Orthopoxvirus-Specific T-Cell Responses in Convalescent Mpox Patients.

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.

Characterizing Patients Presenting on Hospital Admission With Central Line-Associated Bloodstream Infections: A Multicenter Study.

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.

Sonosensitive Cavitation Nuclei-A Customisable Platform Technology for Enhanced Therapeutic Delivery.

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.

The Role of Ultrasound in Modulating Interstitial Fluid Pressure in Solid Tumors for Improved Drug Delivery.

The unique microenvironment of solid tumors, including desmoplasia within the extracellular matrix, enhanced vascular permeability, and poor lymphatic drainage, leads to an elevated interstitial fluid pressure which is a major barrier to drug delivery. Reducing tumor interstitial fluid pressure is one proposed method of increasing drug delivery to the tumor. The goal of this topical review is to describe recent work using focused ultrasound with or without microbubbles to modulate tumor interstitial fluid pressure, through either thermal or mechanical effects on the extracellular matrix and the vasculature. Furthermore, we provide a review on techniques in which ultrasound imaging may be used to diagnose elevated interstitial fluid pressure within solid tumors. Ultrasound-based techniques show high promise in diagnosing and treating elevated interstitial pressure to enhance drug delivery.

Antibiotic stewardship in direct-to-consumer telemedicine: translating interventions into the virtual realm.

Direct-to-consumer (DTC) telemedicine is an increasingly popular modality for delivery of medical care via a virtual platform. As most DTC telemedicine visits focus on infection-related complaints, there is growing concern about the magnitude of antibiotic use associated with this setting. However, there is limited scholarship regarding adapting and implementing antibiotic stewardship principles in this setting as most efforts have been focused on hospitals with more recent work in long-term care facilities and primary care settings. We discuss utilizing the core elements for outpatient antibiotic stewardship as a framework for DTC antibiotic stewardship efforts moving forward.

The inconvincible patient: how clinicians perceive demand for antibiotics in the outpatient setting.

BACKGROUND: Perceived patient demand for antibiotics drives unnecessary antibiotic prescribing in outpatient settings, but little is known about how clinicians experience this demand or how this perceived demand shapes their decision-making. OBJECTIVE: To identify how clinicians perceive patient demand for antibiotics and the way these perceptions stimulate unnecessary prescribing. METHODS: Qualitative study using semi-structured interviews with clinicians in outpatient settings who prescribe antibiotics. Interviews were analyzed using conventional and directed content analysis. RESULTS: Interviews were conducted with 25 clinicians from nine practices across three states. Patient demand was the most common reason respondents provided for why they prescribed non-indicated antibiotics. Three related factors motivated clinically unnecessary antibiotic use in the face of perceived patient demand: (i) clinicians want their patients to regard clinical visits as valuable and believe that an antibiotic prescription demonstrates value; (ii) clinicians want to avoid negative repercussions of denying antibiotics, including reduced income, damage to their reputation, emotional exhaustion, and degraded relationships with patients; (iii) clinicians believed that certain patients are impossible to satisfy without an antibiotic prescription and felt that efforts to refuse antibiotics to such patients wastes time and invites the aforementioned negative repercussions. Clinicians in urgent care settings were especially likely to describe being motivated by these factors. CONCLUSION: Interventions to improve antibiotic use in the outpatient setting must address clinicians' concerns about providing value for their patients, fear of negative repercussions from denying antibiotics, and the approach to inconvincible patients.

2018 Infectious Diseases Society of America Clinical Practice Guideline for the Management of Outpatient Parenteral Antimicrobial Therapy.

A panel of experts was convened by the Infectious Diseases Society of America (IDSA) to update the 2004 clinical practice guideline on outpatient parenteral antimicrobial therapy (OPAT) [1]. This guideline is intended to provide insight for healthcare professionals who prescribe and oversee the provision of OPAT. It considers various patient features, infusion catheter issues, monitoring questions, and antimicrobial stewardship concerns. It does not offer recommendations on the treatment of specific infections. The reader is referred to disease- or organism-specific guidelines for such support.

2018 Infectious Diseases Society of America Clinical Practice Guideline for the Management of Outpatient Parenteral Antimicrobial Therapy.

A panel of experts was convened by the Infectious Diseases Society of America to update the 2004 clinical practice guideline on outpatient parenteral antimicrobial therapy (OPAT) [1]. This guideline is intended to provide insight for healthcare professionals who prescribe and oversee the provision of OPAT. It considers various patient features, infusion catheter issues, monitoring questions, and antimicrobial stewardship concerns. It does not offer recommendations on the treatment of specific infections. The reader is referred to disease- or organism-specific guidelines for such support.

