Understanding noble gas incorporation in mantle minerals: an atomistic study.

Ab initio calculations in forsterite (Mg 2 SiO 4 ) are used to gain insight into the formation of point defects and incorporation of noble gases. We calculate the enthalpies of incorporation both at pre-existing vacancies in symmetrically non-equivalent sites, and at interstitial positions. At high pressure, most structural changes affect the MgO 6 units and the enthalpies of point defects increase, with those involving Mg and Si vacancies increasing more than those involving O sites. At 15 GPa Si vacancies and Mg interstitials have become the predominant intrinsic defects. We use these calculated enthalpies to estimate the total uptake of noble gases into the bulk crystal as a function of temperature and pressure both in the presence and absence of other heterovalent trace elements. For He and Ne our calculated solubilities point to atoms occupying mainly interstitial sites in agreement with previous experimental work. In contrast, Ar most likely substitutes for Mg due to its larger size and the deformation it causes within the crystal. Incorporation energies, as well as atomic distances suggest that the incorporation mainly depend on the size mismatch between host and guest atoms. Polarization effects arising from the polarizability of the noble gas atom or the presence of charged defects are minimal and do not contribute significantly to the uptake. Finally, the discrepancies between our results and recent experiments suggest that there are other incorporation mechanisms such as adsorption at internal and external interfaces, voids and grain boundaries which must play a major role in noble gas storage and solubility.

Evaluation of hospital-onset bacteraemia and fungaemia in the USA as a potential healthcare quality measure: a cross-sectional study.

BACKGROUND: Hospital-onset bacteraemia and fungaemia (HOB) is being explored as a surveillance and quality metric. The objectives of the current study were to determine sources and preventability of HOB in hospitalised patients in the USA and to identify factors associated with perceived preventability. METHODS: We conducted a cross-sectional study of HOB events at 10 academic and three community hospitals using structured chart review. HOB was defined as a blood culture on or after hospital day 4 with growth of one or more bacterial or fungal organisms. HOB events were stratified by commensal and non-commensal organisms. Medical resident physicians, infectious disease fellows or infection preventionists reviewed charts to determine HOB source, and infectious disease physicians with training in infection prevention/hospital epidemiology rated preventability from 1 to 6 (1=definitely preventable to 6=definitely not preventable) using a structured guide. Ratings of 1-3 were collectively considered 'potentially preventable' and 4-6 'potentially not preventable'. RESULTS: Among 1789 HOB events with non-commensal organisms, gastrointestinal (including neutropenic translocation) (35%) and endovascular (32%) were the most common sources. Overall, 636/1789 (36%) non-commensal and 238/320 (74%) commensal HOB events were rated potentially preventable. In logistic regression analysis among non-commensal HOB events, events attributed to intravascular catheter-related infection, indwelling urinary catheter-related infection and surgical site infection had higher odds of being rated preventable while events with neutropenia, immunosuppression, gastrointestinal sources, polymicrobial cultures and previous positive blood culture in the same admission had lower odds of being rated preventable, compared with events without those attributes. Of 636 potentially preventable non-commensal HOB events, 47% were endovascular in origin, followed by gastrointestinal, respiratory and urinary sources; approximately 40% of those events would not be captured through existing healthcare-associated infection surveillance. DISCUSSION: Factors identified as associated with higher or lower preventability should be used to guide inclusion, exclusion and risk adjustment for an HOB-related quality metric.

Meeting the Consultation Surge: A Nationwide Survey of Consult Volume and Mitigation Strategies in Infectious Diseases Fellowship Programs.

High patient volume in fellowship programs can affect learning, wellness, and patient outcomes. Training programs must find ways to mitigate high consultation volume to protect the learning environment. This survey describes average new consults and average censuses for infectious diseases training programs and strategies implemented to mitigate high volume.

Impact of a syndrome-based stewardship intervention on antipseudomonal beta-lactam use, antimicrobial resistance, C. difficile rates, and cost in a safety-net community hospital.

Broad-spectrum antimicrobials are commonly used without indication and contribute to antimicrobial resistance (AMR). We implemented a syndrome-based stewardship intervention in a community hospital that targeted common infectious syndromes and antipseudomonal beta-lactam (APBL) use. Our intervention successfully reduced AMR, C. difficile rates, use of APBLs, and cost.

Changing the culture: impact of a diagnostic stewardship intervention for urine culture testing and CAUTI prevention in an urban safety-net community hospital.

