Excessive interstitial free-water in cortical gray matter preceding accelerated volume changes in individuals at clinical high risk for psychosis.

Recent studies show that accelerated cortical gray matter (GM) volume reduction seen in anatomical MRI can help distinguish between individuals at clinical high risk (CHR) for psychosis who will develop psychosis and those who will not. This reduction is suggested to represent atypical developmental or degenerative changes accompanying an accumulation of microstructural changes, such as decreased spine density and dendritic arborization. Detecting the microstructural sources of these changes before they accumulate into volume loss is crucial. Our study aimed to detect these microstructural GM alterations using diffusion MRI (dMRI). We tested for baseline and longitudinal group differences in anatomical and dMRI data from 160 individuals at CHR and 96 healthy controls (HC) acquired in a single imaging site. Of the CHR individuals, 33 developed psychosis (CHR-P), while 127 did not (CHR-NP). Among all participants, longitudinal data was available for 45 HCs, 17 CHR-P, and 66 CHR-NP. Eight cortical lobes were examined for GM volume and GM microstructure. A novel dMRI measure, interstitial free water (iFW), was used to quantify GM microstructure by eliminating cerebrospinal fluid contribution. Additionally, we assessed whether these measures differentiated the CHR-P from the CHR-NP. In addition, for completeness, we also investigated changes in cortical thickness and in white matter (WM) microstructure. At baseline the CHR group had significantly higher iFW than HC in the prefrontal, temporal, parietal, and occipital lobes, while volume was reduced only in the temporal lobe. Neither iFW nor volume differentiated between the CHR-P and CHR-NP groups at baseline. However, in many brain areas, the CHR-P group demonstrated significantly accelerated changes (iFW increase and volume reduction) with time than the CHR-NP group. Cortical thickness provided similar results as volume, and there were no significant changes in WM microstructure. Our results demonstrate that microstructural GM changes in individuals at CHR have a wider extent than volumetric changes or microstructural WM changes, and they predate the acceleration of brain changes that occur around psychosis onset. Microstructural GM changes, as reflected by the increased iFW, are thus an early pathology at the prodromal stage of psychosis that may be useful for a better mechanistic understanding of psychosis development.

Assessing social cognition in patients with schizophrenia and healthy controls using the reading the mind in the eyes test (RMET): a systematic review and meta-regression.

The reading the mind in the eyes test (RMET) - which assesses the theory of mind component of social cognition - is often used to compare social cognition between patients with schizophrenia and healthy controls. There is, however, no systematic review integrating the results of these studies. We identified 198 studies published before July 2020 that administered RMET to patients with schizophrenia or healthy controls from three English-language and two Chinese-language databases. These studies included 41 separate samples of patients with schizophrenia (total n = 1836) and 197 separate samples of healthy controls (total n = 23 675). The pooled RMET score was 19.76 (95% CI 18.91-20.60) in patients and 25.53 (95% CI 25.19-25.87) in controls (z = 12.41, p < 0.001). After excluding small-sample outlier studies, this difference in RMET performance was greater in studies using non-English v. English versions of RMET (Chi [Q] = 8.54, p < 0.001). Meta-regression analyses found a negative association of age with RMET score and a positive association of years of schooling with RMET score in both patients and controls. A secondary meta-analysis using a spline construction of 180 healthy control samples identified a non-monotonic relationship between age and RMET score - RMET scores increased with age before 31 and decreased with age after 31. These results indicate that patients with schizophrenia have substantial deficits in theory of mind compared with healthy controls, supporting the construct validity of RMET as a measure of social cognition. The different results for English versus non-English versions of RMET and the non-monotonic relationship between age and RMET score highlight the importance of the language of administration of RMET and the possibility that the relationship of aging with theory of mind is different from the relationship of aging with other types of cognitive functioning.

Improving prediction of psychosis in youth at clinical high-risk: pre-baseline symptom duration and cortical thinning as moderators of the NAPLS2 risk calculator.

BACKGROUND: Clinical implementation of risk calculator models in the clinical high-risk for psychosis (CHR-P) population has been hindered by heterogeneous risk distributions across study cohorts which could be attributed to pre-ascertainment illness progression. To examine this, we tested whether the duration of attenuated psychotic symptom (APS) worsening prior to baseline moderated performance of the North American prodrome longitudinal study 2 (NAPLS2) risk calculator. We also examined whether rates of cortical thinning, another marker of illness progression, bolstered clinical prediction models. METHODS: Participants from both the NAPLS2 and NAPLS3 samples were classified as either 'long' or 'short' symptom duration based on time since APS increase prior to baseline. The NAPLS2 risk calculator model was applied to each of these groups. In a subset of NAPLS3 participants who completed follow-up magnetic resonance imaging scans, change in cortical thickness was combined with the individual risk score to predict conversion to psychosis. RESULTS: The risk calculator models achieved similar performance across the combined NAPLS2/NAPLS3 sample [area under the curve (AUC) = 0.69], the long duration group (AUC = 0.71), and the short duration group (AUC = 0.71). The shorter duration group was younger and had higher baseline APS than the longer duration group. The addition of cortical thinning improved the prediction of conversion significantly for the short duration group (AUC = 0.84), with a moderate improvement in prediction for the longer duration group (AUC = 0.78). CONCLUSIONS: These results suggest that early illness progression differs among CHR-P patients, is detectable with both clinical and neuroimaging measures, and could play an essential role in the prediction of clinical outcomes.

