In acute ischemic stroke, a longer time from onset to endovascular treatment (EVT) is associated with worse clinical outcome. We investigated the association of clinical outcome with time from last known well to arrival at the EVT hospital and time from hospital arrival to arterial access for anterior circulation large vessel occlusion patients treated > 6 hours from last known well.

Retrospective analysis of the prospective, multicenter cohort study ESCAPE-LATE. Patients presenting > 6 hours after last known well with anterior circulation large vessel occlusion undergoing EVT were included. The primary outcome was the modified Rankin Scale (mRS) score at 90 days. Secondary outcomes were good (mRS 0–2) and poor clinical outcomes (mRS 5–6) at 90 days, as well as the National Institutes of Health Stroke Scale at 24 hours. Associations of time intervals with outcomes were assessed with univariable and multivariable logistic regression.

Two hundred patients were included in the analysis, of whom 85 (43%) were female. 90-day mRS was available for 141 patients. Of the 150 patients, 135 (90%) had moderate-to-good collaterals, and the median Alberta Stroke Program Early CT Score (ASPECTS) was 8 (IQR = 7–10). No association between ordinal mRS and time from last known well to arrival at the EVT hospital (odds ratio [OR] = 1.01, 95% CI = 1.00–1.02) or time from hospital arrival to arterial access (OR = -0.01, 95% CI = -0.02–0.00) was seen in adjusted regression models.

No relationship was observed between pre-hospital or in-hospital workflow times and clinical outcomes. Baseline ASPECTS and collateral status were favorable in the majority of patients, suggesting that physicians may have chosen to predominantly treat slow progressors in the late time window, in whom prolonged workflow times have less impact on outcomes.

Identifying neuroimaging biomarkers of antidepressant response may help guide treatment decisions and advance precision medicine.

To examine the relationship between anhedonia and functional neurocircuitry in key reward processing brain regions in people with major depressive disorder receiving aripiprazole adjunct therapy with escitalopram.

Data were collected as part of the CAN-BIND-1 study. Participants experiencing a current major depressive episode received escitalopram for 8 weeks; escitalopram non-responders received adjunct aripiprazole for an additional 8 weeks. Functional magnetic resonance imaging (on weeks 0 and 8) and clinical assessment of anhedonia (on weeks 0, 8 and 16) were completed. Seed-based correlational analysis was employed to examine the relationship between baseline resting-state functional connectivity (rsFC), using the nucleus accumbens (NAc) and anterior cingulate cortex (ACC) as key regions of interest, and change in anhedonia severity after adjunct aripiprazole.

Anhedonia severity significantly improved after treatment with adjunct aripiprazole.

There was a positive correlation between anhedonia improvement and rsFC between the ACC and posterior cingulate cortex, ACC and posterior praecuneus, and NAc and posterior praecuneus. There was a negative correlation between anhedonia improvement and rsFC between the ACC and anterior praecuneus and NAc and anterior praecuneus.

Eight weeks of aripiprazole, adjunct to escitalopram, was associated with improved anhedonia symptoms. Changes in functional connectivity between key reward regions were associated with anhedonia improvement, suggesting aripiprazole may be an effective treatment for individuals experiencing reward-related deficits. Future studies are required to replicate our findings and explore their generalisability, using other agents with partial dopamine (D2) agonism and/or serotonin (5-HT2A) antagonism.

Despite replicated cross-sectional evidence of aberrant levels of peripheral inflammatory markers in individuals with major depressive disorder (MDD), there is limited literature on associations between inflammatory tone and response to sequential pharmacotherapies.

To assess associations between plasma levels of pro-inflammatory markers and treatment response to escitalopram and adjunctive aripiprazole in adults with MDD.

In a 16-week open-label clinical trial, 211 participants with MDD were treated with escitalopram 10– 20 mg daily for 8 weeks. Responders continued on escitalopram while non-responders received adjunctive aripiprazole 2–10 mg daily for 8 weeks. Plasma levels of pro-inflammatory markers – C-reactive protein, Interleukin (IL)-1β, IL-6, IL-17, Interferon gamma (IFN)-Γ, Tumour Necrosis Factor (TNF)-α, and Chemokine C–C motif ligand-2 (CCL-2) - measured at baseline, and after 2, 8 and 16 weeks were included in logistic regression analyses to assess associations between inflammatory markers and treatment response.

Pre-treatment levels of IFN-Γ and CCL-2 were significantly higher in escitalopram non-responders compared to responders. Pre-treatment IFN-Γ and CCL-2 levels were significantly associated with a lower of odds of response to escitalopram at 8 weeks. Increases in CCL-2 levels from weeks 8 to 16 in escitalopram non-responders were significantly associated with higher odds of non-response to adjunctive aripiprazole at week 16.

Pre-treatment levels of IFN-Γ and CCL-2 were predictive of response to escitalopram. Increasing levels of these pro-inflammatory markers may predict non-response to adjunctive aripiprazole. These findings require validation in independent clinical populations.

