Cost-Effectiveness of HIV Screening in Emergency Departments: Results From the Pragmatic Randomized HIV Testing Using Enhanced Screening Techniques in Emergency Departments Trial.

STUDY OBJECTIVE: Identification of HIV remains a critical health priority for which emergency departments (EDs) are a central focus. The comparative cost-effectiveness of various HIV screening strategies in EDs remains largely unknown. The goal of this study was to compare programmatic costs and cost-effectiveness of nontargeted and 2 forms of targeted opt-out HIV screening in EDs using results from a multicenter, pragmatic randomized clinical trial. METHODS: This economic evaluation was nested in the HIV Testing Using Enhanced Screening Techniques in Emergency Departments (TESTED) trial, a multicenter pragmatic clinical trial of different ED-based HIV screening strategies conducted from April 2014 through January 2016. Patients aged 16 years or older, with normal mental status and not critically ill, or not known to be living with HIV were randomized to 1 of 3 HIV opt-out screening approaches, including nontargeted, enhanced targeted, or traditional targeted, across 4 urban EDs in the United States. Each screening method was fully integrated into routine emergency care. Direct programmatic costs were determined using actual trial results, and time-motion assessment was used to estimate personnel activity costs. The primary outcome was newly diagnosed HIV. Total annualized ED programmatic costs by screening approach were calculated using dollars adjusted to 2023 as were costs per patient newly diagnosed with HIV. One-way and multiway sensitivity analyses were performed. RESULTS: The trial randomized 76,561 patient visits, resulting in 14,405 completed HIV tests, and 24 (0.2%) new diagnoses. Total annualized new diagnoses were 12.9, and total annualized costs for nontargeted, enhanced targeted, and traditional targeted screening were $111,861, $88,629, and $70,599, respectively. Within screening methods, costs per new HIV diagnoses were $20,809, $23,554, and $18,762, respectively. Enhanced targeted screening incurred higher costs but with similar annualized new cases detected compared with traditional targeted screening. Nontargeted screening yielded an incremental cost-effectiveness ratio of $25,586 when compared with traditional targeted screening. Results were most sensitive to HIV prevalence and costs of HIV tests. CONCLUSION: Nontargeted HIV screening was more costly than targeted screening largely due to an increased number of HIV tests performed. Each HIV screening strategy had similar within-strategy costs per new HIV diagnosis with traditional targeted screening yielding the lowest cost per new diagnosis. For settings with budget constraints or very low HIV prevalences, the traditional targeted approach may be preferred; however, given only a slightly higher cost per new HIV diagnosis, ED settings looking to detect the most new cases may prefer nontargeted screening.

Bartonella quintana Infection in People Experiencing Homelessness in the Denver Metropolitan Area.

BACKGROUND: Bartonella quintana is an important cause of infection amongst people experiencing homelessness that is underdiagnosed due to its nonspecific clinical manifestations. We reviewed cases identified in the Denver metropolitan area in 2016-2021. METHODS: The electronic medical records from 2 large academic medical centers in Colorado were reviewed for demographic, clinical, and laboratory features of patients with B. quintana infection confirmed by blood culture, serologies, and/or molecular testing from July 2016 to December 2021. RESULTS: Fourteen patients with B. quintana infection were identified. The mean age was 49.5 years (SD 12.7 years) and 92.9% of patients were male. Twelve patients had history of homelessness (85.7%) and 11 were experiencing homelessness at the time of diagnosis (78.6%). Most frequent comorbidities included substance use (78.6%), of which 42.9% had alcohol use disorder. The average time to blood culture positivity was 12.1 days (SD 6.2 days). Three patients with bacteremia had negative B. quintana IgG, and 6 of 14 (42.8%) patients had evidence of endocarditis on echocardiography. CONCLUSIONS: B. quintana is an underrecognized cause of serious infection in individuals experiencing homelessness. Serologic and microbiologic testing, including prolonged culture incubation, should be considered in at-risk patients due to ongoing transmission in homeless populations.

Lower Prevalence of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection Among People Experiencing Homelessness Tested in Outdoor Encampments Compared With Overnight Shelters: Denver, Colorado, June-July 2020.

