Childhood and lifetime adversity may reduce brain serotonergic (5-HT) neurotransmission by epigenetic mechanisms.

We tested the relationships of childhood adversity and recent stress to serotonin 1A (5-HT1A) receptor genotype, DNA methylation of this gene in peripheral blood monocytes and in vivo 5-HT1A receptor binding potential (BPF) determined by positron emission tomography (PET) in 13 a priori brain regions, in participants with major depressive disorder (MDD) and healthy volunteers (controls).

Medication-free participants with MDD (n = 192: 110 female, 81 male, 1 other) and controls (n = 88: 48 female, 40 male) were interviewed about childhood adversity and recent stressors and genotyped for rs6295. DNA methylation was assayed at three upstream promoter sites (−1019, −1007, −681) of the 5-HT1A receptor gene. A subgroup (n = 119) had regional brain 5-HT1A receptor BPF quantified by PET. Multi-predictor models were used to test associations between diagnosis, recent stress, childhood adversity, genotype, methylation and BPF.

Recent stress correlated positively with blood monocyte methylation at the −681 CpG site, adjusted for diagnosis, and had positive and region-specific correlations with 5-HT1A BPF in participants with MDD, but not in controls. In participants with MDD, but not in controls, methylation at the −1007 CpG site had positive and region-specific correlations with binding potential. Childhood adversity was not associated with methylation or BPF in participants with MDD.

These findings support a model in which recent stress increases 5-HT1A receptor binding, via methylation of promoter sites, thus affecting MDD psychopathology.

To determine whether a structured OPAT program supervised by an infectious disease physician and led by an OPAT nurse decreased hospital readmission rates and OPAT-related complications and whether it affected clinical cure. We also evaluated predictors of readmission while receiving OPAT.

A convenience sample of 428 patients admitted to a tertiary-care hospital in Chicago, Illinois, with infections requiring intravenous antibiotic therapy after hospital discharge.

In this retrospective, quasi-experimental study, we compared patients discharged on intravenous antimicrobials from an OPAT program before and after implementation of a structured ID physician and nurse-led OPAT program. The preintervention group consisted of patients discharged on OPAT managed by individual physicians without central program oversight or nurse care coordination. All-cause and OPAT-related readmissions were compared using the χ2 test. Factors associated with readmission for OPAT-related problems at a significance level of P < .10 in univariate analysis were eligible for testing in a forward, stepwise, multinomial, logistic regression to identify independent predictors of readmission.

In total, 428 patients were included in the study. Unplanned OPAT-related hospital readmissions decreased significantly after implementation of the structured OPAT program (17.8% vs 7%; P = .003). OPAT-related readmission reasons included infection recurrence or progression (53%), adverse drug reaction (26%), or line-associated issues (21%). Independent predictors of hospital readmission due to OPAT-related events included vancomycin administration and longer length of outpatient therapy. Clinical cure increased from 69.8% before the intervention to 94.9% after the intervention (P < .001).

A structured ID physician and nurse-led OPAT program was associated with a decrease in OPAT-related readmissions and improved clinical cure.

Burnout is well characterised in physicians and residents but not in paediatric cardiology fellows, and few studies follow burnout longitudinally. Training-specific fears have been described in paediatric cardiology fellows but also have not been studied at multiple time points. This study aimed to measure burnout, training-specific fears, and professional fulfilment in paediatric cardiology fellows with the attention to time of year and year-of-training.

This survey-based study included the Professional Fulfillment Index and the Impact of Events Scale as well as an investigator-designed Fellow Fears Questionnaire. Surveys were distributed at three-time points during the academic year to paediatric cardiology fellows at a large Midwestern training programme. Fellow self-reported gender and year-of-training were collected. Descriptive analyses were performed.