Cultures from urinary catheters are often ordered without indication, leading to possible misdiagnosis of catheter-associated urinary tract infections (CAUTI), increasing antimicrobial use, and C difficile. We implemented a diagnostic stewardship intervention for urine cultures from catheters in a community hospital that led to a reduction in cultures and CAUTIs.

Impact of a midline catheter prioritization initiative on device utilization and central line-associated bloodstream infections at an urban safety-net community hospital.

Overuse of peripherally inserted central catheters (PICCs) can lead to idle central line (CL) days and increased risk for CL-associated bloodstream infections (CLABSIs). We established a midline prioritization initiative at a safety-net community hospital. This initiative led to possible CLABSI avoidance and a decline in PICC use.

Feasibility and impact of a monoclonal antibody infusion program in reaching vulnerable underserved communities.

The coronavirus disease 2019 (COVID-19) pandemic has disproportionately impacted Black, indigenous, and people of color (BIPOC). Equitable access to therapeutics is key to addressing health disparities. We established a monoclonal infusion program in the emergency department of a safety-net hospital. Our program successfully reached underserved BIPOC communities and was sustained throughout the pandemic.

Inclusion, Diversity, Access, and Equity in Infectious Diseases Fellowship Training: Tools for Program Directors.

The Infectious Diseases Society of America (IDSA) has set clear priorities in recent years to promote inclusion, diversity, access, and equity (IDA&E) in infectious disease (ID) clinical practice, medical education, and research. The IDSA IDA&E Task Force was launched in 2018 to ensure implementation of these principles. The IDSA Training Program Directors Committee met in 2021 and discussed IDA&E best practices as they pertain to the education of ID fellows. Committee members sought to develop specific goals and strategies related to recruitment, clinical training, didactics, and faculty development. This article represents a presentation of ideas brought forth at the meeting in those spheres and is meant to serve as a reference document for ID training program directors seeking guidance in this area.

Antimicrobial stewardship and drug formulary restrictions during COVID-19: what is restricted and who decides?

COVID-19 therapies were challenging to deploy due to evolving literature and conflicting guidelines. Antimicrobial stewardship can help optimize drug use. We conducted a survey to understand the role of stewardship and formulary restrictions during the pandemic. Restrictions for COVID-19 therapies were common and approval by infectious disease physicians often required.

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.

Remdesivir use and antimicrobial stewardship restrictions during the coronavirus disease 2019 (COVID-19) pandemic in the United States: A cross-sectional survey.

Deploying therapeutics for coronavirus disease 2019 (COVID-19) has proved challenging due to evolving evidence, supply shortages, and conflicting guideline recommendations. We conducted a survey on remdesivir use and the role of stewardship. Use differs significantly from guidelines. Hospitals with remdesivir restrictions were more guideline concordant. Formulary restrictions can be important for pandemic response.

Impact of a culturally sensitive multilingual community outreach model on coronavirus disease 2019 (COVID-19) vaccinations at an urban safety-net community hospital.

We assessed the efficacy of a culturally competent outreach model with promotoras in raising the coronavirus disease 2019 (COVID-19) first-dose vaccination rates in Chicago's at-risk ZIP codes from February through May 2021. Utilizing community members from within target communities may reduce barriers, increase vaccination rates, and enhance COVID-19 prevention.

Rapid Development of an Integrated Network Infrastructure to Conduct Phase 3 COVID-19 Vaccine Trials.

Importance: The COVID-19 pandemic has caused millions of infections and deaths and resulted in unprecedented international public health social and economic crises. As SARS-CoV-2 spread across the globe and its impact became evident, the development of safe and effective vaccines became a priority. Outlining the processes used to establish and support the conduct of the phase 3 randomized clinical trials that led to the rapid emergency use authorization and approval of several COVID-19 vaccines is of major significance for current and future pandemic response efforts. Observations: To support the rapid development of vaccines for the US population and the rest of the world, the National Institute of Allergy and Infectious Diseases established the COVID-19 Prevention Network (CoVPN) to assist in the coordination and implementation of phase 3 efficacy trials for COVID-19 vaccine candidates and monoclonal antibodies. By bringing together multiple networks, CoVPN was able to draw on existing clinical and laboratory infrastructure, community partnerships, and research expertise to quickly pivot clinical trial sites to conduct COVID-19 vaccine trials as soon as the investigational products were ready for phase 3 testing. The mission of CoVPN was to operationalize phase 3 vaccine trials using harmonized protocols, laboratory assays, and a single data and safety monitoring board to oversee the various studies. These trials, while staggered in time of initiation, overlapped in time and course of conduct and ultimately led to the successful completion of multiple studies and US Food and Drug Administration-licensed or -authorized vaccines, the first of which was available to the public less than 1 year from the discovery of the virus. Conclusions and Relevance: This Special Communication describes the design, geographic distribution, and underlying principles of conduct of these efficacy trials and summarizes data from 136 382 prospectively followed-up participants, including more than 2500 with documented COVID-19. These successful efforts can be replicated for other important research initiatives and point to the importance of investments in clinical trial infrastructure integral to pandemic preparedness.

