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BACKGROUND: Since July 23, 2022, global mpox cases reached 92,546, with over 31,000 in the United States. Asymptomatic carriage is a critical mechanism influencing the global dissemination of mpox. Seroprevalence studies are crucial for determining the epidemic's true burden, but uncertainties persist in serologic assay performance and how smallpox vaccination may influence assay interpretation. OBJECTIVES: Our study aimed to assess the performance of several diagnostic assays among mpox-positive, vaccinated, and pre-outbreak negative control samples. This investigation sought to enhance our understanding and management of future mpox outbreaks. STUDY DESIGN: Serum samples from 10 mpox-positive, five vaccinated uninfected, and 137 pre-outbreak controls were obtained for serological testing. The mpox-positive samples were obtained around 100 days post symptom onset, and vaccinated patients were sampled approximately 90 days post-vaccination. Multiple diagnostic assays were employed, including four commercial ELISAs (Abbexa, RayBioTech, FineTest, ProteoGenix) and a multiplex assay (MesoScale Diagnostics (MSD)) measuring five mpox and five smallpox antigens. RESULTS: Three commercial ELISA kits had low specificity (<50â¯%). The Proteogenix ELISA targeting the E8L antigen had a 94â¯% sensitivity and 87â¯% specificity. The E8L antigen on the MSD assay exhibited the greatest distinction between exposure groups, with 98â¯% sensitivity and 93â¯% specificity. CONCLUSIONS: None of the assays could distinguish between mpox-positive and vaccinated samples. The MSD assay targeting the MPXV E8L antigen demonstrated the greatest differentiation between mpox-positive and pre-outbreak negative samples. Our findings underscore the imperative to identify sensitive and specific assays to monitor population-level mpox exposure and infection.
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OBJECTIVE: Diagnostic testing is an important tool to combat the COVID-19 pandemic, yet access to and uptake of testing vary widely 3 years into the pandemic. The WHO recommends the use of COVID-19 self-testing as an option to help expand testing access. We aimed to calculate the cost of providing COVID-19 self-testing across countries and distribution modalities. DESIGN: We estimated economic costs from the provider perspective to calculate the total cost and the cost per self-test kit distributed for three scenarios that differed by costing period (pilot, annual), the number of tests distributed (actual, planned, scaled assuming an epidemic peak) and self-test kit costs (pilot purchase price, 50% reduction). SETTING: We used data collected between August and December 2022 in Brazil, Georgia, Malaysia, Ethiopia and the Philippines from pilot implementation studies designed to provide COVID-19 self-tests in a variety of settings-namely, workplace and healthcare facilities. RESULTS: Across all five countries, 173 000 kits were distributed during pilot implementation with the cost/test distributed ranging from $2.44 to $12.78. The cost/self-test kit distributed was lowest in the scenario that assumed implementation over a longer period (year), with higher test demand (peak) and a test kit price reduction of 50% ($1.04-3.07). Across all countries and scenarios, test procurement occupied the greatest proportion of costs: 58-87% for countries with off-site self-testing (outside the workplace, for example, home) and 15-50% for countries with on-site self-testing (at the workplace). Staffing was the next key cost driver, particularly for distribution modalities that had on-site self-testing (29-35%) versus off-site self-testing (7-27%). CONCLUSIONS: Our results indicate that it is likely to cost between $2.44 and $12.78 per test to distribute COVID-19 self-tests across common settings in five heterogeneous countries. Cost-effectiveness analyses using these results will allow policymakers to make informed decisions on optimally scaling up COVID-19 self-test distribution programmes across diverse settings and evolving needs.