Engineered 3D Microvascular Networks for the Study of Ultrasound-Microbubble-Mediated Drug Delivery.

Localized and targeted drug delivery can be achieved by the combined action of ultrasound and microbubbles on the tumor microenvironment, likely through sonoporation and other therapeutic mechanisms that are not well understood. Here, we present a perfusable in vitro model with a realistic 3D geometry to study the interactions between microbubbles and the vascular endothelium in the presence of ultrasound. Specifically, a three-dimensional, endothelial-cell-seeded in vitro microvascular model was perfused with cell culture medium and microbubbles while being sonicated by a single-element 1 MHz focused transducer. This setup mimics the in vivo scenario in which ultrasound induces a therapeutic effect in the tumor vasculature in the presence of flow. Fluorescence and bright-field microscopy were employed to assess the microbubble-vessel interactions and the extent of drug delivery and cell death both in real time during treatment as well as after treatment. Propidium iodide was used as the model drug while calcein AM was used to evaluate cell viability. There were two acoustic parameter sets chosen for this work: (1) acoustic pressure: 1.4 MPa, pulse length: 500 cycles, duty cycle: 5% and (2) acoustic pressure: 0.4 MPa, pulse length: 1000 cycles, duty cycle: 20%. Enhanced drug delivery and cell death were observed in both cases while the higher pressure setting had a more pronounced effect. By introducing physiological flow to the in vitro microvascular model and examining the PECAM-1 expression of the endothelial cells within it, we demonstrated that our model is a good mimic of the in vivo vasculature and is therefore a viable platform to provide mechanistic insights into ultrasound-mediated drug delivery.

Rates of and Risk Factors for Adverse Drug Events in Outpatient Parenteral Antimicrobial Therapy.

Background: To better monitor patients on outpatient parenteral antimicrobial therapy (OPAT), we need an improved understanding of risk factors for and timing of OPAT-associated adverse drug events (ADEs). Methods: We analyzed a prospective cohort of patients on OPAT discharged from 2 academic medical centers. Patients underwent chart abstraction and a telephone survey. Multivariable analyses estimated adjusted incident rate ratios (aIRR) between clinical and demographic risk factors and clinician-determined clinically significant ADEs. Descriptive data were used to present patient-reported ADEs. Results: Of 339 patients enrolled in the study, 18.0% experienced an ADE (N = 65), of which 49 were significant (14.5%, 2.24/1000 home-OPAT days). Patients with longer courses of therapy had lower rates of ADEs compared with patients treated for 0-13 days (14-27 days: aIRR, 0.44; 95% confidence interval [CI], 0.20-0.99; at least 28 days: aIRR, 0.11; 95% CI, 0.056-0.21). Risk factors for ADEs included female gender and receipt of daptomycin or vancomycin, while treatment for uncomplicated bacteremia and empiric treatment were associated with lower rates of ADEs. Conclusions: OPAT-related ADEs were common and often occurred within 2 weeks of hospital discharge. Patients on OPAT should be monitored more closely for ADEs, including clinical assessment and laboratory monitoring, especially within the first weeks after hospital discharge and particularly among women and patients who receive vancomycin.

Locking Compression Plate Fixation of Equine Tarsal Subluxations.

OBJECTIVE: To report the clinical findings and outcome of locking compression plate (LCP) fixation of tarsal subluxations in horses. STUDY DESIGN: Retrospective case series. ANIMALS: Horses (n = 3) and ponies (2). METHODS: All horses and ponies diagnosed with tarsal subluxations and treated with LCP fixation at our institution between 2011 and 2013 were included. Data were collected from the medical records, including all radiographic and computed tomographic (CT) studies and reviewed. Long-term (>1 year) followup examination, including owner interview, and clinical and radiographic examinations were performed for all cases. RESULTS: Subluxations of the tarsometatarsal (n = 3) and proximal intertarsal (2) joints were diagnosed. CT examinations revealed complex joint injuries, including a combination of avulsion fragments and compression injuries at the opposite side of the joint from the subluxation. The LCP was applied to the plantarolateral or medial side of the limb. All horses survived and were discharged from the hospital. Short-term complications included mild laminitis (n = 1) and peroneus tertius rupture (2). At long-term followup, both ponies were sound and used as intended, whereas all horses showed mild to moderate lameness at the trot and were used for pleasure riding only. Radiographic signs of osteoarthritis developed in the joint affected by subluxation in all cases and in adjacent small tarsal joints in 2 horses and 1 pony. CONCLUSION: LCP fixation of tarsal subluxations resulted in stable fixation and allowed adequate healing. Subluxation of the small tarsal joints represents a complex injury and osteoarthritis commonly develops in the affected and adjacent joints.