A nationwide survey of antimicrobial dispensation practices in pharmacies and bodegas in the Dominican Republic.

In many developing countries, antimicrobials are available without prescriptions in pharmacies and stores. We performed a survey to describe antimicrobial availability, training, and use recommendations for common symptoms in the Dominican Republic. Pharmacy recommendations varied, whereas aminopenicillins are routinely recommended at bodegas. Frontline staff are gatekeepers and potential targets for stewardship education.

Antimicrobial resistance in Escherichia coli and Pseudomonas aeruginosa before and after the coronavirus disease 2019 (COVID-19) pandemic in the Dominican Republic.

Objective: To describe antimicrobial resistance before and after the COVID-19 pandemic in the Dominican Republic. Design: Retrospective study. Setting: The study included 49 outpatient laboratory sites located in 13 cities nationwide. Participants: Patients seeking ambulatory microbiology testing for urine and bodily fluids. Methods: We reviewed antimicrobial susceptibility reports for Escherichia coli isolates from urine and Pseudomonas aeruginosa (PSAR) from bodily fluids between January 1, 2018, to December 31, 2021, from deidentified susceptibility data extracted from final culture results. Results: In total, 27,718 urine cultures with E. coli and 2,111 bodily fluid cultures with PSAR were included in the analysis. On average, resistance to ceftriaxone was present in 25.19% of E. coli isolated from urine each year. The carbapenem resistance rates were 0.15% for E. coli and 3.08% for PSAR annually. The average rates of E. coli with phenotypic resistance consistent with possible extended-spectrum ß-lactamase (ESBL) in urine were 25.63% and 24.75%, respectively, before and after the COVID-19 pandemic. The carbapenem resistance rates in urine were 0.11% and 0.20%, respectively, a 200% increase. The average rates of PSAR with carbapenem resistance in bodily fluid were 2.33% and 3.84% before and after the COVID-19 pandemic, respectively, a 130% percent increase. Conclusions: Resistance to carbapenems in PSAR and E. coli after the COVID-19 pandemic is rising. These resistance patterns suggest that ESBL is common in the Dominican Republic. Carbapenem resistance was uncommon but increased after the COVID-19 pandemic.

Extended-spectrum and AmpC ß-lactamases screening and antibiotic resistance profile of Escherichia coli isolated from urine / Análisis de las ß-lactamasas de espectro extendido y tipo AmpC y el perfil de resistencia a antibióticos de Escherichia coli aisladas de orina

Introduction: Antimicrobial resistance is a global concern since infections by resistant pathogens are associated with higher mortality and morbidity. Objective: To assess the prevalence of Escherichia coli isolates producing extended-spectrum and AmpC beta-lactamase (ESBL) in urine samples from patients at the Hospital Metropolitano de Santiago in Dominican Republic. Methods: Pathogen identification and antibiogram were carried out by the automated systems BD Phoenix or Microscan®. General information and past medical history were gathered from patients with a positive urine culture for E. coli. Manual ESBL/AmpC screening was performed with the commercial ESBL+AmpC screen disc kit from Liofilchem Laboratory, Italy. Results: One or both of the studied phenotypes were present in 36% of the analyzed isolates. Among the risk factors for the detection of E. coli producing ESBL and/or AmpC in urine were male gender, advanced age, placement of urinary catheter, arterial hypertension, neoplasms, and coexistence of two or more comorbidities. Apart from cephalosporins resistance, isolates producing ESBL and/or AmpC also showed higher resistance to other antibiotics, such as gentamicin (66.7%), ciprofloxacin and levofloxacin (83.3%), and ampicillin (91.7%). Furthermore, 85% of the ESBL/AmpC producing samples were multidrug resistant (resistant to 1 or more drugs in at least 3 different antibiotic categories). Conclusions: The high prevalence of antimicrobial resistance found in this study highlights the importance of implementing national and global measures to tackle the problem, especially in developing countries such as the Dominican Republic, where resources are scarce.