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COVID-19 , Infecções por HIV , Humanos , SARS-CoV-2 , Etiópia , Infecções por HIV/epidemiologia , Georgia , Malásia , Pandemias , Brasil , Filipinas , Autoteste , COVID-19/epidemiologiaRESUMO
BACKGROUND: Skilled home healthcare (HH) provided in-person care to older adults during the COVID-19 pandemic, yet little is known about the pandemic's impact on HH care transition patterns. We investigated pandemic impact on (1) HH service volume; (2) population characteristics; and (3) care transition patterns for older adults receiving HH services after hospital or skilled nursing facility (SNF) discharge. METHODS: Retrospective, cohort, comparative study of recently hospitalized older adults (≥ 65 years) receiving HH services after hospital or SNF discharge at two large HH agencies in Baltimore and New York City (NYC) 1-year pre- and 1-year post-pandemic onset. We used the Outcome and Assessment Information Set (OASIS) and service use records to examine HH utilization, patient characteristics, visit timeliness, medication issues, and 30-day emergency department (ED) visit and rehospitalization. RESULTS: Across sites, admissions to HH declined by 23% in the pandemic's first year. Compared to the year prior, older adults receiving HH services during the first year of the pandemic were more likely to be younger, have worse mental, respiratory, and functional status in some areas, and be assessed by HH providers as having higher risk of rehospitalization. Thirty-day rehospitalization rates were lower during the first year of the pandemic. COVID-positive HH patients had lower odds of 30-day ED visit or rehospitalization. At the NYC site, extended duration between discharge and first HH visit was associated with reduced 30-day ED visit or rehospitalization. CONCLUSIONS: HH patient characteristics and utilization were distinct in Baltimore versus NYC in the initial year of the COVID-19 pandemic. Study findings suggest some older adults who needed HH may not have received it, since the decrease in HH services occurred as SNF use decreased nationally. Findings demonstrate the importance of understanding HH agency responsiveness during public health emergencies to ensure older adults' access to care.
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COVID-19 , Transferência de Pacientes , Humanos , Idoso , Estudos Retrospectivos , Transição do Hospital para o Domicílio , Pandemias , COVID-19/epidemiologia , Alta do Paciente , Hospitais , Instituições de Cuidados Especializados de Enfermagem , Serviço Hospitalar de EmergênciaRESUMO
BACKGROUND: There are no systematic measures of central line-associated bloodstream infections (CLABSIs) in patients maintaining central venous catheters (CVCs) outside acute care hospitals. To clarify the burden of CLABSIs in these patients, we characterized patients with CLABSI present on hospital admission (POA). METHODS: Retrospective cross-sectional analysis of patients with CLABSI-POA in 3 health systems covering 11 hospitals across Maryland, Washington DC, and Missouri from November 2020 to October 2021. CLABSI-POA was defined using an adaptation of the acute care CLABSI definition. Patient demographics, clinical characteristics, and outcomes were collected via record review. Cox proportional hazard analysis was used to assess factors associated with the all-cause mortality rate within 30 days. RESULTS: A total of 461 patients were identified as having CLABSI-POA. CVCs were most commonly maintained in home infusion therapy (32.8%) or oncology clinics (31.2%). Enterobacterales were the most common etiologic agent (29.2%). Recurrent CLABSIs occurred in a quarter of patients (25%). Eleven percent of patients died during the hospital admission. Among patients with CLABSI-POA, mortality risk increased with age (hazard ratio vs age <20 years by age group: 20-44 years, 11.2 [95% confidence interval, 1.46-86.22]; 45-64 years, 20.88 [2.84-153.58]; ≥65 years, 22.50 [2.98-169.93]) and lack of insurance (2.46 [1.08-5.59]), and it decreased with CVC removal (0.57 [.39-.84]). CONCLUSIONS: CLABSI-POA is associated with significant in-hospital mortality risk. Surveillance is required to understand the burden of CLABSI in the community to identify targets for CLABSI prevention initiatives outside acute care settings.
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Infecções Relacionadas a Cateter , Humanos , Masculino , Infecções Relacionadas a Cateter/epidemiologia , Infecções Relacionadas a Cateter/microbiologia , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Estudos Transversais , Idoso , Adulto , Cateteres Venosos Centrais/efeitos adversos , Cateteres Venosos Centrais/microbiologia , Hospitalização/estatística & dados numéricos , Cateterismo Venoso Central/efeitos adversos , Fatores de Risco , Bacteriemia/epidemiologia , Maryland/epidemiologia , Adulto JovemRESUMO
Orthopoxvirus-specific T-cell responses were analyzed in 10 patients who had recovered from Mpox including 7 people with human immunodeficiency virus (PWH). Eight participants had detectable virus-specific T-cell responses, including a PWH who was not on antiretroviral therapy and a PWH on immunosuppressive therapy. These 2 participants had robust polyfunctional CD4+ T-cell responses to peptides from the 121L vaccinia virus (VACV) protein. T-cells from 4 of 5 HLA-A2-positive participants targeted at least 1 previously described HLA-A2-restricted VACV epitope, including an epitope targeted in 2 participants. These results advance our understanding of immunity in convalescent Mpox patients.
