Resource Use in the Randomized Master Protocol for Immune Modulators for Treating COVID-19 (ACTIV-1 IM): A Secondary Data Analysis.

Background: Coronavirus disease 2019 (COVID-19) pneumonia requires considerable healthcare resources.

Research Objective: Examine if a single dose of infliximab or abatacept, in addition to remdesivir and steroids, decreased resource utilization among participants hospitalized with COVID-19 pneumonia.

Study Design And Methods: Accelerating COVID-19 Therapeutic Interventions and Vaccines Immunomodulator (ACTIV-1 IM) master protocol was a randomized, placebo-controlled trial examining the potential benefit in time to recovery and mortality of immunomodulators infliximab, abatacept, and cenicriviroc.

Antiretroviral Therapy and Cardiovascular Risk in People With HIV in the United States-An Updated Analysis.

Background: Several antiretroviral therapy (ART) medications have been associated with increased cardiovascular risk, but less is known about the safety of modern ART. We sought to compare the risk of major adverse cardiac events (MACEs) among different ART regimens.

Methods: Using insurance claims databases from 2008 to 2020, we identified adults aged <65 years who newly initiated ART.

Efficacy of infliximab, abatacept, and cenicriviroc for the treatment of adults hospitalized with COVID-19 pneumonia.

A randomized, double-blind, placebo-controlled clinical trial was conducted to investigate the efficacy of infliximab, abatacept, and cenicriviroc in treating patients hospitalized with COVID-19. The patient's clinical status was assessed daily on an 8-point ordinal scale. We evaluated the totality of evidence on the efficacy of the 3 immunomodulators by considering all possible changes in the clinical status of each patient over time.

Abatacept Pharmacokinetics and Exposure Response in Patients Hospitalized With COVID-19: A Secondary Analysis of the ACTIV-1 IM Randomized Clinical Trial.

Importance: The pharmacokinetics of abatacept and the association between abatacept exposure and outcomes in patients with severe COVID-19 are unknown.

Objective: To characterize abatacept pharmacokinetics, relate drug exposure with clinical outcomes, and evaluate the need for dosage adjustments.

Design, Setting, And Participants: This study is a secondary analysis of data from the ACTIV-1 (Accelerating COVID-19 Therapeutic Interventions and Vaccines) Immune Modulator (IM) randomized clinical trial conducted between October 16, 2020, and December 31, 2021.

Leveraging CD4 Cell Count at Entry Into Care to Monitor Success of Human Immunodeficiency Virus Prevention, Treatment, and Public Health Programming in the Greater St Louis Area Between 2017 and 2020.

CD4 cell count at entry into human immunodeficiency virus (HIV) care is a useful indicator of success of multiple steps in HIV public health programming. We demonstrate that CD4 cell count at care initiation was stable in St Louis between 2017 and 2019 but declined in 2020. Missouri efforts in the Ending the HIV Epidemic plan should focus on rapidly identifying individuals with undiagnosed HIV infection.

The STOP COVID 2 Study: Fluvoxamine vs Placebo for Outpatients With Symptomatic COVID-19, a Fully Remote Randomized Controlled Trial.

Background: Prior randomized clinical trials have reported benefit of fluvoxamine ≥200 mg/d vs placebo for patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

Methods: This randomized, double-blind, placebo-controlled, fully remote multisite clinical trial evaluated whether fluvoxamine prevents clinical deterioration in higher-risk outpatients with acute coronavirus disease 2019 (COVID-19). Between December 2020 and May 2021, nonhospitalized US and Canadian participants with confirmed symptomatic infection received fluvoxamine (50 mg on day 1, 100 mg twice daily thereafter) or placebo for 15 days.

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.

Persons with HIV Develop Spike-Specific Lymph Node Germinal Center Responses following SARS-CoV-2 Vaccination.