Plasma complement and coagulation proteins as prognostic factors of negative symptoms: An analysis of the NAPLS 2 and 3 studies.

INTRODUCTION: Negative symptoms impact the quality of life of individuals with psychosis and current treatment options for negative symptoms have limited effectiveness. Previous studies have demonstrated that complement and coagulation pathway protein levels are related to later psychotic experiences, psychotic disorder, and functioning. However, the prognostic relationship between complement and coagulation proteins and negative symptoms is poorly characterised. METHODS: In the North American Prodrome Longitudinal Studies 2 and 3, negative symptoms in 431 individuals at clinical high-risk for psychosis (mean age: 18.2, SD 3.6; 42.5 % female) were measured at multiple visits over 2 years using the Scale of Psychosis-Risk Symptoms. Plasma proteins were quantified at baseline using mass spectrometry. Four factors were derived to represent levels of proteins involved in the activation or regulation of the complement or coagulation systems. The relationships between standardised protein group factors and serial measurements of negative symptoms over time were modelled using generalised least squares regression. Analyses were adjusted for baseline candidate prognostic factors: negative symptoms, positive symptoms, functioning, depressive symptoms, suicidal ideation, cannabis use, tobacco use, antipsychotic use, antidepressant use, age, and sex. RESULTS: Clinical and demographic prognostic factors of follow-up negative symptoms included negative, positive, and depressive symptoms, functioning, and age. Adjusting for all candidate prognostic factors, the complement regulators group and the coagulation regulators group were identified as prognostic factors of follow-up negative symptoms (ß: 0.501, 95 % CI: 0.160, 0.842; ß: 0.430, 95 % CI: 0.080, 0.780 respectively. The relationship between complement regulator levels and negative symptoms was also observed in NAPLS2 alone (ß: 0.501, 95 % CI: -0.037, 1.039) and NAPLS3 alone, additionally adjusting for BMI (ß: 0.442, 95 % CI: 0.127, 0.757). CONCLUSION: The results indicate that plasma complement and coagulation regulator levels are prognostic factors of negative symptoms, independent of clinical and demographic prognostic factors. These results suggest complement and coagulation regulator levels could have potential utility in informing treatment decisions for negative symptoms in individuals at risk.

Differential expression of haptoglobin in individuals at clinical high risk of psychosis and its association with global functioning and clinical symptoms.

BACKGROUND: Immune dysregulation has been observed in patients with schizophrenia or first-episode psychosis, but few have examined dysregulation in those at clinical high-risk (CHR) for psychosis. The aim of this study was to examine whether the peripheral blood-based proteome was dysregulated in those with CHR. Secondly, we examined whether baseline dysregulation was related to current and future functioning and clinical symptoms. METHODS: We used data from participants of the North American Prodromal Longitudinal Studies (NAPLS) 2 and 3 (n = 715) who provided blood samples (Unaffected Comparison subjects (UC) n = 223 and CHR n = 483). Baseline proteomic data was quantified from plasma samples using mass spectrometry. Differential expression was examined between CHR and UC using logistic regression. Psychosocial functioning was measured using the Global Assessment of Functioning scale (GAF). Symptoms were measured using the subscale scores from the Scale of Psychosis-risk Symptoms; positive, negative, general, and disorganised. Three measures of each outcome were included: baseline, longest available follow-up (last follow-up) and most severe follow-up (MSF). Associations between the proteomic data, GAF and symptoms were assessed using ordinal regression. RESULTS: Of the 99 proteins quantified, six were differentially expressed between UC and CHR. However, only haptoglobin (HP) survived FDR-correction (OR:1.45, 95 %CI:1.23-1.69, padj = <0.001). HP was cross-sectionally and longitudinally associated with functioning and symptoms such that higher HP values were associated with poorer functioning and more severe symptoms. Results were evident after stringent adjustment and poorer functioning was observed in both NAPLS cohort separately. CONCLUSION: We demonstrate that elevated HP is robustly observed in those at CHR for psychosis, irrespective of transition to psychosis. HP is longitudinally associated with poorer functioning and greater symptom severity. These results agree with previous reports of increased HP gene expression in individuals at-risk for psychosis and with the dysfunction of the acute phase inflammatory response seen in psychotic disorders.

Linking enlarged choroid plexus with plasma analyte and structural phenotypes in clinical high risk for psychosis: A multisite neuroimaging study.