BACKGROUND: A better understanding of the risk for coronavirus disease 2019 (COVID-19) that people experiencing homelessness (PEH) face in congregate shelters versus unsheltered encampments is critical for an effective pandemic response. METHODS: We analyzed factors associated with current and past severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among PEH in day and overnight shelters and encampments in Denver, Colorado, during June 2-July 28, 2020, and constructed multivariable logistic regression models to examine risk factors for SARS-CoV-2 RNA and seropositivity with age, race/ethnicity, testing location, testing month, and symptom status as predictor variables. RESULTS: A total of 823 participants were tested for SARS-CoV-2 RNA, and 276 individuals were tested for SARS-CoV-2 antibodies. A greater percentage of PEH at overnight shelters tested positive for SARS-CoV-2 RNA (8.6% vs 2.5%, P < .01) and antibodies (21.5% vs 8.7%, P = .03) compared with encampments. In regression models, testing at an overnight shelter compared with testing at encampments (odds ratio [OR] = 3.03, 95% confidence interval [CI]: 1.16-9.02) had increased odds of a positive SARS-CoV-2 RNA result. Age >60 years compared with age <40 years (OR = 5.92; 95% CI: 1.83-20.3), Hispanic ethnicity (OR = 3.43; 95% CI: 1.36-8.95), and non-Hispanic Black race compared with non-Hispanic White race (OR = 3.07; 95% CI: 1.16-8.26), and testing at an overnight shelter compared to testing at encampments (OR = 2.45; 95% CI: 1.04-6.17) had increased odds of a positive antibody result. CONCLUSIONS: Our findings support the need for continuing assessment of mitigation strategies in shelters, increasing access to individual rooms and linkage to housing options for PEH, and supporting people to remain in encampments when these options are not available.

Predictors of 007 triphosphate concentrations in dried blood spots in persons with hepatitis C and active drug or alcohol use.

BACKGROUND: Sofosbuvir is converted to its active form, 007 triphosphate (007-TP), within cells. To date, the association between treatment adherence and 007-TP in dried blood spots (DBS) and factors that influence this relationship remain unknown. OBJECTIVES: To examine relationships between adherence and 007-TP concentrations in DBS and identify factors that influence 007-TP in DBS. METHODS: Persons with HCV or HIV/HCV coinfection and self-reported drug and/or alcohol use were randomized to one of two technology-based approaches for monitoring 12 week adherence to once-daily ledipasvir/sofosbuvir. Convenience blood samples were collected every 2 weeks during treatment. 007-TP in DBS was quantified using LC/MS and analysed using mixed-effects models. RESULTS: A total of 337 observations were available from 58 participants (78% male; 21% black; 22% Hispanic/Latino; 26% cirrhotic; 78% HIV-coinfected). The mean half-life of 007-TP in DBS was 142 h (95% CI 127-156) and concentrations increased by 7.3% (95% CI 2.2-12.6) for every 10% increase in between-visit adherence. Geometric mean (95% CI) 007-TP concentrations in DBS were 301 (247-368), 544 (462-639) and 647 (571-723) fmol/punch by adherence categories of ≤50%, >50 to ≤80%, and >80%. Adherence, time on therapy, increasing age and decreased estimated glomerular filtration rate were associated with higher 007-TP, whereas increased time since last dose, male sex, black race and higher BMI were associated with lower 007-TP. CONCLUSIONS: 007-TP has an extended half-life in DBS and concentrations increased with adherence. Further research is needed to examine additional factors that affect 007-TP and the clinical utility of this measure.

Development of a 2-step algorithm to identify emergency department patients for HIV pre-exposure prophylaxis.

