Initial micafungin treatment does not improve outcomes compared to fluconazole treatment in immunocompromised and critically ill patients with candidaemia.

BACKGROUND: Candidaemia is associated with poor outcomes including high mortality rates. Controversy remains regarding whether fluconazole or an echinocandin is the optimal choice for initial candidaemia treatment, particularly among high-risk patients such as the immunocompromised or critically ill. OBJECTIVES: To understand optimal initial treatment of candidaemia. METHODS: We conducted a retrospective study of immunocompromised or ICU adult patients with candidaemia from 2010 to 2014. Patients who received ≥3 consecutive days of initial treatment with fluconazole or micafungin were included. The primary outcome was complete response at day 14, defined as clinical improvement and blood culture sterilization. Secondary outcomes included microbiological and clinical success, survival and recurrent candidaemia. RESULTS: A total of 197 patients were included; 76 received fluconazole and 121 received micafungin. There was no difference in complete response between the fluconazole and micafungin groups (ICU: 38% versus 40%, P = 0.87; immunocompromised: 57% versus 59%, P = 0.80). Secondary outcomes including survival were also similar. In multivariable analysis, among ICU patients, Pitt bacteraemia score < 4 (P = 0.002) and time to antifungal (P = 0.037) were associated with meeting the primary outcome; white blood cell count > 11 cells × 103/µL on day 0 (P < 0.001) and Candida isolated from a non-blood site (P = 0.025) were associated with not meeting the primary outcome. Among immunocompromised patients, white blood cells > 11 × 103/µL (P = 0.003) and Candida isolated from a non-blood site (P = 0.026) were associated with not meeting the primary outcome. CONCLUSIONS: These data suggest that among ICU or immunocompromised patients, severity of illness rather than initial antifungal choice drove clinical outcomes.

Attitudes and Perceived Barriers to Sexually Transmitted Infection Screening Among Graduate Medical Trainees.

ABSTRACT: Graduate medical training is an opportune time to improve provider delivery of sexually transmitted infection (STI) screening. A survey of trainees found that the majority feel STI screening is their job but identified barriers to successful screening. Training that intentionally address service-specific barriers will be valuable in ending the STI epidemic.

Correlates of verbal and physical violence experienced and perpetrated among cisgender college women: serial cross-sections during one year of the COVID-19 pandemic.

Introduction: Violence against women is a prevalent, preventable public health crisis. COVID-19 stressors and pandemic countermeasures may have exacerbated violence against women. Cisgender college women are particularly vulnerable to violence. Thus, we examined the prevalence and correlates of verbal/physical violence experienced and perpetrated among cisgender women enrolled at a New York City college over one year during the COVID-19 pandemic. Methods: From a prospective cohort study, we analyzed data self-reported quarterly (T1, T2, T3, T4) between December 2020 and December 2021. Using generalized estimated equations (GEE) and logistic regression, we identified correlates of experienced and perpetrated violence among respondents who were partnered or cohabitating longitudinally and at each quarter, respectively. Multivariable models included all variables with unadjusted parameters X 2 p-value ≤0.05. Results: The prevalence of experienced violence was 52% (T1: N = 513), 30% (T2: N = 305), 33% (T3: N = 238), and 17% (T4: N = 180); prevalence of perpetrated violence was 38%, 17%, 21%, and 9%. Baseline correlates of experienced violence averaged over time (GEE) included race, living situation, loneliness, and condom use; correlates of perpetrated violence were school year, living situation, and perceived social support. Quarter-specific associations corroborated population averages: living with family members and low social support were associated with experienced violence at all timepoints except T4. Low social support was associated with higher odds of perpetrated violence at T1/T3. Other/Multiracial identity was associated with higher odds of violence experience at T3. Conclusions: Living situation was associated with experienced and perpetrated violence in all analyses, necessitating further exploration of household conditions, family dynamics, and interpersonal factors. The protective association of social support with experienced and perpetrated violence also warrants investigation into forms of social engagement and cohesion. Racial differences in violence also require examination. Our findings can inform university policy development on violence and future violence research. Within or beyond epidemic conditions, universities should assess and strengthen violence prevention and support systems for young women by developing programming to promote social cohesion.