BACKGROUND: Choroid plexus (ChP) enlargement exists in first-episode and chronic psychosis, but whether enlargement occurs before psychosis onset is unknown. This study investigated whether ChP volume is enlarged in individuals with clinical high-risk (CHR) for psychosis and whether these changes are related to clinical, neuroanatomical, and plasma analytes. METHODS: Clinical and neuroimaging data from the North American Prodrome Longitudinal Study 2 (NAPLS2) was used for analysis. 509 participants (169 controls, 340 CHR) were recruited. Conversion status was determined after 2-years of follow-up, with 36 psychosis converters. The lateral ventricle ChP was manually segmented from baseline scans. A subsample of 31 controls and 53 CHR had plasma analyte and neuroimaging data. RESULTS: Compared to controls, CHR (d = 0.23, p = 0.017) and non-converters (d = 0.22, p = 0.03) demonstrated higher ChP volumes, but not in converters. In CHR, greater ChP volume correlated with lower cortical (r = -0.22, p < 0.001), subcortical gray matter (r = -0.21, p < 0.001), and total white matter volume (r = -0.28,p < 0.001), as well as larger lateral ventricle volume (r = 0.63,p < 0.001). Greater ChP volume correlated with makers functionally associated with the lateral ventricle ChP in CHR [CCL1 (r = -0.30, p = 0.035), ICAM1 (r = 0.33, p = 0.02)], converters [IL1ß (r = 0.66, p = 0.004)], and non-converters [BMP6 (r = -0.96, p < 0.001), CALB1 (r = -0.98, p < 0.001), ICAM1 (r = 0.80, p = 0.003), SELE (r = 0.59, p = 0.026), SHBG (r = 0.99, p < 0.001), TNFRSF10C (r = 0.78, p = 0.001)]. CONCLUSIONS: CHR and non-converters demonstrated significantly larger ChP volumes compared to controls. Enlarged ChP was associated with neuroanatomical alterations and analyte markers functionally associated with the ChP. These findings suggest that the ChP may be a key an important biomarker in CHR.

A hepatitis B virus core antigen-based virus-like particle vaccine expressing SARS-CoV-2 B and T cell epitopes induces epitope-specific humoral and cell-mediated immune responses but confers limited protection against SARS-CoV-2 infection.

The hepatitis B virus core antigen (HBcAg) tolerates insertion of foreign epitopes and maintains its ability to self-assemble into virus-like particles (VLPs). We constructed a ∆HBcAg-based VLP vaccine expressing three predicted severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) B and T cell epitopes and determined its immunogenicity and protective efficacy. The recombinant ∆HBcAg-SARS-CoV-2 protein was expressed in Escherichia coli, purified, and shown to form VLPs. K18-hACE2 transgenic C57BL/6 mice were immunized intramuscularly with ∆HBcAg VLP control (n = 15) or ∆HBcAg-SARS-CoV-2 VLP vaccine (n = 15). One week after the 2nd booster and before virus challenge, five ∆HBcAg-SARS-CoV-2 vaccinated mice were euthanized to evaluate epitope-specific immune responses. There is a statistically significant increase in epitope-specific Immunoglobulin G (IgG) response, and statistically higher interleukin 6 (IL-6) and monocyte chemoattractant protein-1 (MCP-1) expression levels in ∆HBcAg-SARS-CoV-2 VLP-vaccinated mice compared to ∆HBcAg VLP controls. While not statistically significant, the ∆HBcAg-SARS-CoV-2 VLP mice had numerically more memory CD8+ T-cells, and 3/5 mice also had numerically higher levels of interferon gamma (IFN-γ) and tumor necrosis factor (TNF). After challenge with SARS-CoV-2, ∆HBcAg-SARS-CoV-2 immunized mice had numerically lower viral RNA loads in the lung, and slightly higher survival, but the differences are not statistically significant. These results indicate that the ∆HBcAg-SARS-CoV-2 VLP vaccine elicits epitope-specific humoral and cell-mediated immune responses but they were insufficient against SARS-CoV-2 infection.

Characterization and surgical management of aberrant subclavian arteries.

