Tecovirimat Use in Ambulatory and Hospitalized Patients With Monkeypox Virus Infection.

ABSTRACT: In this case series of 20 ambulatory and hospitalized adult patients treated for monkeypox virus at a large academic medical center in Chicago, Illinois, tecovirimat use was reserved for those with or at high risk of severe disease, delayed because of logistical and clinical factors, but well tolerated.

Role of bone biopsy and deep tissue culture for antibiotic stewardship in diabetic foot osteomyelitis.

OBJECTIVES: To describe organisms most frequently identified on bone biopsy or deep tissue culture and determine how culture data impacted antibiotic management in patients with diabetic foot osteomyelitis (DFO). METHODS: We retrospectively reviewed patients admitted with a diabetic foot ulcer (DFU) between 3 March 2018 and 31 December 2019 and selected for patients diagnosed with infectious osteomyelitis (OM) of the lower extremity. We stratified patients by whether a bone biopsy or deep tissue culture was obtained and compared rates of antibiotic utilization with chi-squared and Fisher's exact tests. RESULTS: Of 305 patients with a DFU, 152 (50%) were clinically diagnosed with DFO. Forty-seven patients received 41 deep tissue cultures and 29 bone biopsy cultures for a total of 70 cultures. Of 45 (64%) positive cultures, 36 (80%) had Gram-positive organisms and 19 (42%) had Gram-negative organisms. MDR organisms were isolated in 7 (15%) patients. Culture data resulted in antibiotic changes in 41 (87%) patients. Therapy was narrowed in 29 (62%) patients and broadened due to inadequate empirical coverage in 4 (9%) patients. Culture data from 18 (40%) patients showed susceptibility to an oral treatment regimen with high bioavailability. There was no significant difference in rates of antibiotic utilization at discharge between patients who underwent bone biopsy or deep tissue culture relative to those who did not (77% versus 75%, P = 0.86), although less MRSA coverage was used (34% versus 50%, P = 0.047). CONCLUSIONS: In patients with DFO, deep tissue and bone biopsy cultures were infrequently obtained but resulted in targeted therapy changes in most patients. Culture data usually allowed for narrowing of antibiotics but revealed inadequate empirical coverage in a subset of patients.

Disseminated Streptococcus pneumoniae infection associated with an intrauterine device.

Streptococcus pneumoniae is a common pathogen afflicting a wide variety of disease in both immunocompetent and immunocompromised individuals. Presentation can be variable in initial symptomatology leading to difficulties in diagnosis and management. We present a case of septic shock due to Streptococcus pneumoniae associated with an intrauterine device (IUD) in an immunocompromised patient.

Inflammatory Biomarkers and Mortality Risk Among HIV-Suppressed Men: A Multisite Prospective Cohort Study.

BACKGROUND: Human immunodeficiency virus (HIV)-induced inflammation and immune activation persist after initiation of combination antiretroviral therapy (cART) and HIV suppression and may contribute to mortality risks that exceed those in HIV-uninfected populations, though associations are unclear. METHODS: In the prospective Multicenter AIDS Cohort Study, comprising men who have sex with men from Baltimore, Chicago, Los Angeles, and Pittsburgh, concentrations of 24 biomarkers of inflammation and immune activation were measured in stored serum from HIV-positive men obtained after cART-induced HIV suppression between 1996 and 2009. The outcome was nonaccidental death, with follow-up until 2014. We used Cox proportional hazards models to test whether biomarker concentrations predict time from HIV suppression to death and adjusted for multiple tests. Exploratory factor analysis (EFA) was employed to identify groupings of biomarkers that predict mortality risk. RESULTS: Of 670 men followed up from HIV suppression, 54 died by the end of 2013. After adjustment for age, CD4(+) cell count, hepatitis B or C virus infection, and smoking, concentrations in the highest quartile of 4 biomarkers were significantly associated with mortality risk after controlling the false discovery rate at 5%: interleukin (IL) 6 (hazard ratio, 3.54; 95% confidence interval, 2.06-6.10), soluble IL 2Rα (3.29, 1.85-5.85), soluble CD14 (2.67, 1.55-4.61), and chemokine (CXC motif) ligand 13 (CXCL13; 2.26; 1.29-3.95). EFA yielded 2 biomarker groupings that were independent predictors of mortality risk. CONCLUSIONS: Despite having undetectable HIV RNA levels during cART, men with higher concentrations of several biomarkers (particularly IL 6, soluble IL 2Rα, soluble CD14, and CXCL13) had higher hazards of long-term mortality. Correlations observed among biomarker concentrations may represent underlying inflammatory processes that contribute to mortality risk.

