Nebulized platelet-derived extracellular vesicles attenuate chronic cigarette smoke-induced murine emphysema.

Chronic obstructive pulmonary disease (COPD) is a prevalent lung disease usually resulting from cigarette smoking (CS). Cigarette smoking induces oxidative stress, which causes inflammation and alveolar epithelial cell apoptosis and represents a compelling therapeutic target for COPD. Purified human platelet-derived exosome product (PEP) is endowed with antioxidant enzymes and immunomodulatory molecules that mediate tissue repair. In this study, a murine model of CS-induced emphysema was used to determine whether nebulized PEP can influence the development of CS-induced emphysema through the mitigation of oxidative stress and inflammation in the lung. Nebulization of PEP effectively delivered the PEP vesicles into the alveolar region, with evidence of their uptake by type I and type II alveolar epithelial cells and macrophages. Lung function testing and morphometric assessment showed a significant attenuation of CS-induced emphysema in mice treated with nebulized PEP thrice weekly for 4 weeks. Whole lung immuno-oncology RNA sequencing analysis revealed that PEP suppressed several CS-induced cell injuries and inflammatory pathways. Validation of inflammatory cytokines and apoptotic protein expression on the lung tissue revealed that mice treated with PEP had significantly lower levels of S100A8/A9 expressing macrophages, higher levels of CD4+/FOXP3+ Treg cells, and reduced NF-κB activation, inflammatory cytokine production, and apoptotic proteins expression. Further validation using in vitro cell culture showed that pretreatment of alveolar epithelial cells with PEP significantly attenuated CS extract-induced apoptotic cell death. These data show that nebulization of exosomes like PEP can effectively deliver exosome cargo into the lung, mitigate CS-induced emphysema in mice, and suppress oxidative lung injury, inflammation, and apoptotic alveolar epithelial cell death.

DNA hypomethylation ameliorates erosive inflammatory arthritis by modulating interferon regulatory factor-8.

Epigenetic regulation plays a crucial role in the pathogenesis of autoimmune diseases such as inflammatory arthritis. DNA hypomethylating agents, such as decitabine (DAC), have been shown to dampen inflammation and restore immune homeostasis. In the present study, we demonstrate that DAC elicits potent anti-inflammatory effects and attenuates disease symptoms in several animal models of arthritis. Transcriptomic and epigenomic profiling show that DAC-mediated hypomethylation regulates a wide range of cell types in arthritis, altering the differentiation trajectories of anti-inflammatory macrophage populations, regulatory T cells, and tissue-protective synovial fibroblasts (SFs). Mechanistically, DAC-mediated demethylation of intragenic 5'-Cytosine phosphate Guanine-3' (CpG) islands of the transcription factor Irf8 (interferon regulatory factor 8) induced its re-expression and promoted its repressor activity. As a result, DAC restored joint homeostasis by resetting the transcriptomic signature of negative regulators of inflammation in synovial macrophages (MerTK, Trem2, and Cx3cr1), TREGs (Foxp3), and SFs (Pdpn and Fapα). In conclusion, we found that Irf8 is necessary for the inhibitory effect of DAC in murine arthritis and that direct expression of Irf8 is sufficient to significantly mitigate arthritis.

Evaluating the pediatric mental health care continuum at an American health system.

Objective: To describe trends in the pediatric mental health care continuum and identify potential gaps in care coordination. Methods: We used electronic medical record data from October 2016 to September 2019 to characterize the prevalence of mental health issues in the pediatric population at a large American health system. This was a single institution case study. From the electronic medical record data, primary mental health discharge and readmission diagnoses were identified using International Classification of Diseases (ICD-9-CM, ICD-10-CM) codes. The electronic medical record was queried for mental health-specific diagnoses as defined by International Classification of Diseases classification, analysis of which was facilitated by the fact that only 176 mental health codes were billed for. Additionally, prevalence of care navigation encounters was assessed through electronic medical record query, as care navigation encounters are specifically coded. These encounter data was then segmented by care delivery setting. Results: Major depressive disorder and other mood disorders comprised 49.6% and 89.4% of diagnoses in the emergency department and inpatient settings respectively compared to 9.0% of ambulatory care diagnoses and were among top reasons for readmission. Additionally, only 1% of all ambulatory care encounters had a care navigation component, whereas 86% of care navigation encounters were for mental health-associated reasons. Conclusions: Major depressive disorder and other mood disorders were more common diagnoses in the emergency department and inpatient settings, which could signal gaps in care coordination. Bridging potential gaps in care coordination could reduce emergency department and inpatient utilization through increasing ambulatory care navigation resources, improving training, and restructuring financial incentives to facilitate ambulatory care diagnosis and management of major depressive disorder and mood disorders. Furthermore, health systems can use our descriptive analytic approach to serve as a reasonable measure of the current state of pediatric mental health care in their own patient population.

