To determine the relationship between severe acute respiratory syndrome coronavirus 2 infection, hospital-acquired infections (HAIs), and mortality.

Retrospective cohort.

Three St. Louis, MO hospitals.

Adults admitted ≥48 hours from January 1, 2017 to August 31, 2020.

Hospital-acquired infections were defined as those occurring ≥48 hours after admission and were based on positive urine, respiratory, and blood cultures. Poisson interrupted time series compared mortality trajectory before (beginning January 1, 2017) and during the first 6 months of the pandemic. Multivariable logistic regression models were fitted to identify risk factors for mortality in patients with an HAI before and during the pandemic. A time-to-event analysis considered time to death and discharge by fitting Cox proportional hazards models.

Among 6,447 admissions with subsequent HAIs, patients were predominantly White (67.9%), with more females (50.9% vs 46.1%, P = .02), having slightly lower body mass index (28 vs 29, P = .001), and more having private insurance (50.6% vs 45.7%, P = .01) in the pre-pandemic period. In the pre-pandemic era, there were 1,000 (17.6%) patient deaths, whereas there were 160 deaths (21.3%, P = .01) during the pandemic. A total of 53 (42.1%) coronavirus disease 2019 (COVID-19) patients died having an HAI. Age and comorbidities increased the risk of death in patients with COVID-19 and an HAI. During the pandemic, Black patients with an HAI and COVID-19 were more likely to die than White patients with an HAI and COVID-19.

In three Midwestern hospitals, patients with concurrent HAIs and COVID-19 were more likely to die if they were Black, elderly, and had certain chronic comorbidities.

The ICD and DSM diagnostic categories do not represent entirely distinct entities because several cognitive impairments are shared across psychiatric disorders. Such shared cognitive impairments are hypothesized to be caused by common neurobiological substrates, one of which is transdiagnostic alterations in functional network connectivity (FNC).

To investigate and compare the within-network functional connectivity (WNFC) and between-network functional connectivity (BNFC) in alcohol use disorder (AUD), schizophrenia (SCZ), bipolar affective disorder (BPAD), obsessive-compulsive disorder (OCD) and healthy controls (HC) using resting-state fMRI employing a data-driven exploratory approach.

The current study was a secondary analysis of data from the ADBS project in India. After pre-processing of fMRI data, a spatially and temporally constrained group-independent component analysis in the GIFT toolbox was performed using the NeuroMark templates to generate 53 independent components (ICs). These components were divided into seven functional domains including subcortical (SC), auditory (AU), sensorimotor (SM), visual (VI), cognitive-control (CC), default-mode (DM), and cerebellar (CB). To investigate the FNC correlations associated with group status (patients or HC) univariate models were applied which were subjected to corrections for multiple comparisons at an alpha=0.05 significance level using the FDR.

The overall sample size was 249 [AUD=35, SCZ=44, BPAD=48, OCD=53, and HC=69]. Transdiagnostic WNFC alterations largely involved dysconnectivity in the CC, DM, and SC domains, resulting in ICs with both increased and decreased WNFC. Transdiagnostic BNFC alterations were primarily in the form of increased connectivity of the SC domain with various cortical domains whereas reduced connectivity was noted between AU, VI, SM, and CB domains. There was AUD-specific hyperconnectivity in the CC domain and SCZ-specific hyperconnectivity in the DM domain, and dysconnectivity in the SC domain. BPAD-specific hyperconnectivity was identified in DM and SC domains in addition to increased connectivity between CB and SM domains and decreased connectivity between CB and SC domains. All results were significant at p ≤ 0.05; [FDR] q= 0.05.

Our transdiagnostic WNFC alterations corresponded to the central executive network, default mode network, salience network, and CSTC loop, which provided transdiagnostic evidence for the triple network model of psychopathology and underlined the relevance of subcortical dysconnectivity in this model. Furthermore, our BNFC changes showed subcortical hyperconnectivity with many cortical networks, underscoring its relevance as a potential target for transdiagnostic therapeutic interventions.

