SARS-CoV-2 infects cells lining the blood-retinal barrier and induces a hyperinflammatory immune response in the retina via systemic exposure.

SARS-CoV-2 has been shown to cause wide-ranging ocular abnormalities and vision impairment in COVID-19 patients. However, there is limited understanding of SARS-CoV-2 in ocular transmission, tropism, and associated pathologies. The presence of viral RNA in corneal/conjunctival tissue and tears, along with the evidence of viral entry receptors on the ocular surface, has led to speculation that the eye may serve as a potential route of SARS-CoV-2 transmission. Here, we investigated the interaction of SARS-CoV-2 with cells lining the blood-retinal barrier (BRB) and the role of the eye in its transmission and tropism. The results from our study suggest that SARS-CoV-2 ocular exposure does not cause lung infection and moribund illness in K18-hACE2 mice despite the extended presence of viral remnants in various ocular tissues. In contrast, intranasal exposure not only resulted in SARS-CoV-2 spike (S) protein presence in different ocular tissues but also induces a hyperinflammatory immune response in the retina. Additionally, the long-term exposure to viral S-protein caused microaneurysm, retinal pigmented epithelium (RPE) mottling, retinal atrophy, and vein occlusion in mouse eyes. Notably, cells lining the BRB, the outer barrier, RPE, and the inner barrier, retinal vascular endothelium, were highly permissive to SARS-CoV-2 replication. Unexpectedly, primary human corneal epithelial cells were comparatively resistant to SARS-CoV-2 infection. The cells lining the BRB showed induced expression of viral entry receptors and increased susceptibility towards SARS-CoV-2-induced cell death. Furthermore, hyperglycemic conditions enhanced the viral entry receptor expression, infectivity, and susceptibility of SARS-CoV-2-induced cell death in the BRB cells, confirming the reported heightened pathological manifestations in comorbid populations. Collectively, our study provides the first evidence of SARS-CoV-2 ocular tropism via cells lining the BRB and that the virus can infect the retina via systemic permeation and induce retinal inflammation.

Just in case: undergraduate students identifying and mitigating barriers to their sexual and reproductive health needs.

BACKGROUND: Many U.S. colleges and universities offer access to a healthcare center that provides sexual and reproductive health (SRH) resources, services, and products. The importance of health centers in college and university settings in reducing sexual health disparities in student populations cannot be stressed enough. This article evaluates a student-led, mutual-aid, grassroots health promotion strategy for students with limited access to healthcare services, supplies, and tools via an anonymous and discrete distribution of SRH resources without charge. METHODS: In partnership with faculty, undergraduate students worked to address their school's unmet SRH needs by increasing on-campus access to comprehensive, evidence-based, and sex-positive resources. Referred to as Just in Case, this student-led, grassroots health promotion program provided students with supply kits containing contraceptives, sexual health wellness products, basic hygiene supplies, and education materials. Students were surveyed in a pre- (n = 95) post- (n = 73) pilot study to identify contraception acquisition barriers, discern perceptions of on-campus SRH resources, and elucidate trends in this program's use and impact. Chi-square tests of independence were used to compare survey group responses, and association rule mining was employed in tandem to identify SRH items that students requested. RESULTS: Students identified cost and privacy as significant barriers to acquiring sexual health products on campus. Of the 182 Just in Case supply kits requested by students during the 2022-2023 academic year, condoms were requested most frequently in 75% of fulfilled kits, while emergency contraception and pregnancy tests were asked most often in 61% of kits. 50% of students reported access to contraceptives on campus before this program's implementation, growing to 75% (p < 0.001) 1 year later post-implementation. Similar jumps were observed for reported access to sexual health education (30 to 73%, p < 0.001) and services (36 to 73%, p < 0.001). CONCLUSION: A student-led SRH supply and resource delivery strategy may immediately reduce SRH inequities and decrease barriers to contraceptive use for students with limited access to on-site SRH product availability.

