Hospital-Based Acute Care Use in Survivors of Septic Shock

OBJECTIVES: Septic shock is associated with increased long-term morbidity and mortality. However, little is known about the use of hospital-based acute care in survivors after hospital discharge. The objectives of the study were to examine the frequency, timing, causes, and risk factors associated with emergency department visits and hospital readmissions within 30 days of discharge. DESIGN: Retrospective cohort study. SETTING: Tertiary, academic hospital in the United States. PATIENTS: Patients admitted with septic shock (serum lactate ≥ 4 mmol/L or refractory hypotension) and discharged alive to a nonhospice setting between 2007 and 2010. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The coprimary outcomes were all-cause hospital readmission and emergency department visits (treat-and-release encounters) within 30 days to any of the three health system hospitals. Of 269 at-risk survivors, 63 (23.4%; 95% CI, 18.2-28.5) were readmitted within 30 days of discharge and another 12 (4.5%; 95% CI, 2.3-7.7) returned to the emergency department for a treat-and-release visit. Readmissions occurred within 15 days of discharge in 75% of cases and were more likely in oncology patients (p=0.001) and patients with a longer hospital length of stay (p=0.04). Readmissions were frequently due to another life-threatening condition and resulted in death or discharge to hospice in 16% of cases. The reasons for readmission were deemed potentially related to the index septic shock hospitalization in 78% (49 of 63) of cases. The most common cause was infection related, accounting for 46% of all 30-day readmissions, followed by cardiovascular or thromboembolic events (18%). CONCLUSIONS: The use of hospital-based acute care appeared to be common in septic shock survivors. Encounters often led to readmission within 15 days of discharge, were frequently due to another acute condition, and appeared to result in substantial morbidity and mortality. Given the potential public health implications of these findings, validation studies are needed

Scalability of digital psychological innovations for refugees: A comparative analysis in Egypt, Germany, and Sweden

E-mental health interventions may offer innovative means to increase access to psychological support and improve the mental health of refugees. However, there is limited knowledge about how these innovations can be scaled up and integrated sustainably into routine services. This study examined the scalability of a digital psychological intervention called Step-by-Step (SbS) for refugees in Egypt, Germany, and Sweden. We conducted semi-structured interviews (n = 88) with Syrian refugees, and experts in SbS or refugee' mental health systems in the three countries. Data collection and analysis were guided by a system innovation perspective. Interviewees identified three contextual factors that influenced scalability of SbS in each country: increasing use of e-health, the COVID-19 pandemic, and political instability. Nine factors lay at the interface between the innovation and potential delivery systems, and these were categorised by culture (ways of thinking), structure (ways of organising), and practice (ways of doing). Factors related to culture included: perceived need and acceptability of the innovation. Acceptability was influenced by mental health stigma and awareness, digital trust, perceived novelty of self-help interventions, and attitudes towards non-specialist (e-helper) support. Factors related to structure included financing, regulations, accessibility, competencies of e-helpers, and quality control. Factors related to practice were barriers in the initial and continued engagement of end-users. Many actors with a potential stake in the integration of SbS across the three countries were identified, with nineteen stakeholders deemed most powerful. Several context-specific integration scenarios were developed, which need to be tested. We conclude that integrating novel e-mental health interventions for refugees into routine services will be a complex task due to the many interrelated factors and actors involved. Multi-stakeholder collaboration, including the involvement of end-users, will be essential. Previous article in issu

Definitions and methodology for the grayscale and radiofrequency intravascular ultrasound and coronary angiographic analyses

Objectives: In a prospective study of the natural history of coronary atherosclerosis using angiography and grayscale and radio

A Graphical Null Model for Scaling Biodiversity–Ecosystem Functioning Relationships