None Declared

Anxiety disorders are among the most prevalent mental disorders. However, only a minority of patients receives adequate psychotherapeutic treatment despite strong empirical evidence for the efficacy of CBT in anxiety disorders (Marcks et al. Psychiatr Serv 2009; 60 823-830). App-based psychotherapy can help to reduce this massive treatment gap.

We aimed at evaluating the efficacy of an app-based treatment for anxiety disorders including exposure in virtual reality.

The randomized controlled trial was conducted in two university outpatient treatment centers in Northern Germany. Patients were diagnosed with agoraphobia (AP; with or without panic disorder; n=103), panic disorder (PD; n=84) or social anxiety disorder (SAD; n=110) and were randomly assigned to either the app-based intervention or treatment as usual (up to 6 sessions of supportive therapy). The app was developed based on evaluated CBT manuals and includes 14 hours of audio and video content and 15 disorder specific virtual reality exposure scenarios. Participants in the intervention groups also received two appointments with a therapist during the app-based treatment. Primary outcome was the change in Beck Anxiety Inventory (BAI) score pre to post (after 6 months). Mixed ANOVAs were conducted in intention to treat and completer analyses. Secondary outcomes were disorder specific questionnaires (Liebowitz Social Anxiety Scale LSAS for SAD and Panic and Agoraphobia Scale PAS for AP and PD) and health related quality of life measured with a single item (L-1).

In the ITT analysis, the interaction effect between group and time was significant in patients with AP as well as in patients with PD (AP: p=.014, partial η²=.06; PD: p=.028, partial η²=.06). This indicates a stronger improvement of symptoms in the intervention group compared to the control group. In patients with SAD, there was no significant interaction effect (p=.101, partial η²=.03). The disorder specific measures LSAS and PAS showed a significantly stronger decrease in the intervention group than in the control group for each of the specific disorders. Concerning quality of life, a stronger improvement in the intervention group was only found in patients with PD.

A stronger symptom reduction in the app-based intervention group compared to the control group could be found in patients with AP (BAI/PAS), PD (BAI/PAS) and SAD (LSAS). This is particularly remarkable as the app was compared to an active control group with up to 6 sessions of psychotherapy. Effect sizes were comparable to those found in studies comparing face-to-face CBT to an active control group. The lack of an intervention-specific effect on BAI scores in patients with SAD might be due to the poor sensitivity of the BAI for the specific symptoms of SAD.

None Declared

Prior trials suggest that intravenous racemic ketamine is a highly effective for treatment-resistant depression (TRD), but phase 3 trials of racemic ketamine are needed.

To assess the acute efficacy and safety of a 4-week course of subcutaneous racemic ketamine in participants with TRD. Trial registration: ACTRN12616001096448 at www.anzctr.org.au.

This phase 3, double-blind, randomised, active-controlled multicentre trial was conducted at seven mood disorders centres in Australia and New Zealand. Participants received twice-weekly subcutaneous racemic ketamine or midazolam for 4 weeks. Initially, the trial tested fixed-dose ketamine 0.5 mg/kg versus midazolam 0.025 mg/kg (cohort 1). Dosing was revised, after a Data Safety Monitoring Board recommendation, to flexible-dose ketamine 0.5–0.9 mg/kg or midazolam 0.025–0.045 mg/kg, with response-guided dosing increments (cohort 2). The primary outcome was remission (Montgomery-Åsberg Rating Scale for Depression score ≤10) at the end of week 4.

The final analysis (those who received at least one treatment) comprised 68 in cohort 1 (fixed-dose), 106 in cohort 2 (flexible-dose). Ketamine was more efficacious than midazolam in cohort 2 (remission rate 19.6% v. 2.0%; OR = 12.1, 95% CI 2.1–69.2, P = 0.005), but not different in cohort 1 (remission rate 6.3% v. 8.8%; OR = 1.3, 95% CI 0.2–8.2, P = 0.76). Ketamine was well tolerated. Acute adverse effects (psychotomimetic, blood pressure increases) resolved within 2 h.

Adequately dosed subcutaneous racemic ketamine was efficacious and safe in treating TRD over a 4-week treatment period. The subcutaneous route is practical and feasible.