Artificial Intelligence-Derived Electrocardiogram Assessment of Cardiac Age and Molecular Markers of Senescence in Heart Failure.

OBJECTIVE: To ascertain whether heart failure (HF) itself is a senescent phenomenon independent of age, and how this is reflected at a molecular level in the circulating progenitor cell niche, and at a substrate level using a novel electrocardiogram (ECG)-based artificial intelligence platform. PATIENTS AND METHODS: Between October 14, 2016, and October 29, 2020, CD34+ progenitor cells were analyzed by flow cytometry and isolated by magnetic-activated cell sorting from patients of similar age with New York Heart Association functional classes IV (n = 17) and I-II (n = 10) heart failure with reduced ejection fraction and healthy controls (n = 10). CD34+ cellular senescence was quantitated by human telomerase reverse transcriptase expression and telomerase expression by quantitative polymerase chain reaction, and senescence-associated secretory phenotype (SASP) protein expression assayed in plasma. An ECG-based artificial intelligence (AI) algorithm was used to determine cardiac age and difference from chronological age (AI ECG age gap). RESULTS: CD34+ counts and telomerase expression were significantly reduced and AI ECG age gap and SASP expression increased in all HF groups compared with healthy controls. Expression of SASP protein was closely associated with telomerase activity and severity of HF phenotype and inflammation. Telomerase activity was more closely associated with CD34+ cell counts and AI ECG age gap. CONCLUSION: We conclude from this pilot study that HF may promote a senescent phenotype independent of chronological age. We show for the first time that the AI ECG in HF shows a phenotype of cardiac aging beyond chronological age, and appears to be associated with cellular and molecular evidence of senescence.

Use of heparin to rescue immunosuppressive monocyte reprogramming by glioblastoma-derived extracellular vesicles.

OBJECTIVE: The profound immunosuppression found in glioblastoma (GBM) patients is a critical barrier to effective immunotherapy. Multiple mechanisms of tumor-mediated immune suppression exist, and the induction of immunosuppressive monocytes such as myeloid-derived suppressor cells (MDSCs) is increasingly appreciated as a key part of this pathology. GBM-derived extracellular vesicles (EVs) can induce the formation of MDSCs. The authors sought to identify the molecular consequences of these interactions in myeloid cells in order to identify potential targets that could pharmacologically disrupt GBM EV-monocyte interaction as a means to ameliorate tumor-mediated immune suppression. Heparin-sulfate proteoglycans (HSPGs) are a general mechanism by which EVs come into association with their target cells, and soluble heparin has been shown to interfere with EV-HSPG interactions. The authors sought to assess the efficacy of heparin treatment for mitigating the effects of GBM EVs on the formation of MDSCs. METHODS: GBM EVs were collected from patient-derived cell line cultures via staged ultracentrifugation and cocultured with monocytes collected from apheresis cones from healthy blood donors. RNA was isolated from EV-conditioned and unconditioned monocytes after 72 hours of coculture, and RNA-sequencing analysis performed. For the heparin treatment studies, soluble heparin was added at the time of EV-monocyte coculture and flow cytometry analysis was performed 72 hours later. After the initial EV-monocyte coculture period, donor-matched T-cell coculture studies were performed by adding fluorescently labeled and stimulated T cells for 5 days of coculture. RESULTS: Transcriptomic analysis of GBM EV-treated monocytes demonstrated downregulation of several important immunological and metabolic pathways, with upregulation of the pathways associated with synthesis of cholesterol and HSPG. Heparin treatment inhibited association between GBM EVs and monocytes in a dose-dependent fashion, which resulted in a concomitant reduction in MDSC formation (p < 0.01). The authors further demonstrated that reduced MDSC formation resulted in a partial rescue of immune suppression, as measured by effects on activated donor-matched T cells (p < 0.05). CONCLUSIONS: The authors demonstrated that GBM EVs induce broad but reproducible reprogramming in monocytes, with enrichment of pathways that may portend an immunosuppressive phenotype. The authors further demonstrated that GBM EV-monocyte interactions are potentially druggable targets for overcoming tumor-mediated immune suppression, with heparin inhibition of EV-monocyte interactions demonstrating proof of principle.