None Declared

To assess the proportion of inpatients who received guideline-concordant antibiotics for community-acquired bacterial pneumonia (CABP) in special populations of the All of Us database.

CABP contributes significantly to healthcare burden worldwide. The American Thoracic Society and Infectious Disease Society of America jointly published guidelines for the treatment of CABP. Guideline-concordant antibiotics for CABP are associated with better patient and cost outcomes.

This was a retrospective cohort study of patients with pneumonia (n = 1608; SNOMED 233604007) from 10/1/2018 to 1/01/22 in the All of Us database. Cases were excluded for treatment setting other than inpatient, prior (within 90 days) pneumonia, receipt of intravenous antibiotics, respiratory isolation of methicillin-resistant Staphylococcus aureus (MRSA) or Pseudomonas aeruginosa, and/or other non-community-acquired types of pneumonia. Patients were grouped based on patient age, sex, race, and ethnicity. The proportion of patients on guideline-concordant therapy was compared within groups using chi-square statistics. Significant associations were assessed using multivariate logistic regression models.

A total of 1608 cases were included, and 45% of these patients received guideline-concordant antibiotics. Non-Hispanic White (NHW) patients vs. Black patients were associated with a 36% higher likelihood for receiving guideline-concordant antibiotics (adjusted OR, 1.36; 95% CI 1.02–1.81), whereas NHW vs. Hispanic patients were associated with a 34% lower likelihood for receiving guideline-concordant antibiotics (aOR 0.66; 0.48–0.91).

Black patients with CABP in the All of Us database were less likely to receive guideline-concordant antibiotics, and Hispanic patients were more likely to receive guideline-concordant antibiotics, than NHW patients.

There is limited literature on associations between inflammatory tone and response to sequential pharmacotherapies in major depressive disorder (MDD).

In a 16-week open-label clinical trial, 211 participants with MDD were treated with escitalopram 10–20 mg daily for 8 weeks. Responders continued escitalopram while non-responders received adjunctive aripiprazole 2–10 mg daily for 8 weeks. Plasma levels of pro-inflammatory markers—C-reactive protein, interleukin (IL)-1β, IL-6, IL-17, interferon-gamma (IFN)-Γ, tumor necrosis factor (TNF)-α, and Chemokine C–C motif ligand-2 (CCL-2)—measured at baseline, and after 2, 8 and 16 weeks were included in logistic regression analyzes to assess associations between inflammatory markers and treatment response.

Pre-treatment IFN-Γ and CCL-2 levels were significantly associated with a lower of odds of response to escitalopram at 8 weeks. Increases in CCL-2 levels from weeks 8 to 16 in escitalopram non-responders were significantly associated with higher odds of non-response to adjunctive aripiprazole at week 16.

Higher pre-treatment levels of IFN-Γ and CCL-2 were associated with non-response to escitalopram. Increasing levels of these pro-inflammatory markers may be associated with non-response to adjunctive aripiprazole. These findings require validation in independent clinical populations.

Altered expression of the complement component C4A gene is a known risk factor for schizophrenia. Further, predicted brain C4A expression has also been associated with memory function highlighting that altered C4A expression in the brain may be relevant for cognitive and behavioral traits.

We obtained genetic information and performance measures on seven cognitive tasks for up to 329 773 individuals from the UK Biobank, as well as brain imaging data for a subset of 33 003 participants. Direct genotypes for variants (n = 3213) within the major histocompatibility complex region were used to impute C4 structural variation, from which predicted expression of the C4A and C4B genes in human brain tissue were predicted. We investigated if predicted brain C4A or C4B expression were associated with cognitive performance and brain imaging measures using linear regression analyses.

We identified significant negative associations between predicted C4A expression and performance on select cognitive tests, and significant associations with MRI-based cortical thickness and surface area in select regions. Finally, we observed significant inconsistent partial mediation of the effects of predicted C4A expression on cognitive performance, by specific brain structure measures.

These results demonstrate that the C4 risk locus is associated with the central endophenotypes of cognitive performance and brain morphology, even when considered independently of other genetic risk factors and in individuals without mental or neurological disorders.

Murder-Suicide may be defined as extreme pattern of domestic violence. Research is hampered by the fact that with the death of the perpetrator the files are usually closed and an analysis of the cases is hardly possible. Knowledge about the circumstances of murder-suicide, however, is of special interest for the forensic-psychiatric expert when the perpetrator survives and the need for forensic assessment arises. Since forensic-psychiatric assessment is always based on comparison with similar cases we compared the files of surviving perpetrators of murder-suicide with those of lethal domestic violence.

All forensic-psychiatric expertises about surviving perpetrators of homicide-suicide which occurred in the region of Basle, Switzerland, between 1987 and 2006 (n = 6) were compared with those of perpetrators of homicide in a domestic environment (n = 20) in the same period.

