The Pediatric Acute Care Cardiology Collaborative (PAC3) previously showed decreased postoperative chest tube duration and length of stay in children undergoing 9 Society of Thoracic Surgeons benchmark operations. Here we report how these gains were sustained over time and spread to 8 additional centers within the PAC3 network.

Patient data were prospectively collected across baseline and intervention phases at the original 9 centres (Pioneer) and 8 new centres (Spread). The Pioneer baseline phase was 6/2017–6/2018 and Spread was 5/2019–9/2019. The Pioneer intervention phase was 7/2018–7/2021 and Spread 10/2019–7/2021. The primary outcome measure was postoperative chest tube duration in hours, with the aim of 20% overall reduction. Balancing measures included chest tube reinsertion and readmission for pleural effusion. Statistical process control methods and traditional statistics were used to analyse outcomes over time.

Among 5,042 patients at 17 centres, demographics were comparable. The Pioneer cohort (n = 3,383) sustained a 22.6% reduction in mean chest tube duration (from 91.9 hours to 70.5 hours), while the Spread cohort (n = 1,659) showed a 9.7% reduction (from 73.1 hours to 66.0 hours) in the first 13 months following intervention. Across both cohorts, rates of reinsertion (2.0% versus 2.1%, p = 0.869) and readmission for effusion did not change (0.3% versus 0.5%, p = 0.285).

This multicenter prospective quality improvement study demonstrated sustained reduction in chest tube duration at 9 centres while successfully spreading improvement to 8 additional centres. This project serves as a model for post-operative multicentre quality improvement across a large cohort of congenital cardiac surgery patients.

Using [18F]altanserin, a serotonin 2A receptor (5-HT2AR) antagonist Positron Emission Tomography (PET) tracer, a positive association between cortical 5-HT2AR binding and the inward-directed facets of neuroticism has been demonstrated in healthy individuals. Psilocybin, a 5-HT2AR agonist, shows promise for the treatment of depression, reducing neuroticism and mood symptoms potentially via hypothalamic-pituitary-adrenal (HPA) modulation. 5-HT2AR and neuroticism are both modulated by HPA axis function.

In this study, we examined whether the association between 5-HT2AR binding and the inward facets of neuroticism can be replicated in an independent healthy cohort using the new 5-HT2AR agonist tracer [11C]Cimbi-36, and if their association is moderated by cortisol awakening response (CAR), an index of HPA axis function. If so, this could advance mechanistic insights into interventions that target the 5-HT2AR and reduce neuroticism.

Eighty healthy volunteers underwent [11C]Cimbi-36 PET scans and completed the NEO personality inventory (NEO-PI-R) for the assessment of neuroticism. Salivary samples were available for determination of CAR in 70 of the participants. Using linear latent variable models, we evaluated the association between 5-HT2AR binding and inward facets of neuroticism, namely depression, anxiety, self-consciousness and vulnerability to stress, and whether CAR moderated this association.

The study confirms the positive association between 5-HT2AR binding and the inward facets of neuroticism (β = 0.01, 95% CI = [0.0005: 0.02], P = 0.04), and this association is independent of CAR (P = 0.33).

The findings prompt consideration of whether novel interventions such as psilocybin that actively targets 5-HT2AR and causes changes in personality could be particularly beneficial if implemented as a targeted approach based on neuroticism profiles.

Adverse factors in the psychosocial work environment are associated with the onset of depression among those without a personal history of depression. However, the evidence is sparse regarding whether adverse work factors can also play a role in depression recurrence. This study aimed to prospectively examine whether factors in the psychosocial work environment are associated with first-time and recurrent treatment for depression.

The study included 24,226 participants from the Danish Well-being in Hospital Employees study. We measured ten individual psychosocial work factors and three theoretical constructs (effort–reward imbalance, job strain and workplace social capital). We ascertained treatment for depression through registrations of hospital contacts for depression (International Statistical Classification of Diseases and Related Health Problems version 10 [ICD-10]: F32 and F33) and redeemed prescriptions of antidepressant medication (Anatomical Therapeutic Chemical [ATC]: N06A) in Danish national registries. We estimated the associations between work factors and treatment for depression for up to 2 years after baseline among those without (first-time treatment) and with (recurrent treatment) a personal history of treatment for depression before baseline. We excluded participants registered with treatment within 6 months before baseline. In supplementary analyses, we extended this washout period to up to 2 years. We applied logistic regression analyses with adjustment for confounding.