10/17 (59%) of fellows completed all surveys; 60% were female, 40% in the first-year class, 40% in the second-year class, and 20% in the third-year class. At least half of the fellows reported burnout at each survey time point, with lower mean professional fulfilment scores. The second-year class, who rotate primarily in the cardiac ICU, had higher proportions of burnout than the other two classes. At least half of fellows reported that they “often” or “always” worried about not having enough clinical knowledge or skills and about work–life balance.

Paediatric cardiology fellows exhibit high proportions of burnout and training-specific fears. Interventions to mitigate burnout should be targeted specifically to training needs, including during high-acuity rotations.

Virtual reality has emerged as a unique educational modality for medical trainees. However, incorporation of virtual reality curricula into formal training programmes has been limited. We describe a multi-centre effort to develop, implement, and evaluate the efficacy of a virtual reality curriculum for residents participating in paediatric cardiology rotations.

A virtual reality software program (“The Stanford Virtual Heart”) was utilised. Users are placed “inside the heart” and explore non-traditional views of cardiac anatomy. Modules for six common congenital heart lesions were developed, including narrative scripts. A prospective case–control study was performed involving three large paediatric residency programmes. From July 2018 to June 2019, trainees participating in an outpatient cardiology rotation completed a 27-question, validated assessment tool. From July 2019 to February 2020, trainees completed the virtual reality curriculum and assessment tool during their cardiology rotation. Qualitative feedback on the virtual reality experience was also gathered. Intervention and control group performances were compared using univariate analyses.

There were 80 trainees in the control group and 52 in the intervention group. Trainees in the intervention group achieved higher scores on the assessment (20.4 ± 2.9 versus 18.8 ± 3.8 out of 27 questions answered correctly, p = 0.01). Further analysis showed significant improvement in the intervention group for questions specifically testing visuospatial concepts. In total, 100% of users recommended integration of the programme into the residency curriculum.

Virtual reality is an effective and well-received adjunct to clinical curricula for residents participating in paediatric cardiology rotations. Our results support continued virtual reality use and expansion to include other trainees.

Patients with single ventricle heart disease are living into adulthood due to medical and surgical advancements but have significant physical comorbidities and an increased risk for psychological comorbidities compared to healthy subjects or those with other CHD diagnoses. This study aimed to systematically review psychological functioning in paediatric single ventricle heart disease.

Literature was searched using PubMed, Embase, PsycInfo, CINAHL Complete and Scopus. Peer-reviewed articles that included patients ages 0–25 years with single ventricle heart disease, and quantitative measures of psychological outcomes were included. Meta-analysis using a fixed-effect model was conducted for internalising and externalising t-scores, utilised by the Achenbach Child Behavior Checklist.

Twenty-nine records met the criteria for inclusion. 13/24 studies demonstrated increased risk for internalising disorders, such as anxiety/depression; 16/22 studies demonstrated risk for externalising disorders, such as attention or behavioural problems. Meta-analysis of four studies revealed that paediatric single ventricle heart disease patients had no significant difference in internalising and externalising t-scores compared to normative values.

The current review demonstrates the need for further studies to better understand psychological functioning in patients with single ventricle heart disease, with a majority of studies showing increased risk for psychological problems despite no difference seen in a small meta-analysis. This summary of the literature underscores the need for regular psychological screening, earlier intervention and integrated mental health therapies in paediatric single ventricle heart disease.

Optimal preoperative therapy regimen in the treatment of resectable retroperitoneal sarcoma (RPS) remains unclear. This study compares the impact of preoperative radiation, chemoradiation and chemotherapy on overall survival (OS) in RPS patients.

The National Cancer Database (NCDB) was queried for patients with non-metastatic, resectable RPS (2006–15). The primary endpoint was OS, evaluated by Kaplan–Meier method, log-rank test, Cox multivariable analysis and propensity score matching.