Global biodiversity is declining at rates faster than at any other point in human history. Experimental manipulations at small spatial scales have demonstrated that communities with fewer species consistently produce less biomass than higher diversity communities. Understanding the consequences of the global extinction crisis for ecosystem functioning requires understanding how local experimental results are likely to change with increasing spatial and temporal scales and from experiments to naturally assembled systems. Scaling across time and space in a changing world requires baseline predictions. Here, we provide a graphical null model for area scaling of biodiversity–ecosystem functioning relationships using observed macroecological patterns: the species–area curve and the biomass–area curve. We use species–area and biomass–area curves to predict how species richness–biomass relationships are likely to change with increasing sampling extent. We then validate these predictions with data from two naturally assembled ecosystems: a Minnesota savanna and a Panamanian tropical dry forest. Our graphical null model predicts that biodiversity–ecosystem functioning relationships are scale-dependent. However, we note two important caveats. First, our results indicate an apparent contradiction between predictions based on measurements in biodiversity–ecosystem functioning experiments and from scaling theory. When ecosystem functioning is measured as per unit area (e.g. biomass per m2), as is common in biodiversity–ecosystem functioning experiments, the slope of the biodiversity ecosystem functioning relationship should decrease with increasing scale. Alternatively, when ecosystem functioning is not measured per unit area (e.g. summed total biomass), as is common in scaling studies, the slope of the biodiversity–ecosystem functioning relationship should increase with increasing spatial scale. Second, the underlying macroecological patterns of biodiversity experiments are predictably different from some naturally assembled systems. These differences between the underlying patterns of experiments and naturally assembled systems may enable us to better understand when patterns from biodiversity–ecosystem functioning experiments will be valid in naturally assembled systems. Synthesis. This paper provides a simple graphical null model that can be extended to any relationship between biodiversity and any ecosystem functioning across space or time. Furthermore, these predictions provide crucial insights into how and when we may be able to extend results from small-scale biodiversity experiments to naturally assembled regional and global ecosystems where biodiversity is changing

Adverse Cardiovascular Events Arising From Atherosclerotic Lesions With and Without Angiographic Disease Progression

ObjectivesThe aim of this study was to use angiography and grayscale and intravascular ultrasound–virtual histology to assess coronary lesions that caused events during a median follow-up period of 3.4 years.BackgroundVulnerable plaque-related events are assumed to be the result of substantial progression of insignificant lesions.MethodsIn the PROSPECT (Providing Regional Observations to Study Predictors of Events in the Coronary Tree) study, 697 patients with acute coronary syndromes underwent treatment of all culprit lesions followed by 3-vessel imaging to assess the natural history of culprit and untreated nonculprit (NC) lesions. Future adverse cardiovascular events adjudicated to NC lesions were divided into those with versus without substantial lesion progression (SLP) (≥20% angiographic diameter stenosis increase).ResultsNC lesion events occurred in 72 patients, 44 (61%) with and 28 (39%) without SLP. Myocardial infarctions (n = 6) occurred only in patients with SLP. Conversely, patients without SLP presented only with unstable or increasing angina requiring rehospitalization. Lesions with versus without SLP occurred later (median time to event 401 vs. 223 days, p = 0.07); were less severe at baseline (median diameter stenosis 26.4% vs. 53.8%, p < 0.0001) but more severe at the time of the event (mean diameter stenosis 73.8% vs. 56%, p < 0.0001); and had comparable baseline median plaque burden (68.7% vs. 70.1%, p = 0.17), minimum luminal area (3.7 vs. 4.0 mm2, p = 0.60), and intravascular ultrasound–virtual histology phenotype (83.3% vs. 90.9%, p = 0.68; classified as fibroatheromas at baseline).ConclusionsNC lesions responsible for future cardiovascular events showed angiographic increase during 3.4 years of follow-up, whereas SLP underlay many but not all of them. NC events due to lesions with SLP were angiographically less severe and presented with a delayed time course but were otherwise indistinguishable from NC events that were not associated with SLP

Antigen Presenting Cells Link the Female Genital Tract Microbiome to Mucosal Inflammation, With Hormonal Contraception as an Additional Modulator of Inflammatory Signatures

