Safe Injection Self-Efficacy is associated with HCV and HIV seropositivity among people who inject drugs in the San Diego-Tijuana border region.

Background: Safe injection self-efficacy (SISE) is negatively associated with injection risk behaviors among people who inject drugs (PWID) but has not been examined in differing risk environments. We compared responses to a validated SISE scale between PWID in San Diego, California and Tijuana, Mexico, and examine correlates of SISE among PWID in Tijuana. Methods: PWID were recruited via street outreach for a longitudinal cohort study from October 2020 - September 2021. We compared SISE scale items by city. Due to low variability in SISE scores among San Diego residents, we restricted analysis of factors associated with SISE to Tijuana residents and identified correlates of SISE scores (low, medium, high) using ordinal logistic regression. Results: Of 474 participants, most were male (74%), Latinx (78%) and Tijuana residents (73%). Mean age was 44. Mean SISE scores among San Diego residents were high (3.46 of 4 maximum) relative to Tijuana residents (mean: 1.93). Among Tijuana residents, White race and having previously resided in San Diego were associated with higher SISE scores. HCV and HIV seropositivity, homelessness, fentanyl use, polysubstance co-injection, and greater injection frequency were associated with lower SISE scores. Conclusions: We found profound inequalities between Tijuana and San Diego SISE, likely attributable to differential risk environments. Associations with fentanyl and polysubstance co-injection, injection frequency, and both HIV and HCV seropositivity suggest that SISE contribute to blood-borne infection transmission risks in Tijuana. SISE reflects an actionable intervention target to reduce injection risk behaviors, but structural interventions are required to intervene upon the risk environment.

Ibrexafungerp is efficacious in a neutropenic murine model of pulmonary mucormycosis as monotherapy and combined with liposomal amphotericin B.

Ibrexafungerp (formerly SCY-078) is the first member of the triterpenoid class that prevents the synthesis of the fungal cell wall polymer ß-(1,3)-D-glucan by inhibiting the enzyme glucan synthase. We evaluated the in vivo efficacy of ibrexafungerp against pulmonary mucormycosis using an established murine model. Neutropenic mice were intratracheally infected with either Rhizopus delemar or Mucor circinelloides. Treatment with placebo (diluent control), ibrexafungerp (30 mg/kg, PO BID), liposomal amphotericin B (LAMB 10 mg/kg IV QD), posaconazole (PSC 30 mg/kg PO QD), or a combination of ibrexafungerp plus LAMB or ibrexafungerp plus PSC began 16 h post-infection and continued for 7 days for ibrexafungerp or PSC and through day 4 for LAMB. Ibrexafungerp was as effective as LAMB or PSC in prolonging median survival (range: 15 days to >21 days) and enhancing overall survival (30%-65%) vs placebo (9 days and 0%; P < 0.001) in mice infected with R. delemar. Furthermore, median survival and overall percent survival resulting from the combination of ibrexafungerp plus LAMB were significantly greater compared to all monotherapies (P ≤ 0.03). Similar survival results were observed in mice infected with M. circinelloides. Monotherapies also reduce the lung and brain fungal burden by ~0.5-1.0log10 conidial equivalents (CE)/g of tissue vs placebo in mice infected with R. delemar (P < 0.05), while a combination of ibrexafungerp plus LAMB lowered the fungal burden by ~0.5-1.5log10 CE/g compared to placebo or any of the monotherapy groups (P < 0.03). These results are promising and warrant continued investigation of ibrexafungerp as a novel treatment option against mucormycosis.

Safety and effectiveness assessment of the surpass evolve (SEASE): a post-market international multicenter study.

BACKGROUND: Flow diverters are the first-line treatment for specific intracranial aneurysms (iA). Surpass Evolve (SE) is a new-generation 64-wire flow diverter with a high braid angle. Current literature on the SE is limited. We aimed to report the first international real-world experience evaluating the safety and effectiveness of the SE. METHODS: The Safety and Effectiveness Assessment of the Surpass Evolve (SEASE) was a multicenter retrospective international post-marketing cohort study including consecutive patients treated with SE for iAs between 2020 and 2022. Demographic, clinical, and angiographic data were collected. Primary effectiveness was independent core lab adjudicated complete occlusion rates (Raymond-Roy Class 1) at last follow-up. Primary safety were major ischemic/hemorrhagic events and mortality. RESULTS: In total, 305 patients with 332 aneurysms underwent SE implantation. The patients had a median age of 59 [50-67] years, and 256 (83.9%) were female. The baseline modified Rankin scale score was 0-2 in 291 patients (96.7%). Most aneurysms were unruptured (285, 93.4%) and saccular (309, 93.1%). Previous treatment was present in 76 (22.9%) patients. The median aneurysm size was 5.1 [3.4-9.0] mm, and the median neck width was 3.6 [2.7-5.1] mm. Most aneurysms were in the internal carotid artery C6 ophthalmic segment (126, 38.0%), followed by the communicating segment (58, 17.5%). At median 10.2 [6.4-12.9] months follow-up, 233 (73.0%) aneurysms achieved complete occlusion. After adjusting for confounders, complete occlusion remained consistent. Major stroke and procedure-related mortality were reported in 6 (2%) and 2 (0.7%) cases, respectively. CONCLUSION: These results demonstrate that SE has a consistently high effectiveness and favorable safety for the treatment of iAs.