BACKGROUND: Expanded access to HIV PrEP is a central pillar of the "Ending the HIV Epidemic" initiative. Identification of PrEP eligible individuals in EDs remains understudied. Our goal was to estimate the accuracy of the Denver HIV Risk Score (DHRS), a quantitative HIV risk tool, for determining PrEP eligibility, and to incorporate it into a novel screening algorithm to optimize sensitivity and specificity. METHODS: We performed a prospective cross-sectional study in two urban EDs. Patients were eligible if ≥18 years of age and without HIV. Research staff collected individual HIV risk, components of the DHRS, and PrEP eligibility per 2017 CDC guidelines. Accuracy estimates were calculated for the DHRS alone and the DHRS plus additional PrEP-specific questions. RESULTS: 1002 patients were enrolled with a median age of 39 years; 54.8% were male, 29.5% Black/non-Hispanic, and 22.5% Hispanic. Overall, 119 (11.9%, 95% CI: 9.9%-14.0%) were PrEP eligible; 5% endorsed history of sex with a partner at higher risk for HIV or condomless sex with multiple partners, 4% an STI, and 2% sharing IDU equipment. A DHRS ≥25 had a sensitivity of 92.4% (95% CI: 86.1%-96.5%) and a specificity of 17.2% (95% CI: 14.8%-19.9%) for PrEP eligibility. A 2-step algorithm, "DHRS-PrEP", beginning with a DHRS ≥25, followed by a step with questions specific to IDU, STI, and sexual partners improved the specificity to 100% (95% CI: 99.6%-100%). CONCLUSIONS: Among a heterogeneous ED sample, a substantial proportion was identified as PrEP eligible, and a 2-step algorithm had high sensitivity and specificity for identifying PrEP-eligible patients.

Detection of Severe Acute Respiratory Syndrome Coronavirus 2 on Self-Collected Saliva or Anterior Nasal Specimens Compared With Healthcare Personnel-Collected Nasopharyngeal Specimens.

BACKGROUND: Nasopharyngeal specimens (NPS) are commonly used for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing but can be uncomfortable for patients. Self-collected saliva specimens (SS) or anterior nasal specimens (ANS) for SARS-CoV-2 detection are less invasive, but the sensitivity of these specimen types has not been thoroughly evaluated. METHODS: During September-November 2020, 730 adults undergoing SARS-CoV-2 testing at community testing events and homeless shelters in Denver provided self-collected SS and ANS before NPS collection and answered a short survey about symptoms and specimen preference. Specimens were tested for SARS-CoV-2 by means of real-time reverse-transcription polymerase chain reaction (rRT-PCR); viral culture was performed on a subset of specimens positive by rRT-PCR. The sensitivity of SS and ANS for SARS-CoV-2 detection by rRT-PCR was measured against that of NPS. Subgroup analyses included test outcomes by symptom status and culture results. RESULTS: Sensitivity for SARS-CoV-2 detection by rRT-PCR appeared higher for SS than for ANS (85% vs 80%) and higher among symptomatic participants than among those without symptoms (94% vs 29% for SS; 87% vs 50% for ANS). Among participants with culture-positive SARS-CoV-2 by any specimen type, the sensitivities of SS and ANS by rRT-PCR were 94% and 100%, respectively. SS and ANS were equally preferred by participants; most would undergo NPS collection again despite this method's being the least preferred. CONCLUSIONS: SS were slightly more sensitive than ANS for SARS-CoV-2 detection with rRT-PCR. With both SS and ANS, SARS-CoV-2 was reliably detected among participants with symptoms. Self-collected SS and ANS offer practical advantages, are preferred by patients, and might be most useful for testing people with coronavirus disease 2019 symptoms.

Viral Hepatitis and Human Immunodeficiency Virus Testing and Linkage to Care for Individuals Enrolled in an Opioid Treatment Program.

BACKGROUND: In the United States, many opioid treatment programs (OTPs) do not offer viral hepatitis (VH) or human immunodeficiency virus (HIV) testing despite high prevalence among OTP clients. We initiated an opt-out VH and HIV testing and linkage-to-care program within our OTP. METHODS: All OTP intakes are screened for VH and HIV and evaluated for rescreening annually. A patient navigator reviews laboratory results and provides counseling in the OTP clinic. The medical record is queried to identify individuals with previously diagnosed, untreated VH or HIV. Navigation support is provided for linkage or relinkage to VH or HIV care. RESULTS: Between March 2018 and Februrary 2019, 532 individuals were screened for hepatitis C virus (HCV), 180 tested HCV antibody positive (34%), and 108 were HCV-ribonucleic acid (RNA) positive (20%). Sixty individuals were identified with previously diagnosed, untreated HCV. Of all HCV RNA+, 49% reported current injection drug use (82 of 168). Ninety-five individuals were seen by an HCV specialist (57% of HCV RNA+), 72 started treatment (43%), and 69 (41%) completed treatment. Individuals with primary care providers were most likely to start treatment. Four individuals were diagnosed with hepatitis B; 0 were diagnosed with HIV. CONCLUSIONS: The implementation of an OTP-based screening and navigation protocol has enabled significant gains in the identification and treatment of VH in this high prevalence setting.

