Th17-stimulating protein vaccines confer protection against Pseudomonas aeruginosa pneumonia.

RATIONALE: New vaccine approaches are needed for Pseudomonas aeruginosa, which continues to be a major cause of serious pulmonary infections. Although Th17 cells can protect against gram-negative pathogens at mucosal surfaces, including the lung, the bacterial proteins recognized by Th17 cells are largely unknown and could be potential new vaccine candidates. OBJECTIVES: We describe a strategy to identify Th17-stimulating protein antigens of Pseudomonas aeruginosa to assess their efficacy as vaccines against pneumonia. METHODS: Using a library of in vitro transcribed and translated P. aeruginosa proteins, we screened for Th17-stimulating antigens by coculturing the library proteins with splenocytes from mice immunized with a live-attenuated P. aeruginosa vaccine that is protective via Th17-based immunity. We measured antibody and Th17 responses after intranasal immunization of mice with the purified proteins mixed with the Th17 adjuvant curdlan, and we tested the protective efficacy of vaccination in a murine model of acute pneumonia. MEASUREMENTS AND MAIN RESULTS: The proteins PopB, FpvA, FptA, OprL, and PilQ elicited strong IL-17 secretion in the screen, and purified versions of PopB, FpvA, and OprL stimulated high IL-17 production from immune splenocytes. Immunization with PopB, which is a highly conserved component of the type III secretion system and a known virulence factor, elicited Th17 responses and also enhanced clearance of P. aeruginosa from the lung and spleen after challenge. PopB-immunized mice were protected from lethal pneumonia in an antibody-independent, IL-17-dependent manner. CONCLUSIONS: Screening for Th17-stimulating protein antigens identified PopB as a novel and promising vaccine candidate for P. aeruginosa.

Social Determinants of Health Screening at an Urban Emergency Department Urgent Care During COVID-19.

INTRODUCTION: Social determinants of health (SDoH) impact patients' health outcomes, yet screening methods in emergency departments (ED) are not consistent or standardized. The SDoH-related health disparities may have widened during the coronavirus 2019 (COVID-19) pandemic, especially among patients who primarily receive their medical care in EDs. We sought to identify SDoH among ED urgent care patients during the COVID-19 pandemic at an urban safety-net hospital, assess the impact of the pandemic on their SDoH, study the feasibility of SDoH screening and resource referrals, and identify preferred methods of resource referrals and barriers to accessing resources. METHODS: Research assistants screened ED urgent care patients using a validated SDoH screener, inquiring about the impact of COVID-19 on their SDoH. A printed resource guide was provided. Two weeks later, a follow-up telephone survey assessed for barriers to resource connection and patients' preferred methods for resource referrals. This study was deemed exempt by our institutional review board. RESULTS: Of the 418 patients presented with a screener, 414 (99.0%) patients completed the screening. Of those screened, 296 (71.5%) reported at least one adverse SDoH, most commonly education (38.7%), food insecurity (35.3%), and employment (31.0%). Housing insecurity was reported by 21.0%. Over half of patients (57.0%) endorsed COVID-19 affecting their SDoH. During follow-up, 156 of 234 (67%) attempted calls were successful and 36/156 (23.1%) reported attempting to connect with a resource, with most attempts made for stable housing (11.0%) and food (7.7%). Reasons for not contacting the provided resources included lack of time (37.8%) and forgetting to do so (26.3%). Patients preferred resource guides to be printed (34.0%) and sent via text message to their mobile devices (25.6%). CONCLUSION: Many urgent care patients of this urban ED reported at least one adverse SDoH, the majority of which were exacerbated by the COVID-19 pandemic. This finding further emphasizes the need to allocate more resources to standardize and expand SDoH screening in EDs. Additionally, hospitals should increase availability of printed or electronic SDoH resource guides, resource navigators, and interpreters both during and after ED visits.

2021 SAEM Consensus Conference Proceedings: Research Priorities for Implementing Emergency Department Screening for Social Risks and Needs.

INTRODUCTION: Despite literature on a variety of social risks and needs screening interventions in emergency department (ED) settings, there is no universally accepted or evidence-based process for conducting such interventions. Many factors hamper or promote implementation of social risks and needs screening in the ED, but the relative impact of these factors and how best to mitigate/leverage them is unknown. METHODS: Drawing on an extensive literature review, expert assessment, and feedback from participants in the 2021 Society for Academic Emergency Medicine Consensus Conference through moderated discussions and follow-up surveys, we identified research gaps and rated research priorities for implementing screening for social risks and needs in the ED. We identified three main knowledge gaps: 1) screening implementation mechanics; 2) outreach and engagement with communities; and 3) addressing barriers and leveraging facilitators to screening. Within these gaps, we identified 12 high-priority research questions as well as research methods for future studies. RESULTS: Consensus Conference participants broadly agreed that social risks and needs screening is generally acceptable to patients and clinicians and feasible in an ED setting. Our literature review and conference discussion identified several research gaps in the specific mechanics of screening implementation, including screening and referral team composition, workflow, and use of technology. Discussions also highlighted a need for more collaboration with stakeholders in screening design and implementation. Additionally, discussions identified the need for studies using adaptive designs or hybrid effectiveness-implementation models to test multiple strategies for implementation and sustainability. CONCLUSION: Through a robust consensus process we developed an actionable research agenda for implementing social risks and needs screening in EDs. Future work in this area should use implementation science frameworks and research best practices to further develop and refine ED screening for social risks and needs and to address barriers as well as leverage facilitators to such screening.

Evaluating a social risk screening and referral program in an urban safety-net hospital emergency department.