Long-Term Safety and Immunogenicity of AZD1222 (ChAdOx1 nCoV-19): 2-Year Follow-Up from a Phase 3 Study.

A better understanding of the long-term safety, efficacy, and immunogenicity of COVID-19 vaccines is needed. This phase 3, randomized, placebo-controlled study for AZD1222 (ChAdOx1 nCoV-19) primary-series vaccination enrolled 32,450 participants in the USA, Chile, and Peru between August 2020 and January 2021 (NCT04516746). Endpoints included the 2-year follow-up assessment of safety, efficacy, and immunogenicity. After 2 years, no emergent safety signals were observed for AZD1222, and no cases of thrombotic thrombocytopenia syndrome were reported. The assessment of anti-SARS-CoV-2 nucleocapsid antibody titers confirmed the durability of AZD1222 efficacy for up to 6 months, after which infection rates in the AZD1222 group increased over time. Despite this, all-cause and COVID-19-related mortality remained low through the study end, potentially reflecting the post-Omicron decoupling of SARS-CoV-2 infection rates and severe COVID-19 outcomes. Geometric mean titers were elevated for anti-SARS-CoV-2 neutralizing antibodies at the 1-year study visit and the anti-spike antibodies were elevated at year 2, providing further evidence of increasing SARS-CoV-2 infections over long-term follow-up. Overall, this 2-year follow-up of the AZD1222 phase 3 study confirms that the long-term safety profile remains consistent with previous findings and supports the continued need for COVID-19 booster vaccinations due to waning efficacy and humoral immunity.

Correlates of psychological distress among undergraduate women engaged in remote learning through a New York City college during the COVID-19 pandemic.

OBJECTIVE: The study's objective is to explore psychological distress (PD) among remote learners during COVID-19. PARTICIPANTS: Female undergraduates matriculated at an NYC college in Winter 2020. METHODS: Using the Kessler-6 scale, we defined PD as no/low (LPD), mild/moderate (MPD), and severe (SPD) and assessed if residing in/near NYC modified associations. RESULTS: PD was common (MPD: 34.1%, SPD: 38.9%). Students identifying as Other/Multiracial had lower MPD odds (aOR = 0.39 [0.17-0.88]). SPD was associated with identifying as White (aOR = 2.02 [1.02-3.99]), unbalanced meals (aOR = 2.59 [1.06-6.30]), violence experience (aOR = 1.77 [1.06-2.94]), no social support (aOR = 3.24 [1.37-7.64]), and loneliness (aOR = 2.52 [1.29-4.95]). Among students in/near NYC, moderate/high drug use (aOR = 2.76 [1.15-6.61]), no social support (aOR = 3.62 [1.10-1.19]), and loneliness (aOR = 2.92 [1.11-7.63]) were SPD correlates. CONCLUSIONS: PD was high and associated with food insecurity, violence experience, no social support, and loneliness. Living in/near NYC modified drug use, loneliness, and social support associations. Mental health initiatives should address modifiable risk factors to ameliorate pandemic-associated PD.

Safety, tolerability, pharmacokinetics, and immunological activity of dual-combinations and triple-combinations of anti-HIV monoclonal antibodies PGT121, PGDM1400, 10-1074, and VRC07-523LS administered intravenously to HIV-uninfected adults: a phase 1 randomised trial.