A total of 1,253 patients met the inclusion criteria, with 210 patients (17%) receiving chemoradiation, 850 patients (68%) receiving radiation and 193 patients (15%) receiving chemotherapy. On Cox multivariable analysis, when compared to preoperative chemoradiation, preoperative radiation was not associated with improved OS (hazards ratio [HR] 0·98, 95% CI 0·76–1·25, p = 0·84), while preoperative chemotherapy was associated with worse OS (HR 1·64, 95% CI 1·24–2·18, p < 0·001). Similar findings were observed in 199 and 128 matched pairs for preoperative radiation and chemotherapy, respectively, when compared to preoperative chemoradiation.

Our study suggested an OS benefit in using preoperative chemoradiation compared to chemotherapy alone, but OS outcomes were comparable between preoperative chemoradiation and radiation alone.

Despite its efficacy in treating comorbid insomnia and depression, cognitive behavioral therapy for insomnia (CBT-I) is limited in its accessibility and, in many countries, cultural compatibility. Smartphone-based treatment is a low-cost, convenient alternative modality. This study evaluated a self-help smartphone-based CBT-I in alleviating major depression and insomnia.

A parallel-group randomized, waitlist-controlled trial was conducted with 320 adults with major depression and insomnia. Participants were randomized to receive either a 6-week CBT-I via a smartphone application, proACT-S, or waitlist condition. The primary outcomes included depression severity, insomnia severity, and sleep quality. The secondary outcomes included anxiety severity, subjective health, and acceptability of treatment. Assessments were administered at baseline, post-intervention (week 6) follow-up, and week 12 follow-up. The waitlist group received treatment after the week 6 follow-up.

Intention to treat analysis was conducted with multilevel modeling. In all but one model, the interaction between treatment condition and time at week 6 follow-up was significant. Compared with the waitlist group, the treatment group had lower levels of depression [Center for Epidemiologic Studies Depression Scale (CES-D): Cohen's d = 0.86, 95% CI (−10.11 to −5.37)], insomnia [Insomnia Severity Index (ISI): Cohen's d = 1.00, 95% CI (−5.93 to −3.53)], and anxiety [Hospital Anxiety and Depression Scale – Anxiety subscale (HADS-A): Cohen's d = 0.83, 95% CI (−3.75 to −1.96)]. They also had better sleep quality [Pittsburgh Sleep Quality Index (PSQI): Cohen's d = 0.91, 95% CI (−3.34 to −1.83)]. No differences across any measures were found at week 12, after the waitlist control group received the treatment.

proACT-S is an efficacious sleep-focused self-help treatment for major depression and insomnia.

ClinicalTrials.gov, NCT04228146. Retrospectively registered on 14 January 2020. https://clinicaltrials.gov/ct2/show/NCT04228146

Induction chemotherapy (iC) followed by concurrent chemoradiation has been shown to improve overall survival (OS) for locally advanced pancreatic cancer (LAPC). However, the survival benefit of stereotactic body radiation therapy (SBRT) versus conventionally fractionated radiation therapy (CFRT) following iC remains unclear.

The National Cancer Database (NCDB) was queried for primary stage III, cT4N0-1M0 LAPC (2004–15). Kaplan–Meier analysis, Cox proportional hazards method and propensity score matching were used.

Among 872 patients, 738 patients underwent CFRT and 134 patients received SBRT. Median follow-up was 24·3 and 22·9 months for the CFRT and SBRT cohorts, respectively. The use of SBRT showed improved survival in both the multivariate analysis (hazards ratio 0·78, p = 0·025) and 120 propensity-matched pairs (median OS 18·1 versus 15·9 months, p = 0·004) compared to the CFRT.

This NCDB analysis suggests survival benefit with the use of SBRT versus CFRT following iC for the LAPC.

This National Cancer Database (NCDB) analysis was performed to evaluate the outcomes of adjuvant chemotherapy (AC) versus observation for resected pancreatic adenocarcinoma treated with neoadjuvant therapy (NT).

