To develop and implement antibiotic stewardship activities in urgent care targeting non–antibiotic-appropriate acute respiratory tract infections (ARIs) that also reduces overall antibiotic prescribing and maintains patient satisfaction.

Patients and clinicians at the urgent care clinics of an integrated academic health system.

The stewardship activities started in fiscal 2020 and included measure development, comparative feedback, and clinician and patient education. We measured antibiotic prescribing in fiscal years 2019, 2020, and 2021 for the stewardship targets, potential diagnosis-shifting visits, and overall. We also collected patient satisfaction data for ARI visits.

From FY19 to FY21, 576,609 patients made 1,358,816 visits to 17 urgent care clinics, including 105,781 visits for which stewardship measures were applied and 149,691 visits for which diagnosis shifting measures were applied. The antibiotic prescribing rate decreased for stewardship-measure visits from 34% in FY19 to 12% in FY21 (absolute change, −22%; 95% confidence interval [CI], −23% to −22%). The antibiotic prescribing rate decreased for diagnosis-shifting visits from 63% to 35% (−28%; 95% CI, −28% to −27%), and the antibiotic prescribing rate decreased overall from 30% to 10% (−20%; 95% CI, −20% to −20%). The patient satisfaction rate increased from 83% in FY19 to 89% in FY20 and FY21. There was no significant association between antibiotic prescribing rates of individual clinicians and ARI visit patient satisfaction.

Although it was affected by the COVID-19 pandemic, an ambulatory antimicrobial stewardship program that focused on improving non–antibiotic-appropriate ARI prescribing was associated with decreased prescribing for (1) the stewardship target, (2) a diagnosis shifting measure, and (3) overall antibiotic prescribing. Patient satisfaction at ARI visits increased over time and was not associated with clinicians’ antibiotic prescribing rates.

Mortality remains a substantial problem after acute ischemic stroke, despite advances in acute stroke treatment over the past three decades. Mortality is particularly high among patients with Total Anterior Circulation Stroke (TACS), generally representing patients with middle cerebral artery occlusions. Notably however, these patients also stand to benefit most from new therapies including endovascular thrombectomy (EVT). In this study, we aimed to examine temporal trends in, and factors associated with, 30-day in-hospital mortality after TACS.

Information on all patients with community-onset TACS from 1994 through 2019 was extracted from a prospective acute stroke registry. Multivariate analysis was performed on the primary outcome of 30-day in-hospital mortality, as well as secondary functional outcomes.

We studied 1106 patients hospitalized for community-onset TACS, 456 (41%) of whom experienced 30-day in-hospital mortality. Over the 25 years of observation, 30-day in-hospital mortality rose and then fell. Increased odds of mortality was associated with age and stroke severity. Decreased odds of mortality was associated with alteplase therapy and EVT, as well as presentation to hospital more than 12 hours after stroke onset. Treatment with alteplase, EVT, or both was associated with higher odds of functional independence and discharge home, and shorter lengths of stay in acute care.

Patients receiving alteplase, EVT, or both had lower 30-day in-hospital mortality and better functional outcomes than those who were untreated. These observational data demonstrate the benefits of recanalization therapy in routine clinical practice.

Atrial fibrillation (AF), which is characterized by chaotic patterns of electrical activation of the atria, affects over 4 million people in the US alone. We previously identified nanoscale structural abnormalities in the hearts of AF patients. Specifically, they displayed swelling of gap junction (GJ) –adjacent perinexi, specialized nanodomains rich in cardiac sodium channels (NaV1.5) and located within intercalated disks (IDs; sites of electromechanical contact between adjacent cells). However, the functional consequences of these nanoscale structural changes remain unclear.

We assessed the structural and functional impacts of selectively disrupting different NaV1.5-rich ID nanodomains.

We utilized peptide mimetics of adhesion domains to selectively inhibit adhesion within different ID nanodomains: 1) Nadp1 (target: N-cadherin), 2) dadp1 (target: Desmoglein-2), and 3) βadp1 (target: sodium channel β1 subunit [SCN1b]). Each active peptide was compared against a corresponding inactive control peptide (Nadp1-c, dadp1-c, βadp1-scr). Sub-diffraction confocal imaging revealed ID enrichment of active peptides, but not inactive controls. Furthermore, each active peptide was preferentially localized in ID regions rich in its corresponding protein target. Peptide treatment (100 μM; 60 minutes) of ex vivo mouse hearts revealed profound widening of perinexi by βadp1 and of mechanical junctions by Nadp1. Dadp1 also induced widening of mechanical junctions albeit to a lower degree. STORM single molecule localization microscopy identified about 50&per; of ID-localized NaV1.5 within GJ-adjacent perinexi, while an additional ∼35&per; was located within N-cad-rich ID sites. Nadp1 and βadp1 induced redistribution of ID localized NaV1.5 away from perinexi and mechanical junctions respectively. Dadp1, again, had similar but milder effects compared to Nadp1. Western blot revealed the expression levels of NaV1.5, connexin 43 (Cx43), connexin 40 (Cx40), β1 in peptide treated hearts to be within 10&per; of levels in untreated controls. Optical mapping revealed atrial conduction slowing in hearts treated with Nadp1 (17cm/s, 70.83&per; of control) and βadp1 (13 cm/s, 54.17&per; of control), but not inactive control peptides (24 cm/s). Volume-conducted electrocardiograms (ECG) revealed P wave prolongation in active peptide treated hearts (Nadp1: 26.5ms, βadp1: 31ms), consistent with conduction slowing compared to the inactive control peptides (16ms). Importantly, burst pacing elicited atrial arrhythmias in all hearts treated with Nadp1 and βadp1. Arrhythmia burden (duration, number of arrhythmias) was highest with βadp1.