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Mpox , Orthopoxvirus , Humanos , Antígeno HLA-A2 , Vaccinia virus , Epitopos , Proteínas ViraisRESUMO
Ultrasound-mediated cavitation shows great promise for improving targeted drug delivery across a range of clinical applications. Cavitation nuclei-sound-sensitive constructs that enhance cavitation activity at lower pressures-have become a powerful adjuvant to ultrasound-based treatments, and more recently emerged as a drug delivery vehicle in their own right. The unique combination of physical, biological, and chemical effects that occur around these structures, as well as their varied compositions and morphologies, make cavitation nuclei an attractive platform for creating delivery systems tuned to particular therapeutics. In this review, we describe the structure and function of cavitation nuclei, approaches to their functionalization and customization, various clinical applications, progress toward real-world translation, and future directions for the field.
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Sistemas de Liberação de Medicamentos , Microbolhas , UltrassonografiaRESUMO
Microbubbles utilize high-frequency oscillations under ultrasound stimulation to induce a range of therapeutic effects in cells, often through mechanical stimulation and permeabilization of cells. One of the largest challenges remaining in the field is the characterization of interactions between cells and microbubbles at therapeutically relevant frequencies. Technical limitations, such as employing sufficient frame rates and obtaining sufficient image resolution, restrict the quantification of the cell's mechanical response to oscillating microbubbles. Here, a novel methodology was developed to address many of these limitations and improve the image resolution of cell-microbubble interactions at high frame rates. A compact acoustic device was designed to house cells and microbubbles as well as a therapeutically relevant acoustic field while being compatible with a Shimadzu HPV-X camera. Cell viability tests confirmed the successful culture and proliferation of cells, and the attachment of DSPC- and cationic DSEPC-microbubbles to osteosarcoma cells was quantified. Microbubble oscillation was observed within the device at a frame rate of 5 million FPS, confirming suitable acoustic field generation and ultra high-speed image capture. High spatial resolution in these images revealed observable deformation in cells following microbubble oscillation and supported the first use of digital image correlation for strain quantification in a single cell. The novel acoustic device provided a simple, effective method for improving the spatial resolution of cell-microbubble interaction images, presenting the opportunity to develop an understanding of the mechanisms driving the therapeutic effects of oscillating microbubbles upon ultrasound exposure.
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Acústica , Microbolhas , Células CultivadasRESUMO
Outpatient parenteral antimicrobial therapy (OPAT) has become more common in clinical settings. Correspondingly, OPAT-related publications have also increased; the objective of this article was to summarize clinically meaningful OPAT-related publications in 2022. Seventy-five articles were initially identified, with 54 being scored. The top 20 OPAT articles published in 2022 were reviewed by a group of multidisciplinary OPAT clinicians. This article provides a summary of the "top 10" OPAT publications of 2022.
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OBJECTIVE: Central-line-associated bloodstream infection (CLABSI) surveillance in home infusion therapy is necessary to track efforts to reduce infections, but a standardized, validated, and feasible definition is lacking. We tested the validity of a home-infusion CLABSI surveillance definition and the feasibility and acceptability of its implementation. DESIGN: Mixed-methods study including validation of CLABSI cases and semistructured interviews with staff applying these approaches. SETTING: This study was conducted in 5 large home-infusion agencies in a CLABSI prevention collaborative across 14 states and the District of Columbia. PARTICIPANTS: Staff performing home-infusion CLABSI surveillance. METHODS: From May 2021 to May 2022, agencies implemented a home-infusion CLABSI surveillance definition, using 3 approaches to secondary bloodstream infections (BSIs): National Healthcare Safety Program (NHSN) criteria, modified NHSN criteria (only applying the 4 most common NHSN-defined secondary BSIs), and all home-infusion-onset bacteremia (HiOB). Data on all positive blood cultures were sent to an infection preventionist for validation. Surveillance staff underwent semistructured interviews focused on their perceptions of the definition 1 and 3-4 months after implementation. RESULTS: Interrater reliability scores overall ranged from κ = 0.65 for the modified NHSN criteria to κ = 0.68 for the NHSN criteria to κ = 0.72 for the HiOB criteria. For the NHSN criteria, the agency-determined rate was 0.21 per 1,000 central-line (CL) days, and the validator-determined rate was 0.20 per 1,000 CL days. Overall, implementing a standardized definition was thought to be a positive change that would be generalizable and feasible though time-consuming and labor intensive. CONCLUSIONS: The home-infusion CLABSI surveillance definition was valid and feasible to implement.
