OBJECTIVE:False-reactive results of the fourth-generation HIV-1/2 antigen/antibody (Ag/Ab) Combo assay trigger additional testing, increased costs, and patient anxiety. Large-scale analyses of false-reactive results spanning the COVID-19 pandemic in high-prevalence communities are lacking. This study aims to investigate the frequency of false-reactive HIV-1/2 Ag/Ab Combo screening results before, during, and after the COVID-19 pandemic and to identify associated patient factors. DESIGN:We conducted a retrospective study of HIV-1/2 Ag/Ab Combo assays performed from 2019 to 2024 at a tertiary care medical center in Baltimore, MD. False-reactive proportions were compared across pre-pandemic (January - December 2019; n = 12,347), pandemic (January 2020 - June 2023, n = 33,546), and post-pandemic (July 2023 - December 2024; n = 12,238). Associations between false-reactive results and selected patient factors were assessed. RESULTS:Among 58,131 screens, 1236 (2.1%) were reactive; 185 were false-reactive, yielding a false-reactive proportion of 15.0% among reactive results. The false-reactive proportion increased from 5% pre-pandemic to 17.9% at the onset of the COVID-19 pandemic and remained near 20% during the pandemic, declining to approximately 14% by 2024 post-pandemic. In multivariable analysis, age > 65 or < 21, White race, and American Indian/Alaska Native race were associated with higher odds of false-reactive results, whereas coinfection of syphilis was associated with lower odds. Most false-reactive results clustered at low signal-to-cutoff ratio (S/CO) values. CONCLUSIONS:False-reactive HIV Ag/Ab screening results increased during the pandemic and remained elevated afterward. Associated factors analysis and S/CO distributions may help interpretation of questionable reactive screens. Our findings reinforce the importance of reflex HIV nucleic acid testing (NAT) for discordant results.

Antibiotics are diverse in their utility in clinical care. They are widely prescribed for their antimicrobial effect and used as modulators, although rarely, of non-infectious conditions, to influence immune responses, to decrease morbidity and improve quality of life. This review provides a concise summary of different classes of antibiotics and their unique properties that allow them to be used in the treatment of non-infectious conditions.

We present a case of pseudocellulitis in a patient with chronic wounds from active injection drug use and edema and edema from secondary amyloidosis and highlight diagnostic challenges and approaches to differentiate infection from vascular and other noninfectious causes as well as the opportunity to intervene at a reachable moment to try to mitigate risk related to injection drug use.

To describe the epidemiology and risk factors for Coronavirus disease-19 (COVID-19)–associated mucormycosis (CAM) based on current published literature. COVID-19 is associated with an increased risk of secondary infections. Mucormycosis is an uncommon invasive fungal infection that typically affects people with immunocompromising conditions and uncontrolled diabetes. Treatment of mucormycosis is challenging and is associated with high mortality even with standard care. During the second wave of the COVID 19 pandemic, an abnormally high number of CAM cases were seen particularly in India. Several case series have attempted to describe the risk factors for CAM. A common risk profile identified for CAM includes uncontrolled diabetes and treatment with steroids. COVID-19–induced immune dysregulation as well as some unique pandemic specific risk factors may have played a role.

Objectives: To explore the association between COVID-19 severity and pregnancy using measures such as COVID-19 ordinal scale severity score, hospitalization, intensive care unit (ICU) admission, oxygen supplementation, invasive mechanical ventilation, and death.Methods: We conducted a retrospective, multicenter cohort study to understand the association between COVID-19 severity and pregnancy. We reviewed consecutive charts of adult females, ages 18-45, with laboratory testing for SARS-CoV-2 infection between March 1, 2020, and August 31, 2020. Cases were patients diagnosed with COVID-19 during pregnancy, whereas controls were not pregnant at the time of COVID-19 diagnosis. Primary endpoints were the COVID-19 severity score at presentation (within four hours) and the nadir of the clinical course. The secondary endpoints were the proportion of patients requiring hospitalization, ICU admission, oxygen supplementation, invasive mechanical ventilation, and death.Results: A higher proportion of pregnant women had moderate to severe COVID-19 disease at the nadir of the clinical course than non-pregnant women (25 vs. 16.1 %, p=0.04, respectively). There was a higher rate of hospitalization (25.6 vs. 17.2 %), ICU admission (8.9 vs. 4.4 %), need for vasoactive substances (5.0 vs. 2.8 %), and invasive mechanical ventilation (5.6 vs. 2.8 %) in the pregnant cohort. These differences were not significant after applying propensity score matching.We found a high rate of pregnancy complications in our population (40.7 %). The most worrisome is the rate of hypertensive disorders of pregnancy (20.1 %).Conclusions: In our propensity score-matched study, COVID-19 in pregnancy is associated with an increased risk of disease severity and pregnancy complications.