Peers plus mobile app for treatment in HIV (PATH): protocol for a randomized controlled trial to test a community-based integrated peer support and mHealth intervention to improve viral suppression among Hispanic and Black people living with HIV.

BACKGROUND: Significant disparities continue to exist in the HIV care continuum, whereby Hispanic and Black people living with HIV (PLWH) are less likely to achieve viral suppression compared to their White counterparts. Studies have shown that intervention approaches that involve peer navigation may play an important role in supporting patients to stay engaged in HIV care. However, implementation may be challenging in real-world settings where there are limited resources to support peer navigators. Combining a peer navigation approach with scalable mobile health (mHealth) technology may improve impact and implementation outcomes. METHODS: We combined a peer navigation intervention with a mHealth application and are conducting a randomized controlled trial (RCT) to test the efficacy of this integrated "Peers plus mobile App for Treatment in HIV" (PATH) intervention to improve HIV care engagement, and ultimately sustained viral suppression, among Hispanic and Black PLWH. We will enroll up to 375 PLWH into a two-arm prospective RCT, conducting follow-up assessments every 3 months up to 12 months post-baseline. Participants randomized to the control arm will continue to receive usual care Ryan White Program case management services. Individuals randomized to receive the PATH intervention will receive usual care plus access to two main intervention components: (1) a peer navigation program and (2) a mHealth web application. The primary outcome is sustained HIV viral suppression (undetectable viral load observed at 6- and 12-month follow-up). Secondary outcomes are retention in HIV care, gaps in HIV medical visits, and self-reported ART adherence. Recruitment for the RCT began in November 2021 and will continue until June 2024. Follow-up assessments and medical chart abstractions will be conducted to collect measurements of outcome variables. DISCUSSION: The efficacy trial of PATH will help to fill gaps in our scientific understanding of how a combined peer navigation and mHealth approach may produce effects on HIV care outcomes while addressing potential implementation challenges of peer navigation in Ryan White-funded clinics. TRIAL REGISTRATION: The PATH trial is registered at the United States National Institutes of Health National Library of Medicine (ClinicalTrials.gov) under ID # NCT05427318 . Registered on 22 June 2022.

Modeling Invasive Aspergillosis Risk for the Application of Prophylaxis Strategies.

The epidemiology of invasive aspergillosis (IA) is evolving. To define the patient groups who will most likely benefit from primary or secondary Aspergillus prophylaxis, particularly those whose medical conditions and IA risk change over time, it is helpful to depict patient populations and their risk periods in a temporal visual model. The Sankey approach provides a dynamic figure to understand the risk of IA for various patient populations. While the figure depicted within this article is static, an internet-based version could provide pop-up highlights of any given flow's origin and destination nodes. A future version could highlight links to publications that support the color-coded incidence rates or other actionable items, such as bundles of applicable pharmacologic or non-pharmacologic interventions. The figure, as part of the upcoming Infectious Diseases Society of America's aspergillosis clinical practice guidelines, can guide decision-making in clinical settings.

Treatment outcomes for ARUBA-eligible brain arteriovenous malformations: a comparison of real-world data from the NVQI-QOD AVM registry with the ARUBA trial.