Closing the gap: improving the percentage of Annual Wellness Visits among Medicare patients.

BACKGROUND: The Medicare Annual Wellness Visit (AWV) allows providers to acquire critical information about patients' health through a review of vitals, environmental risks, and medical and family history. These visits are free to those enrolled in Medicare and prioritize patient-provider relationship building and preventative care. Despite this, AWV completion rates are suboptimal. METHODS: A quality improvement project was aimed to increase the percentage of AWVs among Medicare patients in a primary care internal medicine practice from a baseline of 1.7% completion to 2.7% in 3 months from January to April 2023. INTERVENTION: With eligible patients identified, a standardized approach was created where an AWV appointment was ordered, and a patient message explaining the benefit of the appointment was sent by the patient portal. RESULTS: Our AWV intervention resulted in 72 patients being seen for an AWV, which increased the percentage of completed AWVs in the division by 2.1% from 1.7% to 3.8% in 3 months. CONCLUSION: This intervention will continue to improve AWV rates and improve patient care for Medicare patients in internal medicine. It could be applied to other areas of primary care and within other health systems.

Identifying Discrepancies in Gestational Diabetes Mellitus Postpartum Follow-Up During Care Transitions.

BACKGROUND: Gestational diabetes mellitus (GDM) is a common complication of pregnancy that carries lasting risks. For women who have a history of GDM, the risk of developing type 2 diabetes mellitus (T2DM) increases by 50 to 60%. To monitor and prevent the development of T2DM, guidelines suggest screening those with a history of GDM at 6-weeks and 3-years post-delivery. For patients with abnormal lab results at the 6-week mark, it is advised to complete lab work sooner, at the 1-year mark. Data suggests that these guidelines are not being followed globally, and most do not receive adequate screening for T2DM. METHODS: A retroactive chart review of 203 women between 18 and 55 years old with a past medical history significant for GDM was conducted to determine if patients with GDM completed screening for T2DM at 6-week, 1-year, and 3-year timestamps post-delivery. Patient demographics (age, race, ethnicity, language), clinical characteristics (body mass index), provider gender, and whether prediabetes or T2DM developed were recorded. Patients who did not complete the required follow-up received educational materials via the online portal system, and hemoglobin A1c (HbA1c) screening tests were ordered. RESULTS: Ninety days post-intervention, 38 patients (50%) completed the HbA1c screening test, which exceeded our goal of a 5% improvement. Age and BMI 1-year postpartum were found to be significant factors in whether a patient completed HbA1c screening, with 16/18 (89%) completing screening with a healthy BMI 1-year postpartum (18.5 ≤ BMI < 25.0) but only 11/41 (27%) completing screening for patients under 40 years with an unhealthy BMI 1-year postpartum. Of the 38 patients who completed HbA1c screening, 9 (23.7%) had abnormal screening results. CONCLUSION: Follow-up surveillance for T2DM among women with a history of GDM is poor. Electronic health records can be used to identify and rectify gaps in care. Dissemination of standardized educational materials and electronic order entry for patients improved screening between the handoff from obstetrics to primary care.

Characterizing tongue deformations during mastication using changes in planar components of three-dimensional angles.

Understanding of tongue deformations during mammalian mastication is limited, but has benefited from recent developments in multiplanar imaging technology. Here, we demonstrate how a standardized radiopaque marker implant configuration and biplanar fluoroscopy can quantify three-dimensional shape changes during chewing in pigs. Transverse and sagittal components of the three-dimensional angle between markers enable characterizing deformations in anatomically relevant directions. The transverse component illustrates bending to the left or to the right, which can occur symmetrically or asymmetrically, the latter sometimes indicating regional widening. The sagittal component reflects 'arching' or convex deformations in the dorsoventral dimension symmetrically or asymmetrically, the latter characteristic of twisting. Trends are detected in both the transverse and sagittal planes, and combinations thereof, to modify tongue shape in complex deformations. Both the transverse and sagittal components were also measured at key jaw and tongue positions, demonstrating variability particularly with respect to maximum and minimum gape. This highlights the fact that unlike tongue position, tongue deformations are more independent of jaw position, likely in response to the ever-changing bolus shape and position. From a methodological perspective, our study showcases advantages of a repeatable three-marker implant configuration suitable for animals of different sizes and highlights considerations for different implant patterns. This article is part of the theme issue 'Food processing and nutritional assimilation in animals'.

