METHODS: The exposure was living in a food desert based on a spatial overview of food access indicators by income and supermarket access per the Food Access Research Atlas. The outcome was periconceptional diet quality per the Healthy Eating Index (HEI)-2010, analyzed by quartile (Q) from the highest or best (Q4, reference) to the lowest or worst dietary quality (Q1); and secondarily, nonadherence (yes or no) to 12 key aspects of dietary quality. RESULTS: Among 7,956 assessed individuals, 24.9% lived in a food desert. The mean HEI-2010 score was 61.1 of 100 (SD: 12.5). Poorer periconceptional dietary quality was more common among those who lived in a food desert compared with those who did not live in a food desert (Q4: 19.8%, Q3: 23.6%, Q2: 26.5%, and Q1: 30.0% vs. Q4: 26.8%, Q3: 25.8%, Q2: 24.5%, and Q1: 22.9%; overall P < 0.001). Individuals living in a food desert were more likely to report a diet in lower quartiles of the HEI-2010 (i.e., poorer dietary quality) (aOR: 1.34 per quartile; 95% CI: 1.21, 1.49). They were more likely to be nonadherent to recommended standards for 5 adequacy components of the HEI-2010, including fruit, total vegetables, greens and beans, seafood and plant proteins, and fatty acids, and less likely to report excess intake of empty calories. CONCLUSIONS: Nulliparous pregnant individuals living in a food desert were more likely to experience poorer periconceptional diet quality compared with those who did not live in a food desert.

Positive allosteric modulators of the α7 nicotinic acetylcholine receptor: SAR investigation around PNU-120596.

The α7 nicotinic acetylcholine receptor is a calcium permeable, ligand-gated ion channel that modulates synaptic transmission in the hippocampus, thalamus, and cerebral cortex. Previously disclosed work described PNU-120596 that acts as a powerful positive allosteric modulator of the α7 nicotinic acetylcholine receptor. The initial structure-activity relationships around PNU-120596 were gleaned from screening a large thiazole library. Independent systematic examination of the aryl and heteroaryl groups resulted in compounds with enhanced potency and improved physico-chemical properties culminating in the identification of 16 (PHA-758454). In the presence of acetylcholine, 16 enhanced evoked currents in rat hippocampal neurons. In a rat model of impaired sensory gating, treatment with 16 led to a reversal of the gating deficit in a dose-dependent manner. These results demonstrate that aryl heteroaryl ureas, like compound 16, may be useful tools for continued exploration of the unique biology of the α7 nicotinic acetylcholine receptor.

Development of a conceptual model of the capacity for patients to engage in their health care: a group concept mapping study.

BACKGROUND: Patient engagement is seen as a necessary component in achieving the triple aim of improved population health, improved experience of care, and lower per capita health care costs. While there has been a substantial increase in the number of tools and patient-centered initiatives designed to help patients participate in health decisions, there remains a limited understanding of engagement from the perspective of patients and a lack of measures designed to capture the multi-faceted nature of the concept. METHODS: Development of a concept map of patient engagement followed a five-step modified Group Concept Mapping (GCM) methodology of preparation, generation, structuring, analysis and interpretation. We engaged a Project Advisory Committee at each step, along with three rounds of survey collection from clinicians and patients for element generation (272 clinicians, 61 patients), statement sorting (30 clinicians, 15 patients), and ranking and rating of statements (159 clinicians, 67 patients). The survey of three separate samples, as opposed to focus groups of 'experts,' was an intentional decision to gain a broad perspective about the concept of patient engagement. We conducted the structure and analysis steps within the groupwisdom concept mapping software. RESULTS: The final concept map comprised 47 elements organized into 5 clusters: Relationship with Provider, Patient Attitudes and Behaviors, Access, Internal Resources and External Resources. There was considerable agreement in the way elements in each cluster were rated by patients and clinicians. An analysis of the importance of the constitutive elements of patient engagement relative to their addressability highlighted actionable items in the domain of Relationship with Provider, aimed at building trust and enabling patients to ask questions. At the same time, the analysis also identified elements traditionally considered barriers to engagement, like personal access to the internet and the patient's level of digital literacy, as difficult to address by the healthcare system, but also relatively less important for patients. CONCLUSIONS: Through our GCM approach, incorporating perspectives of both patients and clinicians, we identified items that can be used to assess patient engagement efforts by healthcare systems. As a result, our study offers specific insight into areas that can be targeted for intervention by healthcare systems to improve patient engagement.

