SARS-CoV-2 infection is a major cause of morbidity and mortality, often as a result of acute respiratory distress syndrome. Respiratory failure is characterized by a hyperinflammatory immune response, lung vascular injury, and edema formation. The potential for immunomodulatory therapy to prevent lung vascular injury and edema formation is not well understood. Approach and Results We show that SARS-CoV-2 infection in humanized K18-hACE-2 mice activated inflammatory NLRP3-caspase-1 pyroptotic signaling in lungs, release of IL (interleukin)-1β, and downregulation of the lung endothelial adherens junction protein VE-cadherin. Primary human lung microvascular endothelial cells were susceptible to SARS-CoV-2 infection and displayed pyroptosis-like injury. We observed profound lung vascular injury post-SARS-CoV-2 infection and resultant protein-rich lung edema formation. Selective blockade of IL-1 receptor signaling by IL-1RA (IL-1 receptor antagonist) anakinra prevented downregulation of VE-cadherin, as well as accompanying lung vascular hyperpermeability. IL-1RA also significantly increased survival.

These results provide insights into the central role of NLRP3-caspase-1 pyroptotic innate immune signaling and loss of lung endothelial adherens junctions in the mechanism of acute respiratory distress syndrome induced by SARS-CoV-2. Our data show that treatment with IL-1RA during activation of inflammasome provides the ideal scenario for preventing lung vascular injury and respiratory failure in coronavirus disease 2019 (COVID-19).

These results provide insights into the central role of NLRP3-caspase-1 pyroptotic innate immune signaling and loss of lung endothelial adherens junctions in the mechanism of acute respiratory distress syndrome induced by SARS-CoV-2. Our data show that treatment with IL-1RA during activation of inflammasome provides the ideal scenario for preventing lung vascular injury and respiratory failure in coronavirus disease 2019 (COVID-19).

The ISCHEMIA trial (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches) postulated that patients with stable coronary artery disease (CAD) and moderate or severe ischemia would benefit from revascularization. We investigated the relationship between severity of CAD and ischemia and trial outcomes, overall and by management strategy.

In total, 5179 patients with moderate or severe ischemia were randomized to an initial invasive or conservative management strategy. Blinded, core laboratory-interpreted coronary computed tomographic angiography was used to assess anatomic eligibility for randomization. Extent and severity of CAD were classified with the modified Duke Prognostic Index (n=2475, 48%). Ischemia severity was interpreted by independent core laboratories (nuclear, echocardiography, magnetic resonance imaging, exercise tolerance testing, n=5105, 99%). We compared 4-year event rates across subgroups defined by severity of ischemia and CAD. The primary end poinnd point, or cardiovascular death or MI. In the most severe CAD subgroup (n=659), the 4-year rate of cardiovascular death or MI was lower in the invasive strategy group (difference, 6.3% [95% CI, 0.2%-12.4%]), but 4-year all-cause mortality was similar.

Ischemia severity was not associated with increased risk after adjustment for CAD severity. More severe CAD was associated with increased risk. Invasive management did not lower all-cause mortality at 4 years in any ischemia or CAD subgroup. Registration URL https//www.clinicaltrials.gov. Unique identifier NCT01471522.

Ischemia severity was not associated with increased risk after adjustment for CAD severity. More severe CAD was associated with increased risk. Invasive management did not lower all-cause mortality at 4 years in any ischemia or CAD subgroup. Registration URL https//www.clinicaltrials.gov. Unique identifier NCT01471522.

This program evaluation examined integration of primary care nurse practitioners into assertive community treatment (ACT).

From January to June 2019, primary care nurse practitioners in a postgraduate fellowship program were assigned to five ACT teams (N=305 participants). Focus groups explored staff members’ and participants’ experiences. Screening rates for hemoglobin A1c and cholesterol for ACT participants were compared over time.

Staff and participants in ACT described improved engagement in primary care, citing benefit from colocation and consultation. Field visits were not found to be an efficient use of the primary care nurse practitioners’ time to serve most ACT participants. A significant increase in screening was observed after 6 months for the ACT teams with integrated primary care.

An integrated primary care nurse practitioner readily available for participant engagement and consultation with the ACT team, using a cardiometabolic registry to guide care, may offer a sustainable model of integration.