Expansion of wastewater-based disease surveillance to improve health equity in California's Central Valley: sequential shifts in case-to-wastewater and hospitalization-to-wastewater ratios.

Introduction: Over a third of the communities (39%) in the Central Valley of California, a richly diverse and important agricultural region, are classified as disadvantaged-with inadequate access to healthcare, lower socio-economic status, and higher exposure to air and water pollution. The majority of racial and ethnic minorities are also at higher risk of COVID-19 infection, hospitalization, and death according to the Centers for Disease Control and Prevention. Healthy Central Valley Together established a wastewater-based disease surveillance (WDS) program that aims to achieve greater health equity in the region through partnership with Central Valley communities and the Sewer Coronavirus Alert Network. WDS offers a cost-effective strategy to monitor trends in SARS-CoV-2 community infection rates. Methods: In this study, we evaluated correlations between public health and wastewater data (represented as SARS-CoV-2 target gene copies normalized by pepper mild mottle virus target gene copies) collected for three Central Valley communities over two periods of COVID-19 infection waves between October 2021 and September 2022. Public health data included clinical case counts at county and sewershed scales as well as COVID-19 hospitalization and intensive care unit admissions. Lag-adjusted hospitalization:wastewater ratios were also evaluated as a retrospective metric of disease severity and corollary to hospitalization:case ratios. Results: Consistent with other studies, strong correlations were found between wastewater and public health data. However, a significant reduction in case:wastewater ratios was observed for all three communities from the first to the second wave of infections, decreasing from an average of 4.7 ± 1.4 over the first infection wave to 0.8 ± 0.4 over the second. Discussion: The decline in case:wastewater ratios was likely due to reduced clinical testing availability and test seeking behavior, highlighting how WDS can fill data gaps associated with under-reporting of cases. Overall, the hospitalization:wastewater ratios remained more stable through the two waves of infections, averaging 0.5 ± 0.3 and 0.3 ± 0.4 over the first and second waves, respectively.

Saturday Pap Smear Clinic: addressing barriers to cervical cancer screening.

BACKGROUND: The incidence of cervical cancer has decreased by 70% since the 1950s. Preventative measures include vaccination against HPV strains and Papanicolaou tests. Early identification of cervical cancer through routine screening can significantly improve patient outcomes. MATERIALS AND METHODS: At our academic institution, Community Internal Medicine (CIM) Clinic, 63% of female patients aged 21-65 were compliant with cervical cancer screening. The opening of the 'Saturday Pap Smear Clinic' sought to address barriers by offering non-traditional appointment times on Saturday mornings with an all female staff. Our aim was to increase the cervical cancer screening rate by 1% within 12 weeks. Our team compared CIM (intervention) and family medicine (FM) (control) compliance rates from September 2021 to January 2022. Messages were sent to the patient indicating non-compliance and offering options to complete screening. RESULTS: At the start of this study, 5239 CIM patients were cervical cancer screening non-compliant. Postintervention, cervical screening rates among non-compliant women within CIM improved by 1.2%. The intervention cohort, CIM patients, had a significant improvement in compliance compared with the control group, FM patients. White women between the ages of 50 and 65 comprised the majority of patients who used the 'Saturday Pap Smear Clinic'. CONCLUSIONS: The availability of Saturday appointments for cervical cancer screening completion can enhance cervical cancer screening compliance among eligible women. Eliminating barriers for women can improve health outcomes.

Stats on the desats: alarm fatigue and the implications for patient safety.