BACKGROUND: Preclinical and clinical studies suggest that combinations of broadly neutralising antibodies (bnAbs) targeting different HIV envelope epitopes might be required for sufficient prevention of infection. We aimed to evaluate the dual and triple anti-HIV bnAb combinations of PGDM1400 (V2 Apex), PGT121 (V3 glycan), 10-1074 (V3 glycan), and VRC07-523LS (CD4 binding site). METHODS: In this phase 1 trial (HVTN 130/HPTN 089), adults without HIV were randomly assigned (1:1:1) to three dual-bnAb treatment groups simultaneously, or the triple-bnAb group, receiving 20 mg/kg of each antibody administered intravenously at four centres in the USA. Participants received a single dose of PGT121 + VRC07-523LS (treatment one; n=6), PGDM1400 + VRC07-523LS (treatment two; n=6), or 10-1074 + VRC07-523LS (treatment three; n=6), and two doses of PGDM1400 + PGT121 + VRC07-523LS (treatment four; n=9). Primary outcomes were safety, pharmacokinetics, and neutralising activity. Safety was determined by monitoring for 60 min after infusions and throughout the study by collecting laboratory assessments (ie, blood count, chemistry, urinalysis, and HIV), and solicited and unsolicited adverse events (via case report forms and participant diaries). Serum concentrations of each bnAb were measured by binding antibody assays on days 0, 3, 6, 14, 28, 56, 112, 168, 224, 280, and 336, and by serum neutralisation titres against Env-pseudotyped viruses on days 0, 3, 28, 56, and 112. Pharmacokinetic parameters were estimated by use of two-compartment population pharmacokinetic models; combination bnAb neutralisation titres were directly measured and assessed with different interaction models. This trial is registered with ClinicalTrials.gov, NCT03928821, and has been completed. FINDINGS: 27 participants were enrolled from July 31, to Dec 20, 2019. The median age was 26 years (range 19-50), 16 (58%) of 27 participants were assigned female sex at birth, and 24 (89%) participants were non-Hispanic White. Infusions were safe and well tolerated. There were no statistically significant differences in pharmacokinetic patterns between the dual and triple combinations of PGT121, PGDM1400, and VRC07-523LS. The median estimated elimination half-lives of PGT121, PGDM1400, 10-1074, and VRC07-523LS were 32·2, 25·4, 27·5, and 52·9 days, respectively. Neutralisation coverage against a panel of 12 viruses was greater in the triple-bnAb versus dual-bnAb groups: area under the magnitude-breadth curve at day 28 was 3·1, 2·9, 3·0, and 3·4 for treatments one to four, respectively. The Bliss-Hill multiplicative interaction model, which assumes complementary neutralisation with no antagonism or synergism among the bnAbs, best described combination bnAb titres in the dual-bnAb and triple-bnAb groups. INTERPRETATION: No pharmacokinetic interactions among the bnAbs and no loss of complementary neutralisation were observed in the dual and triple combinations. This study lays the foundation for designing future combination bnAb HIV prevention efficacy trials. FUNDING: US National Institute of Allergy and Infectious Diseases, US National Institute on Drug Abuse, US National Institute of Mental Health, and the Eunice Kennedy Shriver National Institute of Child Health and Human Development.

Clinical and Demographic Factors Associated With COVID-19, Severe COVID-19, and SARS-CoV-2 Infection in Adults: A Secondary Cross-Protocol Analysis of 4 Randomized Clinical Trials.