A qualitative study of the dark and bright sides of physicians' electronic health record work outside work hours.

BACKGROUND: The introduction of electronic health records (EHRs) has contributed considerably to EHR work outside work (WOW) hours for physicians. Prior research has identified the pressures associated with stress resulting from EHR WOW, yet developing a nuanced understanding of how physicians appraise and respond to this stress, and the resulting impacts, remains absent from the literature. PURPOSE: Grounded in the technostress model, this study takes a qualitative approach to explore both the pressures and opportunities associated with EHR WOW. METHODS: Thematic analysis of data from semistructured interviews was utilized to examine the pressures and opportunities associated with EHR WOW among primary care pediatricians (n = 15) affiliated with a large Midwestern pediatric health system. RESULTS: The physicians in this study regularly spent time working in the EHR outside work hours. They felt the EHR contributed to their documentation burden, which ultimately increased their EHR WOW, and reported a sense of burden from ubiquitous EHR availability. Conversely, they appreciated the flexibility the EHR provided in terms of work-life balance. Suggestions for improvement under the direct purview of practice management included enhanced EHR usability, improvements in workflow during work hours to free up time to document, and more training on both EHR documentation strategies and ongoing software upgrades. CONCLUSION: Physicians perceive that the EHR exerts certain pressures while affording new opportunities and conveniences. This study provides evidence of both the pressures and opportunities of EHR WOW and their effect on physician well-being. PRACTICE IMPLICATIONS: Specific opportunities are identified for health administrators to enable physicians to better manage EHR WOW.

The role of health care organizations in patient engagement: Mechanisms to support a strong relationship between patients and clinicians.

BACKGROUND: Patient engagement (PE) is critical to improving patient experience and outcomes, as well as clinician work life and lowering health care costs, yet health care organizations (HCOs) have limited guidance about how to support PE. The engagement capacity framework considers the context of engagement and examines precursors to engagement, including patients' self-efficacy, resources, willingness, and capabilities. PURPOSE: The aim of this study was to explore clinician and patient perspectives related to mechanisms through with the HCOs can facilitate PE through the lens of the engagement capacity framework. METHODOLOGY/APPROACH: We administered an online open-ended survey to clinicians and patient advisors across the United States, including questions focused on the influences of, barriers to, and skills and tools required for PE. A common theme emerged focusing on the role of HCOs in facilitating engagement. Our analysis examined all responses tagged with the "health care system" code. RESULTS: Over 750 clinicians and patient advisors responded to our survey. Respondents identified offering advice and support for patients to manage their care (self-efficacy), providing tools to facilitate communication (resources), working to encourage connection with patients (willingness), and training for HCO employees in cultural competency and communication skills (capabilities) as important functions of HCOs related to engagement. CONCLUSION: HCOs play an important role in supporting a strong partnership between the patient and clinicians. Our study identifies important mechanisms through which HCOs can fulfill this role. PRACTICE IMPLICATIONS: HCO leadership and administration can help establish the culture of care provided. Policies and initiatives that provide appropriate communication tools and promote culturally competent care can increase engagement.

Protease-associated import systems are widespread in Gram-negative bacteria.

Bacteria have evolved sophisticated uptake machineries in order to obtain the nutrients required for growth. Gram-negative plant pathogens of the genus Pectobacterium obtain iron from the protein ferredoxin, which is produced by their plant hosts. This iron-piracy is mediated by the ferredoxin uptake system (Fus), a gene cluster encoding proteins that transport ferredoxin into the bacterial cell and process it proteolytically. In this work we show that gene clusters related to the Fus are widespread in bacterial species. Through structural and biochemical characterisation of the distantly related Fus homologues YddB and PqqL from Escherichia coli, we show that these proteins are analogous to components of the Fus from Pectobacterium. The membrane protein YddB shares common structural features with the outer membrane ferredoxin transporter FusA, including a large extracellular substrate binding site. PqqL is an active protease with an analogous periplasmic localisation and iron-dependent expression to the ferredoxin processing protease FusC. Structural analysis demonstrates that PqqL and FusC share specific features that distinguish them from other members of the M16 protease family. Taken together, these data provide evidence that protease associated import systems analogous to the Fus are widespread in Gram-negative bacteria.

Biguanide Pharmaceutical Formulations and the Applications of Bile Acid-Based Nano Delivery in Chronic Medical Conditions.