BACKGROUND: Physiological monitoring systems, like Masimo, used during inpatient hospitalisation, offer a non-invasive approach to capture critical vital signs data. These systems trigger alarms when measurements deviate from preset parameters. However, often non-urgent or potentially false alarms contribute to 'alarm fatigue,' a form of sensory overload that can have adverse effects on both patients and healthcare staff. The Joint Commission, in 2021, announced a target to mitigate alarm fatigue-related fatalities through improved alarm management. Yet, no established guidelines are presently available. This study aims to address alarm fatigue at the Mayo Clinic to safeguard patient safety, curb staff burnout and improve the sensitivity of oxygen saturation monitoring to promptly detect emergencies. METHODS: A quality improvement project was conducted to combat minimise the false alarm burden, with data collected 2 months prior to intervention commencement. The project's goal was to decrease the total alarm value by 20% from 55%-85% to 35%-75% within 2 months, leveraging quality improvement methodologies. INTERVENTIONS: February to April 2021, we implemented a two-pronged intervention: (1) instituting a protocol to evaluate patients' continuous monitoring needs and discontinuing it when appropriate, and (2) introducing educational signage for patients and Mayo Clinic staff on monitoring best practices. RESULTS: Baseline averages of red alarms (158.6), manual snoozes (37.8) and self-resolves (120.7); the first postintervention phase showed reductions in red alarms (125.5), manual snoozes (17.8) and self-resolves (107.8). Second postintervention phase recorded 138 red alarms, 13 manual snoozes and 125 self-resolves. Baseline comparison demonstrated an average of 16.92% reduction of alarms among both interventions (p value: 0.25). CONCLUSION: Simple interventions like education and communication techniques proved instrumental in lessening the alarm burden for patients and staff. The findings underscore the practical use and efficacy of these methods in any healthcare setting, thus contributing to mitigating the prevalent issue of alarm fatigue.

Reduced mitochondrial calcium uptake in macrophages is a major driver of inflammaging.

Mitochondrial dysfunction is linked to age-associated inflammation or inflammaging, but underlying mechanisms are not understood. Analyses of 700 human blood transcriptomes revealed clear signs of age-associated low-grade inflammation. Among changes in mitochondrial components, we found that the expression of mitochondrial calcium uniporter (MCU) and its regulatory subunit MICU1, genes central to mitochondrial Ca2+ (mCa2+) signaling, correlated inversely with age. Indeed, mCa2+ uptake capacity of mouse macrophages decreased significantly with age. We show that in both human and mouse macrophages, reduced mCa2+ uptake amplifies cytosolic Ca2+ oscillations and potentiates downstream nuclear factor kappa B activation, which is central to inflammation. Our findings pinpoint the mitochondrial calcium uniporter complex as a keystone molecular apparatus that links age-related changes in mitochondrial physiology to systemic macrophage-mediated age-associated inflammation. The findings raise the exciting possibility that restoring mCa2+ uptake capacity in tissue-resident macrophages may decrease inflammaging of specific organs and alleviate age-associated conditions such as neurodegenerative and cardiometabolic diseases.

GLI1, a novel target of the ER stress regulator p97/VCP, promotes ATF6f-mediated activation of XBP1.

Upon accumulation of improperly folded proteins in the Endoplasmic Reticulum (ER), the Unfolded Protein Response (UPR) is triggered to restore ER homeostasis. The induction of stress genes is a sine qua non condition for effective adaptive UPR. Although this requirement has been extensively described, the mechanisms underlying this process remain in part uncharacterized. Here, we show that p97/VCP, an AAA+ ATPase known to contribute to ER stress-induced gene expression, regulates the transcription factor GLI1, a primary effector of Hedgehog (Hh) signaling. Under basal (non-ER stress) conditions, GLI1 is repressed by a p97/VCP-HDAC1 complex while upon ER stress GLI1 is induced through a mechanism requiring both USF2 binding and increase histone acetylation at its promoter. Interestingly, the induction of GLI1 was independent of ligand-regulated Hh signaling. Further analysis showed that GLI1 cooperates with ATF6f to induce promoter activity and expression of XBP1, a key transcription factor driving UPR. Overall, our work demonstrates a novel role for GLI1 in the regulation of ER stress gene expression and defines the interplay between p97/VCP, HDAC1 and USF2 as essential players in this process.