BACKGROUND: Significant controversy exists about the management of unruptured cerebral arteriovenous malformations (AVMs). Results from A Randomized Trial of Unruptured Brain Arteriovenous Malformations (ARUBA) suggested that intervention increases the risk of stroke/death compared with medical management. However, numerous study limitations raised concerns about the trial's generalizability. OBJECTIVE: To assess the rate of stroke/death and functional outcomes in ARUBA-eligible patients from a multicenter database, the Neurovascular Quality Initiative-Quality Outcomes Database (NVQI-QOD). METHODS: We performed a retrospective analysis of prospectively collected data of ARUBA-eligible patients who underwent intervention at 18 participating centers. The primary endpoint was stroke/death from any cause. Secondary endpoints included neurologic, systemic, radiographic, and functional outcomes. RESULTS: 173 ARUBA-eligible patients underwent intervention with median follow-up of 269 (25-722.5) days. Seventy-five patients received microsurgery±embolization, 37 received radiosurgery, and 61 received embolization. Baseline demographics, risk factors, and general AVM characteristics were similar between groups. A total of 15 (8.7%) patients experienced stroke/death with no significant difference in primary outcome between treatment modalities. Microsurgery±embolization was more likely to achieve AVM obliteration (P<0.001). Kaplan-Meier survival curves demonstrated no difference in overall death/stroke outcomes between the different treatment modalities' 5-year period (P=0.087). Additionally, when compared with the ARUBA interventional arm, our patients were significantly less likely to experience death/stroke (8.7% vs 30.7%; P<0.001) and functional impairment (mRS score ≥2 25.4% vs 46.2%; P<0.01). CONCLUSION: Our results suggest that intervention for unruptured brain AVMs at comprehensive stroke centers across the United States is safe.

The obesity paradox and ventriculoperitoneal shunting in aneurysmal subarachnoid hemorrhage patients undergoing microsurgical clipping.

BACKGROUND: Aneurysmal subarachnoid hemorrhage (aSAH) can be devastating. Identifying predisposing factors is paramount in reducing aSAH-related mortality. Obesity's negative impact on health is well-established. However, the controversial "obesity paradox" in neurosurgery suggests that obesity may confer a survival advantage in SAH. We hypothesized that obesity would have a negative impact on outcomes following surgical clipping in aSAH. METHODS: A single-institution retrospective review was performed of aSAH patients undergoing surgical clipping from 2017 to 2021. Demographics and clinically relevant variables were collected. Obesity was defined as body mass index >30. Primary outcome was death or severe disability (mRS 4-6) at last follow-up. Secondary outcome was VPS placement. Multivariable Cox proportional-hazards model identified predictors of poor outcome. Kaplan-Meier curves identified survivorship differences between obese and non-obese patients. RESULTS: Poor outcome occurred in 11 of 52 total patients (21.2 %). There were no differences in demographics or distribution of Hunt Hess (HH), modified Fisher Grade (mFG), or external ventricular drain (EVD) placement between obese and non-obese patients. On univariate analysis, hypertension, older age, and non-obesity were predictive of poor outcome. On multivariable analysis, only obesity remained significant, suggesting a protective effect from poor outcome (HR 0.45 [0.21-0.95], p = 0.037). VPS placement occurred in 6 (11.5 %) patients for which obesity was not a significant predictor. CONCLUSIONS: Obesity may have a protective effect against poor outcome following surgical clipping in aSAH. Additionally, obesity does not appear to increase rate of EVD conversion to VPS. Thus, our study suggests that obesity should not preclude patients from open surgical intervention when clinically appropriate.

Financial Vulnerability and Its Association with HIV Transmission Risk Behaviors Among People Who Inject Drugs in Kyrgyzstan.

The Family Resource Scale (FRS) is a three-factor financial vulnerability (FV) measure. FV may impact HIV transmission risks. Cross-sectional data from 279 people who inject drugs (PWID) in Kyrgyzstan surveyed April-October 2021 was used to validate the FRS and estimate associations between FV on past 6-month injection and sexual HIV risk outcomes. The three-factor FRS reflected housing, essential needs, and fiscal independence, and had good internal reliability and structural validity. Greater cumulative, housing, and essential needs FRS scores were associated with increased relative risk on public injection (adjusted risk ratio [aRR], 95% confidence interval [95% CI]: 1.03 [1.01, 1.04]; aRR [95% CI]: 1.06 [1.02, 1.09]; aRR [95% CI]: 1.06 [1.03, 1.08], respectively, all p < 0.001) and preparing injections with unsafe water sources (aRR [95% CI]: 1.04 [1.02, 1.07]; aRR [95% CI]: 1.09 [1.04, 1.15]; aRR [95% CI]: 1.08 [1.03, 1.14], respectively, all p < 0.001). Results suggest that PWID housing- and essential needs-related FV may exacerbate injection HIV transmission risks. Reducing PWIDs' FV may enhance the HIV response in Kyrgyzstan.