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Bacteriemia , Infecções Relacionadas a Cateter , Cateterismo Venoso Central , Infecção Hospitalar , Sepse , Humanos , Infecção Hospitalar/epidemiologia , Infecções Relacionadas a Cateter/diagnóstico , Infecções Relacionadas a Cateter/epidemiologia , Infecções Relacionadas a Cateter/prevenção & controle , Reprodutibilidade dos Testes , Sepse/epidemiologia , Bacteriemia/diagnóstico , Bacteriemia/epidemiologia , Bacteriemia/prevenção & controle , Cateterismo Venoso Central/efeitos adversosRESUMO
Objectives: Access to patient information may affect how home-infusion surveillance staff identify central-line-associated bloodstream infections (CLABSIs). We characterized information hazards in home-infusion CLABSI surveillance and identified possible strategies to mitigate information hazards. Design: Qualitative study using semistructured interviews. Setting and participants: The study included 21 clinical staff members involved in CLABSI surveillance at 5 large home-infusion agencies covering 13 states and the District of Columbia. Methods: Interviews were conducted by 1 researcher. Transcripts were coded by 2 researchers; consensus was reached by discussion. Results: Data revealed the following barriers: information overload, information underload, information scatter, information conflict, and erroneous information. Respondents identified 5 strategies to mitigate information chaos: (1) engage information technology in developing reports; (2) develop streamlined processes for acquiring and sharing data among staff; (3) enable staff access to hospital electronic health records; (4) use a single, validated, home-infusion CLABSI surveillance definition; and (5) develop relationships between home-infusion surveillance staff and inpatient healthcare workers. Conclusions: Information chaos occurs in home-infusion CLABSI surveillance and may affect the development of accurate CLABSI rates in home-infusion therapy. Implementing strategies to minimize information chaos will enhance intra- and interteam collaborations in addition to improving patient-related outcomes.
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In total, 50 healthcare facilities completed a survey in 2021 to characterize changes in infection prevention and control and antibiotic stewardship practices. Notable findings include sustained surveillance for multidrug-resistant organisms but decreased use of human resource-intensive interventions compared to previous surveys in 2013 and 2018 conducted prior to the COVID-19 pandemic.
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Gestão de Antimicrobianos , COVID-19 , Infecção Hospitalar , Humanos , Pandemias/prevenção & controle , Inquéritos e Questionários , Atenção à Saúde , Antibacterianos/uso terapêutico , Infecção Hospitalar/prevenção & controle , Infecção Hospitalar/tratamento farmacológicoRESUMO
Infection prevention and surveillance training approaches for home infusion therapy have not been well defined. We interviewed home infusion staff who perform surveillance activities about barriers to and facilitators for central line-associated bloodstream infection (CLABSI) surveillance and identified barriers to training in CLABSI surveillance. Our findings show a lack of formal surveillance training for staff. This gap can be addressed by adapting existing training resources to the home infusion setting.
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Infecções Relacionadas a Cateter , Cateterismo Venoso Central , Infecção Hospitalar , Terapia por Infusões no Domicílio , Humanos , Infecções Relacionadas a Cateter/prevenção & controle , Infecção Hospitalar/prevenção & controleRESUMO
Antibiotic resistance is increasing worldwide and can be largely attributed to excess antibiotic use. At our institution, 75% of patients were prescribed excess antibiotic days and total duration of therapy was appropriate in only 24.5% of cases per the reviewers. Choice of antibiotic was appropriate in 70.4% of cases.