BACKGROUND:This study aims to determine whether Hepatitis C (HCV) treatment improves health-related quality of life (HRQL) in patients with opioid use disorder (OUD) actively engaged in substance use, and which variables are associated with improving HRQL in patients with OUD during HCV treatment.METHODS:Data are from a prospective, open-label, observational study of 198 patients with OUD or opioid misuse within 1 year of study enrollment who received HCV treatment with the primary endpoint of Sustained Virologic Response (SVR). HRQL was assessed using the Hepatitis C Virus Patient Reported Outcomes (HCV-PRO) survey, with higher scores denoting better HRQL. HCV-PRO surveys were conducted at Day 0, Week 12, and Week 24. A mixed-effects model investigated which variables were associated with changing HCV-PRO scores from Day 0 to Week 24.RESULTS:Patients had a median age of 57 and were predominantly male (68.2%) and Black (83.3%). Most reported daily-or-more drug use (58.6%) and injection drug use (IDU) (75.8%). Mean HCV-PRO scores at Day 0 and Week 24 were 64.0 and 72.9, respectively. HCV-PRO scores at Week 24 improved compared with scores at Day 0 (8.7; p<0.001). Achieving SVR (10.4; p<0.001) and receiving medications for OUD (MOUD) at Week 24 (9.5; p<0.001) were associated with improving HCV-PRO scores. HCV-PRO scores increased at Week 24 for patients who experienced no decline in IDU frequency (8.1; p<0.001) or had a UDS positive for opioids (8.0; p<0.001) or cocaine (7.5; p=0.003) at Week 24.CONCLUSION:Patients with OUD actively engaged in substance use experience improvement in HRQL from HCV cure unaffected by ongoing substance use. Interventions to promote HCV cure and MOUD engagement could improve HRQL for patients with OUD.

Abstract Background Injection drug use (IDU) increases risk for myriad health complications, including infections (e.g., HIV, cellulitis, and endocarditis), tissue injury, and overdose. Despite the prevalence of IDU and associated harms, tools to assess risk and provide harm reduction counseling are uncommon. We sought to create and refine a tool for assessment of IDU practices, using the input of experienced clinicians and people with lived experience of IDU.Figure 1.Study Design. The INJECT-RESPECT tool was evaluated and refined in 3 phases, each seeking input from different groups of stakeholders. IDU, injection drug use; PWID, people who inject drugs. Methods A 3-part process of feedback and refinement was used (Figure 1). The authors developed INJECT-RESPECT version 1 based on existing literature and their experience. In Phase 1, 12 attending physicians in 6 specialties provided feedback on INJECT-RESPECT version 1, which was incorporated into version 2. In Phase 2, 20 people who were hospitalized with infectious complications of IDU were interviewed about INJECT-RESPECT version 2 and asked (1) Were you asked this question? and (2) Is this important to ask? Responses were recorded as “Yes”/“No”. In Phase 3, a focus group was conducted with 7 people with lived experience of IDU, focused on healthcare providers’ approach to discussing IDU practices. Results Of the 20 hospitalized participants in Phase 2, 45% were women and the median age was 37 years (range 24-48 years). Only 7 questions (11%) were asked of most respondents, yet 29 questions (44%) were classified as important by ≥75% of respondents (Table 1). Importance was correlated with whether the question was asked (Spearman correlation coefficient 0.71; p < 0.001; Figure 2). In the focus group, important themes were shame, stigma, and trauma (Figure 3).Table 1.INJECT-RESPECT tool Version 2 and Responses from Hospitalized People who Inject Drugs The INJECT-RESPECT tool Version 2 for assessing IDU-related risks is divided into 13 domains. Bolded questions are designed for priority use, such as a time-limited clinical setting. The proportion of respondents (n = 20) who were asked the question and who thought it was important are reported. The proportions are colored on a spectrum from red (0.0) to yellow (0.5) to green (1.0).Figure 2.Correlation between Question Asked and Question Importance. The importance of the INJECT-RESPECT questions—as assessed by hospitalized people who inject drugs in Phase 2—was positively correlated with whether the participants had been asked the questions. (Spearman correlation coefficient 0.71; 95% CI 0.48 - 0.77; p < 0.001.)Figure 3.Focus Group Results Conclusion People admitted with acute complications of IDU were not asked questions about their IDU practices that they and surveyed clinicians deemed important. Our results suggest more important questions are asked more frequently, but many important questions are rarely asked. One third of questions were rated as not important by ≥50% of respondents; these questions will be refined or removed. The focus group yielded important considerations for discussing IDU. The feedback from Phases 1, 2, and 3 will be used to further improve the INJECT-RESPECT tool. Future efforts will focus on implementing the tool with clinicians and evaluating its real-world use (Figure 4).Figure 4.Future Plans for INJECT-RESPECT INJECT-RESPECT will be refined based on the results of this study. It will be disseminated to clinicians through the EMR, which will also allow evaluation of how it is used. EMR, electronic medical record. Disclosures All Authors: No reported disclosures