Biguanides, particularly the widely prescribed drug metformin, have been marketed for many decades and have well-established absorption profiles. They are commonly administered via the oral route and, despite variation in oral uptake, remain commonly prescribed for diabetes mellitus, typically type 2. Studies over the last decade have focused on the design and development of advanced oral delivery dosage forms using bio nano technologies and novel drug carrier systems. Such studies have demonstrated significantly enhanced delivery and safety of biguanides using nanocapsules. Enhanced delivery and safety have widened the potential applications of biguanides not only in diabetes but also in other disorders. Hence, this review aimed to explore biguanides' pharmacokinetics, pharmacodynamics, and pharmaceutical applications in diabetes, as well as in other disorders.

Patient and physician perspectives on training to improve communication through secure messaging: Clarifying the rules of engagement.

PURPOSE: The aim of the study was to incorporate the perspectives of both patients and providers into the development of training to improve the exchange of secure messages through a patient portal as well as to identify management strategies that support patient engagement. METHODOLOGY: Three patient focus groups (17 patients) and interviews with 21 ambulatory physicians across 17 outpatient clinics at a large Midwestern academic medical center using Epic MyChart were performed. Rigorous thematic analysis was guided by the Systems Engineering Initiative for Patient Safety 2.0 framework adapted to patient portal implementation. RESULTS: Patients and physicians identified strategies at the patient, portal, physician, and health system levels that could help each group navigate the portal to communicate via secure messages more efficiently. Patient-focused training strategies included multimodal materials addressing how to navigate portal features and direction on when, what, and how to message. Changes to the format of the messaging feature and pop-ups with communication tips were also frequently mentioned. Physician and clinic-level strategies focused on how the clinic and health system management could enhance physician training on the patient-facing portal features and on how to manage patient care within the portal. Physicians also requested that the health system administration standardize physician and care team work processes related to secure messages within the portal and communicate clear management expectations of physician portal management. CONCLUSION: As communication via secure messaging has become more common, our study identified patient, physician, portal and health system-level management and training strategies to enhance patient portal use. PRACTICE IMPLICATIONS: Health system administrators and outpatient clinic management could implement these strategies to clarify the rules of engagement in the collaborative work of incorporating a patient portal into the primary care workflow and facilitating provider and patient use.

Pyocin efficacy in a murine model of Pseudomonas aeruginosa sepsis.

BACKGROUND: Bloodstream infections with antibiotic-resistant Pseudomonas aeruginosa are common and increasingly difficult to treat. Pyocins are naturally occurring protein antibiotics produced by P. aeruginosa that have potential for human use. OBJECTIVES: To determine if pyocin treatment is effective in a murine model of sepsis with P. aeruginosa. METHODS: Recombinant pyocins S5 and AP41 were purified and tested for efficacy in a Galleria mellonella infection model and a murine model of P. aeruginosa sepsis. RESULTS: Both pyocins produced no adverse effects when injected alone into mice and showed good in vitro antipseudomonal activity. In an invertebrate model of sepsis using G. mellonella, both pyocins significantly prolonged survival from 1/10 (10%) survival in controls to 80%-100% survival among groups of 10 pyocin-treated larvae. Following injection into mice, both showed extensive distribution into different organs. When administered 5 h after infection, pyocin S5 significantly increased survival from 33% (2/6) to 83% (5/6) in a murine model of sepsis (difference significant by log-rank test, P < 0.05). CONCLUSIONS: Pyocins S5 and AP41 show in vivo biological activity and can improve survival in two models of P. aeruginosa infection. They hold promise as novel antimicrobial agents for treatment of MDR infections with this microbe.

Examining Patients' Capacity to Use Patient Portals: Insights for Telehealth.

BACKGROUND: The increase in telehealth in response to the coronavirus disease 2019 pandemic highlights the need to understand patients' capacity to utilize this care modality. Patient portals are a tool whose use requires similar resources and skills as those required for telehealth. Patients' capacity to use patient portals may therefore provide insight regarding patients' readiness and capacity to use telehealth. OBJECTIVE: The aim of this study was to examine factors related to patients' capacity to use a patient portal and test the impact of these factors on patients' portal use. RESEARCH DESIGN AND SUBJECTS: Using data from a large-scale pragmatic randomized controlled trial of patient portal use, 1081 hospitalized patients responded to survey items that were then mapped onto the 4 dimensions of the Engagement Capacity Framework: self-efficacy, resources, willingness, and capabilities. MEASURES: The outcome variable was frequency of outpatient portal use. We evaluated associations between Engagement Capacity Framework dimensions and patient portal use, using regression analyses. RESULTS: Patients with fewer resources, fewer capabilities, lower willingness, and lower overall capacity to use patient portals used the portal less; in contrast, those with lower perceived self-efficacy used the portal more. CONCLUSIONS: Our findings highlight differences in patients' capacity to use patient portals, which provide an initial understanding of factors that may influence the use of telehealth and offer important guidance in efforts to support patients' telehealth use. Offering patients training tailored to the use of telehealth tools may be particularly beneficial.