How health systems facilitate patient-centered care and care coordination: a case series analysis to identify best practices.

Large- and small-scale transformation of healthcare delivery toward improved patient experience through promotion of patient-centered and coordinated care continues to be at the forefront of health system efforts in the United States. As part of a Quality Improvement (QI) project at a large, midwestern health system, a case series of high-performing organizations was explored with the goal of identifying best practices in patient-centered care and/or care coordination (PCC/CC). Identification of best practices was done through rapid realist review of peer-reviewed literature supporting three PCC/CC interventions per case. Mechanisms responsible for successful intervention outcomes and associated institutional-level facilitators were evaluated, and cross-case analysis produced high-level focus items for health system leadership, including (1) institutional values surrounding PCC/CC, (2) optimization of IT infrastructure to enhance performance and communication, (3) pay structures and employment models that enhance accountability, and (4) organizing bodies to support implementation efforts. Health systems may use this review to gain insight into how institutional-level factors may facilitate small-scale PCC/CC behaviors, or to conduct similar assessments in their own QI projects. Based on our analysis, we recommend health systems seeking to improve PCC/CC at any level or scale to evaluate how IT infrastructure affects provider-provider and provider-patient communication, and the extent to which institutional prioritization of PCC/CC is manifest and held accountable in performance feedback, incentivization, and values shared among departments and settings. Ideally, this evaluation work should be performed and/or supported by cross-department organizing bodies specifically devoted to PCC/CC implementation work.

Platelet-derived exosomes induce cell proliferation and wound healing in human endometrial cells.

Aim: To investigate the regenerative effects of a platelet-derived purified exosome product (PEP) on human endometrial cells. Materials & methods: Endometrial adenocarcinoma cells (HEC-1A), endometrial stromal cells (T HESC) and menstrual blood-derived stem cells (MenSC) were assessed for exosome absorption and subsequent changes in cell proliferation and wound healing properties over 48 h. Results: Cell proliferation increased in PEP treated T HESC (p < 0.0001) and MenSC (p < 0.001) after 6 h and in HEC-1A (p < 0.01) after 12 h. PEP improved wound healing after 6 h in HEC-1A (p < 0.01) and MenSC (p < 0.0001) and in T HESC between 24 and 36 h (p < 0.05). Conclusion: PEP was absorbed by three different endometrial cell types. PEP treatment increased cell proliferation and wound healing capacity.

The uterus has a remarkable ability to heal itself. Every month the inside lining of the uterus grows in preparation for pregnancy and sheds if no pregnancy occurs. Unfortunately, this cycle of growth, shedding and repair can be injured and lead to menstrual changes, pain or even infertility. In this study, we looked how special cell messengers ­ called exosomes ­ could help uterine cells. Exosomes are special messengers that contain substances to help the body heal and regenerate injured cells and tissues. We obtained exosomes created from human transfusion-grade platelets. We studied the exosomes' effects in three different cell types that all are important inside the uterine lining. Specifically, we studied the ability of the exosomes to help cells proliferate and migrate into a wound. In this study, exosomes were recognized by the human endometrial cells and were absorbed. Once they were inside the cells, they increased cell proliferation as well as the ability of the cells to heal a scratch wound. Furthermore, the more exosomes we presented to the cells, the more the cells were able to proliferate and move into a wound for healing. These findings lay the groundwork for future studies in animal models of uterine injury.

Exosome biopotentiated hydrogel restores damaged skeletal muscle in a porcine model of stress urinary incontinence.