Developing a model for understanding patient collection of observations of daily living: A qualitative meta-synthesis of the Project HealthDesign Program.

We conducted a meta-synthesis of five different studies that developed, tested, and implemented new technologies for the purpose of collecting Observations of Daily Living (ODL). From this synthesis, we developed a model to explain user motivation as it relates to ODL collection. We describe this model that includes six factors that motivate patients' collection of ODL data: usability, illness experience, relevance of ODLs, information technology infrastructure, degree of burden, and emotional activation. We show how these factors can act as barriers or facilitators to the collection of ODL data and how interacting with care professionals and sharing ODL data may also influence ODL collection, health-related awareness, and behavior change. The model we developed and used to explain ODL collection can be helpful to researchers and designers who study and develop new, personal health technologies to empower people to improve their health.

Outcomes of HIV-infected patients receiving care at multiple clinics.

Receiving care at multiple clinics may compromise the therapeutic patient-provider alliance and adversely affect the treatment of people living with HIV. We evaluated 12,759 HIV-infected adults in Philadelphia, PA between 2008 and 2010 to determine the effects of using multiple clinics for primary HIV care. Using generalized estimating equations with logistic regression, we examined the relationship between receiving care at multiple clinics (≥ 1 visit to two or more clinics during a calendar year) and two outcomes: (1) use of ART and (2) HIV viral load ≤ 200 copies/mL for patients on ART. Overall, 986 patients (8 %) received care at multiple clinics. The likelihood of attending multiple clinics was greater for younger patients, women, blacks, persons with public insurance, and for individuals in their first year of care. Adjusting for sociodemographic factors, patients receiving care at multiple clinics were less likely to use ART (AOR = 0.62, 95 % CI 0.55-0.71) and achieve HIV viral suppression (AOR = 0.78, 95 % CI 0.66-0.94) than individuals using one clinic. Qualitative data are needed to understand the reasons for visiting multiple clinics.

Colorectal cancer incidence and screening in US Medicaid patients with and without HIV infection.

Non-AIDS defining malignancies, particularly colorectal cancer (CRC), may be more prevalent among persons living with HIV (PLWH). Further, PLWH may be less likely to receive CRC screening (CRCS). We studied the epidemiology of CRC and CRCS patterns in PLWH and HIV-uninfected persons in a large US Medicaid population. We performed a matched cohort study examining CRC incidence in 2006 and CRCS between 1999 and 2007. Study participants were continuously enrolled in the Medicaid programs of California, Florida, New York, Ohio, and Pennsylvania. All PLWH enrollees were matched to five randomly sampled HIV-uninfected enrollees on 5-year age group, gender, and state. Adjusted odds ratios (AORs) for incident CRC (adjusted for comorbidity index) and the presence of CRCS (adjusted for comorbidity index and years in the data-set) among PLWH compared to HIV-uninfected enrollees were calculated. PLWH were not more likely to be diagnosed with CRC after adjusting for comorbidity index (unadjusted OR: 1.73, 95% confidence interval [CI]: 1.37-2.19; AOR 1.29; 95% CI: 0.98-1.70). While CRCS rates were low overall, PLWH were more likely to have received CRCS in unadjusted analyses (35.8% vs. 33.7%; OR 1.10, 95% CI: 1.07-1.13). This relationship was reversed after adjusting for comorbidity index and years in the data-set (AOR: 0.80, 95% CI: 0.77-0.83). Limitations of the study include a focus on the Medicaid population, an inability to detect fecal occult blood tests (FOBT), and having half of patients between 50 and 55 years of age. In conclusion, PLWH were not more likely to be diagnosed with CRC, but in adjusted analyses, were less likely to have received CRCS. As we showed a low rate of CRCS overall in this Medicaid population, researchers, clinicians, and policy-makers should improve access to and uptake of CRCS among all Medicaid patients, and particularly among PLWH.

Characterizing changes to older adults' care transition patterns from hospital to home care in the initial year of COVID-19.

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.

Cost of SARS-CoV-2 self-test distribution programmes by different modalities: a micro-costing study in five countries (Brazil, Georgia, Malaysia, Ethiopia and the Philippines).

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.