The microbiome of the female genital tract (FGT) is closely linked to reproductive health outcomes. Diverse, anaerobe-dominated communities with low Lactobacillus abundance are associated with a number of adverse reproductive outcomes, such as preterm birth, cervical dysplasia, and sexually transmitted infections (STIs), including HIV. Vaginal dysbiosis is associated with local mucosal inflammation, which likely serves as a biological mediator of poor reproductive outcomes. Yet the precise mechanisms of this FGT inflammation remain unclear. Studies in humans have been complicated by confounding demographic, behavioral, and clinical variables. Specifically, hormonal contraception is associated both with changes in the vaginal microbiome and with mucosal inflammation. In this study, we examined the transcriptional landscape of cervical cell populations in a cohort of South African women with differing vaginal microbial community types. We also investigate effects of reproductive hormones on the transcriptional profiles of cervical cells, focusing on the contraceptive depot medroxyprogesterone acetate (DMPA), the most common form of contraception in sub-Saharan Africa. We found that antigen presenting cells (APCs) are key mediators of microbiome associated FGT inflammation. We also found that DMPA is associated with significant transcriptional changes across multiple cell lineages, with some shared and some distinct pathways compared to the inflammatory signature seen with dysbiosis. These results highlight the importance of an integrated, systems-level approach to understanding host-microbe interactions, with an appreciation for important variables, such as reproductive hormones, in the complex system of the FGT mucosa

Residual plaque burden in patients with acute coronary syndromes after successful percutaneous coronary intervention

Objectives: The aim of this study was to characterize and evaluate the clinical impact of untreated atherosclerotic disease after percutaneous coronary intervention (PCI) in patients with acute coronary syndromes (ACS). Background: Residual atherosclerotic disease after successful PCI may predispose future major adverse cardiovascular events (MACE). Compared with intravascular ultrasound (IVUS), angiography underestimates the presence and severity of coronary artery disease. Methods: Following successful PCI of all clinically significant lesions in 697 patients with ACS, 3-vessel grayscale and radiofrequency IVUS was performed. Lesions were prospectively characterized, and patients were followed for a median of 3.4 years. A total of 3,229 untreated lesions (4.89 ± 1.98 lesions/patient) were identified by IVUS, with mean plaque burden (PB) of 49.6 ± 4.2%. Results: By angiography these nonculprit lesions were mild, with mean diameter stenosis of 38.9 ± 15.3%. At least 1 lesion with a PB <70% (PB70 lesion) was found in 220 (33%) patients. By multivariable analysis, a history of prior PCI and angiographic 3-vessel disease were independent predictors of PB70 lesions. Patients with PB70 lesions had greater total percent plaque volume, normalized PB, fibroatheromas, thin-cap fibroatheromas, and normalized volumes of necrotic core and dense calcium. Patients with PB70 lesions had greater 3-year rates of MACE due to untreated nonculprit lesions (20.8% vs. 7.7%, p < 0.0001). Among imaged nonculprit lesions, the proportion of PB70 lesions causing MACE was significantly greater than non-PB70 lesions (8.7% vs. 1.0%, p < 0.0001). Conclusions: After successful PCI of all angiographically significant lesions, overall untreated atherosclerotic burden remains high, and PB70 lesions are frequently present in the proximal and mid-coronary tree. Patients with PB70 lesions have greater atherosclerosis throughout the coronary tree, have more thin-cap fibroatheromas, and are at increased risk for future cardiovascular events. (PROSPECT: An Imaging Study in Patients With Unstable Atherosclerotic Lesions; NCT00180466

Discovery and Rational Mutagenesis of Methionine Sulfoxide Reductase Biocatalysts To Expand the Substrate Scope of the Kinetic Resolution of Chiral Sulfoxides

Methionine sulfoxide reductase A (MsrA) enzymes have recently found applications as nonoxidative biocatalysts in the enantioselective kinetic resolution of racemic sulfoxides. This work describes the identification of selective and robust MsrA biocatalysts able to catalyze the enantioselective reduction of a variety of aromatic and aliphatic chiral sulfoxides at 8–64 mM concentration with high yields and excellent ees (up to 99%). Moreover, with the aim to expand the substrate scope of MsrA biocatalysts, a library of mutant enzymes has been designed via rational mutagenesis utilizing in silico docking, molecular dynamics, and structural nuclear magnetic resonance (NMR) studies. The mutant enzyme MsrA33 was found to catalyze the kinetic resolution of bulky sulfoxide substrates bearing non-methyl substituents on the sulfur atom with ees up to 99%, overcoming a significant limitation of the currently available MsrA biocatalysts