Inadequate recruitment and retention impede clinical trial goals. Emerging decentralized clinical trials (DCTs) leveraging digital health technologies (DHTs) for remote recruitment and data collection aim to address barriers to participation in traditional trials. The ACTIV-6 trial is a DCT using DHTs, but participants’ experiences of such trials remain largely unknown. This study explored participants’ perspectives of the ACTIV-6 DCT that tested outpatient COVID-19 therapeutics.

Participants in the ACTIV-6 study were recruited via email to share their day-to-day trial experiences during 1-hour virtual focus groups. Two human factors researchers guided group discussions through a semi-structured script that probed expectations and perceptions of study activities. Qualitative data analysis was conducted using a grounded theory approach with open coding to identify key themes.

Twenty-eight ACTIV-6 study participants aged 30+ years completed a virtual focus group including 1–4 participants each. Analysis yielded three major themes: perceptions of the DCT experience, study activity engagement, and trust. Participants perceived the use of remote DCT procedures supported by DHTs as an acceptable and efficient method of organizing and tracking study activities, communicating with study personnel, and managing study medications at home. Use of social media was effective in supporting geographically dispersed participant recruitment but also raised issues with trust and study legitimacy.

While participants in this qualitative study viewed the DCT-with-DHT approach as reasonably efficient and engaging, they also identified challenges to address. Understanding facilitators and barriers to DCT participation and DHT interaction can help improve future research design.

The clinical course of major depressive disorder (MDD) is heterogeneous, and early-onset MDD often has a more severe and complex clinical course. Our goal was to determine whether polygenic scores (PGSs) for psychiatric disorders are associated with treatment trajectories in early-onset MDD treated in secondary care.

Data were drawn from the iPSYCH2015 sample, which includes all individuals born in Denmark between 1981 and 2008 who were treated in secondary care for depression between 1995 and 2015. We selected unrelated individuals of European ancestry with an MDD diagnosis between ages 10–25 (N = 10577). Seven-year trajectories of hospital contacts for depression were modeled using Latent Class Growth Analysis. Associations between PGS for MDD, bipolar disorder, schizophrenia, ADHD, and anorexia and trajectories of MDD contacts were modeled using multinomial logistic regressions.

We identified four trajectory patterns: brief contact (65%), prolonged initial contact (20%), later re-entry (8%), and persistent contact (7%). Relative to the brief contact trajectory, higher PGS for ADHD was associated with a decreased odds of membership in the prolonged initial contact (odds ratio = 1.06, 95% confidence interval = 1.01–1.11) and persistent contact (1.12, 1.03–1.21) trajectories, while PGS-AN was associated with increased odds of membership in the persistent contact trajectory (1.12, 1.03–1.21).

We found significant associations between polygenic liabilities for psychiatric disorders and treatment trajectories in patients with secondary-treated early-onset MDD. These findings help elucidate the relationship between a patient's genetics and their clinical course; however, the effect sizes are small and therefore unlikely to have predictive value in clinical settings.

Paediatric ICUs have shared the burden of the COVID-19 pandemic, including subspecialty cardiac ICUs. We sought to address knowledge gaps regarding patient characteristics, acuity, and sequelae of COVID-19 in the paediatric cardiac ICU setting.

Retrospective review of paediatric cardiac ICU admissions with COVID-19-related disease.

Single centre tertiary care paediatric cardiac ICU.

All patients with PCR/antibody evidence of primary COVID-19 infection, and/or Multisystem Inflammatory Syndrome in Children, were admitted between 26 March, 2020 and 31 March, 2021.

None.

Patient-level demographics, pre-existing conditions, clinical symptoms, and outcomes related to ICU admission were captured from medical records.

Among 1064 patients hospitalised with COVID-19/Multisystem Inflammatory Syndrome in Children, 102 patients (9.5%) were admitted to cardiac ICU, 76 of which were symptomatic (median age 12.5 years [IQR 7.5–16.0]). The primary system involved at presentation was cardiovascular in 48 (63%). Vasoactive infusions were required in 62% (n = 47), with eight patients (11%) requiring VA ECMO. Severity of disease was categorised as mild/moderate in 16 (21%) and severe/critical in 60 patients (79%). On univariate analysis, African-American race, presentation with gastrointestinal symptoms or elevated inflammatory markers were associated with risk for severe disease. All-cause death was observed in five patients (7%, n = 5/72) with four patients remaining hospitalised at the time of data query.