Management patterns and outcomes of patients hospitalized with diabetic foot ulcers at one tertiary care hospital.

A diabetic foot ulcer is present in approximately 2.4% of hospitalized patients. Care for diabetic foot ulcers is highly variable. We sought to describe care practice patterns and risk factors for poor outcomes for patients hospitalized with a diabetic foot ulcer in our institution, an 894-bed tertiary care academic hospital located in downtown Chicago, IL. We conducted a retrospective cohort study of patients hospitalized with a diabetic foot ulcer between March 3rd, 2018 and December 31st, 2019. We categorized patients into having an uncomplicated ulcer or a complicated ulcer with cellulitis, wound infection, osteomyelitis, or gangrene. We evaluated rates of diagnostic resource utilization (imaging, cultures, biopsies, and antibiotics) and outcomes of osteomyelitis, amputation, and death. There were 305 patients of interest in the study cohort. A complicated lower extremity ulcer was found in 79% of patients. Amputation was required in 25% of patients, 21% were readmitted, and 13% died. Imaging was obtained in less than 50% of all patients, and in 60% or less of those with osteomyelitis. Bone biopsies were rarely acquired. Empiric antibiotics were prescribed in 77% of patients with osteomyelitis. Male, Black or African-American patients, and those with high Charlson score had the highest risk of poor outcomes. Care practices for patients hospitalized with diabetic foot ulcers were highly variable. Future interventions should target standardization to improve outcomes, with particular attention to health inequities as vulnerable populations have a higher risk of poor outcomes.

Telemedicine and HIV Care Quality Measures During the COVID-19 Pandemic.

BACKGROUND: During the COVID-19 pandemic, telemedicine was adopted to ensure continuity of HIV care. We examined how introducing televisits affected technical quality of care for people with HIV (PWH) during this time. METHODS: PWH receiving HIV care at Howard Brown Health Centers and Northwestern University in Chicago, Illinois were included. HIV care quality indicators were calculated using data extracted from electronic medical records during 4 timepoints every 6 months from March, March 1, 2020 to September 1, 2021. Generalized linear mixed models estimated differences in indicators across timepoints within each site while controlling for multiple observations of individuals. Generalized linear mixed models were also used to compare differences in outcomes among PWH who attended all versus a combination of in-person and televisits versus no televisits across the study time periods. RESULTS: 6447 PWH were included in the analysis. Compared with prepandemic levels, there were significant declines in care utilization and processes of care measures. Measures of HIV virologic suppression, blood pressure control, and HbA1C <7% (in both people with and without diabetes) were stable with no significant differences noted across the study timepoints. Similar trends were observed across all age, race, and sex subgroups. In multivariable models, televisits were not associated with decreased HIV viral suppression. CONCLUSIONS: During the COVID-19 pandemic and rapid implementation of televisits, indicators of care utilization and processes of care decreased compared with prepandemic levels. Among PWH who remained in care, televisits were not associated with worse virologic, blood pressure, and glycemic control in PWH.

Concurrent Testing for COVID-19 and HIV Infection at 6 High-Volume Emergency Departments in a Priority Jurisdiction for Ending the HIV Epidemic in the United States.