Hydroxychloroquine for pre-exposure prophylaxis of COVID-19 in health care workers: a randomized, multicenter, placebo-controlled trial Healthcare Worker Exposure Response and Outcomes of Hydroxychloroquine (HERO-HCQ).

OBJECTIVES: To determine whether hydroxychloroquine (HCQ) is safe and effective at preventing COVID-19 infections among health care workers (HCWs). METHODS: In a 1: 1 randomized, placebo-controlled, double-blind, parallel-group, superiority trial at 34 US clinical centers, 1360 HCWs at risk for COVID-19 infection were enrolled between April and November 2020. Participants were randomized to HCQ or matched placebo. The HCQ dosing included a loading dose of HCQ 600 mg twice on day 1, followed by 400 mg daily for 29 days. The primary outcome was a composite of confirmed or suspected COVID-19 clinical infection by day 30, defined as new-onset fever, cough, or dyspnea and either a positive SARS-CoV-2 polymerase chain reaction test (confirmed) or a lack of confirmatory testing due to local restrictions (suspected). RESULTS: Study enrollment closed before full accrual due to recruitment challenges. The primary end point occurred in 41 (6.0%) participants receiving HCQ and 53 (7.8%) participants receiving placebo. No difference in the proportion of participants experiencing clinical infection (estimated difference of -1.8%, 95% confidence interval -4.6-0.9%, P = 0.20) was identified nor any significant safety issues. CONCLUSION: Oral HCQ taken as prescribed appeared safe among HCWs. No significant clinical benefits were observed. The study was not powered to detect a small but potentially important reduction in infection. TRIAL REGISTRATION: NCT04334148.

Mechanisms to expedite pediatric clinical trial site activation: The DOSE trial experience.

BACKGROUND: Timely trial start-up is a key determinant of trial success; however, delays during start-up are common and costly. Moreover, data on start-up metrics in pediatric clinical trials are sparse. To expedite trial start-up, the Trial Innovation Network piloted three novel mechanisms in the trial titled Dexmedetomidine Opioid Sparing Effect in Mechanically Ventilated Children (DOSE), a multi-site, randomized, double-blind, placebo-controlled trial in the pediatric intensive care setting. METHODS: The three novel start-up mechanisms included: 1) competitive activation; 2) use of trial start-up experts, called site navigators; and 3) supplemental funds earned for achieving pre-determined milestones. After sites were activated, they received a web-based survey to report perceptions of the DOSE start-up process. In addition to perceptions, metrics analyzed included milestones met, time to start-up, and subsequent enrollment of subjects. RESULTS: Twenty sites were selected for participation, with 19 sites being fully activated. Across activated sites, the median (quartile 1, quartile 3) time from receipt of regulatory documents to site activation was 82 days (68, 113). Sites reported that of the three novel mechanisms, the most motivating factor for expeditious activation was additional funding available for achieving start-up milestones, followed by site navigator assistance and then competitive site activation. CONCLUSION: Study start-up is a critical time for the success of clinical trials, and innovative methods to minimize delays during start-up are needed. Milestone-based funds and site navigators were preferred mechanisms by sites participating in the DOSE study and may have contributed to the expeditious start-up timeline achieved. CLINICALTRIALS: gov #: NCT03938857.

Model training periods impact estimation of COVID-19 incidence from wastewater viral loads.