OBJECTIVE: Aberrant subclavian arteries (aSCAs), with or without aortic pathology, are uncommon. The purpose of the present study was to review our experience with the surgical management of aSCA. METHODS: We performed a retrospective review of patients who had undergone surgery for an aSCA between 1996 and 2020. Symptomatic and asymptomatic patients were included. The primary end points were ≤30-day and late mortality. The secondary end points were ≤30-day complications, graft patency, and reinterventions. RESULTS: A total of 46 symptomatic and 3 asymptomatic patients with aSCA had undergone surgery (31 females [62%]; median age, 45 years). An aberrant right subclavian artery was present in 38 (78%) and an aberrant left subclavian artery in 11 patients (22%). Of the 49 patients, 41 (84%) had had a Kommerell diverticulum (KD) and 11 (22%) had had a concomitant distal arch or proximal descending thoracic aortic aneurysm. Symptoms included dysphagia (56%), dyspnea (27%), odynophagia (20%), and upper extremity exertional fatigue (16%). Five patients (10%) had required emergency surgery. The aSCA had been treated by transposition in 32, a carotid to subclavian bypass in 11, and an ascending aorta to subclavian bypass in 6. The KD was treated by resection and oversewing in 19 patients (39%). Fifteen patients (31%) had required distal arch or proximal descending thoracic aortic replacement for concomitant aortic disease and/or KD treatment. Thoracic endovascular aortic repair was used to exclude the KD in six patients (12%). Seven patients (14%) had undergone only bypass or transposition. The 30-day complications included one death from pulseless electrical activity arrest secondary to massive pulmonary embolism. The 30-day major complications (14%) included acute respiratory failure in three, early mortality in one, stroke in one, non-ST-elevation myocardial infarction in one, and temporary dialysis in one patient. The other complications included chylothorax/lymphocele (n = 5; 10%), acute kidney injury (n = 2; 4%), pneumonia (n = 2; 4%), wound infection (n = 2; 4%), atrial fibrillation (n = 2; 4%), Horner syndrome (n = 2; 4%), lower extremity acute limb ischemia (n = 1; 2%), and left recurrent laryngeal nerve injury (n = 1; 2%). At a median follow-up of 53 months (range, 1-230 months), 40 patients (82%) had had complete symptom relief and 9 (18%) had experienced improvement. Six patients had died at a median of 157 months; the deaths were not procedure or aortic related. The primary patency was 98%. Reintervention at ≤30 days had been required for two patients (4%) for ligation of lymphatic vessels and bilateral lower extremity fasciotomy after proximal descending thoracic aorta replacement. One patient had required late explantation of an infected and occluded carotid to subclavian bypass graft, which was treated by cryopreserved allograft replacement. CONCLUSIONS: Surgical treatment of the aSCA can be accomplished with low major morbidity and mortality with excellent primary patency and symptom relief.

The Impact of Patient Sex on Outcomes after Endovascular Treatment of Aortoiliac Occlusive Disease.

BACKGROUND: The aim of this study was to explore the effect of patient sex on short-term and long-term outcomes after endovascular treatment for aortoiliac occlusive disease (AIOD). METHODS: A multicenter retrospective analysis was performed on all patients who underwent iliac artery stenting for AIOD across the 3 participating sites from October 1, 2018 to September 21, 2021. Preoperative clinical, operative, and postoperative data were collected on a dedicated database. Demographics and outcomes were compared between male and female patients and the probability of freedom from amputation and freedom from target lesion reintervention were estimated with the Kaplan-Meier method. RESULTS: Of 574 patients, 346 (60%) were male and 228 (40%) were female. Mean follow-up was 12 months. Female patients were significantly older (69.2 ± 10.2 years vs. 67.8 ± 8.9 years, P = 0.025) and more likely to have Trans-Atlantic Inter-Society Consensus II D disease (P = 0.003). The female cohort had significantly less coronary artery disease (40% vs. 50%, P = 0.013), coronary stenting (14% vs. 21%, P = 0.039), and coronary artery bypass grafting (13% vs. 25%, P < 0.001) than the male cohort, as well as less statin use (69% vs. 80%, P = 0.004). There were no differences in stent type, concomitant open surgery, intraoperative events, or hospital length of stay. For 30-day postoperative complications, female patients had a significantly higher rate of thrombotic acute limb ischemia (2% vs. 0%, P = 0.01), while male patients had a higher rate of amputation (4% vs. 9%, P = 0.048). On mid-term outcomes, there was no difference in freedom from amputation or target lesion reintervention between male and female patients (P = 0.14 and P = 0.32, respectively). CONCLUSIONS: Female patients had lower incidence of cardiovascular risk factors but presented with higher Trans-Atlantic Inter-Society Consensus II classification and had higher rates of 30-day thrombotic acute limb ischemia. Male patients were more likely to require amputation within 30 days. Despite no differences in the mid-term, these short-term findings suggest that patient sex may be a relevant consideration in postoperative management and surveillance after endovascular treatment of AIOD.

Migrant status, clinical symptoms and functional outcome in youth at clinical high risk for psychosis: findings from the NAPLS-3 study.

PURPOSE: Migrant status is a known risk factor for psychosis, but the underlying causes of this vulnerability are poorly understood. Recently, studies have begun to explore whether migrant status predicts transition to psychosis in individuals at clinical high risk (CHR) for psychosis. Results, however, have been inconclusive. The present study assessed the impact of migrant status on clinical symptoms and functional outcome in individuals at CHR for psychosis who took part in the NAPLS-3 study. METHODS: Participants' migrant status was classified as native-born, first-generation, or second-generation migrant. Clinical symptoms were assessed using the Structured Interview for Psychosis-Risk Syndromes (SIPS); functional outcome was measured using the Global Functioning Scales:Social and Role (GF:S; GF:R). Assessments were conducted at baseline, 12-months, 18-months, and 24-months follow-up. Generalized linear mixed models for repeated measures were used to examine changes over time and differences between groups. RESULTS: The overall sample included 710 individuals at CHR for psychosis (54.2% males; Age: M = 18.19; SD = 4.04). A mixed model analysis was conducted, and no significant differences between groups in symptoms or functioning were observed at any time point. Over time, significant improvement in symptoms and functioning was observed within each group. Transition rates did not differ across groups. CONCLUSION: We discuss potential factors that might explain the lack of group differences. Overall, migrants are a heterogeneous population. Discerning the impact of migration from that of neighborhood ethnic density, social disadvantage or socio-economic status of different ethnic groups could help better understand vulnerability and resilience to psychosis.