RESUMEN: La Escala de Recursos Familiares (FRS, por sus siglas en inglés) es una medida de vulnerabilidad financiera (FV, por sus siglas en inglés) de tres factores. La FV puede afectar los riesgos de transmisión del VIH. Se utilizaron datos transversales de 279 personas que se inyectan drogas (PWID, por sus siglas en inglés) en Kirguistán encuestadas de abril a octubre de 2021 para validar la FRS y estimar las asociaciones entre la FV en la inyección y los resultados de riesgo sexual del VIH en los últimos seis meses. La FRS de tres factores reflejaba la vivienda, las necesidades esenciales y la independencia fiscal, y presentaba una buena confiabilidad interna y validez estructural. Mayores puntajes acumulativos de la FRS en vivienda y necesidades esenciales se asociaron con un mayor riesgo relativo en la inyección pública (Riesgo relativo ajustada [aRR], Intervalo de Confianza del 95% [IC95%]: 1.03 [1.01, 1.04]; aRR [IC95%]: 1.06 [1.02, 1.09]; aRR [IC95%]: 1.06 [1.03, 1.08], respectivamente, todos p < 0.001) y la preparación de inyección con fuentes de agua no seguras (aRR [IC95%]: 1.04 [1.02, 1.07]; aRR [IC95%]: 1.09 [1.04, 1.15]; aRR [IC95%]: 1.08 [1.03, 1.14], respectivamente, todos p < 0.001). Los resultados sugieren que la FV relacionada con la vivienda y las necesidades esenciales de las PWID puede exacerbar los riesgos de transmisión del VIH por la inyección. Reducir la FV de las PWID puede mejorar la respuesta al VIH en Kirguistán.

Tuning sterol extraction kinetics yields a renal-sparing polyene antifungal.

Decades of previous efforts to develop renal-sparing polyene antifungals were misguided by the classic membrane permeabilization model1. Recently, the clinically vital but also highly renal-toxic small-molecule natural product amphotericin B was instead found to kill fungi primarily by forming extramembraneous sponge-like aggregates that extract ergosterol from lipid bilayers2-6. Here we show that rapid and selective extraction of fungal ergosterol can yield potent and renal-sparing polyene antifungals. Cholesterol extraction was found to drive the toxicity of amphotericin B to human renal cells. Our examination of high-resolution structures of amphotericin B sponges in sterol-free and sterol-bound states guided us to a promising structural derivative that does not bind cholesterol and is thus renal sparing. This derivative was also less potent because it extracts ergosterol more slowly. Selective acceleration of ergosterol extraction with a second structural modification yielded a new polyene, AM-2-19, that is renal sparing in mice and primary human renal cells, potent against hundreds of pathogenic fungal strains, resistance evasive following serial passage in vitro and highly efficacious in animal models of invasive fungal infections. Thus, rational tuning of the dynamics of interactions between small molecules may lead to better treatments for fungal infections that still kill millions of people annually7,8 and potentially other resistance-evasive antimicrobials, including those that have recently been shown to operate through supramolecular structures that target specific lipids9.

Effects of a social network intervention on HIV seroconversion among people who inject drugs in Ukraine: moderation by network gender composition.

BACKGROUND: Women who inject drugs in Ukraine are disproportionately burdened by HIV. To help address the needs of this population, a greater understanding of how interventions may uniquely benefit women who inject drugs is needed. METHODS: Data come from a randomized controlled trial of a social network intervention targeting people who inject drugs in Ukraine (N = 1195). Indexes, plus two of their injection network members, received HIV testing and counseling (control arm) or HIV testing and counseling plus a social network intervention (intervention arm), in which indexes were trained to influence network members' risk behaviors. We used Cox regressions with interaction terms to assess differences in time to HIV seroconversion between arms by network gender composition and gender of the index. For significant interaction terms, we calculated simple effects, generated survival functions using Kaplan-Meier methods, and compared survival curves using log-rank tests. RESULTS: At 12 months, there were 45 seroconversions among women (40.0 [28.3, 51.7] per 100 person years) and 111 among men (28.4 [23.1, 33.6] per 100 person years) in the control arm; there were 27 seroconversions among women (17.1 [10.7, 23.6] per 100 person years) and 77 among men (18.7 [14.5, 22.9] per 100 person years) in the intervention arm. Network gender composition (but not gender of the index) moderated the intervention effect on HIV incidence (p < 0.05). Specifically, the intervention appeared to be even more protective against HIV acquisition as female gender composition increased. In the intervention arm, the HIV seroconversion hazard rate was 44% lower with 1 network female; 61% lower with 2 network females; and 72% lower with 3 network females. CONCLUSIONS: A greater number of women in an injection network, coupled with the provision of risk-reduction strategies, is associated with HIV risk-mitigation, though the mechanisms through which this occurs remain unclear. Findings can support new research and practice directions that prioritize women who inject drugs and more thoughtfully support their health and wellbeing.