BACKGROUND: The COVID-19 pandemic caused disruptions in access to routine HIV screening. SETTING: We assess HIV and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing across 6 emergency departments (EDs) in Cook County, Illinois. METHODS: We retrospectively analyzed the number of SARS-CoV-2 tests, HIV screens, and the proportion of concurrent tests (encounters with both SARS-CoV-2 and HIV testing), correlating with diagnoses of new and acute HIV infection. RESULTS: Five sites reported data from March 1, 2020, to February 28, 2021, and 1 site from September 1, 2020, to February 28, 2021. A total of 1,13,645 SARS-CoV-2 and 36,094 HIV tests were performed; 17,469 of these were concurrent tests. There were 102 new HIV diagnoses, including 25 acute infections. Concurrent testing proportions ranged from 6.7% to 37% across sites (P < 0.001). HIV testing volume correlated with the number of new diagnoses (r = 0.66, P < 0.01). HIV testing with symptomatic SARS-CoV-2 testing was strongly correlated with diagnosis of acute infections (r = 0.87, P < 0.001); this was not statistically significant when controlling for HIV testing volumes (r = 0.59, P = 0.056). Acute patients were more likely to undergo concurrent testing (21/25) versus other new diagnoses (29/77; odds ratio = 8.69, 95% CI: 2.7 to 27.8, P < 0.001). CONCLUSIONS: Incorporating HIV screening into SARS-CoV-2 testing in the ED can help maintain HIV screening volumes. Although all patients presenting to the ED should be offered opt-out HIV screening, testing individuals with symptoms of COVID-19 or other viral illness affords the opportunity to diagnose symptomatic acute and early HIV infection, rapidly link to care, and initiate treatment.

Characteristics and Specialist Linkage to Care of Patients Diagnosed With Chronic Hepatitis C Across Different Settings in an Urban Academic Hospital: Implications for Improving Diagnosis and Linkage to Care.

INTRODUCTION: Chronic hepatitis C virus (HCV) infection is a significant public health problem. Strategies to identify more HCV infections and improve linkage to care (LTC) are needed. We compared characteristics, treatment and LTC among chronic HCV patients in different health care settings. METHODS: Newly diagnosed HCV antibody positive (anti-HCV+) patients within settings of acute care, inpatient and outpatient in one health system were studied. Proportion of LTC and treatment were analyzed only for HCV RNA positive patients. Chi-square, one-way ANOVA and logistic regression were used to compare the characteristics and outcomes in the three care settings. Patients in acute care settings were excluded from multivariate analyses due to low sample size. RESULTS: About 43, 368, and 1159 anti-HCV+ individuals were identified in acute care, inpatient, and outpatient, respectively. Proportion of RNA positivity in acute, inpatient, and outpatient were 47.8, 60.3 and 29.2%, respectively (p < 0.01). After adjusting for age, insurance type, race, and gender, outpatients had higher odds of LTC and of treatment (OR 4.7 [2.9, 7.6] and 4.5 [2.8, 7.3]). CONCLUSIONS: Inpatients had lower proportion of LTC and treatment compared to outpatients. Use of LTC coordinators and the provision of integrated service for specialty care may improve outcomes.

The value of repeat patient testing for SARS-CoV-2: real-world experience during the first wave.

INTRODUCTION: Reports of false-negative quantitative reverse transcription PCR (RT-qPCR) results from patients with high clinical suspension for coronavirus disease 2019 (COVID-19), suggested that a negative result produced by a nucleic acid amplification assays (NAAs) did not always exclude the possibility of COVID-19 infection. Repeat testing has been used by clinicians as a strategy in an to attempt to improve laboratory diagnosis of COVID-19 and overcome false-negative results in particular. AIM: To investigate whether repeat testing is helpful for overcoming false-negative results. METHODS: We retrospectively reviewed our experience with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing, focusing on the yield of repeat patient testing for improving SARS-CoV-2 detection by NAA. RESULTS: We found that the yield from using repeat testing to identify false-negative patients was low. When the first test produced a negative result, only 6 % of patients tested positive by the second test. The yield decreased to 1.7 and then 0 % after the third and fourth tests, respectively. When comparing the results produced by three assays, the Centers for Disease Control and Prevention (CDC) SARS CoV-2 RT-qPCR panel, Xpert Xpress CoV-2 and ID NOW COVID-19, the ID NOW assay was associated with the highest number of patients who tested negative initially but positive on repeat testing. The CDC SARS CoV-2 RT-qPCR panel produced the highest number of indeterminate results. Repeat testing resolved more than 90 % of indeterminate/invalid results. CONCLUSIONS: The yield from using repeat testing to identify false-negative patients was low. Repeat testing was best used for resolving indeterminate/invalid results.

From Creation to Evaluation: A Comprehensive Global Health Scholars Program for Graduate Medical Education Trainees.

