As clinical trials were rapidly initiated in response to the COVID-19 pandemic, Data and Safety Monitoring Boards (DSMBs) faced unique challenges overseeing trials of therapies never tested in a disease not yet characterized. Traditionally, individual DSMBs do not interact or have the benefit of seeing data from other accruing trials for an aggregated analysis to meaningfully interpret safety signals of similar therapeutics. In response, we developed a compliant DSMB Coordination (DSMBc) framework to allow the DSMB from one study investigating the use of SARS-CoV-2 convalescent plasma to treat COVID-19 to review data from similar ongoing studies for the purpose of safety monitoring.

The DSMBc process included engagement of DSMB chairs and board members, execution of contractual agreements, secure data acquisition, generation of harmonized reports utilizing statistical graphics, and secure report sharing with DSMB members. Detailed process maps, a secure portal for managing DSMB reports, and templates for data sharing and confidentiality agreements were developed.

Four trials participated. Data from one trial were successfully harmonized with that of an ongoing trial. Harmonized reports allowing for visualization and drill down into the data were presented to the ongoing trial’s DSMB. While DSMB deliberations are confidential, the Chair confirmed successful review of the harmonized report.

It is feasible to coordinate DSMB reviews of multiple independent studies of a similar therapeutic in similar patient cohorts. The materials presented mitigate challenges to DSMBc and will help expand these initiatives so DSMBs may make more informed decisions with all available information.

Complex traumas are traumatic experiences that involve multiple interpersonal threats during childhood or adolescence, such as repeated abuse. This type of trauma is hypothesized to lead to more severe psychopathology and poorer cognitive function than other non-complex traumas, such as road traffic accidents. However, empirical testing of this hypothesis has been limited to clinical or convenience samples and cross-sectional designs. To better understand this topic, we aimed to investigate psychopathology and cognitive function in young people exposed to complex, non-complex, or no trauma from a population-representative longitudinal cohort, and to consider the role of pre-existing vulnerabilities.

Participants were from the Environmental Risk (E-Risk) Longitudinal Twin Study, a population-representative birth-cohort of 2,232 children born in England and Wales in 1994-95. At age 18 years (93% participation), we assessed lifetime exposure to complex and non-complex trauma. We also assessed past-year psychopathology including general psychopathology ‘p’ and several psychiatric disorders, as well as current cognitive function including IQ, executive function, and processing speed. Additionally, we prospectively assessed early childhood vulnerabilities including internalizing and externalizing symptoms at age 5, IQ at age 5, family history of mental illness, family socioeconomic status, and sex.

We found that participants who had been exposed to complex trauma had more severe psychopathology and poorer cognitive function across wide-ranging measures at age 18, compared to both trauma-unexposed participants and those exposed to non-complex trauma. Early childhood vulnerabilities had an important role in these presentations, as they predicted risk of later complex trauma exposure, and largely explained associations of complex trauma with cognitive deficits, but not with psychopathology.

By conflating complex and non-complex traumas, current research and clinical practice under-estimate the severity of psychopathology and cognitive deficits linked with complex trauma, as well as the role of pre-existing vulnerabilities. A better understanding of the mental health needs of people exposed to complex trauma and underlying mechanisms could inform the development of new effective interventions.

Children born very preterm (VP) display altered growth in corticolimbic structures compared with full-term peers. Given the association between the cortiocolimbic system and anxiety, this study aimed to compare developmental trajectories of corticolimbic regions in VP children with and without anxiety diagnosis at 13 years.

MRI data from 124 VP children were used to calculate whole brain and corticolimbic region volumes at term-equivalent age (TEA), 7 and 13 years. The presence of an anxiety disorder was assessed at 13 years using a structured clinical interview.

VP children who met criteria for an anxiety disorder at 13 years (n = 16) displayed altered trajectories for intracranial volume (ICV, p < 0.0001), total brain volume (TBV, p = 0.029), the right amygdala (p = 0.0009) and left hippocampus (p = 0.029) compared with VP children without anxiety (n = 108), with trends in the right hippocampus (p = 0.062) and left medial orbitofrontal cortex (p = 0.079). Altered trajectories predominantly reflected slower growth in early childhood (0–7 years) for ICV (β = −0.461, p = 0.020), TBV (β = −0.503, p = 0.021), left (β = −0.518, p = 0.020) and right hippocampi (β = −0.469, p = 0.020) and left medial orbitofrontal cortex (β = −0.761, p = 0.020) and did not persist after adjusting for TBV and social risk.

Region- and time-specific alterations in the development of the corticolimbic system in children born VP may help to explain an increase in anxiety disorders observed in this population.

Complex traumas are traumatic experiences that involve multiple interpersonal threats during childhood or adolescence, such as repeated abuse. These traumas are hypothesised to cause more severe psychopathology and poorer cognitive function than other non-complex traumas. However, empirical testing has been limited to clinical/convenience samples and cross-sectional designs.

To investigate psychopathology and cognitive function in young people exposed to complex, non-complex or no trauma, from a population-representative longitudinal cohort, and to consider the role of pre-existing vulnerabilities.

