Clinical follow-up rather than duplex surveillance after carotid endarterectomy

AbstractPurpose: The value of duplex surveillance and the significance of contralateral carotid disease after endarterectomy have been assessed.Methods: Three hundred five patients were observed prospectively after carotid endarterectomy for a median time of 36 months (range, 6 to 96 months), with duplex surveillance performed at 1 day; 1 week; 3, 6, 9, and 12 months; and then each year after endarterectomy.Results: Thirty patients (10%) had ipsilateral symptoms (13 strokes, 17 transient ischemic attacks [TIAs]) at a median time of 6 months (range, 0 to 60 months). Life table analysis demonstrated that ipsilateral stroke was equally common for patients who had ≥50% restenosis (3% at 36 months) and those who did not (6% at 36 months, p > 0.5). Twenty-three patients (8%) developed symptoms (stroke 5, TIA 14) attributable to the contralateral carotid artery at a median time of 9 months (range, 0 to 36 months) after endarterectomy. By life table analysis, 40% of patients with 70% to 99%, 6% with 50% to 69%, 1% with <50% contralateral internal carotid stenosis, and 5% with contralateral carotid occlusion at the time of endarterectomy had a contralateral TIA in the 36 months after endarterectomy ( p < 0.01). However, contralateral stroke was not significantly more common for patients with severe contralateral internal carotid stenosis demonstrated at the time of endarterectomy (<50% stenosis, 0%; 50% to 69%, 3%; 70% to 99%, 7%; occlusion, 6% stroke rate at 36 months). Seven of the 32 patients who developed progression of contralateral disease had a TIA, compared with 11 of 227 patients who did not develop progression of contralateral disease ( p < 0.01). None of the 12 patients who progressed from a <70% to a 70% to 99% contralateral stenosis had a stroke.Conclusions: After carotid endarterectomy restenosis is rarely associated with symptoms; contralateral stroke is rare and is not associated with progressive internal carotid artery disease suitable for endarterectomy. This study has shown no benefit from long-term duplex surveillance after carotid endarterectomy. Selective clinical follow-up of patients who have high-grade contralateral stenoses would appear more appropriate. (J Vasc Surg 1997;25:55-63.

Risk factors for Coronavirus disease 2019 (Covid-19) death in a population cohort study from the Western Cape province, South Africa

Risk factors for coronavirus disease 2019 (COVID-19) death in sub-Saharan Africa and the effects of human immunodeficiency virus (HIV) and tuberculosis on COVID-19 outcomes are unknown. We conducted a population cohort study using linked data from adults attending public-sector health facilities in the Western Cape, South Africa. We used Cox proportional hazards models, adjusted for age, sex, location, and comorbidities, to examine the associations between HIV, tuberculosis, and COVID-19 death from 1 March to 9 June 2020 among (1) public-sector “active patients” (≥1 visit in the 3 years before March 2020); (2) laboratory-diagnosed COVID-19 cases; and (3) hospitalized COVID-19 cases. We calculated the standardized mortality ratio (SMR) for COVID-19, comparing adults living with and without HIV using modeled population estimates.Among 3 460 932 patients (16% living with HIV), 22 308 were diagnosed with COVID-19, of whom 625 died. COVID19 death was associated with male sex, increasing age, diabetes, hypertension, and chronic kidney disease. HIV was associated with COVID-19 mortality (adjusted hazard ratio [aHR], 2.14; 95% confidence interval [CI], 1.70–2.70), with similar risks across strata of viral loads and immunosuppression. Current and previous diagnoses of tuberculosis were associated with COVID-19 death (aHR, 2.70 [95% CI, 1.81–4.04] and 1.51 [95% CI, 1.18–1.93], respectively). The SMR for COVID-19 death associated with HIV was 2.39 (95% CI, 1.96–2.86); population attributable fraction 8.5% (95% CI, 6.1–11.1)

Integrated Risk Assessment of Suicidal Ideation and Behavior in Drug Development

Suicide is a major public health concern with emerging understanding of its neuropharmacological basis. Treatment-related suicidal ideation and behavior (SIB) as adverse events of psychiatric and non-psychiatric drugs are under increasing public, legal and regulatory scrutiny. Prospective assessment of SIB is emerging as a challenging safety requirement by health authorities worldwide for the development of certain drugs while the underlying risk factors remain ill defined. To help with the understanding and harmoniation of risk factors that trigger a prospective assessment of SIB in clinical trials, Bristol-Meyers-Squibb, Eli Lilly, Novartis, Pfizer and Roche/Genentech present a consensus framework for risk assessment and decision making of SIB during drug development. Application of this strategy is based on chemical and pharmacological similarities of compounds with clinical evidence of suicidal intent, target/indication classes associated with high incidence of SIB, in vitro neuropharmacological activity profile, in vivo ADME properties, the patient population of the underlying indication and regulatory precedents

External-cavity designs for phase-coupled laser diode arrays

International audienceWe describe passive phase-locking architectures based on external-cavity setups to improve the brightness of diode laser bars. Volume Bragg gratings are used to stabilize the lase line. Numerical modelling and experimental results will be presented

Preclinical Studies on LY237733, a Potent and Selective Serotonergic Antagonist

is an ergoline with potent and highly selective 5-hydroxytryptamine (5-HI) antagonist activity

Aryl propanolamines: comparison of activity at human β(3) receptors, rat β(3) receptors and rat atrial receptors mediating tachycardia

1. The in vitro activity of four aryl propanolamines was compared to two prototypic β(3) receptor agonists, CGP 12177 and CL316243 at the human β(3) receptor, the rat β(3) receptor in the stomach fundus and receptors mediating atrial tachycardia. 2. L-739,574 was the most potent (EC(50)=9 nM) and selective agonist at the human β(3) receptor with high maximal response (74% of the maximal response to isoproterenol). 3. A phenol-biaryl ether analogue possessed modest affinity for the human β(3) receptor (EC(50)=246 nM), but was highly efficacious with a maximal response 82% of the maximal response to isoproterenol. The other derivatives were intermediate in potency with low maximal responses. 4. These agonists at the human β(3) receptor did not activate the rat β(3) receptor in the rat stomach fundus. In fact, the aryl propanolamines (10(−6) M) inhibited CL316243-induced activation of the rat β(3) receptor. Thus, agonist activity at the human β(3) receptor translated into antagonist activity at the rat β(3) receptor. 5. L739,574 and the phenol biaryl ether increased heart rate via β(1) receptors. 6. Although CGP12177 produced atrial tachycardia, neither the indole sulphonamide nor biphenyl biaryl ether did, although both had high affinity for the human β(3) receptor. Thus, the atrial tachycardic receptor was not identical to the human β(3) receptor. 7. These studies (a) characterized four aryl propanolamines with high affinity at the human β(3) receptor, (b) found that they were antagonists at the rat β(3) receptor, an observation with profound implications for in vivo rat data, and (c) established that the rodent atrial non-β(1), β(2) or β(3) tachycardic receptor was also unrelated to the human β(3) receptor