Prognosticators of Functional Outcome After Supratentorial Minimally Invasive Intracranial Hemorrhage Evacuation With Tubular Retractor Systems.

BACKGROUND AND OBJECTIVES: Prognosticators of good functional outcome after minimally invasive surgical (MIS) intracranial hemorrhage (ICH) evacuation are poorly defined. This study aims to investigate clinical and radiographic prognosticators of poor functional outcome after MIS evacuation of ICH with tubular retractor systems. METHODS: Single-center retrospective review of adult (age ≥18 years) patients who underwent surgical evacuation of a spontaneous supratentorial ICH evacuation using tubular retractors from 2013 to 2022 was performed. Clinical and radiographic factors, such as antiplatelet/anticoagulant use, initial NIH Stroke Scale, ICH score, premorbid modified Rankin Scale (mRS), intraventricular hemorrhage (IVH) severity according to the modified Graeb scale, and preoperative/postoperative ICH volume, were collected. The main outcome was poor functional outcome, defined as mRS score of 4-6 within 1 year postoperatively. RESULTS: Eighty-eight patients were included. Clinical follow-up data were available for 64 (73%) patients. Of those, 43 (67%) had a poor functional outcome. On multivariate Cox regression, postoperative ICH volume ≥15 mL (hazard ratio [HR] = 2.46 [95% CI: 1.25-4.87]; P = .010) and higher modified Graeb score (HR = 1.04 [95% CI: 1-1.1]; P = .035] significantly increased the risk of poor functional outcome. Elevated postoperative ICH volume was predicted by the presence of lobar ICH (vs nonlobar, OR = 3.32 [95% CI: 1.01-11.55]; P = .043) and higher preoperative ICH volume (OR = 1.05 [1.02-1.08]; P < .001). A minimum of 60% ICH evacuation yielded an improvement in mRS 4-6 rates (HR 0.3 [95% CI: 0.1-0.8], P = .013). In patients without IVH and with a >80% ICH evacuation, the rate of mRS 4-6 was 42% compared with 67% in the whole patient sample ( P = .017). CONCLUSION: Increased IVH volumes and residual postoperative ICH volumes are associated with poor functional outcome after MIS ICH evacuation. Postoperative ICH volume was associated with lobar ICH location as well as preoperative ICH volume. These factors may help to prognosticate patient outcomes and improve selection criteria for MIS ICH evacuation techniques.

Barriers and facilitators to reducing paracetamol use in low back pain: A qualitative study.

BACKGROUND: Paracetamol is widely used for low back pain (LBP), but research questions its efficacy and safety. Patient education booklets have been explored for promoting deprescribing, but barriers and facilitators specific to LBP deprescribing remain unexamined. OBJECTIVE: To identify contextual factors facilitating and obstructing successful deprescribing of paracetamol for LBP after receiving an educational booklet. STUDY DESIGN: This study is part of an uncontrolled cohort feasibility study (CEASE NOW) in the community, recruiting from Musculoskeletal Australia and painaustralia. PATIENT SAMPLE: Twenty-four participants with acute, sub-acute, or chronic LBP, self-reporting paracetamol consumption, were included. METHODS: Thematic content analysis was used to analyze qualitative data on barriers and facilitators. Data were categorized by deprescribing outcomes: i) successful deprescribing, ii) attempted but failed, or iii) no attempt. Semi-structured telephone interviews were conducted within one week after each participant completed the one-month follow-up. RESULTS: Successful deprescribing was facilitated by supportive healthcare professionals, willingness, high self-efficacy, fear of future illness, and diverse strategies for deprescribing plans. Barriers included unsupportive healthcare professionals and fear of flare-ups. Participants not attempting deprescribing believed it unnecessary, perceived it as effortful, unquestioningly trusted healthcare professionals, and lacked risk awareness. CONCLUSIONS: Support from healthcare professionals, patient willingness, perceived necessity, risk awareness, effort, and varied strategies influence deprescribing outcomes for LBP patients using paracetamol. Addressing these factors is crucial when designing interventions to promote safe and effective deprescribing in LBP management.

Update on Outbreak of Fungal Meningitis among U.S. Residents who Received Epidural Anesthesia at Two Clinics in Matamoros, Mexico.