Longitudinal change in neurocognitive functioning in children and adolescents at clinical high risk for psychosis: a systematic review.

Clinical high risk of psychosis (CHR-P) population has become an attractive area of interest in preventing transitions to psychosis. The consequences of developing a psychotic disorder may be worse in cases of early onset. Thus, childhood and adolescence represent a critical developmental window, where opportunities to gain social and adaptive abilities depend on the individuals' neurocognitive performance. There have been previous syntheses of the evidence regarding neurocognitive functioning in CHR-P individuals and its longitudinal changes. However, there has been less focus on children and adolescents at CHR-P. A multistep literature search was performed from database inception until July 15th, 2022. PRIMSA/MOOSE compliant systematic review and PROSPERO protocol were used to identify studies reporting on longitudinal changes in neurocognitive functioning in children and adolescents (mean age of sample ≤ 18 years) at CHR-P and matched healthy control (HC) group. A systematic review of identified studies was then undertaken. Three articles were included, resulting in a total sample size of 151 CHR-P patients [mean (SD) age, 16.48 (2.41) years; 32.45% female] and 64 HC individuals [mean (SD) age, 16.79 (2.38) years; 42.18% female]. CHR-P individuals had worse outcomes in verbal learning, sustained attention and executive functioning domains compared to HC. Individuals taking antidepressants had better outcomes in verbal learning in contrast with those taking antipsychotics. In children and adolescents, neurocognition may be already impaired before the psychosis onset, and remains stable during the transition to psychosis. Further study should be performed to obtain more robust evidence.

White matter changes in psychosis risk relate to development and are not impacted by the transition to psychosis.

Subtle alterations in white matter microstructure are observed in youth at clinical high risk (CHR) for psychosis. However, the timing of these changes and their relationships to the emergence of psychosis remain unclear. Here, we track the evolution of white matter abnormalities in a large, longitudinal cohort of CHR individuals comprising the North American Prodrome Longitudinal Study (NAPLS-3). Multi-shell diffusion magnetic resonance imaging data were collected across multiple timepoints (1-5 over 1 year) in 286 subjects (aged 12-32 years): 25 CHR individuals who transitioned to psychosis (CHR-P; 61 scans), 205 CHR subjects with unknown transition outcome after the 1-year follow-up period (CHR-U; 596 scans), and 56 healthy controls (195 scans). Linear mixed effects models were fitted to infer the impact of age and illness-onset on variation in the fractional anisotropy of cellular tissue (FAT) and the volume fraction of extracellular free water (FW). Baseline measures of white matter microstructure did not differentiate between HC, CHR-U and CHR-P individuals. However, age trajectories differed between the three groups in line with a developmental effect: CHR-P and CHR-U groups displayed higher FAT in adolescence, and 4% lower FAT by 30 years of age compared to controls. Furthermore, older CHR-P subjects (20+ years) displayed 4% higher FW in the forceps major (p < 0.05). Prospective analysis in CHR-P did not reveal a significant impact of illness onset on regional FAT or FW, suggesting that transition to psychosis is not marked by dramatic change in white matter microstructure. Instead, clinical high risk for psychosis-regardless of transition outcome-is characterized by subtle age-related white matter changes that occur in tandem with development.

"Large Diameter" Aortic Endografts are Associated With Aneurysm Sac Expansion.

BACKGROUND: The purpose of this study was to evaluate the association between aortic endograft diameter and long-term outcomes following endovascular aneurysm repair (EVAR) performed in accordance with manufacturer instructions for use (IFU). METHODS: A retrospective review of consecutive patients undergoing on-IFU EVAR (2000-2018) was performed to facilitate a comparative analysis of long-term patient outcomes based on device diameter. "Large diameter" devices were defined as >34 mm. The primary outcome of interest was freedom from sac expansion throughout long-term follow-up. Analyses included standard bivariate analyses, Kaplan-Meier with log-rank comparison, and Cox proportional hazards multivariate analysis. RESULTS: A total of 1,099 underwent on-IFU EVAR from 2000-2018. Follow-up data were available for 980 patients. Of these, 75 patients (7.6%) were treated with >34-mm devices. There were no significant differences in demographics or comorbidities between the 2 groups, although preoperative abdominal aortic aneurysm size was greater in patients undergoing implantation of >34-mm devices (58 ± 8.5 mm vs. 56 ± 17.4 mm; P = 0.05). Median follow-up was 10.3 years. Patients with grafts >34 mm had reduced freedom from sac expansion throughout follow-up (P = 0.038). There were no significant differences in reintervention rates, open conversion, or rupture when stratified by graft diameter. A multivariate Cox regression identified patient age, preoperative abdominal aortic aneurysm size, need for reintervention, and use of >34-mm endografts as independent factors associated with expansion. CONCLUSIONS: The use of large diameter aortic endografts is associated with higher rates of sac expansion during long-term follow-up. Although there is undoubtedly a role for large diameter graft use in selected patients, it is important to recognize that these devices were typically approved post hoc without the same regulatory scrutiny of smaller endografts. These findings underscore the importance of ongoing surveillance for patients treated with >34-mm grafts, irrespective of compliance with manufacturer IFU.