Background The management of invasive infections related to substance use disorder (SUD) needing parenteral antimicrobial therapy is challenging and may have poor treatment outcomes including nonadherence and lack of completion of parenteral antimicrobial therapy. Methods In this retrospective cohort of 201 patients with invasive infections related to SUD, we looked at frequency and determinants of unfavorable outcomes including nonadherence. Results Seventy-nine percent of patients with SUD-related infection completed parenteral antibiotic therapy in skilled nursing facilities. A total of 21.5% of patient episodes had documentation of nonadherence. Nonadherence was higher in patients with active injection drug use (IDU) (28.5% versus 15% in non IDU; adjusted odds ratio [OR] 2.36; 95% confidence interval [CI], 1.1-5.5; P = .024), patients with active SUD in the prior year (24.5% vs 11%, P = .047), patients with use of more than 1 illicit substance (30.3% vs 17%, P = .031), as well as in people experiencing homelessness (32.8% vs 15.7% in stably housed, P = .005). In a multivariate model, nonadherence was significantly associated with IDU (OR, 2.38; 95% CI, 1.03-5.5) and homelessness (OR, 2.25; 95% CI, 1.01-4.8) Medication for opioid use disorder was prescribed at discharge in 68% of overall cohort and was not associated with improved outcomes for any of the above groups. Conclusions Nonadherence to parenteral antimicrobial therapy is high in the most vulnerable patients with unstable high-risk SUD and adverse social determinants of health.

The severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) pandemic has led to an unprecedented public health crisis. The collective global response has led to production of multiple safe and effective vaccines utilizing novel platforms to combat the virus that have propelled the field of vaccinology forward. Significant challenges to universal vaccine effectiveness remain, including immune evasion by SARS-CoV-2 variants, waning of immune response, inadequate knowledge of correlates of protection, and dosing in special populations. This review serves as a detailed evaluation of the development of the current SARS-CoV-2 vaccines, their effectiveness, and challenges to their deployment as a preventive tool.

This essay describes the author’s experience with a socially isolated patient who declined cancer treatment because he had no one to help him after transarterial radioembolization therapy.

Background: People with opioid use disorder and severe infections may complete their prolonged courses of outpatient parenteral antimicrobial therapy at a post-acute care facility due to adherence and safety concerns. We hypothesized that treatment with medications for opioid use disorder, such as methadone and buprenorphine, would increase antibiotic completion in these facilities. Methods: We performed a retrospective cohort study of people with opioid use disorder and severe infections who were discharged from the University of Maryland Medical Center to a post-acute care facility to complete intravenous antibiotic therapy. The primary outcome was completion of outpatient parenteral antimicrobial therapy. We compared the rate of antibiotic completion between patients prescribed and not prescribed medication for opioid use disorder at discharge from the acute care hospital. Results: A total of 161 patient encounters were included; the mean age was 43.4 years and 56% of patients were male. In 48% of the encounters, the patient was homeless and in 68% they recently injected drugs. The most common infectious syndrome was osteoarticular (44.1%). Medication for opioid use disorder was prescribed at discharge in 103 of 161 encounters and was newly started in 27 encounters. Similar rates of outpatient parenteral antimicrobial therapy completion were found in those who received (65/103) and did not receive (33/58) medication for opioid use disorder at discharge (odds ratio: 1.29; 95% confidence interval: 0.68–2.54; p = 0.44). Conclusion: Medication for opioid use disorder prescription at discharge was not associated with completion of outpatient parenteral antimicrobial therapy in a post-acute care facility. Our study is limited by possible selection bias and infrequent initiation of medication for opioid use disorder, which may have minimized the effect on antibiotic completion.