Wastewater-based epidemiology (WBE) has been deployed broadly as an early warning tool for emerging COVID-19 outbreaks. WBE can inform targeted interventions and identify communities with high transmission, enabling quick and effective responses. As the wastewater (WW) becomes an increasingly important indicator for COVID-19 transmission, more robust methods and metrics are needed to guide public health decision-making. This research aimed to develop and implement a mathematical framework to infer incident cases of COVID-19 from SARS-CoV-2 levels measured in WW. We propose a classification scheme to assess the adequacy of model training periods based on clinical testing rates and assess the sensitivity of model predictions to training periods. A testing period is classified as adequate when the rate of change in testing is greater than the rate of change in cases. We present a Bayesian deconvolution and linear regression model to estimate COVID-19 cases from WW data. The effective reproductive number is estimated from reconstructed cases using WW. The proposed modeling framework was applied to three Northern California communities served by distinct WW treatment plants. The results showed that training periods with adequate testing are essential to provide accurate projections of COVID-19 incidence.

Culture media composition influences patient-derived organoid ability to predict therapeutic responses in gastrointestinal cancers.

BACKGROUNDA patient-derived organoid (PDO) platform may serve as a promising tool for translational cancer research. In this study, we evaluated PDO's ability to predict clinical response to gastrointestinal (GI) cancers.METHODSWe generated PDOs from primary and metastatic lesions of patients with GI cancers, including pancreatic ductal adenocarcinoma, colorectal adenocarcinoma, and cholangiocarcinoma. We compared PDO response with the observed clinical response for donor patients to the same treatments.RESULTSWe report an approximately 80% concordance rate between PDO and donor tumor response. Importantly, we found a profound influence of culture media on PDO phenotype, where we showed a significant difference in response to standard-of-care chemotherapies, distinct morphologies, and transcriptomes between media within the same PDO cultures.CONCLUSIONWhile we demonstrate a high concordance rate between donor tumor and PDO, these studies also showed the important role of culture media when using PDOs to inform treatment selection and predict response across a spectrum of GI cancers.TRIAL REGISTRATIONNot applicable.FUNDINGThe Joan F. & Richard A. Abdoo Family Fund in Colorectal Cancer Research, GI Cancer program of the Mayo Clinic Cancer Center, Mayo Clinic SPORE in Pancreatic Cancer, Center of Individualized Medicine (Mayo Clinic), Department of Laboratory Medicine and Pathology (Mayo Clinic), Incyte Pharmaceuticals and Mayo Clinic Hepatobiliary SPORE, University of Minnesota-Mayo Clinic Partnership, and the Early Therapeutic program (Department of Oncology, Mayo Clinic).

Protection Induced by Oral Vaccination with a Recombinant Yersinia pseudotuberculosis Delivering Yersinia pestis LcrV and F1 Antigens in Mice and Rats against Pneumonic Plague.

A newly attenuated Yersinia pseudotuberculosis strain (designated Yptb1) with triple mutation Δasd ΔyopK ΔyopJ and chromosomal insertion of the Y. pestis caf1R-caf1M-caf1A-caf1 operon was constructed as a live vaccine platform. Yptb1 tailored with an Asd+ plasmid (pYA5199) (designated Yptb1[pYA5199]) simultaneously delivers Y. pestis LcrV and F1. The attenuated Yptb1(pYA5199) localized in the Peyer's patches, lung, spleen, and liver for a few weeks after oral immunization without causing any disease symptoms in immunized rodents. An oral prime-boost Yptb1(pYA5199) immunization stimulated potent antibody responses to LcrV, F1, and Y. pestis whole-cell lysate (YPL) in Swiss Webster mice and Brown Norway rats. The prime-boost Yptb1(pYA5199) immunization induced higher antigen-specific humoral and cellular immune responses in mice than a single immunization did, and it provided complete short-term and long-term protection against a high dose of intranasal Y. pestis challenge in mice. Moreover, the prime-boost immunization afforded substantial protection for Brown Norway rats against an aerosolized Y. pestis challenge. Our study highlights that Yptb1(pYA5199) has high potential as an oral vaccine candidate against pneumonic plague.