Among 21,156 (87%) participants without a history of treatment for depression, 350 (1.7%) had first-time treatment during follow-up. Among the 3070 (13%) participants with treatment history, 353 (11%) had recurrent treatment during follow-up. Those with a history of depression generally reported a more adverse work environment than those without such a history. Baseline exposure to bullying (odds ratio [OR] = 1.72, 95% confidence interval [95% CI]: 1.30–2.32), and to some extent also low influence on work schedule (OR = 1.27, 95% CI: 0.97–1.66) and job strain (OR = 1.24, 95% CI: 0.97–1.57), was associated with first-time treatment for depression during follow-up. Baseline exposure to bullying (OR = 1.40, 95% CI: 1.04–1.88), lack of collaboration (OR = 1.31, 95% CI: 1.03–1.67) and low job control (OR = 1.27, 95% CI: 1.00–1.62) were associated with recurrent treatment for depression during follow-up. However, most work factors were not associated with treatment for depression. Using a 2-year washout period resulted in similar or stronger associations.

Depression constitutes a substantial morbidity burden in the working-age population. Specific adverse working conditions were associated with first-time and recurrent treatment for depression and improving these may contribute to reducing the onset and recurrence of depression.

Pain following surgery for cardiac disease is ubiquitous, and optimal management is important. Despite this, there is large practice variation. To address this, the Paediatric Acute Care Cardiology Collaborative undertook the effort to create this clinical practice guideline.

A panel of experts consisting of paediatric cardiologists, advanced practice practitioners, pharmacists, a paediatric cardiothoracic surgeon, and a paediatric cardiac anaesthesiologist was convened. The literature was searched for relevant articles and Collaborative sites submitted centre-specific protocols for postoperative pain management. Using the modified Delphi technique, recommendations were generated and put through iterative Delphi rounds to achieve consensus

60 recommendations achieved consensus and are included in this guideline. They address guideline use, pain assessment, general considerations, preoperative considerations, intraoperative considerations, regional anaesthesia, opioids, opioid-sparing, non-opioid medications, non-pharmaceutical pain management, and discharge considerations.

Postoperative pain among children following cardiac surgery is currently an area of significant practice variability despite a large body of literature and the presence of centre-specific protocols. Central to the recommendations included in this guideline is the concept that ideal pain management begins with preoperative counselling and continues through to patient discharge. Overall, the quality of evidence supporting recommendations is low. There is ongoing need for research in this area, particularly in paediatric populations.

Sleep disorders and psychiatric disease are closely related, and psychiatric diseases are associated with elevated suicide risks. Yet, the association between sleep disorders and suicide remains to be assessed using a consistent measure of sleep disorders.

The aim of this study was to examine whether people with a hospital-diagnosis of sleep disorders had higher suicide rates than people with no diagnosis.

In a cohort study, nationwide data on all persons aged 15+ years living in Denmark during 1980-2016 were analysed. Sleep disorders were identified through diagnoses recorded during contacts to somatic hospitals. Incidence Rate Ratios (IRR) were estimated using Poisson regression models and adjusted for relevant covariates.

In all, 3,674,563 males and 3,688,164 females were included, of whom 82,223 (2.2%, mean age: 50.2, SD: 17.5) males and 40,003 (1.1%, mean age: 50.6, SD: 19.9) females had sleep disorder diagnoses. Compared to those with no sleep disorders, the adjusted IRRs for suicide were 1.6 (95% CI, 1.4-1.7) and 2.2 (95% CI, 1.8-2.6) for males and females with sleep disorders, respectively. Excess rates for narcolepsy were found for males (IRR:1.2, 95% CI, 1.0-1.5) and females (IRR:3.3, 95% CI, 3.0-4.1), and for sleep apnea in males (IRR:1.8, 95% CI, 1.5-2.2). Males and females had IRRs of 4.1 (95% CI, 3.1-5.5) and 7.0 (95% CI, 4.8-10.1), respectively, 6 months after being diagnosed with a sleep disorder.

Sleep disorders were associated with higher suicide rates even after adjusting for pre-existing mental disorders. Our findings suggest attention towards suicidal ideation in patients suffering from sleep disorders is warranted.

Disclosures and Acknowledgements: Adam Spira has received honoraria for serving as a consultant to Merck and from Springer Nature Switzerland AG for guest editing special issues of Current Sleep Medicine Reports. The other authors report no conflict of in

Melatonin is often prescribed to patients experiencing sleep disturbances, which has been linked to elevated risks of suicide. However, it remains to be assessed whether melatonin is associated with suicide and suicide attempts.