Importance: Current data identifying COVID-19 risk factors lack standardized outcomes and insufficiently control for confounders. Objective: To identify risk factors associated with COVID-19, severe COVID-19, and SARS-CoV-2 infection. Design, Setting, and Participants: This secondary cross-protocol analysis included 4 multicenter, international, randomized, blinded, placebo-controlled, COVID-19 vaccine efficacy trials with harmonized protocols established by the COVID-19 Prevention Network. Individual-level data from participants randomized to receive placebo within each trial were combined and analyzed. Enrollment began July 2020 and the last data cutoff was in July 2021. Participants included adults in stable health, at risk for SARS-CoV-2, and assigned to the placebo group within each vaccine trial. Data were analyzed from April 2022 to February 2023. Exposures: Comorbid conditions, demographic factors, and SARS-CoV-2 exposure risk at the time of enrollment. Main Outcomes and Measures: Coprimary outcomes were COVID-19 and severe COVID-19. Multivariate Cox proportional regression models estimated adjusted hazard ratios (aHRs) and 95% CIs for baseline covariates, accounting for trial, region, and calendar time. Secondary outcomes included severe COVID-19 among people with COVID-19, subclinical SARS-CoV-2 infection, and SARS-CoV-2 infection. Results: A total of 57 692 participants (median [range] age, 51 [18-95] years; 11 720 participants [20.3%] aged ≥65 years; 31 058 participants [53.8%] assigned male at birth) were included. The analysis population included 3270 American Indian or Alaska Native participants (5.7%), 7849 Black or African American participants (13.6%), 17 678 Hispanic or Latino participants (30.6%), and 40 745 White participants (70.6%). Annualized incidence was 13.9% (95% CI, 13.3%-14.4%) for COVID-19 and 2.0% (95% CI, 1.8%-2.2%) for severe COVID-19. Factors associated with increased rates of COVID-19 included workplace exposure (high vs low: aHR, 1.35 [95% CI, 1.16-1.58]; medium vs low: aHR, 1.41 [95% CI, 1.21-1.65]; P < .001) and living condition risk (very high vs low risk: aHR, 1.41 [95% CI, 1.21-1.66]; medium vs low risk: aHR, 1.19 [95% CI, 1.08-1.32]; P < .001). Factors associated with decreased rates of COVID-19 included previous SARS-CoV-2 infection (aHR, 0.13 [95% CI, 0.09-0.19]; P < .001), age 65 years or older (aHR vs age <65 years, 0.57 [95% CI, 0.50-0.64]; P < .001) and Black or African American race (aHR vs White race, 0.78 [95% CI, 0.67-0.91]; P = .002). Factors associated with increased rates of severe COVID-19 included race (American Indian or Alaska Native vs White: aHR, 2.61 [95% CI, 1.85-3.69]; multiracial vs White: aHR, 2.19 [95% CI, 1.50-3.20]; P < .001), diabetes (aHR, 1.54 [95% CI, 1.14-2.08]; P = .005) and at least 2 comorbidities (aHR vs none, 1.39 [95% CI, 1.09-1.76]; P = .008). In analyses restricted to participants who contracted COVID-19, increased severe COVID-19 rates were associated with age 65 years or older (aHR vs <65 years, 1.75 [95% CI, 1.32-2.31]; P < .001), race (American Indian or Alaska Native vs White: aHR, 1.98 [95% CI, 1.38-2.83]; Black or African American vs White: aHR, 1.49 [95% CI, 1.03-2.14]; multiracial: aHR, 1.81 [95% CI, 1.21-2.69]; overall P = .001), body mass index (aHR per 1-unit increase, 1.03 [95% CI, 1.01-1.04]; P = .001), and diabetes (aHR, 1.85 [95% CI, 1.37-2.49]; P < .001). Previous SARS-CoV-2 infection was associated with decreased severe COVID-19 rates (aHR, 0.04 [95% CI, 0.01-0.14]; P < .001). Conclusions and Relevance: In this secondary cross-protocol analysis of 4 randomized clinical trials, exposure and demographic factors had the strongest associations with outcomes; results could inform mitigation strategies for SARS-CoV-2 and viruses with comparable epidemiological characteristics.

Outcomes among patients with Staphylococcus aureus bacteremia enrolled in a postdischarge outpatient parenteral antibiotic therapy program at an academic medical center.

We compared patients with Staphylococcus aureus bacteremia enrolled in outpatient parenteral antibiotic therapy monitoring program (OPAT-MP) upon hospital discharge with patients not enrolled. OPAT-MP patients were more likely to attend infectious diseases follow-up appointments. OPAT-related emergency room visits and/or readmissions were more common among non-OPAT-MP patients, but differences were not statistically significant.

Lost2PrEP: Understanding Reasons for Pre-Exposure Prophylaxis and Sexual Health Care Disengagement Among Men Who Have Sex with Men Attending a Sexual Health Clinic at a Large Urban Academic Medical Center in New York City.

