G levels and IS risk, which supports the notion that SHBG could be used as a risk stratification tool for predicting IS in women.Background and Purpose- Loss of cerebral autoregulation in the acute phase of ischemic stroke leaves patients vulnerable to blood pressure (BP) changes. Effective BP management after endovascular thrombectomy may protect the brain from hypoperfusion or hyperperfusion. In this observational study, we compared personalized, autoregulation-based BP targets to static systolic BP thresholds. Methods- We prospectively enrolled 90 patients undergoing endovascular thrombectomy for stroke. Autoregulatory function was continuously measured by interrogating changes in near-infrared spectroscopy-derived tissue oxygenation (a cerebral blood flow surrogate) in response to changes in mean arterial pressure. The resulting autoregulatory index was used to trend the BP range at which autoregulation was most preserved. Percent time that mean arterial pressure exceeded the upper limit of autoregulation or decreased below the lower limit of autoregulation was calculated for each patient. Time above fixed systolic BP thresholds wa poor functional outcome. This approach may present a better strategy compared with the classical approach of maintaining systolic BP below a predetermined value, though a randomized trial is needed to determine the optimal approach for hemodynamic management.Background Having prescribers use clinical video teleconferencing (telemedicine) to prescribe buprenorphine to people with opioid use disorder (OUD) has shown promise but its implementation is challenging. We describe barriers, facilitators and lessons learned while implementing a system to remotely prescribe buprenorphine to Veterans in rural settings. Methods We conducted a quality improvement project aimed at increasing the availability of medications for OUD (MOUD) to Veterans. This project focused on tele-prescribing buprenorphine to rural sites via a hub (centralized prescribers) and spoke (rural clinics) model. After soliciting a wide-range of inputs from site visits, qualitative interviews of key stakeholders at rural sites, and review of preliminary cases, a „how-to” toolkit was developed and iteratively refined to guide tele-prescribing of buprenorphine. After internal and external facilitation strategies were employed, Veterans with OUD at three clinics were transitioned to buprenorphine treatment s. Implementation issues can be addressed by activities that foster collaboration between hubs (centralized prescribers) and spokes (rural clinics) and by a toolkit that operationalizes tele-prescribing procedures.Baby-boomers might be more health-conscious than earlier birth cohorts, but limited evidence has been produced so far. To investigate such changes, this study compared health-related behaviors at age 65 to 70 among three successive five-year birth cohorts (pre-war born 1934-1938; war born 1939-1943 and baby-boom born 1944-1948) representative of the community-dwelling population. Information about alcohol use, smoking, physical activity, and nutrition was compared across the three cohorts (n = 4,270 participants) using Chi-squared test. Alcohol and the mean nutritional intake score did not vary across cohorts, whereas the consumption of nonalcoholic drinks increased significantly from pre-war to war and to baby-boom cohort (p less then .001). Other differences across cohorts were observed only in women the proportion of women who never or rarely engaged in sports decreased from 52.9% in the pre-war cohort to around 43% in subsequent cohorts (p less then .001), while the proportion of women who had never smoked was higher in the pre-war cohort (56.1%) than in the war and the baby-boom cohorts (49.8% and 46.8%, respectively, p less then .001). Overall, these results show some positive changes in older persons’ health behaviors over time. Nevertheless, considerable room remains for improving lifestyles through public health interventions.RATIONALE Atherosclerotic cardiovascular diseases are the leading cause of mortality worldwide. Atherosclerotic cardiovascular diseases are considered as chronic inflammation processes. In addition to risk factors associated with the cardiovascular system itself, pathogenic bacteria such as the periodontitis-associated Porphyromonas gingivalis (P gingivalis) are also closely correlated with the development of atherosclerosis, but the underlying mechanisms are still elusive. OBJECTIVE To elucidate the mechanisms of P gingivalis-accelerated atherosclerosis and explore novel therapeutic strategies of atherosclerotic cardiovascular diseases. METHODS AND RESULTS Bmal1-/- (brain and muscle Arnt-like protein 1) mice, ApoE-/- mice, Bmal1-/-ApoE-/- mice, conditional endothelial cell Bmal1 knockout mice (Bmal1fl/fl; Tek-Cre mice), and the corresponding jet-legged mouse model were used. P gingivalis accelerates atherosclerosis progression by triggering arterial oxidative stress and inflammatory responses in ApoE-/- mice, accompanied by the perturbed circadian clock. Circadian clock disruption boosts P gingivalis-induced atherosclerosis progression. The mechanistic dissection shows that P gingivalis infection activates the TLRs-NF-κB signaling axis, which subsequently recruits DNMT-1 to methylate the BMAL1 promoter and thus suppresses BMAL1 transcription. The downregulation of BMAL1 releases CLOCK, which phosphorylates p65 and further enhances NF-κB signaling, elevating oxidative stress and inflammatory response in human aortic endothelial cells. Besides, the mouse model exhibits that joint administration of metronidazole and melatonin serves as an effective strategy for treating atherosclerotic cardiovascular diseases. CONCLUSIONS P gingivalis accelerates