Pharmacokinetics and renal safety of tenofovir alafenamide with boosted protease inhibitors and ledipasvir/sofosbuvir.

BACKGROUND: Ledipasvir/sofosbuvir increases tenofovir plasma exposures by up to 98% with tenofovir disoproxil fumarate (TDF), and exposures are highest with boosted PIs. There are currently no data on the combined use of the newer tenofovir prodrug, tenofovir alafenamide (TAF), boosted PIs and ledipasvir/sofosbuvir. OBJECTIVES: To compare the plasma and intracellular pharmacokinetics and renal safety of TAF with ledipasvir/sofosbuvir when co-administered with boosted PIs. METHODS: Persons with HIV between 18 and 70 years and on a boosted PI with TDF were eligible. The study was comprised of four phases: (1) TDF 300 mg with boosted PI; (2) TAF 25 mg with boosted PI; (3) TAF 25 mg with boosted PI and ledipasvir/sofosbuvir; and (4) TAF 25 mg with boosted PI. Pharmacokinetic sampling, urine biomarker collection [urine protein (UPCR), retinol binding protein (RBP) and ß2 microglobulin (ß2M) normalized to creatinine] and safety assessments occurred at the end of each phase. Plasma, PBMCs and dried blood spots were collected at each visit. RESULTS: Ten participants were enrolled. Plasma tenofovir exposures were 76% lower and tenofovir-diphosphate (TFV-DP) concentrations in PBMCs increased 9.9-fold following the switch to TAF. Neither of these measures significantly increased with ledipasvir/sofosbuvir co-administration, nor did TAF plasma concentrations. No significant changes in estimated glomerular filtration rate or UPCR occurred, but RBP:creatinine and ß2M:creatinine improved following the switch to TAF. CONCLUSIONS: Ledipasvir/sofosbuvir did not significantly increase plasma tenofovir or intracellular TFV-DP in PBMCs with TAF. These findings provide reassurance that the combination of TAF, boosted PIs and ledipasvir/sofosbuvir is safe in HIV/HCV-coinfected populations.

Rapid Syphilis Testing for Men Who Have Sex With Men in Outreach Settings: Evaluation of Test Performance and Impact on Time to Treatment.

BACKGROUND: Rapid syphilis tests (RST) may shorten time to syphilis diagnosis and treatment while enhancing access to testing in outreach settings. There are limited data on the performance of RST in outreach settings in the US. METHODS: We offered RST (Syphilis Health Check) at 6 outreach sites to men who reported having sex with men and no prior history of syphilis. Clients accepting RST were also tested with laboratory-based rapid plasma reagin (RPR) and reflex Treponema pallidum particle agglutination (TPPA) assay when RPR or RST were positive. Clients with positive RST were immediately referred to a sexually transmitted infection clinic. Those declining RST were screened with RPR and reflex TPPA only. The validity of the RST-based algorithm was compared with the RPR-based algorithm among participants receiving both. Time to treatment for those accepting RST was compared with those declining RST and to a historical control group screened in outreach settings with RPR and reflex TPPA before the availability of RST. RESULTS: Rapid syphilis test was accepted by 690 (64%) of 1081 eligible clients. Compared with RPR-based algorithm, RST sensitivity was 90%; specificity, 98.5%; positive predictive value, 47.4%; and negative predictive value, 98.5. The single false-negative case by RST was determined to be a late latent case by RPR/TPPA. Median time to treatment was 1 day (range, 0-6 days) for 9 of 690 accepting RST, compared to 9 days (range, 7-13 days) for 3 of 391 declining RST, and 9 days (range, 6-21 days) for 25 of 1229 historical controls (P < 0.0001). CONCLUSION: Compared with an RPR-based algorithm, RST identified all early syphilis cases. Although RST had high specificity and negative predictive value, the low positive predictive value resulted in additional assessments in a sexually transmitted infection clinic for some patients. However, RST use in outreach settings significantly decreased time to treatment for new syphilis cases.