Impact of "Defensive Medicine" on the Costs of Diabetes and Associated Conditions.

BACKGROUND: Geographic variation in health care spending is typically attributed to differences in patient health status and provider practice patterns. While medicolegal considerations (i.e., "defensive medicine") anecdotally impact health care spending, this phenomenon is difficult to measure. The purpose of this study was to explore the association between the medicolegal environment and Medicare costs for diabetes and associated conditions of interest to vascular surgeons. Specifically, we hypothesized that an adverse medicolegal environment is associated with higher per capita Medicare costs for diabetic patients. METHODS: Medicare data including the most recent (2018) Medicare Geographic Variation Public Use Files and Chronic Conditions Data Files were linked to National Practitioner Data Bank files from the preceding 5 years (2013-2017), in addition to the US census data and American Medical Association workforce statistics. The state-level medicolegal environment was characterized by K-means clustering across a panel of metrics related to malpractice payment magnitude and prevalence. Per capita Medicare spending for diabetes was compared across 5 distinct medicolegal environments. Costs were standardized and risk-adjusted to account for known geographic variation in health care costs and patient population. Analysis of variance was applied to unadjusted data, followed by multivariate regression modeling. Readmission rates, per capita imaging studies, per capita tests, per capita procedures, and lower extremity amputation rates were compared between the least litigious quintile from the K-means clustering and the 2 most litigious quintiles. RESULTS: The median unadjusted Medicare per capita expenditure on diabetic patients was $15,963 ($14,885-$17,673), ranging from $13,762 (Iowa) to $21,865 (D.C.). A 1.6-fold variation persisted after payment standardization. Cluster analysis based on malpractice-related variables yields 5 distinct medicolegal environments, based on litigation frequency and malpractice payment amounts. Per capita spending on diabetes varied, ranging from $15,799 in states with low payments and infrequent litigation to $18,838 in states with the most adverse medicolegal environment (P < 0.05). After cost standardization and risk adjustment with multiple linear regression, malpractice claim prevalence (per 100 physicians) remained an independent predictor of states with the highest diabetes mellitus spending (P = 0.022). Moreover, diabetic patients in states with adverse medicolegal environments had more procedures, imaging studies, and readmissions (P < 0.05 for all) but did not have significant differences in amputation rates compared to less litigious states. CONCLUSIONS: An adverse medicolegal environment is independently associated with higher health care costs but does not result in improved outcome (i.e. amputation rate) for diabetic Medicare beneficiaries. Across states, a 1% increase in lawsuits/100 physicians was associated with a >10% increase in risk-adjusted standardized per capita costs. These findings demonstrate the potential contribution of "defensive medicine" to variation in health care utilization and spending in a population of interest to vascular surgeons.

Bullying in clinical high risk for psychosis participants from the NAPLS-3 cohort.

PURPOSE: Bullying is associated with a heightened risk for poor outcomes, including psychosis. This study aimed to replicate previous findings on bullying prevalence in clinical high-risk (CHR) individuals, to assess the longitudinal course of clinical and functional variables between bullied and non-bullied CHR and the association of bullying with premorbid functioning, clinical outcome, transition to psychosis and risk of violence. METHODS: The sample consisted of 691 CHR participants and 96 healthy controls. Participants reported whether they had experienced bullying and how long it had lasted. Assessments included DSM-5 diagnoses, attenuated psychotic symptoms, negative symptoms, social and role functioning, depression, stress, premorbid functioning, and risk of violence. The bullied and non-bullied CHR groups were compared at baseline and further longitudinally on clinical and functioning variables and transition to psychosis. RESULTS: Bullying was more prevalent among CHR individuals than healthy controls. Bullied CHR had a higher prevalence of PTSD and more severe depression and stress at baseline than non-bullied CHR. There was no impact of bullying on clinical and functional variables over time. Bullying was not related to final clinical status or transition to psychosis. However, bullied participants had poorer premorbid functioning and a greater risk of violence. CONCLUSION: While bullying may not impact the likelihood of CHR individuals to transition to psychosis, it may be a risk factor for development of the at-risk state and may be related to a greater risk of violence. Future studies should consider bullying perpetration among CHR individuals.

MK-Curve improves sensitivity to identify white matter alterations in clinical high risk for psychosis.