Urinary incontinence afflicts up to 40% of adult women in the United States. Stress urinary incontinence (SUI) accounts for approximately one-third of these cases, precipitating ~200,000 surgical procedures annually. Continence is maintained through the interplay of sub-urethral support and urethral sphincter coaptation, particularly during activities that increase intra-abdominal pressure. Currently, surgical correction of SUI focuses on the re-establishment of sub-urethral support. However, mesh-based repairs are associated with foreign body reactions and poor localized tissue healing, which leads to mesh exposure, prompting the pursuit of technologies that restore external urethral sphincter function and limit surgical risk. The present work utilizes a human platelet-derived CD41a and CD9 expressing extracellular vesicle product (PEP) enriched for NF-κB and PD-L1 and derived to ensure the preservation of lipid bilayer for enhanced stability and compatibility with hydrogel-based sustained delivery approaches. In vitro, the application of PEP to skeletal muscle satellite cells in vitro drove proliferation and differentiation in an NF-κB-dependent fashion, with full inhibition of impact on exposure to resveratrol. PEP biopotentiation of collagen-1 and fibrin glue hydrogel achieved sustained exosome release at 37 °C, creating an ultrastructural "bead on a string" pattern on scanning electron microscopy. Initial testing in a rodent model of latissimus dorsi injury documented activation of skeletal muscle proliferation of healing. In a porcine model of stress urinary incontinence, delivery of PEP-biopotentiated collagen-1 induced functional restoration of the external urethral sphincter. The histological evaluation found that sustained PEP release was associated with new skeletal muscle formation and polarization of local macrophages towards the regenerative M2 phenotype. The results provided herein serve as the first description of PEP-based biopotentiation of hydrogels implemented to restore skeletal muscle function and may serve as a promising approach for the nonsurgical management of SUI.

Cost-effectiveness of an Emergency Department-Based Intensive Care Unit.

Importance: Value in health care is quality per unit cost (V = Q/C), and an emergency department-based intensive care unit (ED-ICU) model has been associated with improved quality. To assess the value of this care delivery model, it is essential to determine the incremental direct cost of care. Objective: To determine the association of an ED-ICU with inflation-adjusted change in mean direct cost of care, net revenue, and direct margin per ED patient encounter. Design, Setting, and Participants: This retrospective economic analysis evaluated the cost of care delivery to patients in the ED before and after deployment of the Joyce and Don Massey Family Foundation Emergency Critical Care Center, an ED-ICU, on February 16, 2015, at a large academic medical center in the US with approximately 75 000 adult ED visits per year. The pre-ED-ICU cohort was defined as all documented ED visits by patients 18 years or older with a complete financial record from September 8, 2012, through June 30, 2014 (660 days); the post-ED-ICU cohort, all visits from July 1, 2015, through April 21, 2017 (660 days). Fiscal year 2015 was excluded from analysis to phase in the new care model. Statistical analysis was performed March 1 through December 30, 2021. Exposures: Implementation of an ED-ICU. Main Outcomes and Measures: Inflation-adjusted direct cost of care, net revenue, and direct margin per patient encounter in the ED. Results: A total of 234 884 ED visits during the study period were analyzed, with 115 052 patients (54.7% women) in the pre-ED-ICU cohort and 119 832 patients (54.5% women) in the post-ED-ICU cohort. The post-ED-ICU cohort was older (mean [SD] age, 49.1 [19.9] vs 47.8 [19.6] years; P < .001), required more intensive respiratory support (2.2% vs 1.1%; P < .001) and more vasopressor use (0.5% vs 0.2%; P < .001), and had a higher overall case mix index (mean [SD], 1.7 [2.0] vs 1.5 [1.7]; P < .001). Implementation of the ED-ICU was associated with similar inflation-adjusted total direct cost per ED encounter (pre-ED-ICU, mean [SD], $4875 [$15 175]; post-ED-ICU, $4877 [$17 400]; P = .98). Inflation-adjusted net revenue per encounter increased by 7.0% (95% CI, 3.4%-10.6%; P < .001), and inflation-adjusted direct margin per encounter increased by 46.6% (95% CI, 32.1%-61.2%; P < .001). Conclusions and Relevance: Implementation of an ED-ICU was associated with no significant change in inflation-adjusted total direct cost per ED encounter. Holding delivery costs constant while improving quality demonstrates improved value via the ED-ICU model of care.

