Second asymptomatic carotid surgery trial (ACST-2): a randomised comparison of carotid artery stenting versus carotid endarterectomy

Background: Among asymptomatic patients with severe carotid artery stenosis but no recent stroke or transient cerebral ischaemia, either carotid artery stenting (CAS) or carotid endarterectomy (CEA) can restore patency and reduce long-term stroke risks. However, from recent national registry data, each option causes about 1% procedural risk of disabling stroke or death. Comparison of their long-term protective effects requires large-scale randomised evidence. Methods: ACST-2 is an international multicentre randomised trial of CAS versus CEA among asymptomatic patients with severe stenosis thought to require intervention, interpreted with all other relevant trials. Patients were eligible if they had severe unilateral or bilateral carotid artery stenosis and both doctor and patient agreed that a carotid procedure should be undertaken, but they were substantially uncertain which one to choose. Patients were randomly allocated to CAS or CEA and followed up at 1 month and then annually, for a mean 5 years. Procedural events were those within 30 days of the intervention. Intention-to-treat analyses are provided. Analyses including procedural hazards use tabular methods. Analyses and meta-analyses of non-procedural strokes use Kaplan-Meier and log-rank methods. The trial is registered with the ISRCTN registry, ISRCTN21144362. Findings: Between Jan 15, 2008, and Dec 31, 2020, 3625 patients in 130 centres were randomly allocated, 1811 to CAS and 1814 to CEA, with good compliance, good medical therapy and a mean 5 years of follow-up. Overall, 1% had disabling stroke or death procedurally (15 allocated to CAS and 18 to CEA) and 2% had non-disabling procedural stroke (48 allocated to CAS and 29 to CEA). Kaplan-Meier estimates of 5-year non-procedural stroke were 2·5% in each group for fatal or disabling stroke, and 5·3% with CAS versus 4·5% with CEA for any stroke (rate ratio [RR] 1·16, 95% CI 0·86–1·57; p=0·33). Combining RRs for any non-procedural stroke in all CAS versus CEA trials, the RR was similar in symptomatic and asymptomatic patients (overall RR 1·11, 95% CI 0·91–1·32; p=0·21). Interpretation: Serious complications are similarly uncommon after competent CAS and CEA, and the long-term effects of these two carotid artery procedures on fatal or disabling stroke are comparable. Funding: UK Medical Research Council and Health Technology Assessment Programme

Frontal white matter integrity as an endophenotype for schizophrenia: diffusion tensor imaging in monozygotic twins and patients' nonpsychotic relatives

Diffusion tensor imaging (DTI) provides anatomical connectivity information by examining the directional organization of white matter microstructure. Anatomical connectivity and its abnormalities may be heritable traits associated with schizophrenia. To further examine this hypothesis, two studies were conducted to compare anatomical connectivity between (a) monozygotic (MZ) twin pairs and random pairings among twins and (b) first-degree relatives of schizophrenia patients and a healthy control group. Analyses focused on frontal regions of the brain following previous findings of anatomical connectivity abnormalities associated with schizophrenia. For Study 1, eighteen MZ twin pairs (11 female pairs, age: M=25.44, SD=5.69) were recruited. For Study 2, twenty two first-degree relatives of schizophrenia patients (14 females, age: M=48.50, SD=8.22), and 30 healthy controls (12 females, age: M=43.83, SD=11.39) were recruited. Fractional anisotropy (FA), a white matter directional organization metric, was measured with DTI. In Study 1, FA values were more strongly correlated between MZ twin pairs than between randomly generated pairs in genu of corpus callosum, anterior cingulum and forceps minor. In Study 2, relatives of schizophrenia patients showed reduced FA values in medial frontal white matter (p<0.05, corrected). The present study suggested that anatomical connectivity in medial prefrontal cortex appeared significantly heritable within MZ twin pairs, an important criterion in the development of an endophenotype. In addition, altered medial frontal white matter integrity found in non-affected relatives of schizophrenia patients seems to suggest that reduced white matter integrity in medial frontal regions of the brain might be associated with the genetic liability to schizophrenia

Introspective accuracy for substance use across a year of treatment for first episode psychosis

Substance use exacerbates psychosis, mania, depression, and poor functioning in people with first episodes of psychosis (FEP) and is associated with poor treatment outcomes, even when it does not reach the level of a formal disorder. Impaired insight and substance use are common issues that may interfere with treatment outcomes among people experiencing FEP, yet both are treatable. Improvements in these domains are associated with better outcomes. Low insight could increase risk for substance use by impairing the ability to self-appraise and assess consequences. Introspective accuracy (IA) is understudied in this area and is one way of considering self-appraisal. This study is an archival review using data collected from NAVIGATE, a coordinated specialty care program treating people with FEP. IA was operationalized as the difference between clinician and client ratings of substance use. We tested whether IA changed over one year of treatment and whether those changes occurred alongside changes in symptoms and illness self-management. No changes in IA were detected in relation to illness self-management. Changes in IA for substance use occurred midway through treatment—individuals with greater symptom remission had more overconfident IA. Prior research on insight has shown a paradox where greater insight accompanies more symptoms. However, past research has also shown a relationship between IA and functional outcomes, like illness self-management, and that overconfidence in one domain can positively bias clinician ratings in another. Our findings suggest either a positive bias for ratings associated with overconfident IA or an insight paradox type effect

Self versus informant reports on the specific levels of functioning scale: Relationships to depression and cognition in schizophrenia and schizoaffective disorder

The goal of the current study was to examine the relationships between insight and both cognitive function and depression in schizophrenia and schizoaffective disorder, and to determine if there were similar relationships across diagnostic categories. We examined discrepancies between self and informant reports of function on the Specific levels of function scale as a metric of insight for interpersonal, social acceptance, work and activities. We examined two samples of individuals with schizophrenia and/or schizoaffective disorder (Ns of 188 and 67 respectively). In Sample 1, cognition was measured using the Dot Probe Expectancy Task. In Sample 2, cognition was measured by averaging several subtests from the MATRICS consensus cognitive battery, as well as additional measures of working memory. In both samples, depression was measured using the Brief Psychiatric Rating Scale. In both samples, we found significant relationships between worse cognition and overestimations of work function, as well as between higher depression levels and underestimation of interpersonal function. These relationships were specific to interpersonal and work function, with significantly stronger correlations with interpersonal and work function compared to the other areas of function. Similar results were found across diagnostic categories. These results have important implications for treatment planning, as they suggest the need to take into account depression and cognitive function when evaluating the patient's self-report of function, and highlight the utility of informant reports in evaluating function and treatment planning. Further, they add to the literature on the similarity across schizophrenia and schizoaffective disorder in a variety of pathological mechanisms