We aimed to investigate whether individuals in treatment with melatonin had higher rates of suicide and suicide attempt when compared to individuals not in treatment.

Using longitudinal data on all persons aged 10+ years living in Denmark between 2007-2016 were obtained. Data from the National Prescription Register was used to identify periods of being in treatment with melatonin based on number of tablets and daily defined dose. Suicide and suicide attempt were identified in hospital and cause of death registries.

Among 5,798,923 included individuals, 10,577 (0.18%) were in treatment with melatonin (mean treatment length 50 days). Out of 5,952 individuals who died by suicide, 22 (0.37%) were in melatonin treatment, while 134 (0.53%) out of 25,136 had a first suicide attempt. After adjustment for sex and age-group, people in treatment with melatonin were found to have a higher rate of suicide (IRR: 4.2; 95% CI, 2.7-6.4) and suicide attempt (IRR: 6.7-fold (95% CI, 5.7-7.9) when compared to those not in treatment.

Treatment with melatonin was associated with higher rates of suicide and suicide attempt. The association might be explained through mediators, such as psychiatric comorbidity and sleep disorders. Our findings indicate that attention towards these issues might be warranted.

No significant relationships.

Benzodiazepines and non-benzodiazepines have been linked to a variety of adverse effects including addiction. Long term use of these drugs has been associated with an increased risk of suicide.

We assessed if individuals in treatment with non-benzodiazepine (n-BZD) and benzodiazepine (BZD) had higher rates of suicide when compared to individuals not in treatment with these drugs.

We utilized a cohort design and national longitudinal data on all individuals aged 10 or above who lived in Denmark between 1995 and 2018. Treatment with either n-BZD or BZD was identified via the Danish National Prescription Registry and suicide deaths were identified in the national cause of death registries.

In a total of 6,494,206 individuals, 10,862 males and 4,214 females died by suicide. Of these, 1,220 (11.2%) males and 792 (18.8%) females had been in treatment with n-BZD, resulting in adjusted IRR for suicide of 4.2 (95% CI, 4.0 – 4.5) and 3.4 (95% CI, 3.1 – 3.7) for males and females, respectively, when compared to those not in treatment. In all, 529 (4.8%) males and 395 (9.3%) females who died by suicide had been in treatment with BZD. The IRRs for suicide were 2.4 (95% CI, 2.2 – 2.6) and 2.5 (95% CI, 2.3 – 2.8) for males and females, respectively, and compared to those not in treatment.

In this study we find that those in treatment experienced higher suicide rates than those not in treatment, this persisted when also adjusting for a large variety of covariates.

No significant relationships.

Glutamatergic dysfunction has been implicated in sensory integration deficits in schizophrenia, yet how glutamatergic function contributes to behavioural impairments and neural activities of sensory integration remains unknown.

Fifty schizophrenia patients and 43 healthy controls completed behavioural assessments for sensory integration and underwent magnetic resonance spectroscopy (MRS) for measuring the anterior cingulate cortex (ACC) glutamate levels. The correlation between glutamate levels and behavioural sensory integration deficits was examined in each group. A subsample of 20 pairs of patients and controls further completed an audiovisual sensory integration functional magnetic resonance imaging (fMRI) task. Blood Oxygenation Level Dependent (BOLD) activation and task-dependent functional connectivity (FC) were assessed based on fMRI data. Full factorial analyses were performed to examine the Group-by-Glutamate Level interaction effects on fMRI measurements (group differences in correlation between glutamate levels and fMRI measurements) and the correlation between glutamate levels and fMRI measurements within each group.

We found that schizophrenia patients exhibited impaired sensory integration which was positively correlated with ACC glutamate levels. Multimodal analyses showed significantly Group-by-Glutamate Level interaction effects on BOLD activation as well as task-dependent FC in a ‘cortico-subcortical-cortical’ network (including medial frontal gyrus, precuneus, ACC, middle cingulate gyrus, thalamus and caudate) with positive correlations in patients and negative in controls.

Our findings indicate that ACC glutamate influences neural activities in a large-scale network during sensory integration, but the effects have opposite directionality between schizophrenia patients and healthy people. This implicates the crucial role of glutamatergic system in sensory integration processing in schizophrenia.