INTRODUCTION: Recently, participation in clinical global health rotations has significantly increased among graduate medical education (GME) trainees. Despite the many benefits these experiences provide, many ethical challenges exist. Well-intentioned partnerships and participants often encounter personal and professional dilemmas related to safety, social responsibility, and accountability. We designed a curriculum to provide trainees of all specialties with a comprehensive educational program aimed at delivering culturally mindful and ethically responsible clinical care in resource-constrained settings. METHODS: The McGaw Global Health Clinical Scholars Program (GHCS) at Northwestern University offers a 2-year curriculum for selected GME trainees across specialties interested in global health. Each trainee must complete the following components: core lectures, peer journal club, specialty-specific lectures, a mentorship agreement, ethics and skill-based simulations, a global health field experience, a poster presentation, and a mentored scholarly project. RESULTS: Since 2014, 84 trainees from 13 specialties have participated in the program with 50 current trainees and 39 graduates. Twenty-five trainees completed exit surveys, of which 95% would recommend this program to other trainees and 84% felt more prepared to deliver global health care. In addition, 78% reported career plans that included global health and/or work with underserved populations. Trainees described "acceptance of differences and respect for those differences" and "understanding sustainability" as learning points from the program. DISCUSSION: Providing a comprehensive global health education program across specialties can be feasible and effective. GME trainees who participated in this program report feeling both more prepared for clinical experiences and more likely to serve the underserved anywhere.

Enhancing Knowledge in Informal Settlements: Assessing Health Beliefs and Behaviors in Nigeria: A cross-sectional survey assessment of perceptions, practices, and resources in underserved urban communities in Lagos.

Background: Community Health Education (CHE) programs have been shown to be effective in relieving the burden on healthcare systems in Sub-Saharan Africa. Objective: This project aimed to determine the baseline level of health literacy, behavioral practices, and accessibility to resources in a set of 16 informal settlements located around Lagos, Nigeria in order to identify topics that should be emphasized in a new teaching curriculum directed at local Community Health Educators. Methods: In June of 2017, a unique cross-sectional survey composed of 37 questions was conducted in informal settlements around Lagos. Sites selected were areas in which future CHE trainings were planned to take place and survey participants were chosen by trained community health educators based on convenience sampling with snowball effect. Survey questions included both multiple-choice and open-ended questions and were asked in the local language. We collected demographic information and assessed health literacy, health behaviors, and community practices. Results were analyzed using descriptive statistics to assess for differences between demographic groups. Findings: Our survey collected 348 total responses. Respondents displayed a high level of knowledge regarding the benefits of hand washing (97.1%) and childhood immunizations (81.0%). Knowledge around infectious diseases and reproductive health was lower, including a large proportion of people (50%) incorrectly indicating that HIV could be spread through a mosquito bite. Malaria was reported to be the most prevalent disease affecting both adults (40.0%) and children (58.3%). Health access was limited, with most people not reporting access to a nearby health center (55.8%). Conclusions: Areas of knowledge that should be emphasized in future versions of CHE training curricula include infectious diseases, reproductive health, and reinforcement of the importance of sanitation and clean water. The curriculum should address the reality of limited health access and develop strategies to improve this.

Amplified transmission of HIV-1: comparison of HIV-1 concentrations in semen and blood during acute and chronic infection.

OBJECTIVES: This study was conducted to compare viral dynamics in blood and semen between subjects with antibody negative, acute HIV-1 infection and other subjects with later stages of infection. DESIGN: A prospective cohort study was embedded within a cross-sectional study of HIV screening in a Lilongwe, Malawi STD clinic. METHODS: Blood samples from HIV antibody negative or indeterminate volunteers were used to detect HIV RNA in plasma using a pooling strategy. Blood and seminal plasma HIV-1 RNA concentrations were measured over 16 weeks. RESULTS: Sixteen men with acute HIV infection and 25 men with chronic HIV infection were studied. Blood viral load in subjects with acute HIV infection was highest about 17 days after infection (mean +/- SE, 6.9 +/- 0.5 log10 copies/ml), while semen viral load peaked about 30 days after infection (4.5 +/- 0.4 log10 copies/ml). Semen viral load declined by 1.7 log10 to a nadir by week 10 of HIV infection. Semen and blood viral loads were more stable in chronically infected subjects over 16 weeks. Higher semen levels of HIV RNA were noted in subjects with low CD4 cell counts. CONCLUSIONS: These results provide a biological explanation for reported increases in HIV transmission during the very early (acute) and late stages of infection. Recognizing temporal differences in HIV shedding in the genital tract is important in the development of effective HIV prevention strategies.