COVID-19 disproportionately affects persons with HIV (PWH) in worldwide locations with limited access to SARS-CoV-2 vaccines. PWH exhibit impaired immune responses to some, but not all, vaccines. Lymph node (LN) biopsies from PWH demonstrate abnormal LN structure, including dysregulated germinal center (GC) architecture.

The Geographic Distribution of Dimorphic Mycoses in the United States for the Modern Era.

Background: The dimorphic mycoses (DMs) of the United States-Histoplasma, Coccidioides, and Blastomyces-commonly known as endemic mycoses of North America (in addition to Paracoccidioides) are increasingly being diagnosed outside their historical areas of endemicity. Despite this trend, the maps outlining their geographic distributions have not been updated in more than half a century using a large, nationwide database containing individual-patient-level data.

Methods: This was a retrospective analysis of >45 million Medicare fee-for-service beneficiaries from 1 January 2007 through 31 December 2016.

Abatacept for Treatment of Adults Hospitalized with Moderate or Severe Covid-19.

Background: We investigated whether abatacept, a selective costimulation modulator, provides additional benefit when added to standard-of-care for patients hospitalized with Covid-19.

Methods: We conducted a master protocol to investigate immunomodulators for potential benefit treating patients hospitalized with Covid-19 and report results for abatacept. Intravenous abatacept (one-time dose 10 mg/kg, maximum dose 1000 mg) plus standard of care (SOC) was compared with shared placebo plus SOC.

Infliximab for Treatment of Adults Hospitalized with Moderate or Severe Covid-19.

Background: Immune dysregulation contributes to poorer outcomes in severe Covid-19. Immunomodulators targeting various pathways have improved outcomes. We investigated whether infliximab provides benefit over standard of care.

Creation and Internal Validation of a Clinical Predictive Model for Fluconazole Resistance in Patients With Bloodstream Infection.

Background: Fluconazole is recommended as first-line therapy for candidemia when risk of fluconazole resistance (fluc-R) is low. Lack of methods to estimate resistance risk results in extended use of echinocandins and prolonged hospitalization. This study aimed to develop a clinical predictive model to identify patients at low risk for fluc-R where initial or early step-down fluconazole would be appropriate.

Quantifying inequities in COVID-19 vaccine distribution over time by social vulnerability, race and ethnicity, and location: A population-level analysis in St. Louis and Kansas City, Missouri.

Background: Equity in vaccination coverage is a cornerstone for a successful public health response to COVID-19. To deepen understanding of the extent to which vaccination coverage compares with initial strategies for equitable vaccination, we explore primary vaccine series and booster rollout over time and by race/ethnicity, social vulnerability, and geography.

Methods And Findings: We analyzed data from the Missouri Department of Health and Senior Services on all COVID-19 vaccinations administered across 7 counties in the St.

Rationale of using the dual chemokine receptor CCR2/CCR5 inhibitor cenicriviroc for the treatment of COVID-19.

Coronavirus Disease 2019 (COVID-19), caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), has created a global pandemic infecting over 230 million people and costing millions of lives. Therapies to attenuate severe disease are desperately needed. Cenicriviroc (CVC), a C-C chemokine receptor type 5 (CCR5) and C-C chemokine receptor type 2 (CCR2) antagonist, an agent previously studied in advanced clinical trials for patients with HIV or nonalcoholic steatohepatitis (NASH), may have the potential to reduce respiratory and cardiovascular organ failures related to COVID-19.

Integrase Strand Transfer Inhibitors Are Associated With Incident Diabetes Mellitus in People With Human Immunodeficiency Virus.

Background: Integrase strand transfer inhibitors (INSTIs) are associated with weight gain in people with HIV (PWH). Less is known about the risk of other metabolic outcomes such as diabetes mellitus and hyperglycemia.

Methods: IBM® MarketScan® databases for commercially and Medicaid-insured adults were used to identify PWH newly initiating antiretroviral therapy (ART).

SARS-CoV-2 active infection prevalence and seroprevalence in the adult population of St. Louis County.

