Mechanical ventilation interacts with endotoxemia to induce extrapulmonary organ dysfunction

INTRODUCTION: Multiple organ dysfunction syndrome (MODS) is a common complication of sepsis in mechanically ventilated patients with acute respiratory distress syndrome, but the links between mechanical ventilation and MODS are unclear. Our goal was to determine whether a minimally injurious mechanical ventilation strategy synergizes with low-dose endotoxemia to induce the activation of pro-inflammatory pathways in the lungs and in the systemic circulation, resulting in distal organ dysfunction and/or injury. METHODS: We administered intraperitoneal Escherichia coli lipopolysaccharide (LPS; 1 μg/g) to C57BL/6 mice, and 14 hours later subjected the mice to 6 hours of mechanical ventilation with tidal volumes of 10 ml/kg (LPS + MV). Comparison groups received ventilation but no LPS (MV), LPS but no ventilation (LPS), or neither LPS nor ventilation (phosphate-buffered saline; PBS). RESULTS: Myeloperoxidase activity and the concentrations of the chemokines macrophage inflammatory protein-2 (MIP-2) and KC were significantly increased in the lungs of mice in the LPS + MV group, in comparison with mice in the PBS group. Interestingly, permeability changes across the alveolar epithelium and histological changes suggestive of lung injury were minimal in mice in the LPS + MV group. However, despite the minimal lung injury, the combination of mechanical ventilation and LPS resulted in chemical and histological evidence of liver and kidney injury, and this was associated with increases in the plasma concentrations of KC, MIP-2, IL-6, and TNF-α. CONCLUSION: Non-injurious mechanical ventilation strategies interact with endotoxemia in mice to enhance pro-inflammatory mechanisms in the lungs and promote extra-pulmonary end-organ injury, even in the absence of demonstrable acute lung injury

Use of a Community Center Primary Care Clinic and Subsequent Emergency Department Visits among Unhoused Women

Funding/Support: Dr Stewart was supported by grants T32AI007044 and K23MH124466 from the National Institutes of Health (NIH), and Dr Stadeli was supported by training grant T32DK070555 from the NIH. The use of REDCap (Research Electronic Data Capture) software (Vanderbilt University) was supported by grants UL1TR002319, KL2TR002317, and TL1TR002318 from the Institute of Translational Health Science and from the National Center for Advancing Translational Sciences/NIH. The Safe. Healthy. Empowered (SHE) Clinic pilot program was supported by grants from Lahai Health for the period of April 1, 2018 through March 31, 2019, and by the City of Seattle Human Services Department. A mobile van owned and operated by Puget Sound Christian Clinic was used in the study.This cohort study evaluates the association between use of a community center primary care clinic and subsequent nonemergent emergency department (ED) visits by unhoused women who exchange sex and inject drugs.Peer reviewe

2533. HIV Training Pathways in Residency: A National Survey of Curricula and Outcomes

Abstract Background Despite dramatic advances in the care of people with HIV (PWH), the shortage of HIV providers is worsening. An approach to this workforce shortage has been integration of robust HIV training into residency. We created a national survey to describe curricula and outcomes of formal HIV training pathways and how this may impact the HIV workforce shortage. Methods We designed a cross-sectional study of Internal Medicine (IM) and Family Medicine (FM) Residency HIV pathways in the United States. We identified programs via literature review, internet search, and snowball sampling. A draft survey was piloted with two pathway directors, and in January 2019, the final survey was sent via email to all pathway directors. This survey included 33-items, predominantly quantitative, and focused on program organization, curricular content, graduate outcomes, and challenges. We used descriptive statistics to summarize numeric responses. Results Twenty-five residency programs with dedicated HIV pathways were identified; 11 IM and 15 FM. The majority of the programs are in the West and Northeast United States. Twenty-four (96%) of programs have completed the survey. Since the first program was established in 2006, 228 residents have graduated from HIV pathways in the United States (151 IM, 77 FM). Programs have varying goals, application procedures, clinical requirements, didactic structures, graduation requirements, and assessments of competency. Of graduates, 108 (47%) have American Academy of HIV Medicine (AAHIVM) certification. Ninety-two (42%) of graduates are reported as currently providing primary care to ≥ 20 PWH (the majority in the West and Northeast United States). The most commonly cited reported barrier to graduates finding jobs caring for PWH are lack of job opportunities in their geographic area. Conclusion HIV pathways in IM and FM programs are heterogenous in their structure and curricula. Less than 50% of pathway graduates remain in the HIV provider workforce, and the majority of those work in the West and Northeast United States. The impact of these programs might be enhanced by interventions to increase graduate retention in this workforce and to launch pathways in the areas of greatest need, such as the Southern United States. Disclosures All authors: No reported disclosures

Non-occupational post-exposure prophylaxis for HIV: 10-year retrospective analysis in Seattle, Washington.