Improved detection of acute HIV-1 infection in sub-Saharan Africa: development of a risk score algorithm.

OBJECTIVE: Individuals with acute (preseroconversion) HIV infection (AHI) are important in the spread of HIV. The identification of AHI requires the detection of viral proteins or nucleic acids with techniques that are often unaffordable for routine use. To facilitate the efficient use of these tests, we sought to develop a risk score algorithm for identifying likely AHI cases and targeting the tests towards those individuals. DESIGN: A cross-sectional study of 1448 adults attending a sexually transmitted infections (STI) clinic in Malawi. METHODS: Using logistic regression, we identified risk behaviors, symptoms, HIV rapid test results, and STI syndromes that were predictive of AHI. We assigned a model-based score to each predictor and calculated a risk score for each participant. RESULTS: Twenty-one participants (1.45%) had AHI, 588 had established HIV infection, and 839 were HIV-negative. AHI was strongly associated with discordant rapid HIV tests and genital ulcer disease (GUD). The algorithm also included diarrhea, more than one sexual partner in 2 months, body ache, and fever. Corresponding predictor scores were 1 for fever, body ache, and more than one partner; 2 for diarrhea and GUD; and 4 for discordant rapid tests. A risk score of 2 or greater was 95.2% sensitive and 60.5% specific in detecting AHI. CONCLUSION: Using this algorithm, we could identify 95% of AHI cases by performing nucleic acid or protein tests in only 40% of patients. Risk score algorithms could enable rapid, reliable AHI detection in resource-limited settings.

Acute HIV revisited: new opportunities for treatment and prevention.

Inability to recognize incident infection has traditionally limited both scientific and public health approaches to HIV disease. Recently, some laboratories have begun adding HIV nucleic acid amplification testing to HIV diagnostic testing algorithms so that acute (antibody-negative) HIV infections can be routinely detected within the first 1-3 weeks of exposure. In this review article, we will highlight critical opportunities for HIV treatment and prevention that are presented by these diagnostic strategies.

The role of sexually transmitted diseases in HIV transmission.

More than 42 million people worldwide are now infected with HIV, in spite of sustained prevention activities. Although the spread of HIV has been primarily sexual, epidemiological studies have indicated that the efficiency of the spread of HIV is poor, perhaps as infrequently as 1 in every 1,000 episodes of sexual intercourse. However, sexually transmitted diseases (STDs) that cause ulcers or inflammation greatly increase the efficiency of HIV transmission--by increasing both the infectiousness of, and the susceptibility to HIV infection. STDs might be particularly important in the early stages of a localized HIV epidemic, when people with risky sexual behaviour are most likely to become infected. In China, eastern Europe and Russia, there has been a remarkable increase in the incidence of STDs in recent years, and this is reflected in the rapid increase in the spread of HIV in these areas. Targeted STD detection and treatment should have a central role in HIV prevention in these emerging epidemics.

Effect of prolonged freezing of semen on exosome recovery and biologic activity.

Exosomes are important vehicles of intercellular communication that shape host responses to physiologic, tumorigenic, and pathogenic conditions. The composition and function of exosomes are dynamic and depends on the state and condition of the cellular source. In prior work, we found that semen exosomes (SE) from healthy donors who do not use illicit drugs potently inhibit HIV-1. Following semen donation, specimens are either used immediately or frozen for use at a later time. It has been shown that short-term freezing of semen has no effect on SE-mediated HIV-1 inhibition. However, the effect of illicit drugs and prolonged freezing on SE bioactivity is unknown. Here, we show preservation of SE physical properties, (morphology, concentration, intensity/size) irrespective of illicit drug use or duration of semen freezing. Interestingly, illicit drugs and prolonged freezing decreased the levels of SE-bound CD63/CD9 and acetylcholinesterase activity respectively. Furthermore, we show differential effects of illicit drug use and prolonged freezing on SE-mediated HIV-1 inhibition. Our results highlight the importance of the source of SE and condition of semen storage on SE content and function. In-depth evaluation of donor drug-use and duration of semen storage on SE cargo and bioactivity will advance our understanding of SE composition and function.