Participants were from the Environmental Risk Longitudinal Twin Study, a population-representative birth cohort of 2232 British children. At age 18 years (93% participation), we assessed lifetime exposure to complex and non-complex trauma, past-year psychopathology and current cognitive function. We also prospectively assessed early childhood vulnerabilities: internalising and externalising symptoms at 5 years of age, IQ at 5 years of age, family history of mental illness, family socioeconomic status and sex.

Participants exposed to complex trauma had more severe psychopathology and poorer cognitive function at 18 years of age, compared with both trauma-unexposed participants and those exposed to non-complex trauma. Early childhood vulnerabilities predicted risk of later complex trauma exposure, and largely explained associations of complex trauma with cognitive deficits, but not with psychopathology.

By conflating complex and non-complex traumas, current research and clinical practice underestimate the severity of psychopathology, cognitive deficits and pre-existing vulnerabilities linked with complex trauma. A better understanding of the mental health needs of people exposed to complex trauma could inform the development of new, more effective interventions.

To identify attention profiles at 7 and 13 years, and transitions in attention profiles over time in children born very preterm (VP; <30 weeks’ gestation) and full term (FT), and examine predictors of attention profiles and transitions.

Participants were 167 VP and 60 FT children, evaluated on profiles across five attention domains (selective, shifting and divided attention, processing speed, and behavioral attention) at 7 and 13 years using latent profile analyses. Transitions in profiles were assessed with contingency tables. For VP children, biological and social risk factors were tested as predictors with a multinomial logistic regression.

At 7 and 13 years, three distinct profiles of attentional functioning were identified. VP children were 2–3 times more likely to show poorer attention profiles compared with FT children. Transition patterns between 7 and 13 years were stable average, stable low, improving, and declining attention. VP children were two times less likely to have a stable average attention pattern and three times more likely to have stable low or improving attention patterns compared with FT children. Groups did not differ in declining attention patterns. For VP children, brain abnormalities on neonatal MRI and greater social risk at 7 years predicted stable low or changing attention patterns over time.

VP children show greater variability in attention profiles and transition patterns than FT children, with almost half of the VP children showing adverse attention patterns over time. Early brain pathology and social environment are markers for attentional functioning.

Fungal endocarditis classically involves dense heterogenous vegetations. However, several patients with fungal infections were noted to have myocardial changes ranging from focal brightening to nodular thickening of chordae or papillary muscles. This study evaluates whether these findings are associated with fungal infections.

In a retrospective case–control study, paediatric inpatients with fungal infections (positive blood, urine, or catheter tip culture) in a 5-year period were matched 1:1 to inpatients without positive fungal cultures. Echocardiograms were scored on a 5-point scale by two independent readers for presence of myocardial brightenings, nodular thickenings, and vegetations. Clinical data were compared.

Of 67 fungal cases, positive culture sites included blood (n = 44), vascular catheter tip (n = 7), and urine (n = 29); several had multiple positive sites. “Positive” echo findings (score ≥ 2+) were more frequent in the Fungal Group (33 versus 18%, p = 0.04). Fungal Group patients with “positive” versus “negative” echo findings had similar proportion of bacterial infections. Among fungal cases, those with “positive” echo findings had longer hospital length of stay than cases with “negative” echos (median 58 versus 40 days, p = 0.03) but no difference in intensive care unit admission, extracorporeal membranous oxygenation support, or mortality.

Myocardial and papillary muscle brightening with nodular thickening on echocardiogram appear to be associated with fungal infections. There may be prognostic implications of these findings as patients with “positive” echo have longer length of stay. Further studies are needed to better understand the mechanism and temporal progression of these changes and determine the prognostic value of this scoring system.

Patients diagnosed with glioblastoma (GBM) are treated with surgery followed by fractionated radiotherapy with concurrent and adjuvant temozolomide. Patients are monitored with serial magnetic resonance imaging (MRI). However, treatment-related changes frequently mimic disease progression. We reviewed a series of patients undergoing surgery for presumed first-recurrence GBM, where pathology reports were available for tissue diagnosis, in order to better understand factors associated with a diagnosis of treatment-related changes on final pathology.

Patient records at a single institution between 2005 and 2015 were retrospectively reviewed. Pathology reports were reviewed to determine diagnosis of recurrent GBM or treatment effect. Survival analysis was performed interrogating overall survival (OS) and progression-free survival (PFS). Correlation with radiation treatment plans was also examined.

One-hundred-twenty-three patients were identified. One-hundred-sixteen patients (94%) underwent resection and seven underwent biopsy. Treatment-related changes were reported in 20 cases (16%). These patients had longer median OS and PFS from the time of recurrence than patients with true disease progression. However, there was no significant difference in OS from the time of initial diagnosis. Treatment effect was associated with surgery within 90 days of completing radiation. In patients receiving radiation at our institution (n = 53), larger radiation target volume and a higher maximum dose were associated with treatment effect.

Treatment effect was associated with surgery nearer to completion of radiation, a larger radiation target volume, and a higher maximum point dose. Treatment effect was associated with longer PFS and OS from the time of recurrence, but not from the time of initial diagnosis.