Childhood trauma and adversity are common across societies and have strong associations with physical and psychiatric morbidity throughout the life-course. One possible mechanism through which childhood trauma may predispose individuals to poor psychiatric outcomes is via associations with brain structure. This study aimed to elucidate the associations between childhood trauma and brain structure across two large, independent community cohorts.

The two samples comprised (i) a subsample of Generation Scotland (n=1,024); and (ii) individuals from UK Biobank (n=27,202). This comprised n=28,226 for mega-analysis. MRI scans were processed using Free Surfer, providing cortical, subcortical, and global brain metrics. Regression models were used to determine associations between childhood trauma measures and brain metrics and psychiatric phenotypes.

Childhood trauma associated with lifetime depression across cohorts (OR 1.06 GS, 1.23 UKB), and related to early onset and recurrent course within both samples. There was evidence for associations between childhood trauma and structural brain metrics. This included reduced global brain volume, and reduced cortical surface area with highest effects in the frontal (β=−0.0385, SE=0.0048, p(FDR)=5.43x10−15) and parietal lobes (β=−0.0387, SE=0.005, p(FDR)=1.56x10−14). At a regional level the ventral diencephalon (VDc) displayed significant associations with childhood trauma measures across both cohorts and at mega-analysis (β=−0.0232, SE=0.0039, p(FDR)=2.91x10−8). There were also associations with reduced hippocampus, thalamus, and nucleus accumbens volumes.

Associations between childhood trauma and reduced global and regional brain volumes were found, across two independent UK cohorts, and at mega-analysis. This provides robust evidence for a lasting effect of childhood adversity on brain structure.

Many clinical trials leverage real-world data. Typically, these data are manually abstracted from electronic health records (EHRs) and entered into electronic case report forms (CRFs), a time and labor-intensive process that is also error-prone and may miss information. Automated transfer of data from EHRs to eCRFs has the potential to reduce data abstraction and entry burden as well as improve data quality and safety.

We conducted a test of automated EHR-to-CRF data transfer for 40 participants in a clinical trial of hospitalized COVID-19 patients. We determined which coordinator-entered data could be automated from the EHR (coverage), and the frequency with which the values from the automated EHR feed and values entered by study personnel for the actual study matched exactly (concordance).

The automated EHR feed populated 10,081/11,952 (84%) coordinator-completed values. For fields where both the automation and study personnel provided data, the values matched exactly 89% of the time. Highest concordance was for daily lab results (94%), which also required the most personnel resources (30 minutes per participant). In a detailed analysis of 196 instances where personnel and automation entered values differed, both a study coordinator and a data analyst agreed that 152 (78%) instances were a result of data entry error.

An automated EHR feed has the potential to significantly decrease study personnel effort while improving the accuracy of CRF data.

There has been a notable increase in requests for psychiatric reports from District Courts for persons remanded to Ireland’s main remand prison, Cloverhill. We aimed to identify if reports were prepared for persons with severe mental illness and if they led to therapeutic benefits such as diversion to healthcare. Measures of equitability between Cloverhill and other District Courts were explored.

For District Court-requested reports completed by the Prison Inreach and Court Liaison Service (PICLS) at Cloverhill Prison from 2015 to 2017, we recorded clinical variables and therapeutic outcomes such as diversion to inpatient psychiatric settings.

Of 236 cases, over half were diverted to inpatient or outpatient psychiatric care. One-third of remand episodes were admitted to a psychiatric hospital, mainly in non-forensic settings. Nearly two-thirds had major mental illness, mainly schizophrenia and related conditions. Almost half had active psychosis. Cases in Cloverhill District Court and other District Courts were similarly likely to have active psychosis (47% overall) and hospital admission (33% overall). Voluntary reports were more likely to identify active psychosis, with over 90% diverted to inpatient or outpatient community treatment settings.

This is the first large scale study of diversion outcomes following requests for psychiatric advice from District Courts in Ireland. Requests were mainly appropriate. Over half led to diversion from the criminal justice system to healthcare settings. There is a need for a complementary network of diversion initiatives at every stage of the criminal justice system to effectively divert mentally ill individuals to appropriate settings at the earliest possible stage.

The Clinical and Translational Science Award Program (CTSA) Trial Innovation Network (TIN) was launched in 2016 to increase the efficiency and effectiveness of multisite trials by supporting the development of national infrastructure. With the advent of the COVID-19 pandemic, it was therefore well-positioned to support clinical trial collaboration. The TIN was leveraged to support two initiatives: (1) to create and evaluate a mechanism for coordinating Data and Safety Monitoring Board (DSMB) activities among multiple ongoing trials of the same therapeutic agents, and (2) to share data across clinical trials so that smaller, likely underpowered studies, could be combined to produce meaningful and actionable data through pooled analyses. The success of these initiatives was understood to be dependent upon the willingness of investigators, study teams, and US National Institutes of Health research networks to collaborate and share information.

To inform these two initiatives, we conducted semistructured interviews with members of CTSA hubs and clinical research stakeholders that probed barriers and facilitators to collaboration. Thematic analysis identified topics relevant across institutions, individuals, and DSMBs.

The DSMB coordination initiative was viewed as less controversial, while the data pooling initiative was seen as complex because of its potential impact on publication, authorship, and the rewards of discovery. Barriers related to resources, centralization, and technical work were significant, but interviewees suggested these could be handled by the provision of central funding and supportive frameworks. The more intractable findings were related to issues around credit and ownership of data.

Based on our interviews, we conclude with nine recommended actions that can be implemented to support collaboration.

Dialysis patients may not have access to conventional renal replacement therapy (RRT) following disasters. We hypothesized that improvised renal replacement therapy (ImpRRT) would be comparable to continuous renal replacement therapy (CRRT) in a porcine acute kidney injury model.

Following bilateral nephrectomies and 2 hours of caudal aortic occlusion, 12 pigs were randomized to 4 hours of ImpRRT or CRRT. In the ImpRRT group, blood was circulated through a dialysis filter using a rapid infuser to collect the ultrafiltrate. Improvised replacement fluid, made with stock solutions, was infused pre-pump. In the CRRT group, commercial replacement fluid was used. During RRT, animals received isotonic crystalloids and norepinephrine.

There were no differences in serum creatinine, calcium, magnesium, or phosphorus concentrations. While there was a difference between groups in serum potassium concentration over time (P < 0.001), significance was lost in pairwise comparison at specific time points. Replacement fluids or ultrafiltrate flows did not differ between groups. There were no differences in lactate concentration, isotonic crystalloid requirement, or norepinephrine doses. No difference was found in electrolyte concentrations between the commercial and improvised replacement solutions.

The ImpRRT system achieved similar performance to CRRT and may represent a potential option for temporary RRT following disasters.

One year of antipsychotic treatment from symptom remission is recommended following a first episode of psychosis (FEP).

To investigate the effectiveness of commonly used antipsychotic medications in FEP.

A retrospective cohort study of naturalistic treatment of patients (N = 460) accepted by FEP services across seven UK sites. Treatment initiation to all-cause discontinuation determined from case files.

Risk of treatment discontinuation is greatest within 3 months of treatment initiation. Risperidone had longest median survival time. No significant differences were observed in time to discontinuation between commonly used antipsychotics on multivariable Cox regression analysis. Poor adherence and efficacy failure were the most common reasons for discontinuation.

Effectiveness differences appear not to be a current reason for antipsychotic choice in FEP. Adherence strategies and weighing up likely adverse effects should be the clinical focus.