BACKGROUND: Public health officials are responding to an outbreak of fungal meningitis among patients who received procedures under epidural anesthesia at two clinics (River Side Surgical Center and Clinica K-3) in Matamoros, Mexico, during January 1-May 13, 2023. This report describes outbreak epidemiology and outlines interim diagnostic and treatment recommendations. METHODS: Interim recommendations for diagnosis and management were developed by the Mycoses Study Group Research Education and Consortium (MSGERC) based on the clinical experience of clinicians caring for patients during the current outbreak or during previous outbreaks of healthcare-associated fungal meningitis in Durango, Mexico, and the United States. RESULTS: As of July 7, 2023, the situation has evolved into a multistate and multinational fungal meningitis outbreak. A total of 185 residents in 22 U.S. states and jurisdictions have been identified who might be at risk of fungal meningitis because they received epidural anesthesia at the clinics of interest in 2023. Among these patients, 11 suspected, 10 probable, and 10 confirmed U.S. cases have been diagnosed, with severe vascular complications and eight deaths occurring. Fusarium solani species complex has been identified as the causative agent, with antifungal susceptibility testing of a single isolate demonstrating poor in vitro activity for most available antifungals. Currently, triple therapy with intravenous voriconazole, liposomal amphotericin B, and fosmanogepix is recommended. CONCLUSIONS: Efforts to understand the source of this outbreak and optimal treatment approaches are ongoing, but infectious diseases physicians should be aware of available treatment recommendations. New information will be available on CDC's website.

High-Throughput Screening of the Repurposing Hub Library to Identify Drugs with Novel Inhibitory Activity against Candida albicans and Candida auris Biofilms.

Candidiasis is one of the most frequent nosocomial infections affecting an increasing number of at-risk patients. Candida albicans remains the most frequent causative agent of candidiasis, but, in the last decade, C. auris has emerged as a formidable multi-drug-resistant pathogen. Both species are fully capable of forming biofilms, which contribute to resistance, increasing the urgency for new effective antifungal therapies. Repurposing existing drugs could significantly accelerate the development of novel therapies against candidiasis. Here, we have screened the Repurposing Hub library from the Broad Institute, containing over 6000 compounds, in search for inhibitors of C. albicans and C. auris biofilm formation. The primary screen identified 57 initial hits against C. albicans and 33 against C. auris. Confirmatory concentration-dependent assays were used to validate the activity of the initial hits and, at the same time, establish their anti-biofilm potency. Based on these results, ebselen, temsirolimus, and compound BAY 11-7082 emerged as the leading repositionable compounds. Subsequent experiments established their spectrum of antifungal activity against yeasts and filamentous fungi. In addition, their in vivo activity was examined in the murine models of hematogenously disseminated C. albicans and C. auris infections. Although promising, further in vitro and in vivo studies are needed to confirm their potential use for the therapy of candidiasis and possibly other fungal infections.

A Brief Peer-Led Intervention to Increase COVID-19 Vaccine Uptake Among People Who Inject Drugs in San Diego County: Results From a Pilot Randomized Controlled Trial.

Background: We evaluated the impact of a brief peer-led intervention on COVID-19 vaccination among people who inject drugs (PWID) presenting at syringe services program (SSP) locations in San Diego County, California. Methods: Between March and July 2022, PWID aged ≥18 years without recent voluntary COVID-19 testing who were not up to date on COVID-19 vaccinations received a single-session motivational interviewing intervention (LinkUP) or an attention-matched didactic control condition from trained peer counselors at SSP sites randomized by week. Following either 30-minute session, counselors offered referrals to local vaccination services. Multivariable log binomial regression via generalized estimating equations assessed LinkUP effects on (1) acceptance of COVID-19 vaccination referrals immediately postintervention and (2) COVID-19 vaccine uptake at 6-month follow-up. Results: COVID-19 vaccination outcomes were obtained on 135 (90.6%) of 149 participants. In multivariable analysis, participants receiving LinkUP had greater acceptance of COVID-19 vaccination referrals than controls (adjusted relative risk, 3.50; 95% CI, 1.01-12.2) and were marginally more likely to report receiving a new COVID-19 vaccine dose (adjusted relative risk, 1.57; 95% CI, .99-2.48). After 6 months, 20% reported receiving a new vaccine dose; however, if COVID-19 vaccine had been available at SSPs, this proportion could have been as high as 34.3% (45.3% LinkUP vs 24.3% control; P = .01). Conclusions: A brief peer-led SSP-based intervention significantly improved COVID-19 vaccination among PWID. Further improvements could likely be obtained by supporting SSPs to offer COVID-19 vaccination on-site instead of relying on referrals. Clinical Trials Registration: ClinicalTrials.gov NCT05181657.