Pre-exposure prophylaxis (PrEP) prevents HIV, but low rates of retention in care limit its effectiveness. We conducted a prospective survey-based study to investigate reasons for PrEP disengagement among men who have sex with men attending a sexual health clinic at a large urban academic medical center in New York City who were lost to follow up; surveys asked about current PrEP status, reasons for disengagement, attitudes toward PrEP, substance use, sexual practices, and behavioral/social determinants of health. Outreach attempts were made to 634 patients; majority of eligible participants were unable to be contacted (59%). Among those who agreed to participate (n = 175), 21% asked to re-establish care. Among those who completed the questionnaire (n = 86), 36% were taking PrEP. The most common reasons for PrEP discontinuation were cost/lack of insurance coverage (31%), decreased HIV risk perception (29%), and side effects (16%). Among those with decreased perception of risk, 62% were less sexually active, 38% were no longer engaging in anal sex, and 31% were using condoms for prevention. Participants reported that free medication (60%), having a sexual partner recommend PrEP (13%), and being able to receive PrEP from a primary care provider (13%) would encourage restarting PrEP. Findings were limited by low response rate (12% of eligible subjects completed the survey) and lack of Spanish-language questionnaires. Understanding reasons for loss-to-PrEP follow-up is essential for HIV prevention. Many people lost to follow up still desired PrEP, underscoring the importance of outreach, benefits navigators, and expansion of PrEP into primary care settings.

An Atypical Case of Neurosyphilis in a Patient With HIV: A Case Report.

Epidemiological trends have demonstrated re-emergence of neurosyphilis in the twenty-first century. As prevalence rises in clinical practice, neurosyphilis must be considered in the differential diagnosis even if initial diagnostic workup is unrevealing, especially in patients with human immunodeficiency virus (HIV). Co-infection of neurosyphilis and HIV can result in atypical presentations. In this report, we discuss a challenging diagnosis of neurosyphilis in a man with HIV who presented with atypical imaging findings and initially negative cerebrospinal fluid (CSF) nontreponemal testing. Our patient underwent repeated CSF evaluation and a comprehensive diagnostic workup, including brain biopsy, to arrive at the appropriate diagnosis. He received antibiotic treatment with excellent outcome. We review typical imaging features of neurosyphilis and highlight other neurological diseases that may mimic these radiographic findings. We discuss CSF testing and interpretation in this high-risk patient population.

Cycle Thresholds Among Solid Organ Transplant Recipients Testing Positive for SARS-CoV-2.

BACKGROUND: The optimal duration of transmission-based precautions among immunocompromised patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is unknown. METHODS: Retrospective review of patients with solid organ transplant with positive SARS-CoV-2 polymerase chain reaction result from nasopharyngeal specimens admitted to the hospital between March 13, 2020 and May 15, 2020. RESULTS: Twenty-one percent of solid organ transplant recipients with positive SARS-CoV-2 polymerase chain reaction detected ≥20 d after symptom onset (or after first positive test among asymptomatic individuals) had a low cycle threshold (ie, high viral load). The majority of these patients were asymptomatic or symptomatically improved. CONCLUSIONS: Solid organ transplant recipients may have prolonged high viral burden of SARS-CoV-2. Further data are needed to understand whether cycle threshold data can help inform strategies for prevention of healthcare-associated transmission of SARS-CoV-2 and for appropriate discontinuation of transmission-based precautions.

Characterising the long-term clinical outcomes of 1190 hospitalised patients with COVID-19 in New York City: a retrospective case series.