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Antibacterianos , Transferência de Pacientes , Humanos , Antibacterianos/uso terapêutico , Melhoria de Qualidade , Resistência Microbiana a Medicamentos , Instalações de SaúdeRESUMO
Antibiotic overuse is common in ambulatory care settings, underscoring the importance of outpatient antibiotic stewardship to ensure safe and effective antibiotic prescription. In response to this need, the Agency for Healthcare Research and Quality (AHRQ) developed the AHRQ Safety Program for Improving Antibiotic Use in Ambulatory Care. The Safety Program successfully assisted 389 outpatient practices across the United States to establish ambulatory antibiotic stewardship. Herein, we have used lessons learned from the AHRQ Safety Program to describe a step-by-step framework to assist practices with establishing antibiotic stewardship in the outpatient setting. Steps include obtaining support from practice leadership; establishing an antibiotic stewardship team; garnering support from practice members; determining how to access antibiotic prescribing data; building communication skills around antibiotic use in the practice; implementing educational content around an infectious syndrome; monitoring antibiotic prescription data; and implementing a sustainability plan.
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Bacterial biofilms are a major and ongoing concern for public health, featuring both inherited genetic resistance traits and a conferred innate tolerance to traditional antibiotic therapies. Consequently, there is a growing need for novel methods of drug delivery, to increase the efficacy of antimicrobial agents. This research evaluated the anti-biofilm and bactericidal effects of ultrasound responsive gas-microbubbles (MBs) of either air or nitric oxide, using an in vitro Pseudomonas aeruginosa biofilm model grown in artificial wound medium. The four lipid-based MB formulations evaluated were room-air MBs (RAMBs) and nitric oxide MBs (NOMBs) with no electrical charge, as well as cationic (+) RAMBs+ and NOMBs+. Two principal treatment conditions were used: i) ultrasound stimulated MBs only, and ii) ultrasound stimulated MBs with a sub-inhibitory concentration (4 µg/mL) of the antibiotic gentamicin. The total treatment time was divided into a 60 second passive MB interaction period prior to 40 second ultrasound exposure; each MB formulation was tested in triplicate. Ultrasound stimulated RAMBs and NOMBs without antibiotic achieved reductions in biofilm biomass of 93.3% and 94.0%, respectively. Their bactericidal efficacy however was limited, with a reduction in culturable cells of 26.9% and 65.3%, respectively. NOMBs with sub-inhibitory antibiotic produced the most significant reduction in biofilm biomass, corresponding to a 99.9% (SD ± 5.21%); and a 99.9% (SD ± 0.07%) (3-log) reduction in culturable bacterial cells. Cationic MBs were initially manufactured to promote binding of MBs to negatively charged biofilms, but these formulations also demonstrated intrinsic bactericidal properties. In the absence of antibiotic, the bactericidal efficacy of RAMB+ and NOMB+ was greater that of uncharged counterparts, reducing culturable cells by 84.7% and 86.1% respectively; increasing to 99.8% when combined with antibiotic. This study thus demonstrates the anti-biofilm and bactericidal utility of ultrasound stimulated MBs, and specifically is the first to demonstrate the efficacy of a NOMB for the dispersal and potentiation of antibiotics against bacterial biofilms in vitro. Importantly the biofilm system and complex growth-medium were selected to recapitulate key morphological features of in vivo biofilms. The results us offer new insight for the development of new clinical treatments, for example, in chronic wounds.
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Óxido Nítrico , Pseudomonas aeruginosa , Antibacterianos/farmacologia , Biofilmes , Cátions/farmacologia , Microbolhas , Óxido Nítrico/metabolismo , Óxido Nítrico/farmacologiaRESUMO
As outpatient parenteral antimicrobial therapy (OPAT) becomes more common, it may be difficult to stay current with recent related publications. A group of multidisciplinary OPAT clinicians reviewed and ranked all OPAT publications published in 2021. This article provides a high-level summary of the OPAT manuscripts that were voted the "top 10" publications of 2021.