Outcomes of Preexposure Prophylaxis Referrals From Public STI Clinics and Implications for the Preexposure Prophylaxis Continuum.

BACKGROUND: Human immunodeficiency virus preexposure prophylaxis (PrEP) uptake remains low in high-risk populations. Sexually transmitted infection (STI) clinics reach PrEP-eligible persons and may be ideal settings to model PrEP implementation. METHODS: Consenting PrEP-eligible patients identified at Chicago Department of Public Health STI Clinics were actively referred to PrEP partner sites between June 1, 2015, and May 31, 2016. Outcomes included successful contact by a partner site, linkage to a partner site, and receipt of a PrEP prescription. Bivariable and time to event analyses were conducted to determine significant associations of outcomes. RESULTS: One hundred thirty-seven patients were referred; 126 (92%) were men who have sex with men, and mean age was 29 years. Ninety-eight (72%) were contacted by a PrEP partner, 43 (31%) were linked, and 40 (29%) received a prescription. Individuals aged 25 years and older were more likely to link (odds ratio, 3.10; 95% confidence interval, 1.30-7.41) and receive a PrEP prescription (odds ratio, 2.70; 95% confidence interval, 1.12-6.45) compared with individuals 24 years and younger. The average time between each step was greater for those 24 years and younger compared with those aged 25 years and older for all steps. Time to event analyses revealed that those aged 25 years and older were significantly more likely to receive a prescription compared to those aged 24 years and younger (hazard ratio, 3.62; 95% risk limits, 1.47-8.92). CONCLUSIONS: Preexposure prophylaxis active referrals from STI clinics to partner sites are feasible, though drop out was prominent in the initial steps of the continuum. Youth were less likely to link or receive prescriptions, indicating the need for tailored interventions for this vulnerable population.

Barriers to Hepatitis C Treatment and Interest in Telemedicine-Based Care Among Clients of a Syringe Access Program.

Background: Sharing equipment for injection drug use is the most common mode of hepatitis C virus (HCV) transmission in the United States, yet people who inject drugs (PWID) historically have low rates of HCV treatment. New strategies are needed to expand access to HCV treatment among PWID. Co-locating HCV treatment at syringe access programs (SAPs) reduces barriers to treatment, and telemedicine-based treatment programs could expand access further. Methods: To evaluate interest in a co-localized or telemedicine-based program at an SAP in Denver, Colorado, we surveyed 171 SAP clients to understand barriers to HCV treatment and comfort with various appointment modalities. Results: Eighty-nine of the surveyed SAP clients (52%), 50 of whom had not completed treatment, reported current or prior HCV infection. The most commonly cited reasons for not seeking HCV treatment were ongoing drug use, logistic barriers, and medical system barriers. Eighty-eight percent of clients with HCV reported that they would be more likely to get treatment if they were able to do so at the SAP, and the rate was higher among people who reported reluctance to seek medical care in general (98% vs 77%, P = .011). In-person appointments were preferred, though 77% of respondents were comfortable with a video appointment. However, only 60% of SAP clients reported having access to a phone, and fewer (48%) had access to video capability. Conclusions: These findings suggest that telemedicine-based treatment at an SAP could improve access to HCV treatment, but successful implementation would require attention to barriers impacting clients' ability to participate in telemedicine appointments.

Mycoplasma genitalium: Key Information for the Primary Care Clinician.

Mycoplasma genitalium (MG) is an emerging sexually transmitted infection, which appears to be a cause of urethritis and cervicitis and has been associated with pelvic inflammatory disease (PID), epididymitis, proctitis, infertility, complications during pregnancy, and human immunodeficiency virus (HIV) transmission. Three Food and Drug Administration (FDA) approved tests are available. Testing should be focused to avoid inappropriate antibiotic use. The Center of Disease Control and Prevention (CDC) guidelines recommend testing for persistent male urethritis, cervicitis, and proctitis and state that testing should be considered in cases of PID. Testing is also recommended for sexual contacts of patients with MG. Testing is not recommended in asymptomatic patients, including pregnant patients, who do not have a history of MG exposure. Although resistance-guided therapy is recommended, there are currently no FDA approved tests for MG macrolide resistance, and tests are not widely available in the United States. The CDC recommends 2-step treatment with doxycycline followed by azithromycin or moxifloxacin. Moxifloxacin is recommended if resistance testing is unavailable or testing demonstrates macrolide resistance..