Transdisciplinary Imagination: Addressing Equity and Mistreatment in Perinatal Care.

Inequities in birth outcomes are linked to experiential and environmental exposures. There have been expanding and intersecting wicked problems of inequity, racism, and quality gaps in childbearing care during the pandemic. We describe how an intentional transdisciplinary process led to development of a novel knowledge exchange vehicle that can improve health equity in perinatal services. We introduce the Quality Perinatal Services Hub, an open access digital platform to disseminate evidence based guidance, enhance health systems accountability, and provide a two-way flow of information between communities and health systems on rights-based perinatal services. The QPS-Hub responds to both community and decision-makers' needs for information on respectful maternity care. The QPS-Hub is well poised to facilitate collaboration between policy makers, healthcare providers and patients, with particular focus on the needs of childbearing families in underserved and historically excluded communities.

Nucleotide receptors mediate protection against neonatal sepsis and meningitis caused by alpha-hemolysin expressing Escherichia coli K1.

Neonatal meningitis-associated Escherichia coli (NMEC) is among the leading causes of bacterial meningitis and sepsis in newborn infants. Several virulence factors have been identified as common among NMEC, and have been shown to play an important role in the development of bacteremia and/or meningitis. However, there is significant variability in virulence factor expression between NMEC isolates, and relatively little research has been done to assess the impact of variable virulence factor expression on immune cell activation and the outcome of infection. Here, we investigated the role of NMEC strain-dependent P2X receptor (P2XR) signaling on the outcome of infection in neonatal mice. We found that alpha-hemolysin (HlyA)-expressing NMEC (HlyA+ ) induced robust P2XR-dependent macrophage cell death in vitro, while HlyA- NMEC did not. P2XR-dependent cell death was inflammasome independent, suggesting an uncoupling of P2XR and inflammasome activation in the context of NMEC infection. In vivo inhibition of P2XRs was associated with increased mortality in neonatal mice infected with HlyA+ NMEC, but had no effect on the survival of neonatal mice infected with HlyA- NMEC. Furthermore, we found that P2XR-dependent protection against HlyA+ NMEC in vivo required macrophages, but not neutrophils or NLRP3. Taken together, these data suggest that HlyA+ NMEC activates P2XRs which in turn confers macrophage-dependent protection against infection in neonates. In addition, our findings indicate that strain-dependent virulence factor expression should be taken into account when studying the immune response to NMEC.

Clicks away from reduced healthcare expenditures: leveraging the electronic health record to reinforce education efforts.

OBJECTIVES: Lupron 11.25 mg has both a narrow indication and a high cost compared to other Lupron presentations. Prior to our study initiation there was no clear distinction between presentations when ordering within the health-system's Electronic Health Record (EHR). This resulted in inappropriate product selection, payment and billing errors that negatively impact our healthcare system. To reinforce prior education efforts, a new approach was considered leveraging the EHR with information to steer prescribers to the proper Lupron presentation based on indication. This study aimed to reduce off-label prescribing for Lupron 11.25 mg (NDC 00074-3663-03) by 25% by 02/28/2022 without negatively impacting the insurance collection rate. METHODS: Baseline Lupron 11.25 mg adult kit administrations one year prior to intervention and off-label prescribing was found to account for 22.7% of administrations. In December 2021 intervention order questions were added to Lupron 11.25 mg in the EHR. One and two-month data was obtained after implementing order questions within the EHR. Lupron 11.25 mg administrations were classified into one of four categories to determine impact on off-label prescribing. RESULTS: In the one- and two-month post-implementation periods off-label prescribing was 0% and 15.3% respectively, a reduction of 22.7% to and 7.4% respectively from the baseline assessment. There were no clinical denials found in either post-implementation reporting period. CONCLUSION: This report adds to the body of evidence that leveraging the EHR can lead to healthcare savings and illustrates how patient and healthcare system burden can be reduced by prompting thought and direction when a medication has indication specific dose requirements.