The prevalence of congenital heart disease (CHD) in adults is rising necessitating a greater understanding of acquired diseases such as community-acquired pneumonia, which remains a leading cause of age-related mortality and morbidity in the general population. We hypothesise that the CHD population, given cardiopulmonary mechanics and altered immune function, bears a uniquely high risk for pneumonia-related hospitalisations and mortality.

A countrywide cohort study was performed to calculate the relative risk and cumulative incidence of pneumonia hospitalisations and resultant 30-day mortality amongst the adult CHD population, matched 1:10 with non-CHD persons by gender, age, and adjusted for comorbidities. Cox proportional hazard regression quantified the impact of CHD severity and extracardiac defects.

The CHD cohort includes 17,162 adults. The majority demonstrate mild/moderate CHD complexity. The cumulative incidence of pneumonia hospitalisation was higher for adults with CHD (hazard ratio 1.90; 95% confidence interval: 1.74–2.06) than the comparison cohort. This risk was increased for those with extracardiac defects or a syndrome (hazard ratio: 4.34; 95% confidence interval: 3.39–5.54). Additionally, CHD individuals with severe/univentricular subtypes demonstrate a heightened risk compared to the non-CHD cohort (hazard ratio: 2.35; 95% confidence interval: 1.94–2.84), as well as compared to those with mild/moderate CHD (hazard ratio: 1.28; 95% confidence interval: 1.07–1.53). In addition, pneumonia hospitalisation mortality was elevated above the comparison population with a 30-day mortality rate ratio of 1.31 (95% confidence interval: 1.00–1.73).

Adults with CHD are at elevated risk of pneumonia hospitalisations and pneumonia-associated mortality. This risk is further elevated in those with severe CHD and extracardiac defects.

Advanced practice providers (APPs) are being employed at increasing rates in order to meet new in-hospital care demands. Utilising the Paediatric Acute Care Cardiology Collaborative (PAC3) hospital survey, we evaluated variations in staffing models regarding first-line providers and assessed associations with programme volume, acuity of care, and post-operative length of stay (LOS).

The PAC3 hospital survey defined staffing models and resource availability across member institutions. A resource acuity score was derived for each participating acute care cardiology unit. Surgical volume was obtained from The Society of Thoracic Surgeons database. Pearson’s correlation coefficients were used to evaluate the relationship between staffing models and centre volume as well as unit acuity. A previously developed case-mix adjustment model for total post-operative LOS was utilised in a multinomial regression model to evaluate the association of APP patient coverage with observed-to-expected post-operative LOS.

Surveys were completed by 31 (91%) PAC3 centres in 2017. Nearly all centres (94%) employ APPs, with a mean of 1.7 (range 0–5) APPs present on weekday rounds. The number of APPs present has a positive correlation with surgical volume (r = 0.49, p < 0.01) and increased acuity (r = 0.39, p = 0.03). In the multivariate model, as coverage by APPs increased from low to moderate or high, there was greater likelihood of having a shorter-than-expected post-operative LOS (p < 0.001).

The incorporation of paediatric acute care cardiology APPs is associated with reduced post-operative LOS. Future studies are necessary to understand how APPs impact these patient-specific outcomes.

Adverse psychosocial working environments characterized by job strain (the combination of high demands and low control at work) are associated with an increased risk of depressive symptoms among employees, but evidence on clinically diagnosed depression is scarce. We examined job strain as a risk factor for clinical depression.

We identified published cohort studies from a systematic literature search in PubMed and PsycNET and obtained 14 cohort studies with unpublished individual-level data from the Individual-Participant-Data Meta-analysis in Working Populations (IPD-Work) Consortium. Summary estimates of the association were obtained using random-effects models. Individual-level data analyses were based on a pre-published study protocol.

We included six published studies with a total of 27 461 individuals and 914 incident cases of clinical depression. From unpublished datasets we included 120 221 individuals and 982 first episodes of hospital-treated clinical depression. Job strain was associated with an increased risk of clinical depression in both published [relative risk (RR) = 1.77, 95% confidence interval (CI) 1.47–2.13] and unpublished datasets (RR = 1.27, 95% CI 1.04–1.55). Further individual participant analyses showed a similar association across sociodemographic subgroups and after excluding individuals with baseline somatic disease. The association was unchanged when excluding individuals with baseline depressive symptoms (RR = 1.25, 95% CI 0.94–1.65), but attenuated on adjustment for a continuous depressive symptoms score (RR = 1.03, 95% CI 0.81–1.32).

Job strain may precipitate clinical depression among employees. Future intervention studies should test whether job strain is a modifiable risk factor for depression.