The NCDB was queried for primary stages I–II cT1-3N0-1M0 resected pancreatic adenocarcinoma treated with NT (2004–2015). Baseline patient, tumour and treatment characteristics were extracted. The primary end point was overall survival (OS). With a 6-month conditional landmark, Kaplan–Meier analysis, multivariable Cox proportional hazards method and 1:1 propensity score matching was used to analyse the data.

A total of 1,737 eligible patients were identified, of which 1,247 underwent post-operative observation compared to 490 with AC. The overall median follow-up was 34·7 months. The addition of AC showed improved survival on the multivariate analysis (HR 0·78, p < 0·001). AC remained statistically significant for improved OS, with a median OS of 26·3 months versus 22·3 months and 2-year OS of 63·9% versus 52·9% for the observation cohort (p < 0·001). Treatment interaction analysis showed OS benefit of AC for patients with smaller tumours.

Our findings suggest a survival benefit for AC compared to observation following NT and surgery for resectable pancreatic adenocarcinoma, especially in patients with smaller tumours.

To describe epidemiologic and genomic characteristics of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak in a large skilled-nursing facility (SNF), and the strategies that controlled transmission.

This cohort study was conducted during March 22–May 4, 2020, among all staff and residents at a 780-bed SNF in San Francisco, California.

Contact tracing and symptom screening guided targeted testing of staff and residents; respiratory specimens were also collected through serial point prevalence surveys (PPSs) in units with confirmed cases. Cases were confirmed by real-time reverse transcription–polymerase chain reaction testing for SARS-CoV-2, and whole-genome sequencing (WGS) was used to characterize viral isolate lineages and relatedness. Infection prevention and control (IPC) interventions included restricting from work any staff who had close contact with a confirmed case; restricting movement between units; implementing surgical face masking facility-wide; and the use of recommended PPE (ie, isolation gown, gloves, N95 respirator and eye protection) for clinical interactions in units with confirmed cases.

Of 725 staff and residents tested through targeted testing and serial PPSs, 21 (3%) were SARS-CoV-2 positive: 16 (76%) staff and 5 (24%) residents. Fifteen cases (71%) were linked to a single unit. Targeted testing identified 17 cases (81%), and PPSs identified 4 cases (19%). Most cases (71%) were identified before IPC interventions could be implemented. WGS was performed on SARS-CoV-2 isolates from 4 staff and 4 residents: 5 were of Santa Clara County lineage and the 3 others were distinct lineages.

Early implementation of targeted testing, serial PPSs, and multimodal IPC interventions limited SARS-CoV-2 transmission within the SNF.

The Cognitive Battery of the National Institutes of Health Toolbox (NIH-TB) is a collection of assessments that have been adapted and normed for administration across the lifespan and is increasingly used in large-scale population-level research. However, despite increasing adoption in longitudinal investigations of neurocognitive development, and growing recommendations that the Toolbox be used in clinical applications, little is known about the long-term temporal stability of the NIH-TB, particularly in youth.

The present study examined the long-term temporal reliability of the NIH-TB in a large cohort of youth (9–15 years-old) recruited across two data collection sites. Participants were invited to complete testing annually for 3 years.

Reliability was generally low-to-moderate, with intraclass correlation coefficients ranging between 0.31 and 0.76 for the full sample. There were multiple significant differences between sites, with one site generally exhibiting stronger temporal stability than the other.

Reliability of the NIH-TB Cognitive Battery was lower than expected given early work examining shorter test-retest intervals. Moreover, there were very few instances of tests meeting stability requirements for use in research; none of the tests exhibited adequate reliability for use in clinical applications. Reliability is paramount to establishing the validity of the tool, thus the constructs assessed by the NIH-TB may vary over time in youth. We recommend further refinement of the NIH-TB Cognitive Battery and its norming procedures for children before further adoption as a neuropsychological assessment. We also urge researchers who have already employed the NIH-TB in their studies to interpret their results with caution.