Despite treatment guidelines in place since 2005, non-occupational post-exposure HIV prophylaxis (nPEP) remains an underutilized prevention strategy. We conducted a retrospective chart review of patients presenting to a publicly-funded HIV clinic in Seattle, Washington for nPEP between 2000 and 2010 (N = 360). nPEP prescriptions were provided for 324 (90%) patients; 83% of prescription decisions were appropriate according to Centers for Disease Control and Prevention guidelines, but only 31% (N = 111/360) of patients were considered "high risk." In order to use limited resources most efficiently, public health agencies should target messaging for this high-cost intervention to individuals with high-risk HIV exposures

Presentations for nPEP by exposure risk level.^†

†<p>Risk levels (inappropriate, appropriate and high risk) here and elsewhere in this manuscript specifically describe a determination of whether nPEP should be provided <i>from a public health perspective</i>. Individual providers should make case-by-case determinations for their patients informed by the CDC guidance for nPEP provision.</p>a<p>Inappropriate risk  = 1) evaluated >72 hours; 2) risk event did not include receptive or insertive anal or vaginal intercourse or intravenous drug use (IDU); 3) used a condom; OR 4) source contact was known to be HIV-negative.</p>b<p>Appropriate risk  =  patients 1) evaluated for PEP ≤72 hours; 2) risk event included receptive or insertive anal or vaginal intercourse or intravenous drug use (IDU); 3) did not report using a condom or experienced condom malfunction; and 4) source contact was known to be HIV-positive or was of unknown HIV status.</p>c<p>High risk  =  patients appropriate for nPEP and also: 1) were identified as MSM; and 2) engaged in RAI.</p>‡<p>Same as age categories used in CDC HIV Surveillance Report Volume 17, Number 4.</p

Risk behaviors among patients exposed to HIV-positive contact or contact with unknown HIV status (N = 351).^*

<p>*Nine (2.5%) patients were excluded from this table because they reported that their source contact was HIV-negative or because data about their source contact was missing.</p>†<p>Four (1%) patients reported that his/her contact was HIV negative: one reported a regular source contact, one reported an anonymous source contact, and data for source contact type was missing for two of these patients.</p>‡<p>Information about source contact was missing for five (1.5%) patients.</p

Characterising HIV transmission risk among US patients with HIV in care: a cross-sectional study of sexual risk behaviour among individuals with viral load above 1500 copies/mL

ObjectivesViral load and sexual risk behaviour contribute to HIV transmission risk. High HIV viral loads present greater transmission risk than transient viral ‘blips’ above an undetectable level. This paper therefore characterises sexual risk behaviour among patients with HIV in care with viral loads>1500 copies/mL and associated demographic characteristics.MethodsThis cross-sectional study was conducted at six HIV outpatient clinics in USA. The study sample comprises 1315 patients with HIV with a recent viral load >1500 copies/mL. This study sample was drawn from a larger sample of individuals with a recent viral load >1000 copies/mL who completed a computer-assisted self-interview (CASI) regarding sexual risk practices in the last 2 months. The study sample was 32% heterosexual men, 38% men who have sex with men (MSM) and 30% women.ResultsNinety per cent of the sample had their viral load assay within 60 days of the CASI. Thirty-seven per cent reported being sexually active (vaginal or anal intercourse) in the last 2 months. Most of the sexually active participants reported always using condoms (56.9%) or limiting condomless sex to seroconcordant partners (serosorting; 29.2% overall and 42.9% among MSM). Among sexually active participants who reported condomless anal or vaginal sex with an at-risk partner (14%), most had viral loads>10 000 copies/mL (62%).ConclusionsA relatively small number of patients with HIV in care with viral loads above 1500 copies/mL reported concurrent sexual transmission risk behaviours. Most of the individuals in this small group had markedly elevated viral loads, increasing the probability of transmission. Directing interventions to patients in care with high viral loads and concurrent risk behaviour could strengthen HIV prevention and reduce HIV infections.Trial registration numberNCT02044484, completed