Client Perspectives on the Development of a Rapid PrEP Initiative at a Sexual Health Center in New Orleans, Louisiana.

Uptake of PrEP remains suboptimal, especially in the Southern United States. Same-day or "Rapid PrEP Initiatives" (RPIs) in sexual health centers (SHCs) could facilitate access and overcome barriers to PrEP. We studied the adaptation of an RPI from Denver, Colorado to an SHC in New Orleans, Louisiana. Through focus group discussions (FGDs) with local SHC staff and PrEP providers, we developed a preliminary RPI model. In 5 FGDs with SHC clients referred for or taking PrEP, we gathered adaptation recommendations and feedback on model acceptability, feasibility, and utility. Providers and clients voiced unanimous support for the RPI. Clients favored the ease of same-day PrEP initiation and emphasized a desire for navigational support, financial counseling, and integration of PrEP care with their other clinical needs. Clients recommended that SHC providers discuss PrEP and HIV with all patients, regardless of providers' perception of risk. Next steps include small-scale implementation and evaluation.

Client Perspectives on the Development of a Same-Day PrEP Initiation Protocol at a Sexual Health Center in New Orleans, LouisianaUptake of PrEP remains low, especially in the Southern United States. Same-day or "Rapid PrEP Initiatives" (RPIs) in sexual health centers (SHCs) could facilitate access and overcome barriers to PrEP. RPIs provide eligible clients with an opportunity to start PrEP on the same day they receive screening for sexually transmitted infections. We studied the adaptation of an RPI from Denver, Colorado, to an SHC in New Orleans, Louisiana. Through focus group discussions (FGDs) with local SHC staff and PrEP providers, we developed a preliminary RPI model. In five FGDs with SHC clients referred for or taking PrEP, we gathered adaptation recommendations and feedback on RPI model acceptability, feasibility, and utility. Providers and clients voiced unanimous support for the RPI. Clients favored the ease of same-day PrEP initiation and emphasized a desire for navigational support, financial counseling, and integration of PrEP care with their other clinical needs. Clients recommended that SHC providers discuss PrEP and HIV with all patients, regardless of providers' perception of risk. Next steps include small-scale implementation and evaluation.

The neighborhood built environment and COVID-19 hospitalizations.

Research on the associations between the built environment and COVID-19 outcomes has mostly focused on incidence and mortality. Also, few studies on the built environment and COVID-19 have controlled for individual-level characteristics across large samples. In this study, we examine whether neighborhood built environment characteristics are associated with hospitalization in a cohort of 18,042 individuals who tested positive for SARS-CoV-2 between May and December 2020 in the Denver metropolitan area, USA. We use Poisson models with robust standard errors that control for spatial dependence and several individual-level demographic characteristics and comorbidity conditions. In multivariate models, we find that among individuals with SARS-CoV-2 infection, those living in multi-family housing units and/or in places with higher particulate matter (PM2.5) have a higher incident rate ratio (IRR) of hospitalization. We also find that higher walkability, higher bikeability, and lower public transit access are linked to a lower IRR of hospitalization. In multivariate models, we did not find associations between green space measures and the IRR of hospitalization. Results for non-Hispanic white and Latinx individuals highlight substantial differences: higher PM2.5 levels have stronger positive associations with the IRR of hospitalization for Latinx individuals, and density and overcrowding show stronger associations for non-Hispanic white individuals. Our results show that the neighborhood built environment might pose an independent risk for COVID-19 hospitalization. Our results may inform public health and urban planning initiatives to lower the risk of hospitalization linked to COVID-19 and other respiratory pathogens.

The Determining Effective Testing in Emergency Departments and Care Coordination on Treatment Outcomes (DETECT) for Hepatitis C (Hep C) Linkage-to-Care Trial: rationale and design of an emergency department-based randomized clinical trial of linkage-to-care strategies for hepatitis C.