These results suggest that disruption of NaV1.5-rich ID nanodomains impairs electrical impulse propagation and promotes arrhythmias in the atria. Furthermore, the magnitude of functional impacts are likely determined by the amount of sodium channels contained within the nanodomains disrupted.

Although the efficacy of endovascular thrombectomy (EVT) for acute ischemic stroke caused by intracranial anterior circulation large vessel occlusion (LVO) is proven, demonstration of local effectiveness is critical for health system planning and resource allocation because of the complexity and cost of this treatment.

Using our prospective registry, we identified all patients who underwent EVT for out-of-hospital LVO stroke from February 1, 2013 through January 31, 2017 (n = 44), and matched them 1:1 in a hierarchical fashion with control patients not treated with EVT based on age (±5 years), prehospital functional status, stroke syndrome, severity, and thrombolysis administration. Demographics, in-hospital mortality, discharge disposition from acute care, length of hospitalization, and functional status at discharge from acute care and at follow-up were compared between cases and controls.

For EVT-treated patients (median age 66, 50% women), the median onset-to-recanalization interval was 247 min, and successful recanalization was achieved in 30/44 (91%). Alteplase was administered in 75% of cases and 57% of controls (p = 0.07). In-hospital mortality was 11% among the cases and 36% in the control group (p = 0.006); this survival benefit persisted during follow-up (p = 0.014). More EVT patients were discharged home from acute care (50% vs. 18%, p = 0.002). Among survivors, there were nonsignificant trends in favor of EVT for median length of hospitalization (14 vs. 41 days, p = 0.11) and functional independence at follow-up (51% vs. 32%, p = 0.079).

EVT improved survival and decreased disability. This demonstration of single-center effectiveness may help facilitate expansion of EVT services in similar health-care jurisdictions.

Endovascular thrombectomy (EVT) is efficacious for ischemic stroke caused by proximal intracranial large-vessel occlusion involving the anterior cerebral circulation. However, evidence of its cost-effectiveness, especially in a real-world setting, is limited. We assessed whether EVT ± tissue plasminogen activator (tPA) was cost-effective when compared with standard care ± tPA at our center.

We identified patients treated with EVT ± tPA after the Endovascular treatment for Small Core and Anterior circulation Proximal occlusion with Emphasis on minimizing computed tomography to recanalization times trial from our prospective stroke registry from February 1, 2013 to January 31, 2017. Patients admitted before February 2013 and treated with standard care ± tPA constitute the controls. The sample size was 88. Cost-effectiveness was assessed using the net monetary benefit (NMB). Differences in average costs and quality-adjusted life years (QALYs) were estimated using the augmented inverse probability weighted estimator. We accounted for sampling and methodological uncertainty in sensitivity analyses.

Patients treated with EVT ± tPA had a net gain of 2.89 [95% confidence interval (CI): 0.93–4.99] QALYs at an additional cost of $22,200 (95% CI: −28,902–78,244) per patient compared with the standard care ± tPA group. The NMB was $122,300 (95% CI: −4777–253,133) with a 0.85 probability of being cost-effective. The expected savings to the healthcare system would amount to $321,334 per year.

EVT ± tPA had higher costs and higher QALYs compared with the control, and is likely to be cost-effective at a willingness-to-pay threshold of $50,000 per QALY.

Despite knowing for many decades that depressive psychopathology is common in first-episode schizophrenia spectrum disorders (FES), there is limited knowledge regarding the extent and nature of such psychopathology (degree of comorbidity, caseness, severity) and its demographic, clinical, functional and treatment correlates. This study aimed to determine the pooled prevalence of depressive disorder and caseness, and the pooled mean severity of depressive symptoms, as well as the demographic, illness, functional and treatment correlates of depressive psychopathology in FES.

This systematic review, meta-analysis and meta-regression was prospectively registered (CRD42018084856) and conducted in accordance with PRISMA and MOOSE guidelines.

Forty studies comprising 4041 participants were included. The pooled prevalence of depressive disorder and caseness was 26.0% (seven samples, N = 855, 95% CI 22.1–30.3) and 43.9% (11 samples, N = 1312, 95% CI 30.3–58.4), respectively. The pooled mean percentage of maximum depressive symptom severity was 25.1 (38 samples, N = 3180, 95% CI 21.49–28.68). Correlates of depressive psychopathology were also found.

At least one-quarter of individuals with FES will experience, and therefore require treatment for, a full-threshold depressive disorder. Nearly half will experience levels of depressive symptoms that are severe enough to warrant diagnostic investigation and therefore clinical intervention – regardless of whether they actually fulfil diagnostic criteria for a depressive disorder. Depressive psychopathology is prominent in FES, manifesting not only as superimposed comorbidity, but also as an inextricable symptom domain.