Fungal Endocarditis: Pathophysiology, Epidemiology, Clinical Presentation, Diagnosis, and Management.

Fungal endocarditis accounts for 1% to 3% of all infective endocarditis cases, is associated with high morbidity and mortality (>70%), and presents numerous challenges during clinical care. Candida spp. are the most common causes of fungal endocarditis, implicated in over 50% of cases, followed by Aspergillus and Histoplasma spp. Important risk factors for fungal endocarditis include prosthetic valves, prior heart surgery, and injection drug use. The signs and symptoms of fungal endocarditis are nonspecific, and a high degree of clinical suspicion coupled with the judicious use of diagnostic tests is required for diagnosis. In addition to microbiological diagnostics (e.g., blood culture for Candida spp. or galactomannan testing and PCR for Aspergillus spp.), echocardiography remains critical for evaluation of potential infective endocarditis, although radionuclide imaging modalities such as 18F-fluorodeoxyglucose positron emission tomography/computed tomography are increasingly being used. A multimodal treatment approach is necessary: surgery is usually required and should be accompanied by long-term systemic antifungal therapy, such as echinocandin therapy for Candida endocarditis or voriconazole therapy for Aspergillus endocarditis.

Abatacept, Cenicriviroc, or Infliximab for Treatment of Adults Hospitalized With COVID-19 Pneumonia: A Randomized Clinical Trial.

Importance: Immune dysregulation contributes to poorer outcomes in COVID-19. Objective: To investigate whether abatacept, cenicriviroc, or infliximab provides benefit when added to standard care for COVID-19 pneumonia. Design, Setting, and Participants: Randomized, double-masked, placebo-controlled clinical trial using a master protocol to investigate immunomodulators added to standard care for treatment of participants hospitalized with COVID-19 pneumonia. The results of 3 substudies are reported from 95 hospitals at 85 clinical research sites in the US and Latin America. Hospitalized patients 18 years or older with confirmed SARS-CoV-2 infection within 14 days and evidence of pulmonary involvement underwent randomization between October 2020 and December 2021. Interventions: Single infusion of abatacept (10 mg/kg; maximum dose, 1000 mg) or infliximab (5 mg/kg) or a 28-day oral course of cenicriviroc (300-mg loading dose followed by 150 mg twice per day). Main Outcomes and Measures: The primary outcome was time to recovery by day 28 evaluated using an 8-point ordinal scale (higher scores indicate better health). Recovery was defined as the first day the participant scored at least 6 on the ordinal scale. Results: Of the 1971 participants randomized across the 3 substudies, the mean (SD) age was 54.8 (14.6) years and 1218 (61.8%) were men. The primary end point of time to recovery from COVID-19 pneumonia was not significantly different for abatacept (recovery rate ratio [RRR], 1.12 [95% CI, 0.98-1.28]; P = .09), cenicriviroc (RRR, 1.01 [95% CI, 0.86-1.18]; P = .94), or infliximab (RRR, 1.12 [95% CI, 0.99-1.28]; P = .08) compared with placebo. All-cause 28-day mortality was 11.0% for abatacept vs 15.1% for placebo (odds ratio [OR], 0.62 [95% CI, 0.41-0.94]), 13.8% for cenicriviroc vs 11.9% for placebo (OR, 1.18 [95% CI 0.72-1.94]), and 10.1% for infliximab vs 14.5% for placebo (OR, 0.59 [95% CI, 0.39-0.90]). Safety outcomes were comparable between active treatment and placebo, including secondary infections, in all 3 substudies. Conclusions and Relevance: Time to recovery from COVID-19 pneumonia among hospitalized participants was not significantly different for abatacept, cenicriviroc, or infliximab vs placebo. Trial Registration: ClinicalTrials.gov Identifier: NCT04593940.

Screening the medicine for malaria venture's Pandemic Response Box to identify novel inhibitors of Candida albicans and Candida auris biofilm formation.