BACKGROUND: Hepatitis C (HCV) poses a major public health problem in the USA. While early identification is a critical priority, subsequent linkage to a treatment specialist is a crucial step that bridges diagnosed patients to treatment, cure, and prevention of ongoing transmission. Emergency departments (EDs) serve as an important clinical setting for HCV screening, although optimal methods of linkage-to-care for HCV-diagnosed individuals remain unknown. In this article, we describe the rationale and design of The Determining Effective Testing in Emergency Departments and Care Coordination on Treatment Outcomes (DETECT) for Hepatitis C (Hep C) Linkage-to-Care Trial. METHODS: The DETECT Hep C Linkage-to-Care Trial will be a single-center prospective comparative effectiveness randomized two-arm parallel-group superiority trial to test the effectiveness of linkage navigation and clinician referral among ED patients identified with untreated HCV with a primary hypothesis that linkage navigation plus clinician referral is superior to clinician referral alone when using treatment initiation as the primary outcome. Participants will be enrolled in the ED at Denver Health Medical Center (Denver, CO), an urban, safety-net hospital with approximately 75,000 annual adult ED visits. This trial was designed to enroll a maximum of 280 HCV RNA-positive participants with one planned interim analysis based on methods by O'Brien and Fleming. This trial will further inform the evaluation of cost effectiveness, disparities, and social determinants of health in linkage-to-care, treatment, and disease progression. DISCUSSION: When complete, the DETECT Hep C Linkage-to-Care Trial will significantly inform how best to perform linkage-to-care among ED patients identified with HCV. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT04026867 Original date: July 1, 2019 URL: https://clinicaltrials.gov/ct2/show/NCT04026867.

Airway smooth muscle STIM1 and Orai1 are upregulated in asthmatic mice and mediate PDGF-activated SOCE, CRAC currents, proliferation, and migration.

Airway smooth muscle cell (ASMC) remodeling contributes to the structural changes in the airways that are central to the clinical manifestations of asthma. Ca(2+) signals play an important role in ASMC remodeling through control of ASMC migration and hypertrophy/proliferation. Upregulation of STIM1 and Orai1 proteins, the molecular components of the store-operated Ca(2+) entry (SOCE) pathway, has recently emerged as an important mediator of vascular remodeling. However, the potential upregulation of STIM1 and Orai1 in asthmatic airways remains unknown. An important smooth muscle migratory agonist with major contributions to ASMC remodeling is the platelet-derived growth factor (PDGF). Nevertheless, the Ca(2+) entry route activated by PDGF in ASMC remains elusive. Here, we show that STIM1 and Orai1 protein levels are greatly upregulated in ASMC isolated from ovalbumin-challenged asthmatic mice, compared to control mice. Furthermore, we show that PDGF activates a Ca(2+) entry pathway in rat primary ASMC that is pharmacologically reminiscent of SOCE. Molecular knockdown of STIM1 and Orai1 proteins inhibited PDGF-activated Ca(2+) entry in these cells. Whole-cell patch clamp recordings revealed the activation of Ca(2+) release-activated Ca(2+) (CRAC) current by PDGF in ASMC. These CRAC currents were abrogated upon either STIM1 or Orai1 knockdown. We show that either STIM1 or Orai1 knockdown significantly inhibited ASMC proliferation and chemotactic migration in response to PDGF. These results implicate STIM1 and Orai1 in PDGF-induced ASMC proliferation and migration and suggest the potential use of STIM1 and Orai1 as targets for ASMC remodeling during asthma.

The variable presentations and broadening geographic distribution of hepatic fascioliasis.

We report 2 unrelated cases of hepatic fascioliasis in travelers returning to the United States from Africa and the Middle East. The first case presented with acute infection. Prominent clinical features included abdominal pain, elevated liver transaminases, serpiginous hepatic lesions, pericapsular hematoma, and marked peripheral eosinophilia. The second case was diagnosed in the chronic stage of infection and presented with right upper quadrant abdominal pain, cystic hepatic lesions, and an adult fluke in the common bile duct. We review the life cycle of Fasciola species, the corresponding clinical features during the stages of human infection, diagnostic methods, and the evolving understanding of the epidemiology of human fascioliasis, particularly emphasizing fascioliasis in African countries.