Safety of Off-Label Use of Ferumoxtyol as a Contrast Agent for MRI: A Systematic Review and Meta-Analysis of Adverse Events.

BACKGROUND: Ferumoxytol has been studied as an alternative to gadolinium-based MRI contrast agents, but regulatory body warnings currently limit its use. PURPOSE: Estimate the adverse event rate in patients undergoing MRI with ferumoxytol as a contrast agent. STUDY TYPE: Systematic review. POPULATION: Thirty-nine studies including 5411 ferumoxytol administrations in 4336 patients. ASSESSMENT: Multiple databases were searched for studies using ferumoxytol as an off-label MRI contrast agent in any patient population as of April 2020. Studies were eligible for inclusion if they reported the number and severity of adverse events (classified by American College of Radiology [ACR] severity of acute reactions). Risk of bias was assessed using the ROBINS-I tool. STATISTICAL TESTS: The proportion of administrations with adverse events was calculated using random effects meta-analysis of proportions. RESULTS: No deaths related to ferumoxytol administration were reported. Sixteen studies reported immediate adverse events in 3849 patients undergoing 4901 ferumoxytol administrations. Ninety-seven immediate adverse events were reported and the pooled adverse event proportion for immediate adverse events was 0.02 (95% confidence interval [CI] 0.02-0.02). Twenty-three studies reported time-unspecified adverse events in 487 patients undergoing 510 ferumoxytol administrations. Five time-unspecified adverse events were reported; the pooled adverse event proportion for time-unspecified adverse events was 0.01 (95% CI 0.00-0.04). 88% of adverse events were mild (90/102), 11% (11/102) were moderate, and 1% (1/102) was severe. Sixteen studies were at low risk of bias, 23 studies were at serious risk of bias. Subgroup analysis by patient population revealed no significant variability (adult vs. pediatric). No studies evaluated the use of ferumoxytol as an alternative to patients who had a prior hypersensitivity reaction to gadolinium-based contrast agents (GBCAs). DATA CONCLUSION: The overall adverse event rate for off-label ferumoxytol use as an MRI contrast agent is 2%, with rare severe reactions and no deaths. To date, there are no studies evaluating the safety of ferumoxytol as an alternative to GBCAs in patients with a prior hypersensitivity reaction. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY STAGE: 5.

Identifying Opportunities to Strengthen the Public Health Informatics Infrastructure: Exploring Hospitals' Challenges with Data Exchange.

Policy Points Even though most hospitals have the technological ability to exchange data with public health agencies, the majority continue to experience challenges. Most challenges are attributable to the general resources of public health agencies, although workforce limitations, technology issues such as a lack of data standards, and policy uncertainty around reporting requirements also remain prominent issues. Ongoing funding to support the adoption of technology and strengthen the development of the health informatics workforce, combined with revising the promotion of the interoperability scoring approach, will likely help improve the exchange of electronic data between hospitals and public health agencies. CONTEXT: The novel coronavirus 2019 (COVID-19) pandemic has highlighted significant barriers in the exchange of essential information between hospitals and local public health agencies. Thus it remains important to clarify the specific issues that hospitals may face in reporting to public health agencies to inform focused approaches to improve the information exchange for the current pandemic as well as ongoing public health activities and population health management. METHODS: This study uses cross-sectional data of acute-care, nonfederal hospitals from the 2017 American Hospital Association Annual Survey and Information Technology supplement. Guided by the technology-organization-environment framework, we coded the responses to a question regarding the challenges that hospitals face in submitting data to public health agencies by using content analysis according to the type of challenge (i.e., technology, organization, or environment), responsible entity (i.e., hospital, public health agency, vendor, multiple), and the specific issue described. We used multivariable logistic and multinomial regression to identify characteristics of hospitals associated with experiencing the types of challenges. FINDINGS: Our findings show that of the 2,794 hospitals in our analysis, 1,696 (61%) reported experiencing at least one challenge in reporting health data to a public health agency. Organizational issues were the most frequently reported type of challenge, noted by 1,455 hospitals. The most common specific issue, reported by 1,117 hospitals, was the general resources of public health agencies. An advanced EHR system and participation in a health information exchange both decreased the likelihood of not reporting experiencing a challenge and increased the likelihood of reporting an organizational challenge. CONCLUSIONS: Our findings inform policy recommendations such as improving data standards, increasing funding for public health agencies to improve their technological capabilities, offering workforce training programs, and increasing clarity of policy specifications and reporting. These approaches can improve the exchange of information between hospitals and public health agencies.