Abstract Background Patients with substance use disorder (SUD) are frequently admitted to hospitals for invasive infections and may have poor infection outcomes including non-adherence and lack of completion of therapy. Methods In this retrospective cohort of 263 hospital encounters among 201 patients for invasive infections due to SUD to an urban tertiary care facility, we looked at characteristics of SUD to assess whether there were differences in infections, their management, SUD interventions and parenteral antibiotic outcomes between groups. Results Among people with SUD, 79% of antibiotic courses were completed in skilled nursing facilities. Most common infectious syndromes were osteoarticular infections (123, 47%), infective endocarditis (IE) (54, 20%) and non-IE endovascular infection (23, 9%). Among SUD specific interventions, 64% of episodes had documentation of a consultation by substance use services and 68% episodes had documentation of medication for opioid use disorder (MOUD) being prescribed at discharge. Overall, completion of therapy was documented in 163 (62%) of encounters. Overall, treatment non-adherence was seen in 63 encounters (24%). Non-adherence was documented 32% of episodes with documentation of injection drug use (IDU), 28% of encounters where active substance use was documented in the prior year and 33% of encounters where use of more than one substance was documented (P< 0.05 for all 3 groups). Drug or catheter related adverse events seemed to be significantly higher in the IDU group (3.64/1000 OPAT days) and catheter abuse was documented in 7 encounters of which 6 were with IDU or active SUD active documented. Cumulatively an unfavorable outcome (including failure, 30-day readmission, drug or PICC related adverse event, non-adherence or death) seemed to occur in 58% of IDU encounters as compared to non-IDU encounters (42.5%, P=0.011). Medication for opioid use disorder (MOUD) was prescribed at discharge in 68% of overall cohort and was not associated with improved outcomes for any of the above groups. Demographics, infection details and outcomes by type of SUD Conclusion In patients hospitalized with SUD-related infections, interventions need to be focused on those with high risk, unstable SUD through MOUD optimization along transitions of care and linkage to care to improve OPAT outcomes and overall health events Disclosures Shyam Kottilil, MD, PhD, Arbutus Pharmaceuticals: Grant/Research Support|Gilead: Grant/Research Support|Merck: Grant/Research Support|Regeneron Pharmaceuticals: Advisor/Consultant|Silverback Therapeutics: Advisor/Consultant|The Liver Company: Advisor/Consultant|Yufan Biotechnologies: Advisor/Consultant.

weeks post SVR.Cirrhosis was defined based on FibroScan ® >14.5 kPa and/or a combination of endoscopy and imaging criteria.Only those treated with DAA therapy between January 2015 and December 2016 were included.Patients were followed-up with until November 2021 or until HCC occurred.Results: Our study included 71 patients of whom 64.8% were males with a mean age of 61 (±8) years.Of our total cohort, 62% had genotype 1, 55% were Child Pugh A (CPA), 24% were CPA with a previous decompensation, and 21% were CP B/C.During a median follow up of 60 months (IQR 41-70), 25.4% (18) of patients had developed HCC.Patients who developed HCC had more advanced liver disease (CP B/C 53.3% vs 20.5% CPA vs 11.8% CPA previous decompensation; p = 0.031), a lower baseline albumin (34.7 vs 38.4; p = 0.004) and an elevated YKL-40 at 36 weeks after SVR (4789 vs 3333; p = 0.036) compared to those who had not developed HCC (table 1).Between start of treatment and 36 weeks post SVR, the mean decrease in YKL-40 was significantly greater in those who did not develop HCC (from 5098 to 3333, p < 0.001; vs 4752 to 4789 p = 0.987).There was no difference in the dynamics of HA between the two groups.In the multivariate analysis, YKL-40 at 36 weeks post SVR (HR 1; CI 95% 1-1) was an independent factor associated with HCC.Child Pugh status A (HR 0.36; IC 95% 0.142-0.937)was an independent factor associated with lower HCC.Conclusion: HCC occurrence was higher in patients with CP B/C and those who did not decrease YKL-40 after achieving SVR.YKL-40 could be a predictive factor of HCC occurrence however further studies with a larger sample are necessary to confirm these results.