Phase I trial of adjuvant mature autologous dendritic cell/allogeneic tumor lysate vaccines in combination with temozolomide in newly diagnosed glioblastoma.

Background: Glioblastoma (GBM) has poor prognosis despite aggressive treatment. Dendritic cell (DC) vaccines are promising, but widespread clinical use has not been achieved, possibly reflecting manufacturing issues of antigen choice and DC potency. We previously optimized vaccine manufacture utilizing allogeneic human GBM tumor cell lysate and potent, mature autologous DCs. Here, we report a phase I study using this optimized DC vaccine in combination with standard therapy. Methods: Following surgical resection and radiation with concurrent temozolomide (TMZ), newly diagnosed adult GBM patients received intradermal DC vaccines plus TMZ. Primary endpoints were safety and feasibility. Immune and treatment responses were recorded. Results: Twenty-one patients were enrolled in this study. One progressed between leukapheresis and vaccine manufacture. Twenty patients received treatment per protocol. Vaccine doses (≥15) were generated following a single leukapheresis for each patient. No dose-limiting vaccine toxicities were encountered. One patient had symptomatic, histologically proven pseudoprogression. Median progression-free survival was 9.7 months. Median overall survival was 19 months. Overall survival was 25% at 2 years and 10% at 4 years. One patient remains progression-free 5 years after enrollment. Specific CD8 T-cell responses for the tumor-associated antigen gp100 were seen post-vaccination. Patients entered the trial with a leukocyte deficit compared to healthy donors which partly normalized over the course of therapy. Conclusions: This vaccine platform is safe and highly feasible in combination with standard therapy for newly diagnosed patients. Imaging, histological, survival, and immunological data suggest a positive biological response to therapy that warrants further investigation.

Intranasal Fentanyl for On-the-Hill Analgesia by Ski Patrol.

INTRODUCTION: Intranasal fentanyl offers a means for safe and effective pain management in austere environments. Prehospital analgesia traditionally involves intravenous or intramuscular medication. However, for wilderness rescuers, these methods are often impractical. METHODS: We conducted a retrospective review of health records to evaluate the safety and efficacy of intranasal fentanyl administered by EMT-Basic certified ski patrollers. Our primary aim was to measure the reduction in initial pain scores to subsequent measurements at 5, 10, and 15 min using the pain numeric rating scale (0-10). Clinically significant reduction in severe pain has been established as ≥1.8 points. We used paired t-tests and multilevel modeling to measure statistical significance and potential interactions and reviewed patient charts for adverse events, including respiratory depression or the use of naloxone. RESULTS: We compiled the results from the winter seasons for 2007 through 2012 and 2016 through 2020. A total of 247 patients were included. The initial pain score was 8.6±1.5 (mean±SD). The decrease in pain scores from 0 to 5, 10, and 15 min, respectively, was -1.8, -2.4, and -2.9 (P<0.0001), which demonstrated a clinically and statistically significant decrease in pain scores. There were no adverse events. CONCLUSIONS: Traditional standard of care analgesics are invasive, elongate scene times, and increase the risk of environmental exposure and provider needlestick. Intranasal fentanyl offers a safe, noninvasive, and rapid analgesia that is well-suited for austere winter environments, such as those encountered at ski resorts. This study demonstrates the safety and efficacy of the administration of intranasal fentanyl by EMT-Basic certified providers.

STAT3 is a biologically relevant therapeutic target in H3K27M-mutant diffuse midline glioma.