COVID-19 and its cardiovascular sequelae were associated with important morbidity and significant mortality in a notable minority of paediatric patients admitted to a paediatric cardiac ICU. Further study is required to quantify the risk of morbidity and mortality for COVID-19 and sequelae.

Clarifying the relationship between depression symptoms and cardiometabolic and related health could clarify risk factors and treatment targets. The objective of this study was to assess whether depression symptoms in midlife are associated with the subsequent onset of cardiometabolic health problems.

The study sample comprised 787 male twin veterans with polygenic risk score data who participated in the Harvard Twin Study of Substance Abuse (‘baseline’) and the longitudinal Vietnam Era Twin Study of Aging (‘follow-up’). Depression symptoms were assessed at baseline [mean age 41.42 years (s.d. = 2.34)] using the Diagnostic Interview Schedule, Version III, Revised. The onset of eight cardiometabolic conditions (atrial fibrillation, diabetes, erectile dysfunction, hypercholesterolemia, hypertension, myocardial infarction, sleep apnea, and stroke) was assessed via self-reported doctor diagnosis at follow-up [mean age 67.59 years (s.d. = 2.41)].

Total depression symptoms were longitudinally associated with incident diabetes (OR 1.29, 95% CI 1.07–1.57), erectile dysfunction (OR 1.32, 95% CI 1.10–1.59), hypercholesterolemia (OR 1.26, 95% CI 1.04–1.53), and sleep apnea (OR 1.40, 95% CI 1.13–1.74) over 27 years after controlling for age, alcohol consumption, smoking, body mass index, C-reactive protein, and polygenic risk for specific health conditions. In sensitivity analyses that excluded somatic depression symptoms, only the association with sleep apnea remained significant (OR 1.32, 95% CI 1.09–1.60).

A history of depression symptoms by early midlife is associated with an elevated risk for subsequent development of several self-reported health conditions. When isolated, non-somatic depression symptoms are associated with incident self-reported sleep apnea. Depression symptom history may be a predictor or marker of cardiometabolic risk over decades.

Somatoform pain disorder (SPD) is frequently associated with sleep disorders, specifically restless legs syndrome and insomnia, which in turn lowers the pain threshold and worsens pain.

The aim of the present study was to investigate differences in wake-EEG by low-resolution electromagnetic tomography (LORETA) and objective and subjective sleep and awakening quality in SPD patients as compared with controls and study acute and chronic effects of trazodone CR on these variables and pain measures.

Fifteen patients with SPD (F45.4) and co-morbid insomnia (F51.0) were compared with 15 controls and participated in a single-blind, placebo-controlled, cross-over study on the acute effect of 100 mg trazodone CR, followed by a six-week open titration period. Statistics involved clinical, EEG-LORETA, PSG and psychometry.

LORETA showed reduced power, mainly in the beta band in almost all pain matrix areas (SI, SII, ACC, SMA, PFC, PPC, insula, amygdala, hippocampus). PSG demonstrated a lack of deep sleep and increased arousals and stage shifts, with opposite changes induced by trazodone after acute and chronic therapy. Improvement of sleep was associated with improvement of pain, evaluated by visual-analog scales.

Our LORETA findings demonstrate a dysfunctional pain modulation in SPD. Trazodone induced changes in subjective and objective sleep and awakening quality that were opposite to the differences between SPD patients and controls (key-lock principle) and associated with pain improvement.

Experience-dependent cortical plasticity observed during post-training sleep has been hypothesized to be part of the global process of memory consolidation. Combining the temporal resolution of microstructure detectors and the spatial resolution of low-resolution brain electromagnetic tomography (LORETA) makes it possible to investigate when and where the experience-dependent reactivation occurs under normal (undisturbed) sleeping conditions.

After an adaptation night, in the 2nd and 3rd night 48 young healthy volunteers were randomly assigned either to a control condition or to an experimental condition (declarative memory task: paired-associate word list or procedural memory task: mirror tracing). Sleep stages and sleep microstructures (slow waves, spindles and theta bursts) were detected automatically by means of the Somnolyzer 24x7. Changes in LORETA sources (experimental minus control night) were correlated with changes in memory performance (morning minus evening recall).