Background: The true prevalence of COVID-19 is difficult to estimate due to the absence of random population-based testing. To estimate current and past COVID-19 infection prevalence in a large urban area, we conducted a population-based survey in St. Louis County, Missouri.

Is France Once Again Looking for a Scapegoat?

On September 10, 2021, a special tribunal established by the French government launched an inquiry into the activities of former health minister Dr. Agnes Buzyn who was charged with "endangering the lives of others". It is surprising to learn of this accusation and inquiry into the actions of a public health official whose response to the epidemic was, to all appearances, exemplary.

Attributable Mortality of Candida Bloodstream Infections in the Modern Era: A Propensity Score Analysis.

Background: This study quantifies the mortality attributable to Candida bloodstream infections (BSI) in the modern era of echinocandins.

Methods: We conducted a retrospective cohort study of adult patients admitted to Barnes Jewish Hospital, a 1368-bed tertiary care academic hospital, in Saint Louis, Missouri, from 1 February 2012 to 30 April 2019. We identified 626 adult patients with Candida BSI that were frequency-matched with 6269 control patients that had similar Candida BSI risk-factors.

Outcomes Associated With Social Distancing Policies in St Louis, Missouri, During the Early Phase of the COVID-19 Pandemic.

Importance: In the absence of a national strategy in response to the COVID-19 pandemic, many public health decisions fell to local elected officials and agencies. Outcomes of such policies depend on a complex combination of local epidemic conditions and demographic features as well as the intensity and timing of such policies and are therefore unclear.

Objective: To use a decision analytical model of the COVID-19 epidemic to investigate potential outcomes if actual policies enacted in March 2020 (during the first wave of the epidemic) in the St Louis region of Missouri had been delayed.

Clinical predictive models of invasive Candida infection: A systematic literature review.

Clinical predictive models (CPM) serve to identify and categorize patients into risk categories to assist in treatment and intervention recommendations. Predictive accuracy and practicality of models varies depending on methods used for their development, and should be evaluated. The aim of this study was to summarize currently available CPM for invasive candidiasis, analyze their performance, and assess their suitability for use in clinical decision making.

Association of Adverse Events With Antibiotic Treatment for Urinary Tract Infection.

Background: Little is known about the relative harms of different antibiotic regimens prescribed to treat uncomplicated urinary tract infection (UTI). We sought to compare the risk of adverse events associated with commonly used oral antibiotic regimens for the outpatient treatment of uncomplicated UTI.

Methods: Using data from the IBM® MarketScan® Commercial Database, we identified 1 169 033 otherwise healthy, nonpregnant women aged 18-44 years with uncomplicated UTI who initiated an oral antibiotic with activity against common uropathogens from 1 July 2006 to 30 September 2015.

Re-engineering The Clinical Research Enterprise in Response to COVID-19: The Clinical Translational Science Award (CTSA) experience and proposed playbook for future pandemics.

The 2020 COVID-19 pandemic has had a profound impact on the clinical research enterprises at the 60 Clinical and Translational Science Award (CTSA) Hubs throughout the nation. There was simultaneously a need to expand research to obtain crucial data about disease prognosis and therapy and enormous limitations on conducting research as localities and institutions limited travel and person-to-person contact. These imperatives resulted in major changes in the way research was conducted, including expediting Institutional Review Board review, shifting to remote interactions with participants, centralizing decision-making in prioritizing research protocols, establishing biobanks, adopting novel informatics platforms, and distributing study drugs in unconventional ways.

Long-Term Mortality after Infection in People with HIV.

Histoplasmosis is a common opportunistic infection in people with HIV (PWH); however, no study has looked at factors associated with the long-term mortality of histoplasmosis in PWH. We conducted a single-center retrospective study on the long-term mortality of PWH diagnosed with histoplasmosis between 2002 and 2017. Patients were categorized into three groups based on length of survival after diagnosis: early mortality (death < 90 days), late mortality (death ≥ 90 days), and long-term survivors.