BACKGROUND: H3K27M-mutant diffuse midline glioma (DMG) is a lethal brain tumor that usually occurs in children. Despite advances in our understanding of its underlying biology, efficacious therapies are severely lacking. METHODS: We screened a library of drugs either FDA-approved or in clinical trial using a library of patient-derived H3K27M-mutant DMG cell lines with cell viability as the outcome. Results were validated for clinical relevance and mechanistic importance using patient specimens from biopsy and autopsy, patient-derived cell lines, inhibition by gene knockdown and small molecule inhibitors, and patient-derived xenografts. RESULTS: Kinase inhibitors were highly toxic to H3K27M-mutant DMG cells. Within this class, STAT3 inhibitors demonstrated robust cytotoxic activity in vitro. Mechanistic analyses revealed one form of activated STAT3, phospho-tyrosine- 705 STAT3 (pSTAT3), was selectively upregulated in H3K27M-mutant cell lines and clinical specimens. STAT3 inhibition by CRISPR/Cas9 knockout, shRNA or small molecule inhibition reduced cell viability in vitro, and partially restored expression of the polycomb repressive mark H3K27me3, which is classically lost in H3K27M-mutant DMG. Putative STAT3-regulated genes were enriched in an H3K27M-knockout DMG cell line, indicating relative gain of STAT3 signaling in K27M-mutant cells. Treatment of patient-derived intracranial xenografts with WP1066, a STAT3 pathway inhibitor currently in clinical use for pediatric brain tumors, resulted in stasis of tumor growth, and increased overall survival. Finally, pSTAT3(Y705) was detected in circulating plasma extracellular vesicles of patients with H3K27M-mutant DMG. CONCLUSIONS: STAT3 is a biologically relevant therapeutic target in H3K27M-mutant DMG. STAT3 inhibition should be considered in future clinical trials.

Prehospital Supraglottic Airways: An NAEMSP Position Statement and Resource Document.

Supraglottic airway (SGA) devices provide effective conduits for oxygenation and ventilation and may offer protection from gastric aspiration. SGA devices are widely used by EMS clinicians as both rescue and primary airway management devices. While in common use for more than four decades, major developments in SGA education, science, and technology have influenced clinical strategies of SGA insertion and use in prehospital airway management for patients of all ages. NAEMSP recommends:SGAs have utility as a primary or secondary EMS airway intervention. EMS agencies should select SGA strategies that best suit available resources and local clinician skillset, as well as the nature of their clinical practice setting.EMS agencies that perform endotracheal intubation must also equip their clinicians with SGA devices and ensure adequate training and competence.In select situations, drug-assisted airway management may be used by properly credentialed EMS clinicians to facilitate SGA insertion.Confirmation of initial and continuous SGA placement using waveform capnography is strongly encouraged as a best practice.When it is functioning properly, EMS clinicians should refrain from converting an SGA to an endotracheal tube. The decision to convert an SGA to an endotracheal tube must consider the patient's condition, the effectiveness of SGA ventilations, and the clinical context and course of initial SGA insertionSGA training, competency, and clinical use must be continuously evaluated by EMS agencies using focused quality management programs.

Pediatric brain tumor cell lines exhibit miRNA-depleted, Y RNA-enriched extracellular vesicles.

BACKGROUND: Medulloblastoma (MB) and diffuse infiltrative pontine glioma (DIPG) are malignant pediatric tumors. Extracellular vesicles (EVs) and their bioactive cargoes have been implicated in tumorigenesis. Most studies have focused on adult tumors, therefore the role of EVs and the noncoding RNA (ncRNA) landscape in pediatric brain tumors is not fully characterized. The overall aim of this pilot study was to isolate EVs from MB and DIPG patient-derived cell lines and to explore the small ncRNA transcriptome. METHODS: EVs from 3 DIPG and 4 MB patient-derived cell lines were analyzed. High-throughput next generation sequencing interrogated the short non-coding RNA (ncRNA) transcriptome. Known and novel miRNAs were quantified. Differential expression analysis, in silico target prediction, and functional gene enrichment were performed. RESULTS: EV secretomes from MB and DIPG patient-derived cell lines demonstrated discrete ncRNA biotypes. Notably, miRNAs were depleted and Y RNAs were enriched in EV samples. Hierarchical cluster analysis revealed high discrimination in miRNA expression between DIPG and MB cell lines and RNA-Seq identified novel miRNAs not previously implicated in MB or DIPG pathogenesis. Known and putative target genes of dysregulated miRNAs were identified. Functional annotation analysis of the target genes for differentially expressed EV-and parental-derived miRNAs revealed significant cancer-related pathway involvement. CONCLUSIONS: This hypothesis-generating study demonstrated that pediatric brain tumor-derived cell lines secrete EVs comprised of various ncRNA cargoes. Validation of these findings in patient samples may provide new insights into the pediatric brain tumor microenvironment and identification of novel therapeutic candidates.