Diffusion kurtosis imaging (DKI) is a diffusion MRI approach that enables the measurement of brain microstructural properties, reflecting molecular restrictions and tissue heterogeneity. DKI parameters such as mean kurtosis (MK) provide additional subtle information to that provided by popular diffusion tensor imaging (DTI) parameters, and thus have been considered useful to detect white matter abnormalities, especially in populations that are not expected to show severe brain pathologies. However, DKI parameters often yield artifactual output values that are outside of the biologically plausible range, which diminish sensitivity to identify true microstructural changes. Recently we have proposed the mean-kurtosis-curve (MK-Curve) method to correct voxels with implausible DKI parameters, and demonstrated its improved performance against other approaches that correct artifacts in DKI. In this work, we aimed to evaluate the utility of the MK-Curve method to improve the identification of white matter abnormalities in group comparisons. To do so, we compared group differences, with and without the MK-Curve correction, between 115 individuals at clinical high risk for psychosis (CHR) and 93 healthy controls (HCs). We also compared the correlation of the corrected and uncorrected DKI parameters with clinical characteristics. Following the MK-curve correction, the group differences had larger effect sizes and higher statistical significance (i.e., lower p-values), demonstrating increased sensitivity to detect group differences, in particular in MK. Furthermore, the MK-curve-corrected DKI parameters displayed stronger correlations with clinical variables in CHR individuals, demonstrating the clinical relevance of the corrected parameters. Overall, following the MK-curve correction our analyses found widespread lower MK in CHR that overlapped with lower fractional anisotropy (FA), and both measures were significantly correlated with a decline in functioning and with more severe symptoms. These observations further characterize white matter alterations in the CHR stage, demonstrating that MK and FA abnormalities are widespread, and mostly overlap. The improvement in group differences and stronger correlation with clinical variables suggest that applying MK-curve would be beneficial for the detection and characterization of subtle group differences in other experiments as well.

Telemedicine in vascular surgery during the coronavirus disease-2019 pandemic: A multisite healthcare system experience.

OBJECTIVE: To assess the introduction of telemedicine as an alternative to the traditional face-to-face encounters with vascular surgery patients in the era of the coronavirus disease 2019 (COVID-19) pandemic. METHODS: A retrospective review of prospectively collected data on face-to-face and telemedicine interactions was conducted at a multisite health care system from January to August 2020 in vascular surgery patients during the COVID-19 pandemic. The end point is direct patient satisfaction comparison between face-to-face and telemedicine encounters/interactions prior and during the pandemic. RESULTS: There were 6262 patient encounters from January 1, 2020, to August 6, 2020. Of the total encounters, 790 (12.6%) were via telemedicine, which were initiated on March 11, 2020, after the World Health Organization's declaration of the COVID-19 pandemic. These telemedicine encounters were readily adopted and embraced by both the providers and patients and remain popular as an option to patients for all types of visits. Of these patients, 78.7% rated their overall health care experience during face-to-face encounters as very good and 80.6% of patients rated their health care experience during telemedicine encounters as very good (P = .78). CONCLUSIONS: Although the COVID-19 pandemic has produced unprecedented consequences to the practice of medicine and specifically of vascular surgery, our multisite health care system has been able to swiftly adapt and adopt telemedicine technologies for the care of our complex patients. Most important, the high quality of patient-reported satisfaction and health care experience has remained unchanged.

Proximal fixation of endovascular aortic device may not be associated with renal function decline after abdominal aortic aneurysm repair.

OBJECTIVE: Significant debate exists among providers who perform endovascular abdominal aortic aneurysm repair (EVAR) regarding the renal function change between suprarenal (SuF) and infrarenal (InF) fixation devices. The purpose of this study is to review our institution's experience using these devices in terms of renal function. METHODS: This is a retrospective review of all elective EVARs performed within a three-site health system (Florida, Minnesota, and Arizona) during the period of 2000 to 2018. The primary outcome was renal function decline on long-term follow-up depending on the anatomical fixation of the device (SuF vs InF). Secondary outcomes were length of hospitalization (LOH) and progression to hemodialysis. Multivariable regression analysis was performed to test for associations affecting LOH. RESULTS: There were 1130 elective EVARs included in our review. Of those, 670 (59.3%) had SuF and 460 (40.7%) InF. Long-term follow-up was 4.8 ± 3.7 years, and the rate of change in creatinine and estimated glomerular filtration rate (eGFR) were not statistically significant among groups (SuF vs InF). LOH was higher in those individuals with a SuF device (3.4 ± 2.2 vs 2.3 ± 1.0 days; P < .001). Ten patients with chronic kidney disease progressed to hemodialysis at 6.7 ± 3.8 years from EVAR. On Kaplan-Meier analysis, patients with chronic kidney disease with SuF were more likely to progress to hemodialysis (P = .039). On multivariable regression, female sex (Coef, 2.4; 95% confidence interval [CI], 0.17-0.41; P = .02), SuF (Coef, 9.5; 95% CI, 0.11-1.11; P < .0001), and intraoperative blood loss of greater than 150 mL (Coef, 15.4; 95% CI, 0.11-1.76; P < .0001) were predictors of prolonged LOH. CONCLUSIONS: Our three-site, single-institution data indicate that, although the starting eGFR was statistically lower in those individuals undergoing elective EVAR with InF, device fixation type did not affect the creatinine and eGFR on long-term follow-up. However, caution should be exercised at the time of abdominal aortic aneurysm repair in those individuals who already presented with renal dysfunction.

Women have similar mortality but higher morbidity than men after elective endovascular abdominal aortic aneurysm repair.