Enteral feeding prior to cardiac surgery has benefits in pre-operative and post-operative patient statuses. In 2020, to increase pre-operative feeding for single-ventricle patients prior to stage 1 palliation, an enteral feeding algorithm was created. The aim of this study is to monitor the impact of our practice change with the primary outcome of necrotising enterocolitis incidence from birth to 2 weeks following surgical intervention.

This is a single-site, retrospective cohort study including patients from 1 March, 2018 to 1 July, 2022. Variables assessed include demographics, age at cardiac surgery, primary cardiac diagnosis, necrotising enterocolitis pre-operative and 2 weeks post-operative cardiac surgery, feeding route, feeding type, volume of trophic enteral feeds, and near-infrared spectroscopy.

Following implementation of a pre-operative enteral feeding algorithm, the rate of neonates fed prior to surgery increased (39.5–75%, p = .001). The feedings included a mean volume of 28.24 ± 11.16 ml/kg/day, 83% fed breastmilk only, 44.4% tube fed, and 55.5% of infants had all oral feedings. Comparing enterally fed neonates and those not enterally fed, the necrotising enterocolitis incidence from birth to 2 weeks post-op was not significantly increased (p = 0.926).

As a result of implementing our feeding algorithm, the frequency of infants fed prior to stage I Norwood or Hybrid surgeries increased to 75%, and there was no significant change in the incidence of necrotising enterocolitis. This study confirmed that pre-operative enteral feeds are safe and are not associated with increased incidence of necrotising enterocolitis.

To evaluate the potential superiority of donanemab vs. aducanumab on the percentage of participants with amyloid plaque clearance (≤24.1 Centiloids [CL]) at 6 months in patients with early symptomatic Alzheimer's disease (AD) in phase 3 TRAILBLAZER-ALZ-4 study. The amyloid cascade in AD involves the production and deposition of amyloid beta (Aβ) as an early and necessary event in the pathogenesis of AD.

Participants (n = 148) were randomized 1:1 to receive donanemab (700 mg IV Q4W [first 3 doses], then 1400 mg IV Q4W [subsequent doses]) or aducanumab (per USPI: 1 mg/kg IV Q4W [first 2 doses], 3 mg/kg IV Q4W [next 2 doses], 6 mg/kg IV Q4W [next 2 doses] and 10 mg/kg IV Q4W [subsequent doses]).

Baseline demographics and characteristics were well-balanced across treatment arms (donanemab [N = 71], aducanumab [N = 69]). Twenty-seven donanemab-treated and 28 aducanumab-treated participants defined as having intermediate tau.

Upon assessment of florbetapir F18 PET scans (6 months), 37.9% donanemab-treated vs. 1.6% aducanumab-treated participants achieved amyloid clearance (p < 0.001). In the intermediate tau subpopulation, 38.5% donanemab-treated vs. 3.8% aducanumab-treated participants achieved amyloid clearance (p = 0.008).

Percent change in brain amyloid levels were −65.2%±3.9% (baseline: 98.29 ± 27.83 CL) and −17.0%±4.0% (baseline: 102.40 ± 35.49 CL) in donanemab and aducanumab arms, respectively (p < 0.001). In the intermediate tau subpopulation, percent change in brain amyloid levels were −63.9%±7.4% (baseline: 104.97 ± 25.68 CL) and −25.4%±7.8% (baseline: 102.23 ± 28.13 CL) in donanemab and aducanumab arms, respectively (p ≤ 0.001).

62.0% of donanemab-treated and 66.7% of aducanumab-treated participants reported an adverse event (AE), there were no serious AEs due to ARIA in donanemab arm and 1.4% serious AEs (one event) due to ARIA were reported in aducanumab arm.

This study provides the first active comparator data on amyloid plaque clearance in patients with early symptomatic AD. Significantly higher number of participants reached amyloid clearance and amyloid plaque reductions with donanemab vs. aducanumab at 6 months.

Previously presented at the Clinical Trials on Alzheimer's Disease - 15th Conference, 2022.