Objective: The emergency department (ED) is an opportune venue to screen for unmet social needs and connect patients with social services. This quality improvement study incorporates both qualitative and quantitative data to examine unmet social needs among ED patients and program implementation. Methods: From September 2020 to December 2021, an urban safety-net hospital adult ED implemented a social needs screening and referral program. Trained emergency staff screened eligible patients for 5 social needs (housing, food, transportation, utilities, employment), giving resource guides to patients who screened positive (THRIVE+). We collected screening data from the electronic health record, conducted semi-structured interviews with THRIVE+ patients and clinical staff, and directly observed discharge interactions. Results: Emergency staff screened 58.5% of eligible patients for social risk. Of the screened patients, 27.0% reported at least 1 unmet social need. Of those, 74.8% requested assistance. Screened patients reported housing insecurity (16.3%) as the most prevalent unmet social need followed by food insecurity (13.3%) and unemployment (8.7%). Among interviewed patients, 57.1% recalled being screened, but only 24.5% recalled receiving resource guides. Patients who received guides reported little success connecting with resources and supported universal guide dissemination. Staff expressed preference for warm handoff to social services. Of 13 observed discharge interactions, clinical staff only discussed guides with 2 patients, with no positive endorsement of the guides in any observed interactions. Conclusions: An ED social needs screening program can be moderately feasible and accepted. We identified housing as the most prevalent need. Significant gaps exist between screening and referral, with few patients receiving resources. Further training and workflow optimization are underway.

Improving Medical Students' Skills to Address Social Determinants of Health during the Internal Medicine Clerkship.

We developed a quality improvement educational experience to equip third-year medical students (MS3) with tools to address social determinants of health (SDOH) during their internal medicine clerkship. Students used THRIVE, Boston Medical Center's SDOH screening tool and resource referral platform, to screen patients for social needs and provide them with information on resources. We evaluated changes in students' knowledge, attitudes, confidence, and practices in regard to addressing SDOH. Feasibility and acceptability of the experience were also evaluated. Analysis of pre-and post-experience surveys revealed improvement in MS3 confidence providing resources to help patients address SDOH (p<.001, n=41). Of all MS3 (n=158), 63% accessed the THRIVE Directory, and 45% successfully utilized it to print or e-mail resources. One MS3 focus group revealed challenges and time constraints faced by students. While benefits were identified, simplification of the workflow is needed to improve the feasibility and acceptability of the experience.

The limits of evidence in drug approval and availability: a case study of cilostazol and naftidrofuryl for the treatment of intermittent claudication.

PURPOSE: Despite numerous efforts to develop effective medications for the treatment of intermittent claudication (IC) over the past 4 decades, a gold standard medical management option has yet to be defined. Although not life-threatening, IC interferes with mobility and activities of daily living, significantly impairing quality of life and potentially causing depression. Cilostazol, the leading pharmacologic agent for IC in the United States, was approved by the US Food and Drug Administration (FDA) in 1999 based on controversial data. Meanwhile, naftidrofuryl, the first-line pharmacologic agent for IC in the United Kingdom and Europe, has never been approved by the FDA and therefore is not available in the United States. The clinical data for cilostazol and naftidrofuryl are plagued by flaws related to lack of protocol standardization, objective endpoints, and strict eligibility criteria in study subjects, making identification of a true treatment effect impossible. Furthermore, no prospective randomized trial comparing the efficacy of cilostazol and naftidrofuryl has been conducted, because the manufacturers of these agents have much to lose and little to gain from such a study. OBJECTIVE: This article provides an overview of the pharmacology of cilostazol and naftidrofuryl, and the clinical studies leading to their approval and clinical acceptance. It further explores the possible sources of bias in analyzing these clinical trials, some of which have been brought to light by the National Institute for Health and Clinical Excellence (NICE) of the United Kingdom in its technology appraisal guidance. It also speculates the ways in which economic incentives may affect drug-marketing decisions. METHODS: A literature review of pharmacology and clinical trials for cilostazol and naftidrofuryl was performed in PubMed. The majority of included clinical trials were initially identified through the most recent Cochrane review articles as well as the FDA's approval packet for cilostazol. The technology appraisal guidance of the National Institute for Health and Care Excellence of the United Kingdom and the manufacturer's response to this guidance document were located via an online search engine. FINDINGS: The clinical data for cilostazol and naftidrofuryl are plagued by flaws related to lack of protocol standardization, objective endpoints, and strict eligibility criteria in study subjects, making identification of a true treatment effect difficult. Furthermore, no prospective randomized trial comparing the efficacy of cilostazol and naftidrofuryl has been conducted. IMPLICATIONS: The history of the evaluation, approval, and marketing of these drugs illustrates the limitations of data in the regulatory approval and marketing of agents whose benefit is subjective and difficult to quantify. Implementation of a standardized protocol with strict eligibility criteria, objective quantifiable measurement of drug effect, and validated endpoints will eventually allow development of an ideal pharmacotherapy for IC.

Disinfection of needleless connectors with chlorhexidine-alcohol provides long-lasting residual disinfectant activity.

The optimal disinfection method for needleless connectors (NCs) is unclear. We used an experimental model of microbial NC contamination to test different scrub times (swipe, 5, 15, 30 seconds) of chlorhexidine-alcohol versus alcohol and for residual disinfectant activity. Swipe with alcohol did not adequately disinfect NCs, particularly when contaminated with Staphylococcus aureus or Pseudomonas aeruginosa. With ≥5-second scrub, chlorhexidine-alcohol and alcohol performed similarly, but chlorhexidine-alcohol showed residual disinfectant activity for up to 24 hours.