atherosclerosis via the NF-κB-BMAL1-NF-κB signaling loop. Melatonin and metronidazole are promising auxiliary medications toward atherosclerotic cardiovascular diseases.Background and Purpose- While combination aspirin and clopidogrel reduces recurrent stroke compared with aspirin alone in patients with transient ischemic attack (TIA) or minor stroke, the effect on disability is uncertain. Methods- The POINT trial (Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke) randomized patients with TIA or minor stroke (National Institutes of Health Stroke Scale score ≤3) within 12 hours of onset to dual antiplatelet therapy (DAPT) with aspirin plus clopidogrel versus aspirin alone. The primary outcome measure was a composite of stroke, myocardial infarction, or vascular death. We performed a post hoc exploratory analysis to examine the effect of treatment on overall disability (defined as modified Rankin Scale score >1) at 90 days, as well as disability ascribed by the local investigator to index or recurrent stroke. We also evaluated predictors of disability. Results- At 90 days, 188 of 1964 (9.6%) of patients enrolled with TIA and 471 of 2586 (18.2%) of those enrollnt ischemic stroke, subsequent myocardial infarction, and serious adverse events were associated with disability. Conclusions- In addition to reducing recurrent stroke in patients with acute minor stroke and TIA, DAPT might reduce stroke-related disability. Registration- URL https//www.clinicaltrials.gov. Unique identifier NCT00991029.Background and Purpose- The TST trial (Treat Stroke to Target) evaluated the benefit of targeting a LDL (low-density lipoprotein) cholesterol of 4 mm, in a French and Korean population. The follow-up lasted a median of 5.3 years in French patients (similar to the median follow-up time in the SPARCL trial [Stroke Prevention by Aggressive Reduction in Cholesterol Level]) and 2.0 years in Korean patients. Exposure duration to statin is a well-known driver for cardiovascular risk reduction. We report here the TST results in the French cohort. Methods- One thousand seventy-three French patients were assigned to less then 70 mg/dL (1.8 mmol/L) and 1075 to 100±10 mg/dL (90-110 mg/dL, 2.3-2.8 mmol/L). To achieve these goals, investigators used the statin and dosage of their choice and added ezetimibe on top if needed. The primary outcome was the composite of ischemic stroke, myocardial infarction, new symptoms requiring urgent coronary or carotid revascularization and vascular death. Results- After a median follow-up of 5.3 years, the achieved LDL cholesterol was 66 (1.69 mmol/L) and 96 mg/dL (2.46 mmol/L) on average, respectively. The primary end point occurred in 9.6% and 12.9% of patients, respectively (HR, 0.74 [95% CI, 0.57-0.94]; P=0.019). Cerebral infarction or urgent carotid revascularization following transient ischemic attack was reduced by 27% (P=0.046). Cerebral infarction or intracranial hemorrhage was reduced by 28% (P=0.023). The primary outcome or intracranial hemorrhage was reduced by 25% (P=0.021). Intracranial hemorrhages occurred in 13 and 11 patients, respectively (HR, 1.17 [95% CI, 0.53-2.62]; P=0.70). Conclusions- After an ischemic stroke of documented atherosclerotic origin, targeting a LDL cholesterol of less then 70 mg/dL during 5.3 years avoided 1 subsequent major vascular event in 4 (number needed to treat of 30) and no increase in intracranial hemorrhage. Registration- URL https//www.clinicaltrials.gov. Unique identifier NCT01252875.Background and Purpose- Mobile stroke units (MSUs) are increasingly used worldwide to provide prehospital triage and treatment. The benefits of MSUs in giving earlier thrombolysis have been well established, but the impacts of MSUs on endovascular thrombectomy (EVT) and effect on disability avoidance are largely unknown. We aimed to determine the clinical impact and disability reduction for reperfusion therapies in the first operational year of the Melbourne MSU. Methods- Treatment time metrics for MSU patients receiving reperfusion therapy were compared with control patients presenting to metropolitan Melbourne stroke units via standard ambulance within MSU operating hours. The primary outcome was median time difference in first ambulance dispatch to treatment modeled using quantile regression analysis. Time savings were subsequently converted to disability-adjusted life years avoided using published estimates. Results- In the first 365-day operation of the Melbourne MSU, prehospital thrombolysis was adminiser EVT. These findings highlight the benefits of prehospital notification and direct triage to EVT centers with facilitated workflow on arrival by the MSU.Background and Purpose- Industry payments to physicians raise concerns regarding conflicts of interest that could impact patient care. We explored nonresearch and nonownership payments from industry to vascular neurologists to identify trends in compensation. Methods- Using Centers for Medicare and Medicaid Services and American Board of Psychiatry and Neurology data, we explored financial relationships between industry and US vascular neurologists from 2013 to 2018. We analyzed payment characteristics, including payment categories, payment distribution among physicians, regional trends, and biomedical manufacturers. Furthermore, we analyzed the top 1% (by compensation) of vascular neurologists with detailed payment categories, their position, and their contribution to stroke guidelines. Results- The number of board certified vascular neurologist increased from 1169 in 2013 to 1746 in 2018. The total payments to vascular neurologist increased from $99 749 in 2013 to $1 032 302 in 2018. During the study period, 16% to 17% of vascular neurologists received industry payments.