Several hypotheses may explain the association between substance use, posttraumatic stress disorder (PTSD), and depression. However, few studies have utilized a large multisite dataset to understand this complex relationship. Our study assessed the relationship between alcohol and cannabis use trajectories and PTSD and depression symptoms across 3 months in recently trauma-exposed civilians.

In total, 1618 (1037 female) participants provided self-report data on past 30-day alcohol and cannabis use and PTSD and depression symptoms during their emergency department (baseline) visit. We reassessed participant's substance use and clinical symptoms 2, 8, and 12 weeks posttrauma. Latent class mixture modeling determined alcohol and cannabis use trajectories in the sample. Changes in PTSD and depression symptoms were assessed across alcohol and cannabis use trajectories via a mixed-model repeated-measures analysis of variance.

Three trajectory classes (low, high, increasing use) provided the best model fit for alcohol and cannabis use. The low alcohol use class exhibited lower PTSD symptoms at baseline than the high use class; the low cannabis use class exhibited lower PTSD and depression symptoms at baseline than the high and increasing use classes; these symptoms greatly increased at week 8 and declined at week 12. Participants who already use alcohol and cannabis exhibited greater PTSD and depression symptoms at baseline that increased at week 8 with a decrease in symptoms at week 12.

Our findings suggest that alcohol and cannabis use trajectories are associated with the intensity of posttrauma psychopathology. These findings could potentially inform the timing of therapeutic strategies.

Researchers have identified genetic and neural risk factors for externalizing behaviors. However, it has not yet been determined if genetic liability is conferred in part through associations with more proximal neurophysiological risk markers.

Participants from the Collaborative Study on the Genetics of Alcoholism, a large, family-based study of alcohol use disorders were genotyped and polygenic scores for externalizing (EXT PGS) were calculated. Associations with target P3 amplitude from a visual oddball task (P3) and broad endorsement of externalizing behaviors (indexed via self-report of alcohol and cannabis use, and antisocial behavior) were assessed in participants of European (EA; N = 2851) and African ancestry (AA; N = 1402). Analyses were also stratified by age (adolescents, age 12–17 and young adults, age 18–32).

The EXT PGS was significantly associated with higher levels of externalizing behaviors among EA adolescents and young adults as well as AA young adults. P3 was inversely associated with externalizing behaviors among EA young adults. EXT PGS was not significantly associated with P3 amplitude and therefore, there was no evidence that P3 amplitude indirectly accounted for the association between EXT PGS and externalizing behaviors.

Both the EXT PGS and P3 amplitude were significantly associated with externalizing behaviors among EA young adults. However, these associations with externalizing behaviors appear to be independent of each other, suggesting that they may index different facets of externalizing.

There has been increased interest in repurposing anti-inflammatories for the treatment of bipolar depression. Evidence from high-income countries suggests that these agents may work best for specific depressive symptoms in a subset of patients with biochemical evidence of inflammation but data from lower-middle income countries (LMICs) is scarce. This secondary analysis explored the relationship between pretreatment inflammatory markers and specific depressive symptoms, clinical measures, and demographic variables in participants with bipolar depression in Pakistan.

The current study is a cross-sectional secondary analysis of a randomized controlled trial of two anti-inflammatory medications (minocycline and celecoxib) for bipolar depression (n = 266). A series of logistic and linear regression models were completed to assess the relationship between C-reactive protein (CRP) (CRP > or < 3 mg/L and log10CRP) and clinical and demographic features of interest and symptoms of depression. Baseline clinical trial data was used to extract clinical and demographic features and symptoms of depression were assessed using the 24-item Hamilton Depression Rating Scale.

The prevalence of low-grade inflammation (CRP > 3 mg/L) in the sample was 70.9%. After adjusting for baseline body mass index, socioeconomic status, age, gender, symptoms related to anhedonia, fatigue, and motor retardation were most associated with low-grade inflammation.

Bipolar disorder (BD) patients from LMICs may experience higher rates of peripheral inflammation than have been reported in Western populations with BD. Future trials of repurposed anti-inflammatory agents that enrich for participants with these symptom profiles may inform the development of personalized treatment for bipolar depression in LMICs.