Abstract Background Daily oral preexposure prophylaxis (PrEP) with tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC) prevents human immunodeficiency (HIV) among people who inject drugs (PWID). Despite rising HIV incidence and injection drug use (IDU), PrEP use remains low and there is limited research about uptake, adherence, and retention among PWID. Methods The ANCHOR investigation evaluated a community-based care model collocating hepatitis C virus (HCV) treatment, medication for opioid use disorder (OUD), and PrEP in individuals in Washington, DC, and Baltimore, Maryland. PrEP counseling was conducted from HCV treatment day 0 until week 24. Subjects could start any time during this window, were followed for 48 weeks, and were assessed for adherence by self-report and dried blood spot TDF analysis. Results One hundred ninety-eight participants were enrolled, of whom 185 (93%) were HIV negative. Twenty-nine individuals (15.7% of HIV-negative cohort) initiated PrEP. One hundred sixteen participants (62.7%) met 2014 Centers for Disease Control and Prevention (CDC) PrEP criteria due to IDU (82 [44.3%]), sex (9 [4.9%]), or both practices (25 [13.5%]). Providers recommended PrEP to 94 individuals (50.8%), and recommendation was associated with PrEP uptake. Median treatment duration was 104 days (interquartile range, 28–276 days), with 8 participants retained through week 48. Adherence was variable over time by self-report and declined by TDF analysis. No HIV seroconversions occurred. Conclusions This cohort of people with HCV and OUD experienced low uptake of PrEP despite the majority meeting CDC criteria. High rates of disruption and discontinuation, compounded by variable adherence, made TDF/FTC a suboptimal prevention strategy. Emerging modalities like long-acting formulations may address these barriers, but PWID have been excluded from their development to date.

A 53-year-old woman with rheumatoid arthritis presented with a rash that had been present for 2-months with more recent perioral lesions and dysphagia.

The severe surge of coronavirus disease 2019 (COVID-19) cases on the Indian subcontinent in early 2021 was marked by an unusually high number of COVID-19-associated mucormycosis (CAM) cases reported during this same period. This is significantly higher than predicted based on available data about prevalence and risk factors for this condition. This may be due to an unusual alignment of multiple risk factors for this condition. There is high background prevalence of mucormycosis in India likely from a high prevalence of risk factors, including undiagnosed or poorly controlled diabetes. COVID-19-induced immune dysregulation and immune suppression from steroid therapy increase the risk. The role of environmental exposure is unclear. System factors such as lack of access to healthcare during a pandemic may result in delayed diagnosis or suboptimal management with potentially poor outcomes. Here, we review currently identified risk factors and pathogenesis of CAM in a pandemic surge.

This preprint investigates SARS-CoV-2 variant breakthrough rates and finds VOCs more prevalent in COVID19+ vaccinees relative to the unvaccinated. Reviewers deem claims compelling, but warn findings do not concern disease severity and larger follow-up studies are needed.

An 85-year-old man with an indwelling suprapubic catheter for bladder outlet obstruction due to prostatic hyperplasia and urethral stricture presented to the hospital with lethargy and weakness. His suprapubic catheter accidentally fell out 3 days prior. His medical history included recurrent urinary tract infections (UTIs), chronic kidney disease secondary to uncontrolled type 2 diabetes mellitus, and a prior transurethral resection of the prostate performed 13 years previously.

Background Respiratory infections have long been associated with higher maternal and perinatal morbidity. Early data did not report an increased risk of SARS-CoV-2 infection or disease severity in pregnancy. However, surveillance data from the Center for Disease Control and Prevention (CDC) indicates a higher risk of severe disease and death in pregnant women with symptomatic SARS-CoV-2 infection, although this data is subject to ascertainment bias. Objective To explore the association between COVID-19 disease severity and pregnancy in our university-based hospital system using measures such as COVID-19 ordinal scale severity score, hospitalization, intensive care unit admission, oxygen supplementation, invasive mechanical ventilation, and death. Study design We conducted a retrospective, multicenter case-control study to understand the association between COVID-19 disease severity and pregnancy. We reviewed consecutive charts of adult females, ages 18-45, with laboratory-confirmed SARS-CoV-2 infection in six months between March 1, 2020, and August 31, 2020. Cases were patients diagnosed with COVID-19 during pregnancy, whereas controls were not pregnant at the time of COVID-19 diagnosis. Primary endpoints were the COVID-19 severity score at presentation (within four hours) and the nadir of the clinical course. The secondary endpoints were the proportion of patients requiring hospitalization, intensive care unit admission, oxygen supplementation, invasive mechanical ventilation, and death. Results A higher proportion of pregnant women had moderate to severe COVID-19 disease at the nadir of the clinical course than nonpregnant women (25% vs. 16.1%, p =0.04, respectively). While there was a higher rate of hospitalization (25.6% vs. 17.2%), ICU admission (8.9% vs. 4.4%), need for vasoactive substances (5.0% vs. 2.8%), and invasive mechanical ventilation (5.6% vs. 2.8%) in the pregnant group, this difference was not significant after the propensity score matching was applied. We found a high rate of pregnancy complications in our population (40.7%). The most worrisome is the rate of hypertensive disorders of pregnancy (20.1%). Conclusions In our propensity score-matched study, COVID-19 in pregnancy is associated with an increased risk of disease severity and an increased risk of pregnancy complications.