There were comparatively more women but less foreigners among the perpetrators of homicide -suicide, their socioeconomic level was much higher and there were more children among the victims. The most frequent psychiatric diagnosis in both groups was personality disorder, but the range in the domestic murder group, however, went from no diagnosis at all to psychosis, i. e. assumed full criminal responsibility to assumed not guilty by reason of insanity. There was no case of not guilty by reason of insanity among the homicide-suicide group.

The disparities of these two patterns of domestic violence are much greater than we expected, which underpins the need for specific forensic assessment as well as preventive actions.

Drugs which affect the level of dopamine have also an impact on the level of prolactine and hence influence the sexual conduct of patients. Hypersexuality is a well known side effect of the treatment of Parkinson's' disease, whereas hyposexuality is a side effect of the drug-treatment of schizophrenia by classical and some atypical antipsychotics. The novel antipsychotic drug Aripiprazole, however, has a partial dopaminergic effect, causes no hyperprolactinaemia and might alter the sexual conduct of some schizophrenic patients.

Three case reports of patients with iatrogenic forensic-psychiatric relevant hypersexuality.

Case 1: Comparatively young Parkinson-Patient with sexual desinhibition, frequent visits in brothels contracting debts and sexual harassment towards women after treatment with Ropinirol.

Case 2: Chronic hebephrenic patient with homoerotic paedophilia, who only started molesting boys after changing medication from Olanzapine to Aripiprazole.

Case 3: Chronic-paranoid young schizophrenic patient with no criminal record who seriously assaulted a foreign woman short time after changing from Amisulpiride to Aripiprazole.

Hypersexuality as side effect of the treatment of Parkinson's disease is well known, it might be more important an issue, if the patient is young. Hypersexuality as side effect of the treatment with partial dopaminergic drugs should be considered in the drug treatment of schizophrenic patients.

Recent studies suggest that the menopausal transition may constitute a period of greater risk for the development of new onset/recurrent depressive episodes. In addition, the presence of vasomotor and other menopause-related complaints may adversely affect quality of life and overall functioning. With the long-term safety of hormone therapies being questioned, non-hormonal strategies are needed for the management of symptomatic midlife women. This report is a preliminary analysis of a study investigating the effects of quetiapine extended-release (Seroquel XR) in symptomatic perimenopausal and postmenopausal women with major depressive disorder (MDD).

Peri and postmenopausal women, age 40 to 60 years, suffering from MDD and reporting menopause-related symptoms were recruited into a 2-week, placebo lead-in phase, followed by an open trial (8 weeks) with quetiapine extended-release, flexible dose, 150-300 mg/day. The primary outcome measure (i.e. changes in depressive symptoms) was assessed via Montgomery-Åsberg Depression Rating Scale (MADRS) scores. Other measures included: Hamilton Depression Rating Scale (HAM-D), menopause-related symptoms (Greene Climacteric Scale - GCS), Clinical Global Impression (CGI-S), sleep characteristics (Pittsburgh Sleep Quality Index - PSQI) and the impact of hot flashes on daily functioning (Hot Flash-Related Daily Interference Scale (HFRDIS).

Thirty-nine women (mean age 49.3±4.3 years) were enrolled in the placebo lead-in phase. Of those, 25 were considered eligible for the 8-week trial with quetiapine extended-release. This interim analysis (LOCF) included 18 women who completed 4 to 8 weeks of treatment with quetiapine extended-release (median MADRS total scores at baseline = 28 ±6.1; median final dose of quetiapine extended-release=200 mg/day). At the end of the study, 13 out of 18 (72.2%) participants achieved remission (total MADRS scores < 10). Overall, subjects showed significant reduction in total MADRS (p< 0.001) and HAM-D scores (p< 0.001). Treatment with quetiapine extended-release improved menopause-related symptoms, as shown by a decrease in Greene Climacteric Scale total scores (p< 0.001) and sub-scores for psychological (p< 0.001), vasomotor (p=0.001), and somatic (p=0.001) complaints (Wilcoxon tests). Quetiapine extended-release did affect menopause-related sexual dysfunction (changes in CGS sexual sub-scores, p=0.06). There was a substantial reduction in overall burden associated with vasomotor symptoms, i.e., decreased HFRDIS scores (p< 0.001). Lastly, sleep efficiency, perceived sleep quality, and daily sleep disturbances improved significantly after treatment with quetiapine extended-release (p< 0.001 for all PSQI sub-scores).

This is the first study examining the efficacy of Seroquel XR for the treatment of Major Depressive Disorder in a population of symptomatic peri and postmenopausal women. Treatment with Seroquel XR not only reduced depressive symptomatology but also improved vasomotor symptoms and sleep complaints. Larger randomized, placebo-controlled studies are warranted to better explore the efficacy and predictors of response with quetiapine extended-release for this specific population.