Candida spp. are opportunistic yeasts capable of forming biofilms, which contribute to resistance, increasing the urgency for new effective antifungal therapies. Repurposing existing drugs could significantly accelerate the development of novel therapies against candidiasis. We screened the Pandemic Response Box containing 400 diverse drug-like molecules active against bacteria, viruses or fungi, for inhibitors of Candida albicans and Candida auris biofilm formation. Initial hits were identified based on the demonstration of >70% inhibitory activity. Dose-response assays were used to confirm the antifungal activity of initial hits and establish their potency. The spectrum of antifungal activity of the leading compounds was determined against a panel of medically important fungi, and the in vivo activity of the leading repositionable agent was evaluated in murine models of C. albicans and C. auris systemic candidiasis. The primary screening identified 20 hit compounds, and their antifungal activity and potency against C. albicans and C. auris were validated using dose-response measurements. From these experiments, the rapalog everolimus, emerged as the leading repositionable candidate. Everolimus displayed potent antifungal activity against different Candida spp., but more moderate levels of activity against filamentous fungi. Treatment with everolimus increased survival of mice infected with C. albicans, but not those with C. auris. The screening of the Pandemic Response Box resulted in the identification of several drugs with novel antifungal activity, with everolimus emerging as the main repositionable candidate. Further in vitro and in vivo studies are needed to confirm its potential therapeutic use.

Drug checking in the fentanyl era: Utilization and interest among people who inject drugs in San Diego, California.

BACKGROUND: In North America, overdose rates have steeply risen over the past five years, largely due to the ubiquity of illicitly manufactured fentanyls in the drug supply. Drug checking services (DCS) represent a promising harm reduction strategy and characterizing experiences of use and interest among people who inject drugs (PWID) is a priority. METHODS: Between February-October 2022, PWID participating in a cohort study in San Diego, CA and Tijuana, Mexico completed structured surveys including questions about DCS, socio-demographics and substance use behaviors. We used Poisson regression to assess factors associated with lifetime DCS use and characterized experiences with DCS and interest in free access to DCS. RESULTS: Of 426 PWID, 72% were male, 59% Latinx, 79% were experiencing homelessness and 56% ever experienced a nonfatal overdose. One third had heard of DCS, of whom 57% had ever used them. Among the latter, most (98%) reported using fentanyl test strips (FTS) the last time they used DCS; 66% did so less than once per month. In the last six months, respondents used FTS to check methamphetamine (48%), heroin (30%) or fentanyl (29%). Relative to White/non-Latinx PWID, those who were non-White/Latinx were significantly less likely to have used DCS [adjusted risk ratio (aRR): 0.22; 95% CI: 0.10, 0.47), as were PWID experiencing homelessness (aRR:0.45; 95% CI: 0.28, 0.72). However, a significant interaction indicated that non-White/Latinx syringe service program (SSP) clients were more likely to have used DCS than non-SSP clients (aRR: 2.79; CI: 1.09, 7.2). Among all PWID, 44% expressed interest in free access to FTS, while 84% (of 196 PWID) expressed interest in advanced spectrometry DCS to identify and quantify multiple substances. CONCLUSIONS: Our findings highlight low rates of DCS awareness and utilization, inequities by race/ethnicity and housing situation, high interest in advanced spectrometry DCS versus FTS, and the potential role of SSPs in improving access to DCS, especially among racial/ethnic minorities.

A multistep mediation model examining how consultation in prolonged exposure therapy affects PTSD treatment outcomes.

Prolonged exposure therapy (PE) is an evidence-based psychotherapy (EBP) for posttraumatic stress disorder (PTSD) that is underutilized in the military health system. Previous research suggests that postworkshop consultation is important for successful implementation. However, little is known about how consultation may relate to EBP adoption or patient outcomes. The present study addressed these gaps by examining associations between consultation, provider self-efficacy, use of PE, and patient outcomes using a multistep mediation model. This study used data from Foa et al. (2020), a two-armed randomized implementation trial comparing two PE training models: standard training (workshop only) and extended training (workshop + 6-8 months of postworkshop expert consultation) at three U.S. Army sites. Participants were patients with PTSD (N = 242) receiving care from the participating providers (N = 103). Providers who received extended training reported greater PE self-efficacy compared to standard training providers, but self-efficacy was unrelated to their use of PE components or to patient outcomes. Extended training providers used more PE components and had superior patient outcomes than standard training providers, and patient outcomes were mediated by the use of PE components. To our knowledge, this is the first study to demonstrate that EBP consultation leads to improved clinical outcomes for patients through increased use of the EBP. PE adoption (i.e., use of PE components in therapy) was not explained by increases in self-efficacy among providers who received extended training. Therefore, future research should assess how other factors may influence provider behavior in implementing EBPs. (PsycInfo Database Record (c) 2023 APA, all rights reserved).