OBJECTIVE: Sex disparities regarding outcomes for women after open and endovascular abdominal aortic aneurysm repair have been well-documented. The purpose of this study was to review whether these disparities were also present at our institution for elective endovascular aneurysm repair (EVAR) and whether specific factors predispose female patients to negative outcomes. METHODS: All elective EVARs were identified from our three sites (Florida, Minnesota, and Arizona) from 2000 to 2018. The primary outcome was in-hospital mortality and three-year mortality. Secondary outcomes included complications requiring return to the operating room, length of hospitalization (LOH), intensive care unit (ICU) days, and location of discharge after hospitalization. Multivariable logistic regression models were used to assess for the risk of complications. RESULTS: There were 1986 EVARs; 1754 (88.3%) were performed in male and 232 (11.7%) in female patients. Female patients were older (79 years [interquartile range (IQR), 72-83 years] vs 76 years [IQR, 70-81 years]; P < .001), had a lower body mass index (median, 26.1 kg/m2 [IQR, 22.1-31.0 kg/m2] vs 28.3 kg/m2 [IQR, 25.3-31.6 kg/m2]; P < .001 and hematocrit (median, 37.6% [IQR, 33.4%-40.6%] vs 39.4% [IQR, 35.6%-42.6%]; P < .001) and had higher glomerular filtration rate (median, 84.4 mL/min per 1.73m2 [IQR, 62.3-103 mL/min/1.73 m2] vs 51.1 mL/min/1.73 m2 [IQR, 41.8-60.8 mL/min/1.73 m2]; P < .001. Female patients were also more likely to be active smokers (15.3% vs 13.1%; P < .001) and have chronic obstructive pulmonary disease (24.7% vs 15.3%; P = .001). They were less likely to have coronary artery disease (31.6% vs 45.6%; P < .001). Aneurysms in women were slightly smaller in size (median, 54 mm [IQR, 50.0-58.0 mm] vs 55 mm [IQR, 51.0-60.0 mm]; P = .004). In-hospital mortality and mortality at the 3-year follow-up was not significant between female and male patients (0.86% vs 0.17%; P = .11 and 38.4% vs 36.2%; P = .57). However, female patients returned to the operating room with a greater frequency than male patients (3.9% vs 1.4%; P = .011). LOH (mean, 3.4 ± 3.8 days vs 2.5 ± 2.4 days; P < .001) and ICU days (mean, 0.3 ± 2.0 days vs 0.1 ± 0.5 days; P < .001) were longer for female patients. After hospitalization, female patients were discharged to rehabilitation facilities in greater proportion (12.7% vs 3.1%; P < .001) than their male counterparts. On multivariable analysis, female sex was associated with a return to the operating room (odds ratio, 6.4; 95% confidence interval [CI], 1.4-3.5; P = .02), longer LOH (Coef 4.0; 95% CI, 1.0-2.5; P = .00007), more ICU days (Coef 2.8; 95% CI, 1.1-3.0; P = .005), and a greater likelihood of posthospitalization rehabilitation facility placement (odds ratio, 5.8; 95% CI, 1.5-2.4; P = .0001). CONCLUSIONS: Our three-site, single-institution data support sex disparities to the detriment of female patients regarding return to the operating room after EVAR, LOH, ICU days, and discharge to rehabilitation facility. However, we found no differences for in-hospital or 3-year mortality.

Calculating individualized risk components using a mobile app-based risk calculator for clinical high risk of psychosis: findings from ShangHai At Risk for Psychosis (SHARP) program.

BACKGROUND: Only 30% or fewer of individuals at clinical high risk (CHR) convert to full psychosis within 2 years. Efforts are thus underway to refine risk identification strategies to increase their predictive power. Our objective was to develop and validate the predictive accuracy and individualized risk components of a mobile app-based psychosis risk calculator (RC) in a CHR sample from the SHARP (ShangHai At Risk for Psychosis) program. METHOD: In total, 400 CHR individuals were identified by the Chinese version of the Structured Interview for Prodromal Syndromes. In the first phase of 300 CHR individuals, 196 subjects (65.3%) who completed neurocognitive assessments and had at least a 2-year follow-up assessment were included in the construction of an RC for psychosis. In the second phase of the SHARP sample of 100 subjects, 93 with data integrity were included to validate the performance of the SHARP-RC. RESULTS: The SHARP-RC showed good discrimination of subsequent transition to psychosis with an AUC of 0.78 (p < 0.001). The individualized risk generated by the SHARP-RC provided a solid estimation of conversion in the independent validation sample, with an AUC of 0.80 (p = 0.003). A risk estimate of 20% or higher had excellent sensitivity (84%) and moderate specificity (63%) for the prediction of psychosis. The relative contribution of individual risk components can be simultaneously generated. The mobile app-based SHARP-RC was developed as a convenient tool for individualized psychosis risk appraisal. CONCLUSIONS: The SHARP-RC provides a practical tool not only for assessing the probability that an individual at CHR will develop full psychosis, but also personal risk components that might be targeted in early intervention.