Overnight improvements in the mirror tracing task were correlated with increased slow-wave sources in the right posterior parietal cortex (r = .70,p < 0.01) during NREM sleep and with desynchronized (r = −.76,p < 0.01) and synchronized (r = .62,p < 0.01) rolandic mu rhythm sources during periods with theta bursts in REM sleep. Overnight improvements in the declarative memory task were significantly correlated with increased spindle sources (r = .52, p < .01) in frontal, temporal and cingulate brain regions.

The present study supports the hypotheses of (1) a use-dependent reset of synaptic plasticity during slow-wave sleep (restorative function), (2) an experience-dependent reactivation during spindle episodes (stabilizing function) and (3) an off-line neuronal reprocessing during REM sleep (improvement without further training for novel tasks).

In contrast to the abundance of visual qualitative EEG reports in patho-endocrinology, there is a paucity of quantitative EEG findings.

Electrophysiology may be utilized for differential diagnosis of hypersomnolence.

To investigate long-term daytime sleepiness in a young female neurologist with the tentative diagnosis of narcolepsy in addition to moderate depression/anxiety and congenital thyroid hypoplasia treated with thyroxin.

Three-night polysomnography, multiple sleep latency test (MSLT), visual EEG/ERP-mapping, LORETA, psychometrics and blood analyses were performed.

Polysomnography revealed normal sleep efficiency and sleep architecture, but a high arousal index of up to 63/h TST. The MSLT showed a shortened mean sleep latency of 3.7 min. without REM-sleep onsets, objectifying the high Epworth Sleepiness score of 18. Visual EEG evaluation exhibited a fast alpha rhythm with intermittent theta and delta intrusions and paroxysmal activities. EEG-mapping showed an accelerated dominant frequency and ubiquitous increase in absolute (especially delta and beta) power, ERP revealed shortened N1 latency and very high amplitudes in all components (P300 > 5 SD). LORETA demonstrated significant regional increases in delta, alpha-2 and beta-1 power in the anterior cingulate, orbital, ventromedial, dorsolateral prefrontal cortex and temporal cortex, predominantly right hemispherically. Psychometry showed increased anxiety (SAS) and depression (SDS) and reduced quality of life. Finally, hormonal analysis pointed to thyrotoxicosis factitia (ICD-10 E05.4).

Diagnostic investigations clearly elucidated the pathogenesis of the presenting diagnosis of organic hypersomnia triggered by increased sleep-microarousals due to thyrotoxicosis factitia. Discontinuation of hormone substitution led to a normalization process that will be discussed.

Earlier studies reported that subjective sleep quality correlates with objective polysomnographically measured sleep initiation and continuity, but less with sleep architecture.

This study aimed to investigate relations between subjective and objective sleep in normals (N), insomnia comorbid with generalized anxiety disorder (G) and apnea (A).

One hundred and seventy-seven normals (50.9±19.6a), 100 insomniac G patients (37.9±10.6a) and 51 A patients (51.3±9.7a) completed the self-rating scale for sleep and awakening quality (Saletu et al. 1997) regarding two polysomnographic nights analyzed by the Somnolyzer (Anderer et al. 2005). Correlations were calculated based on changes between the first (adaptation) and second polysomnographic night to diminish inter-individual variances of sleep perception.

In N, subjective sleep quality (S-QUA) demonstrated correlations (p < 0.01) with sleep efficiency (EFF), wake after sleep onset (WASO), S2, S1%, REM, S1, frequency of awakenings (FW), latency to continuous sleep (L-CONT), sleep latency (S-LAT) and slow-wave sleep, while awakening quality (A-QUA) showed weak (p < 0.05) correlations with EFF and WASO. Somatic complaints (S-COM) correlated (p < 0.05) with WASO and REM. In G, correlations (p < 0.01) were obtained between S-QUA and EFF, WASO, S2, L-CONT and S-LAT (p < 0.05), while A-QUA correlated with S2, WASO and EFF. In A, S-QUA correlated (p < 0.01) with EFF, S2, S1%, S2%, L-CONT, WASO and less (p < 0.05) with S-LAT and S1. A-QUA correlated with S2, S2% (p < 0.01), L-CONT and EFF (p < 0.05). S-COM correlated with S-CONT (p < 0.01) and S-LAT (p < 0.05).

EFF, WASO, S2 and less S-LAT determine good S-QUA in all groups.