OBJECTIVE: To characterise the long-term outcomes of patients with COVID-19 admitted to a large New York City medical centre at 3 and 6 months after hospitalisation and describe their healthcare usage, symptoms, morbidity and mortality. DESIGN: Retrospective cohort through manual chart review of the electronic medical record. SETTING: NewYork-Presbyterian/Columbia University Irving Medical Center, a quaternary care academic medical centre in New York City. PARTICIPANTS: The first 1190 consecutive patients with symptoms of COVID-19 who presented to the hospital for care between 1 March and 8 April 2020 and tested positive for SARS-CoV-2 on reverse transcriptase PCR assay. MAIN OUTCOME MEASURES: Type and frequency of follow-up encounters, self-reported symptoms, morbidity and mortality at 3 and 6 months after presentation, respectively; patient disposition information prior to admission, at discharge, and at 3 and 6 months after hospital presentation. RESULTS: Of the 1190 reviewed patients, 929 survived their initial hospitalisation and 261 died. Among survivors, 570 had follow-up encounters (488 at 3 months and 364 at 6 months). An additional 33 patients died in the follow-up period. In the first 3 months after admission, most encounters were telehealth visits (59%). Cardiopulmonary symptoms (35.7% and 28%), especially dyspnoea (22.1% and 15.9%), were the most common reported symptoms at 3-month and 6-month encounters, respectively. Additionally, a large number of patients reported generalised (26.4%) or neuropsychiatric (24.2%) symptoms 6 months after hospitalisation. Patients with severe COVID-19 were more likely to have reduced mobility, reduced independence or a new dialysis requirement in the 6 months after hospitalisation. CONCLUSIONS: Patients hospitalised with SARS-CoV-2 infection reported persistent symptoms up to 6 months after diagnosis. These results highlight the long-term morbidity of COVID-19 and its burden on patients and healthcare resources.

Supervised Machine Learning Approach to Identify Early Predictors of Poor Outcome in Patients with COVID-19 Presenting to a Large Quaternary Care Hospital in New York City.

BACKGROUND: The progression of clinical manifestations in patients with coronavirus disease 2019 (COVID-19) highlights the need to account for symptom duration at the time of hospital presentation in decision-making algorithms. METHODS: We performed a nested case-control analysis of 4103 adult patients with COVID-19 and at least 28 days of follow-up who presented to a New York City medical center. Multivariable logistic regression and classification and regression tree (CART) analysis were used to identify predictors of poor outcome. RESULTS: Patients presenting to the hospital earlier in their disease course were older, had more comorbidities, and a greater proportion decompensated (<4 days, 41%; 4-8 days, 31%; >8 days, 26%). The first recorded oxygen delivery method was the most important predictor of decompensation overall in CART analysis. In patients with symptoms for <4, 4-8, and >8 days, requiring at least non-rebreather, age ≥ 63 years, and neutrophil/lymphocyte ratio ≥ 5.1; requiring at least non-rebreather, IL-6 ≥ 24.7 pg/mL, and D-dimer ≥ 2.4 µg/mL; and IL-6 ≥ 64.3 pg/mL, requiring non-rebreather, and CRP ≥ 152.5 mg/mL in predictive models were independently associated with poor outcome, respectively. CONCLUSION: Symptom duration in tandem with initial clinical and laboratory markers can be used to identify patients with COVID-19 at increased risk for poor outcomes.

History of Depression and Increased Risk of Sternal Wound Infection After Cardiothoracic Surgery: A Novel and Potentially Modifiable Risk Factor.

BACKGROUND: Sternal wound infection (SWI) is a leading cause of postoperative disease and death; the risk factors for SWI remain incompletely understood. The goal of the current study was to investigate the relationship between a preoperative history of depression and the risk of SWI after cardiothoracic surgery. METHODS: Among patients undergoing cardiothoracic surgery in a major academic medical center between 2007 and 2012, those in whom SWI developed (n = 129) were matched, by date of surgery, with those in whom it did not (n = 258). Multivariable logistic regression was used to examine the strength of relationships between risk factors and development of infection. History of depression was defined as a composite variable to increase the sensitivity of detection. RESULTS: History of depression as defined by our composite variable was associated with increased risk of SWI (adjusted odds ratio, 2.4; 95% confidence interval, 1.2-4.7; P = .01). Staphylococcus aureus was the most common organism isolated. CONCLUSIONS: History of depression was associated with increased risk of SWI. Future prospective studies are warranted to further investigate this relationship. Depression is highly treatable, and increased efforts to identify and treat depression preoperatively may be a critical step toward preventing infection-related disease and death.