An integrated primary care nurse practitioner readily available for participant engagement and consultation with the ACT team, using a cardiometabolic registry to guide care, may offer a sustainable model of integration.Initiatives that support and incentivize the integration of behavioral health and general medical care have become a focus of government strategies to achieve the triple aim of improved health, better patient experience, and reduced costs. The authors describe the components of four large-scale national initiatives aimed at integrating care for a wide range of behavioral health needs. Commonalities across these national initiatives highlight health care and social services needs that must be addressed to improve care for people with co-occurring behavioral health and general medical conditions. These findings can inform how to design, test, select, and align the most promising strategies for integrated care in a variety of settings.Individuals with psychiatric disorders often struggle to initiate and engage in treatment. Financial incentives improve treatment engagement, including treatment attendance, medication adherence, and abstinence from substance use. The U.S. Department of Veterans Affairs (VA) recently made the first large-scale, successful effort to implement incentive-based interventions in substance use disorder treatment. Health care systems, including the VA, can increase the impact of these interventions by extending them to target a range of psychiatric disorders, adapting them for specific clinical contexts, using insights from behavioral economics, and partnering with corporations to fund incentives and implement interventions.

Atrial fibrillation is a risk factor for dementia, and oral anticoagulant use is associated with a decreased risk of dementia in patients with atrial fibrillation. We aimed to investigate whether the risk of dementia would be different between patients treated with direct oral anticoagulants (DOACs) compared with those with warfarin.

Using the Korean nationwide claims database from January 2014 to December 2017, we identified oral anticoagulant-naive nonvalvular atrial fibrillation patients aged ≥40 years. For the comparisons, warfarin and DOAC groups were balanced using the inverse probability of treatment weighting method. The primary outcome was incident dementia.

Among 72 846 of total study patients, 25 948 were treated with warfarin, and 46 898 were treated with DOAC (17 193 with rivaroxaban, 9882 with dabigatran, 11 992 with apixaban, and 7831 with edoxaban). During mean 1.3±1.1 years of follow-up, crude incidence of dementia was 4.87 per 100 person-years (1.20 per 100 person-years for vascular deappeared more beneficial than warfarin, in those aged 65 to 74 years or with a history of stroke. For specific DOACs, only edoxaban was associated with a lower risk of dementia than warfarin.

Depression and quality of life (QOL) have an interdependent and transactional nature in stroke survivor-caregiver dyads. While the strong relationship between depression and physical and emotional QOL in stroke survivor-caregiver dyads is well known, it is less clear if this relationship is moderated by caregiver preparedness, which could easily be targeted with interventions. In this study, we examined the moderating role of caregiver preparedness on the association between depression and QOL in stroke survivor-caregiver dyads.

We used a longitudinal design with follow-ups every 3 months over a 1-year period. Considering the nonindependent nature of the data (survivors and their caregivers), we used multilevel modeling to analyze data at the dyad level. We implemented 4 longitudinal dyadic moderation models (one for each QOL domain physical, psychological, social, and environmental) using hierarchical linear modeling.

A sample of 222 stroke survivor-caregiver dyads was analyzed. Stroke survivors were oegiver preparedness could be helpful to motivate clinicians to develop and implement interventions for stroke survivor-caregiver dyads.

Cognitive impairment no dementia (CIND) and dementia are common stroke outcomes, with significant health and societal implications for aging populations. These outcomes are not included in current epidemiological models. We aimed to develop an epidemiological model to project incidence and prevalence of stroke, poststroke CIND and dementia, and life expectancy, in Ireland to 2035, informing policy and service planning.

We developed a probabilistic Markov model (the StrokeCog model) applied to the Irish population aged 40 to 89 years to 2035. Data sources included official population and hospital-episode statistics, longitudinal cohort studies, and published estimates. Key assumptions were varied in sensitivity analysis. Results were externally validated against independent sources. The model tracks poststroke progression into health states characterized by no cognitive impairment, CIND, dementia, disability, stroke recurrence, and death.

We projected 69 051 people with prevalent stroke in Ireland in 203ological model of stroke, poststroke CIND, and dementia draws on the best available evidence. Sensitivity analysis indicated that findings were robust to assumptions, and where there was uncertainty a conservative approach was taken. The StrokeCog model is a useful tool for service planning and cost-effectiveness analysis and is available for adaptation to other national contexts.

Mechanical thrombectomy is an established procedure for treatment of acute ischemic stroke. Mechanical thrombectomy success is commonly assessed by the Thrombolysis in Cerebral Infarction (TICI) score, assigned by visual inspection of X-ray digital subtraction angiography data. However, expert-based TICI scoring is highly observer-dependent. This represents a major obstacle for mechanical thrombectomy outcome comparison in, for instance, multicentric clinical studies. Focusing on occlusions of the M1 segment of the middle cerebral artery, the present study aimed to develop a deep learning (DL) solution to automated and, therefore, objective TICI scoring, to evaluate the agreement of DL- and expert-based scoring, and to compare corresponding numbers to published scoring variability of clinical experts.

The study comprises 2 independent datasets. For DL system training and initial evaluation, an in-house dataset of 491 digital subtraction angiography series and modified TICI scores of 236 patients with M1 occlusions was collected.