Introducción: La resistencia antimicrobiana es un grave problema global, pues las infecciones causadas por patógenos resistentes están asociadas con una mayor mortalidad y morbilidad. Objetivos: Analizar la prevalencia de aislados de Escherichia coli productores de β-lactamasas de espectro extendido (BLEE) y tipo AmpC procedentes de muestras de orina de pacientes del Hospital Metropolitano de Santiago en la República Dominicana. Métodos: La identificación del patógeno y el antibiograma fueron llevados a cabo mediante los sistemas automáticos BD Phoenix o Microscan®. Se recolectó información general y la historia médica de pacientes con un cultivo de orina positivo para E. coli. La detección de BLEE/AmpC se realizó de manera manual con el estuche comercial ESBL+AmpC de Liofilchem Laboratory, de Italia. Resultados: Un 36 % de las muestras analizadas mostraron uno o ambos fenotipos estudiados. Como factores de riesgo para la detección en orina de E. coli productoras de BLEE o AmpC se encontraron: sexo masculino, edad avanzada, colocación de un catéter urinario, hipertensión, neoplasmas y coexistencia de comorbilidades. Además de resistencia a las cefalosporinas, los aislados productores de BLEE y AmpC revelaron también elevada resistencia a otros antibióticos como gentamicina (66,7 %), ciprofloxacina y levofloxacina (83,3 %), y ampicilina (91,7 %). Un 85,0 % de las muestras productoras de BLEE/AmpC fueron multidrogorresistentes. Conclusiones: La elevada prevalencia de resistencia antimicrobiana encontrada en este estudio refleja la importancia de tomar medidas nacionales y globales para contener el problema, especialmente en países en desarrollo como República Dominicana, donde los recursos son escasos.

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. Primary outcome was time-to-recovery by day 28. Key secondary endpoints included 28-day mortality. Results: Between October 16, 2020 and December 31, 2021, a total of 1019 participants received study treatment (509 abatacept; 510 shared placebo), constituting the modified intention-to-treat cohort. Participants had a mean age 54.8 (SD 14.6) years, 60.5% were male, 44.2% Hispanic/Latino and 13.7% Black. No statistically significant difference for the primary endpoint of time-to-recovery was found with a recovery-rate-ratio of 1.14 (95% CI 1.00-1.29; p=0.057) compared with placebo. We observed a substantial improvement in 28-day all-cause mortality with abatacept versus placebo (11.0% vs. 15.1%; odds ratio [OR] 0.62 [95% CI 0.41- 0.94]), leading to 38% lower odds of dying. Improvement in mortality occurred for participants requiring oxygen/noninvasive ventilation at randomization. Subgroup analysis identified the strongest effect in those with baseline C-reactive protein >75mg/L. We found no statistically significant differences in adverse events, with safety composite index slightly favoring abatacept. Rates of secondary infections were similar (16.1% for abatacept; 14.3% for placebo). Conclusions: Addition of single-dose intravenous abatacept to standard-of-care demonstrated no statistically significant change in time-to-recovery, but improved 28-day mortality. Trial registration: ClinicalTrials.gov ( NCT04593940 ).

Immunoglobulin G4 associated autoimmune cholangitis and pancreatitis following the administration of nivolumab: A case report.

BACKGROUND: Immune checkpoint inhibitors have significantly improved survivals for an increasing range of malignancies but at the cost of several immune-related adverse events, the management of which can be challenging due to its mimicry of other autoimmune related disorders such as immunoglobulin G4 (IgG4) related disease when the pancreaticobiliary system is affected. Nivolumab, an IgG4 monoclonal antibody, has been associated with cholangitis and pancreatitis, however its association with IgG4 related disease has not been reported to date. CASE SUMMARY: We present a case of immune-related pancreatitis and cholangiopathy in a patient who completed treatment with nivolumab for anal squamous cell carcinoma. Patients IgG4 levels was normal on presentation. She responded to steroids but due to concerns for malignant biliary stricture, she opted for surgery, the pathology of which suggested IgG4 related disease. CONCLUSION: We hypothesize this case of IgG4 related cholangitis and pancreatitis was likely triggered by nivolumab.