Utility of material-specific fat images derived from rapid-kVp-switch dual-energy renal mass CT for diagnosis of renal angiomyolipoma.

BACKGROUND: Renal angiomyolipoma (AML) are benign masses that require detection of macroscopic fat for accurate diagnosis. PURPOSE: To evaluate fat material-specific images derived from dual-energy computed tomography (DECT) to diagnose renal AML. MATERIAL AND METHODS: This retrospective case-control study evaluated 25 renal AML and 44 solid renal masses (41 renal cell carcinomas, three other tumors) imaged with rapid-kVp-switch DECT (120 kVp non-contrast-enhanced [NECT], 70-keV corticomedullary [CM], and 120-kVp nephrographic [NG]-phase CECT) during 2017-2018. A radiologist measured attenuation (Hounsfield Units [HU]) on NECT, CM-CECT, NG-CECT, and fat concentration (mg/mL) using fat-water base-pair images. RESULTS: At NECT, 100% (44/44) non-AML and 4.0% (1/25) AML measured >-15 HU. At CM-CECT and NG-CECT, 24.0% (6/25) and 20.0% (5/25) AML measured >-15 HU (size 6-20 mm). To diagnose AML, area under receiver operating characteristic curve (AUC) using -15 HU was: 0.98 (95% confidence interval [CI] 0.98-1.00) NECT, 0.88 (95% CI 0.79-0.91) CM-CECT, and 0.90 (95% CI 0.82-0.98) NG-CECT. At DECT, fat concentration was higher in AML (163.7 ± 333.9 [-553.0 to 723.5] vs. -2858.1 ± 460.3 [-2421.2 to -206.0] mg/mL, P<0.001). AUC to diagnose AML using ≥-206.0 mg/mL threshold was 0.98 (95% CI 0.95-1.0) with sensitivity/specificity of 92.0%/96.7%. Of AML, 8.0% (2/25) were incorrectly classified; one of these was fat-poor. AUC was higher for fat concentration compared to HU measurements on CM-CECT and NG-CECT (P=0.009-0.050) and similar to NECT (P=0.98). CONCLUSION: DECT material-specific fat images can help confirm the presence of macroscopic fat in renal AML which may be useful to establish a diagnosis if unenhanced CT is unavailable.

Bacterial iron acquisition mediated by outer membrane translocation and cleavage of a host protein.

Iron is an essential micronutrient for most bacteria and is obtained from iron-chelating siderophores or directly from iron-containing host proteins. For Gram-negative bacteria, classical iron transport systems consist of an outer membrane receptor, a periplasmic binding protein, and an inner membrane ABC transporter, which work in concert to deliver iron from the cell surface to the cytoplasm. We recently showed that Pectobacterium spp. are able to acquire iron from ferredoxin, a small and stable 2Fe-2S iron sulfur cluster containing protein and identified the ferredoxin receptor, FusA, a TonB-dependent receptor that binds ferredoxin on the cell surface. The genetic context of fusA suggests an atypical iron acquisition system, lacking a periplasmic binding protein, although the mechanism through which iron is extracted from the captured ferredoxin has remained unknown. Here we show that FusC, an M16 family protease, displays a highly targeted proteolytic activity against plant ferredoxin, and that growth enhancement of Pectobacterium due to iron acquisition from ferredoxin is FusC-dependent. The periplasmic location of FusC indicates a mechanism in which ferredoxin is imported into the periplasm via FusA before cleavage by FusC, as confirmed by the uptake and accumulation of ferredoxin in the periplasm in a strain lacking fusC The existence of homologous uptake systems in a range of pathogenic bacteria suggests that protein uptake for nutrient acquisition may be widespread in bacteria and shows that, similar to their endosymbiotic descendants mitochondria and chloroplasts, bacteria produce dedicated protein import systems.