Quantifying Ambulatory Care Use Preceding Emergency Department Visits and Hospitalizations for Ambulatory Care Sensitive Conditions.

Ambulatory Care Sensitive Conditions (ACSC) represent a significant source of health care spending in the United States. Existing literature is largely descriptive and there is limited information about how an emergency department (ED) visit or hospitalization for ACSCs is related to prior ambulatory care visits. A retrospective, observational study was conducted using health records from a large midwestern health system during a 20-month period between 2012 and 2014. Our primary variables were (1) type of care setting (i.e., ED visit or hospitalization) and (2) whether the patient received ambulatory care services in the 14, 30, and 60 days before the ED visit or hospital admission. Of patients seen in the ED for ACSCs, 11.9%, 16.3%, and 21.67% were seen in ambulatory care in the 14, 30, and 60 days prior, respectively. Of those hospitalized for ACSCs, 29.1%, 39.9%, and 53% were seen in ambulatory care in the 14, 30, and 60 days prior, respectively. These results highlight a potential lost opportunity to address ACSCs in the ambulatory care setting. Such knowledge can inform interventions to reduce avoidable ACSC-related acute care use and health care costs, and improve patient outcomes.

The prevalence, management, and thirty-day outcomes of symptomatic atrial fibrillation in a Tanzanian emergency department.

INTRODUCTION: Data describing atrial fibrillation (AF) care in emergency centres (ECs) in sub-Saharan Africa is lacking. We sought to describe the prevalence and outcomes of AF in a Tanzanian EC. METHODS: In a prospective, observational study, adults presenting with chest pain or shortness of breath to a Tanzanian EC were enrolled from January through October 2019. Participants underwent electrocardiogram testing which were reviewed by two independent physician judges to determine presence of AF. Participants were asked about their medical history and medication use at enrollment, and a follow-up questionnaire was administered via telephone thirty days later to assess mortality, interim stroke, and medication use. RESULTS: Of 681 enrolled patients, 53 (7.8%) had AF. The mean age of participants with AF was 68.1, with a standard deviation (sd) of 21.1 years, and 23 of the 53 (43.4%) being male. On presentation, none of the participants found to have AF reported a previous history of AF. The median CHADS-VASC score among participants was 4 with an interquartile range (IQR) of 2-4. No participants were taking an anticoagulant at baseline. On index presentation, 49 (92.5%) participants with AF were hospitalised with 52 (98.1%) participants completing 30-day follow-up. 18 (34%) participants died, and 5 (9.6%) suffered a stroke. Of the surviving 31 participants with AF and a CHADS-VASC score ≥ 2, none were taking other anti-coagulants at 30 days. Compared to participants without AF, participants with AF were more likely to be hospitalised (OR 5.25, 95% CI 2.10-17.95, p < 0.001), more likely to die within thirty days (OR 1.93, 95% CI 1.03-3.50, p = 0.031), and more likely to suffer a stroke within thirty days (OR 5.91, 95% CI 1.76-17.28, p < 0.001). DISCUSSION: AF is common in a Tanzanian EC, with thirty-day mortality being high, but use of evidence-based therapies is rare. There is an opportunity to improve AF care and outcomes in Tanzania.

Hospital Participation Decisions In Medicare Bundled Payment Program Were Influenced By Third-Party Conveners.

The Bundled Payments for Care Improvement initiative Advanced Model (BPCI Advanced) is a voluntary Medicare bundled payment model in which hospitals may participate with third-party conveners-private consulting firms that share in the financial risk built into the program. We found that nonteaching and for-profit status was associated with a higher probability of hospital partnership with third-party conveners in BPCI Advanced. Among hospitals participating in at least one inpatient clinical episode, hospitals that partnered with third-party conveners were more likely to select episodes with higher target prices: A $1,000 increase in episode target price was associated with a 1.66-percentage-point increase in the probability of episode participation in BPCI Advanced compared with a 0.72-percentage-point increase for participating hospitals without third-party conveners. Hospitals with third-party conveners also were more likely than those without them to select inpatient clinical episodes with greater opportunities to reduce spending on postacute care and readmissions. These findings have important implications for understanding the role of private consulting firms in the program and for planning potential program modifications in the future.